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αlpha™ User manual

1. Forename s Anne Machine a 5 D Q 0 Hospital Number A127126 Number fetuses Date of birth LMP 02 03 13 Weight 65 4 kg e BPD 2 mm Type of measure Correction BPD 1 mm Di CT a sf Ethnic group Integrated screening Caucasian v v Auto Save Previous NTD None Sonographer Q N Z Edit started 06 08 2013 15 57 55 Sample number 1 2391897 1of1 05 08 13 Previous Down s None Age at prev preg Date of sample Prev Pre eclampsia No v Sample number 2 Interpretation Down s NTD and pre eclamy Date of 2nd sample Smoker No p MS AFP ng mL Diabetes None IVF pregnancy Donor date of birth Date embryo transfer 0 No v uE3 ng mL T hCG 2T miu mL Inh A pg mL Date egg collection NT mm Doctor 00000004 Dr Gareth Hills Q PAPP A mg L Report address 00000002 Charterhouse Su Q GA by scan Sp On FB hCG 1T ng mL Nasal bone fetus 1 Nasal bone fetus 2 Number fetuses Scan measure 17 0 17 1 13 01 14 Figure 64 Edit report alph d Version 8 When you have made the required changes press Correction to preview the revised report and to print and edit it See Figure 65 NOTE The revised report is only saved in the alpha da
2. D a SOL Manager ES Select server SQLEXPRESS v Refresh Log on credentials v Windows Authentication User name Password Connect to a database Existing Attach d SQL database file FAsql copy mdf Browse SQL log file F sql copy ldf Browse V Copy to C Program Files Microsoft SQL Server MSSQL1 _ Browse Database Name alphas Test connection OK Cancel Figure 11 Attaching a new database to alpha Adding another computer to a multiuser configuration You can add another computer to a multiuser configuration with the following procedure You may require administrator rights on the new computer to follow this procedure 1 alpha Locate the alpha 8 installation CD or the MSI file used to install alpha 8 The name of this file will be of the type SetupAlpha8 0 xxxxx yy msi Contact your alpha distributor if you are unable to find this On the computer you wish to add to the multiuser configuration run the alpha 8 MSI installation file A screen similar to that in Figure 12 will be shown Select Components and this will install the components necessary to run the alpha software Version 8 Page 31 4 Make a shortcut from the desktop to the file alpha exe in the folder on server containing the alpha 8 software 5 Insert the dongle into a free USB port in the new computer see section 2 2 2 Please wait
3. Language 3 report of third Integer v w doctor Reason for positive Reason code or un interpretable v v i result Integrated test flags v Age at expected Age at EDD calculated data of delivery Integer v v Derived Whole Years calculated Donor s age at EES expected date of Integer v v v calculated deliver y wi Expected date of delivery calculated If there is a value then MoM values were adjusted using EDD calculated Vv Date v Completed years Long RFP Pointer Integer Vv Vv measurements taken in a previous 8 Record number of matched pregnancy pregnancy Version 8 Page 212 Maternal Serum Comment t and export OH sj o Oo ab E 2 2 D c O ES Been O O z e 2 x lt c iL ui Type of l Dae v v v ae Entered rate v ae Entered wi wi wi Data transfer impor lt lt AS IS LI m HD O O lt lt ht RE Marker6 Assay Date usedtodetermine Date v a2 Entered O Marker Assay Date o ect regression Dae v v v v a2 Deel Marker 12 Assay Date Entered AFP level flag pe Derived UES level flag Specifies if the hCG level flag marker measurement was Marker 4 level flag below the entered Marker 5 level flag value Marker 6 level flag AS lt ers LILIS ISIS lt Derived Derived Contains lt if measurement was below the entered Derive
4. vis Type of 8 l Database record Record number Integer v number Forename s Patients forename Text 5 a Patient ID code identification code Address 1 Patient s address Text Address 2 Patient s address Text Vv O1 wi wi wi wi wi SS wi wi 4 OD Ka O1 alo AE a Address 3 Patient s address Text Postcode Patients post code Text Phone number Aen POONG Text number Doctor Doctor s name or Text 50 doctor code Report address Address code Text 8 Patient s date of birth Age at expected date of delivery in Integer a v v wi wi wi wi wi wi wi Date of birth Date v v v v wi wi esch Age at EDD Version 8 Bn O E Bn O Us lt Ee gt O ZS LL import and export CH Ou 2 Ben Ou OH Been O CH Ben Ou j c LLI Entered Entered Entered Comment Mandatory import field Doctor s name or code up to eight letters or numbers identifying the doctor for this report For import and export see note 12 Code up to eight letters or numbers identifying the address for this report For import and export see note 12 Mandatory import field Whole Years 12 years lt age lt 55 years Page 193 Maternal Serum Type of data entry screen J fJ TE menstrual period S Expected date of Ka LMP or EDD from 1 LMP or EDD date certain GA from LMP Tex
5. Appendix D Equations used in calculations Median Equations Marker Expected median Equation type Second trimester i 70 A x 0 9996379 GA ays 170 82 x GA days 170 82 Log quadratic S A B x e 0 08268 x GA days 100 Total hCG Exponential 7 Free B hCG A B x e 0 054975 x GA days 100 Exponential AX 1 000429 GA days 120 x GA days 120 Log quadratic 62 Inhibin A log inhibin A k 0 0003838 x GA days 0 0002311 x GA days 120 0 000004029 x GA days 120 SS translucency Ductus venosus Constant Constant pulsatility index Log cubic 97 m oO alpha Version 8 Page 187 Weight Adjustment One of the following equations can be Log linear 1 Adjusted MoM 4 x BWeight kg g All markers MoM Ee 4 wessen Linear reciprocal 7 Weight kg Ultrasound gestation BPD CRL AC One of the following equations can be chosen Equation Type Linear GA days A Bxx mm Quadratic GA days A B x x mm C x x mm Cubic GA days A B x x mm C x x mm D x x mm Ultrasound gestation Head Circumference measured g The following equation can be selected for gestational age when head circumference is directly measured _ 0 010451HC 0 000029919HC2 0 43156 x 107 HC 41 854 Gestational age days 7 x e where HC head circumference measured in mm Ultrasound gestation Head Circumference derive
6. REPORT DATE RANGE All periods ei aom CODES Median uE3 Include all codes OPTIONS alpha displays a graph showing An error bar is shown for each Eloge the observed median MoM for the measurement and points which are On selected marker in each day week outside the 95 confidence interval month or quarter around 1 MoM are coloured red Refresh results Jan 2003 Mar 2003 May 2003 Jul 2003 Sep 2003 Report Date Count Median MoM SE Selecting this button shows a tabulation of the All periods 1812 1 00 Q marker between the dates specified by the orange 15 12 2002 20 12 2003 1770 1 00 and purple lines Figure 86 Median Analysis for uE The Median Analysis graph can be moved horizontally and vertically by moving the mouse with the right button held down Moving the mouse wheel will zoom in and out of the graph Moving the mouse with the mouse wheel held down will select an area to zoom into when the mouse wheel is released Pressing the Tabulated Selected Period button shows a tabulation see Section 5 2 of the selected marker for the date range specified by the position of the orange and purple lines Press the Print button for a printed copy of the Median Analysis Patterns of markers which are consistently high or low may indicate that the current estimates of the normal median are incorrect and need to be changed See Section 5 9 4 for further information on monitoring and
7. 035 01 01 02 Forename s Jenny 050 01 01 02 Hospital Number 1342ZYD 055 01 01 02 Date of birth 02 03 82 060 01 01 02 LMP 10 09 13 067 01 01 02 EDD 20 06 14 070 01 01 02 Date of sample 07 12 13 071 01 01 02 Date of 2nd sample 07 01 14 085 01 01 02 Sample number 1 52413 100 01 01 02 Sample number 2 52601 120 01 01 02 Previous NTD None 125 01 01 02 Previous Down s None 127 01 01 02 Prev Pre eclampsia No 130 01 01 02 Insulin dependent diabetes None 131 01 01 02 Smoker No Figure 61 Part of report exported in packet format 4 3 Searching You use the search option to reprint copies of reports from the database or to find patient records that have been entered but not yet reported alph a Version 8 4 3 1 Basic search A simple search is performed by entering a search term in the text box in the patients screen Figure 53 For example the search for JONES in Figure 62 finds one patient in a batch and one patient in the alpha database with the last name JONES lf text is entered as a search term alpha will search all text fields for exact matching entries or for entries with begin with the search term For example the search term JEN would return matches for a record with first name JENNIFER and also a record with last name JENKINS If a date is entered as a search term alpha will sea
8. Been Ur OU Le Ben Fe vis First or repeat No longer used Entered Type of e First extra fetus Text 5 EEE Measurement 1 measurement Type of ease Second extra fetus Text 5 Measurement 2 measurement Femur length 1 eh etus Temur Integer I3 Entered length Femur length 2 S laidS remit Integer I3 Entered lengh measurement ee Date GA by clinical measurement Date 312 Entered estimated Date oral Date OC stopped contraception Date 312 Entered stopped No longer used geg ane kgs or lbs Weight Weight Text 6 F5 Entered 30 kg lt weight lt 200 kg 65 lbs lt weight lt 440 Ibs RE TAE pat e Previous Down e EE Integer N Entered SE dene pregnancy if any non inherited Version 8 Page 196 Maternal Serum Comment Benn O mm ES 3 gt Ke x D c Le O z Sc O CH o 2 D x Q m E G IL LLI j T Ou N c st Been Ur OU Le Ben Fe vis Type of ech E NN s syndrome Number of rae pregnancies if any inherited translocation type unknown 0 none Entered 1 one 2 two or more I1 Entered B hte insulin dependent diabetes mellitus 1 black 2 non black 3 not known Entered 4 group 4 5 group 5 6 group 6 v v 32 Entered Mandatory import fied import Mandatory import fied Je e GG l Previous NTD Integer affected with open NTD Ethnic group Ethnic group I
9. The tabulation information is transferred to the regression facility by pressing the Regression button in the Tabulation screen Figure 101 shows the regression of the data shown in Figure 116 alph d Version 8 L ro CO alpha 8 0 Regressions MS AFP KR Regression details Regression Gestational age Observed axBGA days MARKER UNITS alpha plots the observed AFP iu mL measurements yellow circles and A the expected AFP measurements B PLOT OPTIONS blue line from the regression _ Logarithmic Y Axis equation which alpha fitted to the measurements CH Update medians alpha calculates This represents a 16 4 increase the coefficients in in median MS AFP per week mpare the new the regression Ss REH equation for this alpha indicates the regression with MAk rate of change with the regression gestational age currently in use OVERLAY SETTING No overlay M Median MS AFP iu mL CH D Use the overlay setting to 120 130 Gestational Age Days Median GA Days Observed iu mL Expected 102 21 9 109 25 5 These are the results transferred from the tabulation 115 29 25 121 34 128 136 143 Figure 101 Regression of MS AFP with gestational age If the data is to be entered manually a table should be prepared showing for each gestational age or CRL group the number of samples and median marker level See section 3 13 3 When the Regres
10. F A 4 S e the field to the left in the missin To 00000102 14 oe information results j 00000103 25 12 0 4 0 00000104 20 0 0 15 0 00000106 8 0 0 125 O EE e E Press the button to remove this column from the results 00000108 50 20 60 00000109 13 30 8 15 4 00000110 33 15 2 6 1 00000111 1 0 0 0 0 00000112 60 SF ie Mate OT A i 00000113 13 23 1 7 7 00000114 31 16 1 0 0 00000115 5 0 0 0 0 00000116 17 11 8 0 0 00000117 13 77 154 00000119 27 11 1 148 00000120 18 00 111 00000121 10 0 0 10 0 00000122 1 0 0 0 0 00000123 78 3 9 00000124 12 5 3 1 00000125 0 0 0 0 Figure 88 Missing information adding additional fields 5 6 Nuchal translucency monitor The Nuchal Translucency Monitor feature in alpha provides a facility for quick and easy monitoring of sonographer or site specific nuchal translucency medians This will be useful for users who need to regularly monitor NT medians for a large number of different sonographers When the NT monitor option is selected a screen similar to that in Figure 89 is shown For each selected sonographer or address code a graph showing the NT measurements taken and fitted regression equation is displayed for the selected date range The number of measurements median MoM standard deviation and increase per week is also displayed The graph can be plotted with a linear or logarithmic Y axis The axis range will scale automatically t
11. GA by scan Scan Type of ultrasound measurement for Entered GA by scan measure Integer y 4 other 5 not known Version 8 Page 219 O D Type of field Comment Field name Dag hm O Q gt lt ce Cc bel Bn _ o CO z gt Q D O ES Been Oo D 2 D g x lt c LL LL T Ou N ur c lt x Ben Ur OU c ul Ben Fe vis impor Date of ultrasound Date of scan Date v scan Amniotic Fluid wi 1 BPD 2 CRL 3 AC 4 HC 3l2 Entered 10 mm lt BPD lt 110 mm 5 mm lt CRL lt 100 mm 30 mm lt AC lt 400 mm 80 mm lt HC lt 320 mm i Ultrasound machine number Number of fetuses Date of scan Number B from ultrasound Integer v fetuses scan Date of scan Type of Type of ultrasound M Integer v measure measurement Date of scan First fetus Text Measurement measurement 1 A Date of scan Second fetus Text 5 Measurement 2 measurement First fetus femur Integer v Femur length 2 i EEN Integer v v DN m Version 8 Page 220 Date of scan Machine Integer v on 1 BPD v l1 Entered 2 CRL 3 AC Vv wi wi wi Vv m m m v m m m m Amniotic Fluid Comment OH Se 3 E O 2 2x S maii o os O O Do2 D x 2 E LC LL LLI T Ou N ur Leg st Ben Ur OU c ul Ben Fe vis 1 black
12. Is a peod From False Av rale M ass ci False positive rate 01 01 1380 be 20 10 2006 H S Deech rale i Fact bimeater ZS 626 Detection rate e Becond reese ER DAPR CO 1 64 ee ibe i Odds of being affected given a Ce iti Insert isi Refresh b 4 Wadan PradiHeg riak positive result Peck ecl ck caii Mechel e ba d Dow s Uralleczed Obid prevalence 1 ml gt in D Tey P a75 Validation plot 1m B IEN ro 4 F43 943 1in131 Je 350 38 3 767 198 8 Less then 1 in 550 12000 3 3 9 120 J170 8 All aai 16 17 8 13650 768 No of Down s Unaffected No of Figure 98 Outcome Validation Plot 5 7 6 Abnormality Codes alpha Outcome allows you to record the presence of abnormalities using the 10 edition of the international classification of diseases ICD codes To view the list of abnormality codes Abnormality Codes Select from the side bar This section allows the user to add custom codes which can be used instead of the ICD code To enter a custom code Figure 99 or make changes to a code click in the code column and enter a custom code You must have a user security level of 5 to make any changes The code for free text 99999 cannot be changed ICD Code Down s syndrome Unknown Free text code None Not reported Figure 99 Custom codes alpha Version 8 Page 136 Click Save ave to keep any changes to the list 5 7 7 Data Transfer Data transfer is used to export dat
13. Version 8 Pa Maternal serum test report summary 09 08 2013 17 07 16 Ka From 01 01 2004 to 01 01 2005 All tests All women regardless of race Include all codes The number of first tests repeat tests and Type of report Maternal serum tests 98 9 scan updates in the selected period 0 8 Updated Maternal serum results 0 3 Total 100 0 If any reports were corrected after 01 01 2005 the tables take account of any changes and do not include the original report Repeat Maternal serum tests This table provides a breakdown of first tests according to the reported screening or diagnostic result This table can be used to determine the screen positive rate The table also indicates the number of tests in which a high risk of trisomy 18 trisomy 13 or Smith Lemli Opitz syndrome was reported Percent 272 4 8 1 1 0 4 15 0 3 0 1 0 1 4295 75 8 945 16 7 43 0 8 5665 100 0 Reason Screening result Positive Increased risk of Down s syndrome Raised AFP Previous Down s only Previous NTD only Uninterpretable Test done too early Test done too late Negative Negative for Down s syndrome and NTD Negative for Down s syndrome only Negative for NTD only Total Increased risk of trisomy 18 was reported in 14 first tests 0 2 Completed tests 15 9 52 7 31 5 100 0 First trimester tests
14. WARNING All intellectual property rights subsisting in alpha are vested in Logical Medical Systems Limited and the user shall have no rights to use copy modify or merge the software save as is permitted by the user s licence agreement with Logical Medical Systems Limited The user should note that there may be intellectual property rights owned by third parties which could be affected by the use of alpha Logical Medical Systems Limited gives no warranty or indemnity that use of alpha will not infringe any third party s intellectual property rights The user is responsible for ensuring that it has any third party rights necessary to use alpha Logical Medical Systems Limited is not responsible for clinical decisions or actions that are taken in conjunction with the use of alpha All interpretations produced by alpha should be assessed by an experienced physician in conjunction with the other factors judged relevant by that physician screening for Down s syndrome open neural tube defects and pre eclampsia does not detect all affected pregnancies and some women with unaffected pregnancies will be classified screen positive Not all pregnancies affected with trisomy 18 Edward s syndrome trisomy 13 or Smith Lemli Opitz syndrome can be identified and some women with unaffected pregnancies will be classified as being at increased risk of having a pregnancy with one or both of these disorders Should the user s computer fail
15. When you are satisfied with the test reports you create final reports which can be printed or written to an XPS or alpha export file You can only create final reports if test reports have been created for records in the batch file Once this has been done you will be able to select Final report from the dropdown next to the button alpha then displays a preview of the final reports See Figure 58 alpha 8 0 i o d Click on the thumbnail to view the report and hover over the thumbnail to view the patient s name A Patients DOWN S SYNDROME AND NEURAL TUBE DEFECT SCREENING Report dated 06 Aug 13 Last name Forename s Hospital Number lo of birth EDD Date of sample Sample number 1 CLINICAL DETAILS AND TEST RESULTS Previous NTD Previous Down s Prev Pre eclampsia Insulin dependent diabetes Smoker Maternal age atEDD Scan measure Gestation at date of sample Gestation used Weight Ethnic group MS AFP level uE3 level SMITH Sally V123891239 Other than BPD alone 17 weeks 3 days by dates 18 weeks 0 days by scan Scan estimate 56 2 kg Caucasian 15 ng mL 1 ng mL Total hCG level 24102 miu mL Inhibin A level 300 pg mL INTERPRETATION SCREEN POSITIVE Increased risk of Down s syndrome 1 in 65 at term 1 in 8 100 Screening result Reason Risk of Down s Risk of NTD Comment Down s risk due to maternal age alone is
16. 2 non black D Entered 2 not known 4 group 4 5 group 5 6 group 6 0 none 1 insulin dependent diabetes mellitus 0 none v II Entered 1 one 2 two or more 1 raised MS AFP v II Entered 2 suspicion of NTD on ultrasound 3 previous suspicious AF AFP AChE i Type of 8 l measurement Date GA by clinical GA by clinical On measurement Date estimated Date oral Date OC stopped contraception Date stopped First or repeat No longer used e Ethnic group Ethnic group Integer v v v wi wi Diabetes Diabetic status Number of previous Previous NTD pregnancies if any affected with open NTD A Reason for Amnio reason i l Integer amniocentesis Version 8 Page 221 v wi wi wi wi wi wi wi Amniotic Fluid Comment OH Se 3 E O 2 2x S maii o os O O Do2 D x 2 m E LC LL LLI T Ou N ur c lt x Ben Ur OU c ul Ben Fe vis tt Type of EE 4 family history of NTD 5 increased risk of Down s syndrome 6 unrelated to NTD or Down s risk 7 advanced maternal age 8 abnormal ultrasound finding 9 increased risk of trisomy 18 Date ofsampi Date ofsample Dato v v v a Entered 1 clear Sample 2 cloudy AF appearance appearance Integer Entered 3 frankly bloodstained Seet significantly discoloured ve wies E T caii faint AChE NTD band AChE NTD band Integer
17. 2 trimester PAPP A PIGF MAP AFP UE total hCG Free BhCG inhibin A PIGF STANDARD DEVIATION 1 trimester 2 trimester PAPP A PIGF MAP AFP UE total hCG Free BhCG inhibin A PIGF TRUNCATION LIMITS 1 trimester 24 trimester PAPP A PIGF MAP AFP uE hCG free B hCG inhibin A PIGF Derived from reference alpha Version 8 Unaffected pregnancies 0 000 0 000 0 000 0 000 0 000 0 000 0 000 0 000 0 000 0 2345 0 1611 0 0353 0 155 0 112 0 238 0 282 0 188 0 210 All pregnancies 0 20 to 3 00 0 40 to 2 50 0 90 to 1 20 0 82 to 2 50 0 50 to 1 76 0 66 to 3 00 0 59 to 3 00 0 72 to 3 00 0 30 to 1 40 Pre eclampsia pregnancies 0 0915 0 1079 0 0294 0 022 0 060 0 060 0 063 0 139 0 174 0 2540 0 1654 0 0369 0 174 0 125 0 275 0 318 0 265 0 286 Page 262 CORRELATION COEFFICIENTS First trimester Second trimester aa ee a ae re i a i aa Parameter PAPP A PIGF MAP AFP uE Total Free B Inhibin PIGF hCG hCG A Unaffected First trimester PAPP A 1 PIGF 0 3009 1 MAP 0 007 0 0346 1 Second trimester AFP 0 1160 0 1477 0 1 uE 0 1213 0 0547 0 0 275 1 Total hCG 0 0624 0 0854 o 0 197 0 096 1 Free B hCG 0 0627 0 0854 0 0 184 0 096 0 85 1 Inhibin A 0 0237 0 1509 O 0 074 0 023 0 343 0 356 1 PIGF
18. 2a GC E v A15 A15 v A14 A15 A15 A15 A10 A10 Vv Vv Vv 15 CO 2 Vv CH Ou Ben Ou OH Ben O CH Ben _ Leg LLI Derived Entered Entered Entered Q Entere CL Entere Q Entere Entered Entered Entered Entered Entered Entered Comment Doctor s name or code up to eight letters or numbers identifying the doctor for this report For import and export see note 12 Code up to eight letters or numbers identifying the address for this report For import and export see note 12 Whole Years 12 years lt age lt 55 years Page 218 Amniotic Fluid Comment OH Se 3 E O 2 2x S maii o en os O O go D x 2 m E LC TT WS LLI T Ou N ur Leg st Ben Ur OU c ul Ben Fe vis el Type of l menstrual period Expected date of peo EN delivery from LMP LMP date certainty Integer GA by dates GA from LMP Text 4 v Date on which GA GA by dates On from LMP Date estimated V Entered v Entered 1 LMP date certain 2 LMP date doubtful Weeks days eg 17 4 V Entered v 2 Entered 1X 11 v 2 Entered 2 2 1X 11 V Entered delivery from scan Text 4 GA by scan On from scan Date estimated fetuses for GA by scan v v Entered Weeks days eg 17 4 v 312 Entered Entered 1 BPD in singleton fetus 2 one BPD in twins 3 both BPDs in twins
19. 42 SLAO FENIN E 42 3 1 11 Recurrent false positives 2 0 0 ccccceeccccseseceeceeseeeceeseeeceaaeeecseueeessaeeessaeeeeseseeessageesssaeees 43 3 112 Scanu pdate ie 44 oa C un TEE 44 J32 EECHER hee 44 reel el Le TE 44 3 2 1 1 Median e UE 44 3 2 1 2 Weight adjustment eouatons ccccccccccsseseceeeeeeseeeeeeeeeeeeeeeeseeeeeeeesseeeeeeeesaegeeeeeeeas 45 3 2 1 3 Equations used to estimate gestational age from fetal ultrasound measurements 45 3 2 2 Overview of Coefficients Gcreen 46 3 2 3 CHANGING coefficients 20 0 cccceececceeceeeeeeeeecaeeeeeeeeeaeaseeeeesaeaseeeeesaaaeeeesseeaseeeeessaeeeesesaaees 49 3 2 4 Evaluating coefficients cccccccccccseeceecseeeeeeeeeeeeesseeeeeeseaeeeeseaeeeessaeeeesaeeeessaeeeesseseeesaasees 52 3 2 5 Current and historical Coefficient values cccccccccceecceseeeeeeeeeeeeeeaaeeseeceeeeeeseaeaaeeeeeeeeeseaas 53 33 Ee elei 54 3 4 Analyser BC dE 55 SA a 55 ENEE ee ee ne en eee eee ee ee eee 57 So OSU Tale e 58 3 5 HERE 58 20 Re 60 Se DOCO OES E E E E 61 Sne elle e E E E E E E T EE 63 SE FPO SONO GE 63 3410 Impor soting E 64 Sell Integrated test Options EE 66 IA LICNO e a E atin eaten akan pha uuitedhll shed sahameteNnsnuuehecien 66 Je WE EN 68 3 13 1 Changing marker names annnneneannnnonennnnneenrnnnsrnrnressnnrrrrsnnrrrrnrnrrreosnnrrrrrnrrresernrreennnne 68 3 13 2 Reviewing marker details 69 CN KE E e EE 69 ENEE EE ere 70 lS ao E 71 3 13 2 4 Correlation
20. Gestational age based on Dates No 0 3161 0 2202 0 2651 0 1705 0 1955 0 1497 0 1377 0 2424 0 3020 0 2249 0 2893 0 2091 0 2731 0 0757 0 1556 0 1498 0 1292 0 2307 0 2639 0 1828 Jon Bestwick personal communication alph G Version 8 Yes 0 2959 0 2111 0 2637 0 1705 0 1955 0 1416 0 1370 0 2397 0 2996 0 2213 0 2670 0 1994 0 2718 0 0757 0 1556 0 1417 0 1284 0 2279 0 2612 0 1779 Scan No 0 2313 0 3006 0 2151 0 2587 0 1705 0 1955 0 1485 0 1251 0 2422 0 2987 0 2249 0 1550 0 1275 0 1105 0 2722 0 2037 0 2669 0 0757 0 1556 0 1486 0 1156 0 2305 0 2602 0 1828 Page 245 Standard deviations of the screening markers log MoM in each trimester of pregnancy Yes 0 2313 0 2802 0 2069 0 2569 0 1705 0 1955 0 1398 0 1238 0 2395 0 2965 0 2213 0 1550 0 1275 0 1105 0 2495 0 1950 0 2651 0 0757 0 1556 0 1399 0 1142 0 2276 0 2577 0 1779 Truncation limits MoM for Down s syndrome screening markers Marker Truncation limits 10 completed weeks 0 50 2 50 11 completed weeks 0 70 2 50 12 completed weeks 0 80 2 50 13 completed weeks 0 85 2 50 First trimester 10 13 weeks PAPP A 0 2 3 0 Total hCG 0 3 3 0 Free B hCG 0 3 5 0 DVPI 0 9 1 5 PIGF 0 4 2 5 Second trimester 14 22 weeks AED I 0 5 2 5 Ca B 49 J Total hCG S 03 50 Free B ee 03 50 Inhibin A t For MoM values outside the specified
21. Nicolaides KH 1995 Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation Br J Obstet Gynaecol 102 957 962 21 Wald NJ George L Smith D Densem J Petterson K 1996 Serum screening for Down s syndrome between 8 and 14 weeks of pregnancy Br J Obstet Gynaecol 103 407 412 22 Wald NJ Densem JW George L Muttukrishna S Knight PG 1996 Prenatal screening for Down s syndrome using inhibin A as a serum marker Prenat Diagn 16 143 153 23 Watt HC Wald NJ Smith D Kennard A Densem J 1996 Effect of allowing for ethnic group in prenatal screening for Down s syndrome Prenat Diagn 16 691 698 24 Wald NJ Watt HC George L 1996 Maternal serum inhibin A in pregnancies with insulin dependent diabetes mellitus implications for screening for Down s syndrome Prenat Diagn 16 923 926 25 Watt HC Wald NJ George L 1996 Maternal serum inhibin A levels in twin pregnancies implications for screening for Down s syndrome Prenat Diagn 16 927 929 26 Neveux LM Palomaki GE Larrivee DA Knight GJ Haddow JE 1996 Refinements in managing maternal weight adjustment for interpreting prenatal screening results Prenat Diagn 16 1115 1119 27 Wald NJ Densem JW George L Muttukrishna S Knight PG 1997 Inhibin A in Down s syndrome pregnancies revised estimate of standard deviation Prenat Diagn 17 285 290 28 Wald NJ Hackshaw AK 1997 Combining ultrasound and
22. On sch i SLOS posterior risk SLOS riskos Seon O SE Pre eclampsia prior Long fsk rounded unrounded risk unrounded Integer Shows if risk has Pre Eclampsia risk flag been trimmed or Text 1 Bees risk has been trimmed capped gt risk has been capped Pre Eclampsia risk LHS Pre eclampsia risk Version 8 Page 208 wi wi wi wi wi wi wi wi wi wi wi Vv Maternal Serum Field name O gt Q Pre Eclampsia risk RHS Pre Eclampsia risk LHS unrounded Pre Eclampsia risk RHS unrounded Pre Eclampsia risk post Trisomy 13 prior risk Trisomy 13 prior risk unrounded Trisomy 13 risk flag Trisomy 13 risk LHS Trisomy 13 risk RHS O Q Version 8 Comment u am ss 3 gt Keng x d e hs e H Vi e D o2 D x 2 aa c iL E LLI Type of field left hand side Integer Pre eclampsia risk right hand side _ T Ou N c lt Been Ur OU Le Ben Fe vis V Derived the screening cut off and should not be reported in twin or diabetic pregnancies Trisomy 13 risk right hand side rounded v 7 Derived wi rounded Ge DH H Pre eclampsia risk Long Pre eclampsia risk unrounded H Pre eclampsia posterior risk See v A12 Derived note 14 risk rounded ES meted risk unrounded ONEA Shows if risk has Si e sha Capped Trisomy 13 risk left Lo
23. This table shows the type of tests carried out Second trimester tests Standard integrated tests Total Previous test Repeat test Be Dee SES Further tables show how the screening or Raised MS AFP 1 100 0 1 2 2 2 4 1 diagnostic result changed following a Increased risk of Down s 1 50 0 1 2 0 syndrome repeat sample or a scan update Neither 1 50 0 45 97 8 46 93 9 Total 1 100 2 100 46 100 49 100 0 NOTE This table includes 4 repeat tests reported after 01 01 2005 Alpha Version 8 0 13218 8 Page 1 of 2 Pa Maternal serum Report Summary 09 08 2013 17 07 18 Bied Previous test Updated test Raised MS AFP Increased risk of Both Neither Down s syndrome Increased risk of Down s 8 72 7 8 47 1 syndrome Neither 1 100 0 3 27 3 5 100 0 9 52 9 Total 1 100 11 100 5 100 17 100 0 NOTE This table includes 1 updated result reported after 01 01 2005 Alpha Version 8 0 13218 8 Page 2 of 2 Figure 108 Report Summary alph d version 8 5 11 Risk Analysis The Risk Analysis option presents in a graphical format a cumulative total of the number and percentage of screening reports with risks greater than or equal to various cut off levels When this option is selected a screen similar to that in Figure 109 is shown You can select for which conditions Down s syndrome NTD trisomy 18 trisomy 13 SLOS and pre eclampsia and which t
24. defined name to ensure the definition of the field is retained Default value 2 Caucasian Figure 47 Screen Design enter default value alpha will confirm when the screen design you have entered is valid Your screen designs must include the following prompts Surname or ID Code Date of Birth or Age at EDD only required for MS data entry screen At least one estimate of gestational age GA Date of Sample At least one maternal serum or ultrasound marker or AF AFP Data entered using the prompts are used by alpha for the interpretation or for other purposes All input data are stored in the database The spare fields Spare 1 6 are not used in the interpretation but you can choose whether they are printed on the reports if they are printed they appear immediately above the CLINICAL DETAILS section of the report The screen may be redesigned at any time However the format of the reports including reprinted reports will always be governed by the current screen design 3 18 Sonographer codes Sonographer codes provide a way of recording the names of sonographers associated with reports using a code to represent each sonographer s name A similar facility is provided for recording the names of doctors Section 3 7 Doctor codes and addresses Section 3 3 Address codes Using codes reduces data entry time and helps reduce errors The codes used may be up to eight characters long Further information of the use o
25. group 4 5 group 5 6 group 6 lf this prompt is included in the screen the ethnic group entered is used to select ethnic group specific median equations and weight correction equations see section 5 13 6 for more information In addition ethnic group specific prevalences for spina bifida anencephaly and pre eclampsia are selected see Section 3 1 4 for more information Page 178 Date of sample Date of second sample Previous amnio Interpretation Amniotic sacs Chorionic sacs Integrated screening Sonographer Smoker alph d Version 8 3x2 Cp a 3X2 Date blood sample taken Dates earlier than 280 days before the current date are not accepted Date second blood sample taken integrated screening only Dates earlier than 280 days before the current date are not accepted Date of last amniocentesis performed or attempted in this pregnancy The result is uninterpretable if an amniocentesis has been performed or attempted This is because amniocentesis sometimes causes feto maternal transfusion which can increase the maternal serum AFP level 1 Down s syndrome and NTD 2 NTD only 3 Down s syndrome only 4 Down s syndrome NTD and pre eclampsia 5 Down s syndrome and pre eclampsia Specifies the type of interpretation required If left blank an interpretation is provided for Down s syndrome and NTD except for second trimester tests performed at 14 weeks and first trimester tests whe
26. population The adjustment factors may be derived from your own screening data or from the scientific literature see Appendix Q Suggested factors for adjusting MoM values for differences between ethnic groups To specify ethnic group adjustment factors select the desired serum marker and ethnic group under Adjustment for ethnic group in the Parameter settings screen Specify a reference population and correction factors for adjusting MoM values for differences in the markers levels and in maternal weight between the specified ethnic group and the reference population lf the Ethnic group prompt is not included in the MS screen design you do not need to specify the method of adjusting for ethnic group 3 1 4 Background prevalences The NTD prevalence parameters specify the background prevalence of open NTD s in the absence of screening and selective abortion They are used only in estimating the risk of having a pregnancy with an open NTD In general reporting the risk of NTD is not recommended since the criterion used to categorise a screening result as positive or negative is not the risk but the AFP level If the anencephaly prevalence is unknown a rate of 95 of the corresponding spina bifida prevalence could be used Prevalence rates for women of different ethnic groups need only be set if you have included the Ethnic group prompt in the MS screen design The pre eclampsia prevalence parameter specifies the background preva
27. 0 3223 0 4643 0 0 302 0 102 0 165 0 177 0 144 1 Pre eclampsia First trimester PAPP A 1 PIGF 0 3544 1 MAP 0 0355 0 0129 1 Second trimester AFP 0 1160 0 1477 0 1 uE 0 1213 0 0547 0 0 222 1 Total hCG 0 0624 0 0854 0 0 306 0 279 1 Free B hCG 0 0627 0 0854 0 0 362 0 308 0 939 1 Inhibin A 0 0237 0 1509 0 0 353 0 438 0 519 0 453 1 PIGE 0 3223 0 4643 0 0 149 0 343 0 214 0 187 0 443 1 Correlations assumed to be zero tt Correlation between PIGF and total hCG assumed to be the same as for PIGF and free BhCG Correlations assumed to be the same as for unaffected pregnancies The likelihood ratio obtained from the maternal serum markers Is multiplied by either the likelihood ratio for when a previous pregnancy has or has not been affected with pre eclampsia Likelihood ratio when a previous pregnancy has been affected with pre eclampsia OUER 2 11p Likelihood ratio when a previous pregnancy has not been affected with pre eclampsia or is a first pregnancy _ p 1 51p 8 3p 2 35p 4 where p is the prevalence Jon Bestwick personal communication alpha Version 8 Appendix P Factors used for adjusting MoM values Serum marker levels differ on average between twin and singleton pregnancies and some differ between women with and without insulin dependent diabetes mellitus between smokers and non smokers and between wo
28. 1 in 900 Figure 58 Final report The print and export buttons include the special functions shown in Table 9 when used for final reporting Table 9 Print and export options available in final reporting Button Drop down item Purpose Oo tea Print all reports Positive only Print only positive reports Standard Write reports to a standard export file See Section 4 2 6 1 Only shown if Standard export report is selected in Report Export Format Selection Section 3 20 3 Write reports to a packet export file See Section 4 2 6 2 Only shown if Packet export report is selected in Report Export Format selection Section 3 20 3 Packet When the final reports have been printed or written to file using the options in Table 9 alpha returns to the final report preview screen You can make further selections at this point to create extra copies of the reports for example if you require both printed and exported reports alph d Version 8 Once you close the final report preview screen m The reports are merged into the alpha database m The results if requested are written to the export text file Section 3 9 m The batch file is deleted lf the final reports are not printed or written to file or only positive reports are printed these operations are not carried out and the reports remain in the batch file Once the reports have been merged into the database you can obtain additional copies of the repor
29. 121 5 124 4b 18 128 0 62 5 92 19 136 0 37 30 20 143 0 KE 5 46 E 149 0 11 9 16 ER 156 0 3 10 20 Figure 40 Derivation of normal medians for serum markers Figure 40 relates to a second trimester marker For a first trimester marker you would tabulate the data for weeks 10 11 12 and 13 The tabulated median data may then be entered directly into alpha s regression facility which derives the coefficients of the regressed median equation See Section 5 9 1 Provided the fit is sufficiently good the coefficients derived in the regression may be entered into alpha See Section 3 2 Coefficients 3 13 3 2 Normal median equations Ultrasound markers For a new ultrasound marker such as nuchal translucency you will need to provide the coefficients for the equation which is used to calculate normal median values of the marker at different crown rump length CRL measurements Normal median values should be established by measuring the ultrasound marker and the CRL between 10 and 13 weeks in approximately 200 women from the population to be screened Measurements should preferably be uniformly distributed between CRL bands at least 50 in each band Preferably sonographer specific normal medians will be established for each sonographer who provides ultrasound marker measurements in your screening programme Having collected the measurements group the data in 10 mm CRL bands For each group find the median CRL measurements the
30. 13 Week17 1 in 350 943 45 1in14 E 1585 1428 REPORT DATE RANGE 1 in 400 94 7 49 lini5s Week 18 7 793 ES de E GEES The number of tests in each F S Week 19 o 1 in 500 954 59 ni gestational week is shown H 25 To Week 20 B CODES Hover over the pie chart segments to Week 21 Include all codes v show the percentage of the population Miss screened Click the segments to SE Refresh results MATERNAL AGE RANGE identify the group it represents si Figure 113 Screening performance table for Integrated test 5 13 Tabulations Using the Tabulations option you can monitor the variation of the serum marker and AF AFP with gestational age or NT with CRL and check the accuracy with which the normal median equations are estimating the expected marker levels Tabulated data on screening markers and AF AFP can also be passed automatically to the Regression section see Section 5 9 in order to recalculate new values for regression equation coefficients see Section 5 9 The tabulation of nuchal translucency with crown rump length can be used as an indication of whether an individual sonographer s NT measurements are acceptable for use in screening The tabulation displays both the rate of increase of NT with gestational age and the estimated standard deviation of the NT MoM values expressed in logio These can then be compared with published estimates for example those in reference The options av
31. 1939 0 1417 0 2411 UE Total Free B hCG hCG 0 0193 0 0357 0 8764 0 0627 0 4441 0 4242 Page 249 Correlation coefficients for the screening markers in unaffected pregnancies gestational age based on scan with adjustment for maternal 49 Unless stated otherwise weight First trimester Total hCG Free B hCG PAPP A PIGF DVPI Second trimester AFP UE Total hCG Free B hCG Inhibin A Version 8 First trimester NT 10 weeks 0 0630 0 0325 0 0429 0 0093 0 0714 l 0 0079 0 0495 0 0549 0 0502 0 0415 NT 11 weeks 0 0758 0 0391 0 0516 0 0093 0 07148 0 0095 0 0596 0 0661 0 0604 0 0499 NT 12 13 weeks 0 0821 0 0423 0 0559 0 0093 0 0714 i 0 0103 0 0645 0 0716 0 0654 0 0540 Total hCG 0 7178 0 2198 0 0675 0 0306 0 7191 0 7236 0 3167 Free B hCG 0 1395 0 1526 0 0285 0 0167 0 0255 0 5606 0 7605 0 2937 PAPP A 0 28207 0 0269 0 1160 0 1213 0 0624 0 0627 0 0237 PIGF 0 14777 0 0547 0 08547 0 1509 AFP 0 1981 0 1535 0 0974 0 2033 Second trimester UE3 0 0416 0 0585 0 0875 Total hCG 0 8651 0 4293 Free B hCG 0 4092 Page 250 Correlation coefficients for the screening markers in Down s syndrome pregnancies gestational age based on dates without adjustment for maternal weight Total hCG First trime
32. 2 060995 0 9891762 5 01 01 1980 Weight adjustment PAPP A Overall 0 0049946 64 95892 10 01 01 1980 Weight adjustment F8 hCG Overall 2 375735 0 9876558 5 19 01 2010 Biparietal diameter GA Machine 1 52 33097 1456614 0 0110454 3 54E 05 9 01 01 1980 Crown rump length GA Machine 1 38 59628 1 307924 0 0111987 5 17E 05 9 01 01 1980 Figure 28 Current coefficients 3 3 Address codes Address codes provide a way of recording the destination addresses of reports using a code to represent each address A similar facility is provided for recording the names of doctors Section 3 6 and sonographers Section 3 18 Sonographer codes Using codes reduces data entry time and helps reduce errors The codes used may be up to eight characters long The address codes screen Figure 29 provides facilities for viewing editing and deleting stored addresses and adding new addresses alph d Version 8 2 th Et Setup 144 Cl alpha 8 0 Addresses Search Edit New Delete Coe Address Line 1 Address Line 2 Address Line 3 Address Line 4 00000001 The Surgery 24 Park Lane LONDON NE3 ZA9 00000002 Charterhouse Surgery The Square LONDON EC2B HU8 Search for an address by Edit an existing address create entering a search term a new address or delete an here address with these buttons Figure 29 Addresses screen 3 4 Analyser import 3 4 1 Overview Text files containing analyte measurements from an analyser or laboratory i
33. 2983 0 4102 0 2371 6 0 2280 0 2084 0 3104 0 4179 0 2475 14 22 n a n a n a 0 3118 0 4249 n a 0 1308 0 1549 0 3384 pha versions T Unaffected means set to 0 n a Not applicable The median DVPI MoM in Down s syndrome pregnancies 0 1903 11 13 weeks The regression equations used to estimate the biochemical marker median in affected pregnancies in the first trimester are median total hCG 10 0 8662 0 01213 x gestational age in days 49 i 0 3271 0 i i median free B hCG 10 0 3 0 00768 x gestational age in days 49 median PAPP A 10 1 1444 0 00965 x gestational age in days 49 median PIGF 10 0 7573536 0 0103592x gestational age in days 91 The regression equation used to estimate the NT median in affected pregnancies is median NT MoM 10 0 8554679 0064686 x gestational age in days N B There are intellectual property rights covering the use of screening markers and screening tests e g the Integrated Test and users need to ensure that they have the right to use them Maternal weight correction Down s syndrome First trimester 10 13 weeks NT PAPP A Total hCG Free B hCG DVPI PIGF Second trimester 14 22 weeks AFP UE Total hCG Free B hCG Inhibin A Unaffected First trimester 10 13 weeks NT 10 weeks 11 weeks 12 13 weeks PAPP A Total hCG Free B hCG DVPI DIGET Second trimester 14 22 weeks AFP UE Total hCG Free B hCG Inhibin A
34. 3 days in the table of observed and expected values You can use the expected values to calculate the percentage by which the regressed medians at 13 weeks 3 days and 14 weeks 3 days should be reduced when calculating AF AFP MoM values See Section 3 1 9 The graph can be shown with a logarithmic y axis by selecting the Plot Option Logarithmic Y axis With this option selected data which fits to a log linear relationship will be displayed as a straight line The overlay setting can be used to compare overlay the regression currently in use Press the Print button for a printed copy of the regression 5 9 2 Regressions with weight Maternal weight regressions are only needed if Weight has been chosen as a data entry prompt AF AFP MoM values and MoM values of ultrasound markers such as nuchal translucency are not weight corrected The weight tabulation information is transferred to the regression facility by pressing the Regression button in the Tabulation screen Figure 102 shows the regression of the data shown in Figure 118 If the data is to be entered manually a table should be prepared showing for each weight group the observed median MoM values unadjusted for weight See section 3 13 3 3 When the Regressions option is selected a blank table is provided into which this information is entered Once the table contains three or more complete rows of data weight observed median and number of samples if known alpha displays th
35. 45 Total Median Age Expected Prevalence 5 685 32 eene VEER All ages _ From SCH Ethnic groups Reported prevalences TEST TEES Smoking Diabetes Previous NTD All tests 140 9 3 0 33 0 26 No value entered IVF Previous Down s Previous Pre Eclampsia Refresh results gt e ae 1 60 0 42 0 00 E 458 5 685 Hover over the pie chart segments to E show the percentage of the population Ge screened Click the segments to Wa identify the group it represents White H 3210 Figure 100 Population 5 9 Regressions Using the Regressions option you can derive new coefficients for calculating the expected median values of the screening markers and AF AFD and for adjusting maternal serum MoM values for maternal weight The options available on the Regressions screen will depend on the screening markers installed in alpha The information required for regressions can once a satisfactory number of reports have been produced and stored in the database be transferred automatically from the corresponding tabulation See section 5 2 Alternatively the information required can be entered manually This process may be followed when the marker is first being used in alpha or when a change to a different formulation of the marker is being carried out alpha can update median or weight correction equations if you wish following a regression 5 9 1 Regressions with gestational age or crown rump length
36. 8 Integer v wi wi wi Integer v Text v Date v v v wi wi wi wi wi wi Amniotic Fluid Vv Vv O a Zen ES H x PES w O SS gt go 2a GC E 312 CH Ben Ou OH Ben O CH Ben _ Cc LLI Derived Comment 1 English 2 German 3 ltalian 4 French 5 Greek 6 Czech 7 Spanish 8 Portuguese 9 Russian 10 Turkish 11 Slovak 12 Vietnamese 13 Romanian 14 Chinese 15 Polish For positive and un interpretable results only See note 16 Page 226 Amniotic Fluid 2 ae O Type of EB Field name a S 5 x S Comment Wes lt 2 S S S S 3 N D SIS SS S C o A E lt A LU ZS Lu Specifies if the MS AFP measurement l AF AFP level flag EE S Text 1 v Derived entered value Specifies if the marker MS AFP AF AFP MoM flag Kriterie Text 1 v Derived value shown Age at expected Age at EDD decimal a Single v v Derived Years and decimal fraction decimal fraction Version 8 Page 227 NOTES 1 Fields For fields labelled the alternative wording chosen by the user if provided will be used in the list of available fields Only fields in the data entry screen will appear in the import or export specification For import fields shaded yellow grouped fields must all be blank or all be completed Fields can be imported in any order except for the grouped fields 2 Marker names and numbers Marker numbers 4 to 12 a
37. 83 322 EE 84 3 23 Window envelope E 86 e d nee E 89 41 E 6 6 gene ene en ee E oe ee ne ee ee eee eee ae eer 90 Ae TACO PUIG EE 93 SC WR 2 eu 93 Mee 2 MOCKING TOW Wiel MC S es cccxecececeemendesceeseteceececsuicxoeeeeuqsensed EEEE EEEE EEEE 94 4 2 2 1 Current pregnancy Repeat Iert 94 4 2 2 2 Previous pregnancy Recurrent false positives 95 42 2 3 Ee e ite Bee ancezccevecicentccsebcdenidalissencnuandereehcodaansetocecdstenescnsaaderdeveustanesdededesesonseust 96 4 2 2 4 Breaking and making matches after creating test reports cccceeeeeeeeeeeeeeeeeeeeeeees 96 keo e Een EE 96 4 2 4 MoM values printed on reports ccccceecccccecseeeeeeeeeeeeeeeeeeeeeeseeeesseeeeeeeseseeeeeeeeesaaeeeeessaaaees 98 42 9 Geg entialtesUng ME 98 A26 EXPO RODON FOMAI scorse EE 99 Ae Oly e a E EE 99 4202 PaK DOIN EE 100 E Une E 101 alph d Version 8 431 Ce ANG EE 102 432 Avan a Se de E 103 4 4 Edit reports Correct and update 104 Eege 106 4 5 1 Import from text TE 106 452 Analyser MMO eegener 107 AO EPO EE 108 Ar KE 108 4 7 1 Unreported recordS AA 109 4 7 2 Reported records AAA 109 LO PN E 109 A Oe e E 109 OS een EE 111 Dil eut e Tu te wicsicssnadendiasndencausavdsniasndyoaiaaaciadineateniaiaadloniabsdsiatd bai A a EAEE e TA SEA DATEER 111 5 1 1 Marker Mohd 112 5 1 2 Report summary cccccccesecccceeeeeeceeneeecceaseeeceuseeessauseecseaseeesaageeeesaeeeeseaseeessanseessageeeeseags 112 5 1 3 Test
38. AAA Ce 2 Jk 1 Setup alpha 8 0 Import settings Amniotic Fluid Doctor Report address GA by scan GA by scan On I GA by scan Number fetuses I GA by scan Scan measure 1 Integrated screening I Sonographer Lab number Spare 1 I Date of 2nd sample FB hCG OT I MS AFP Assay Date I uE3 Assay Date Il T hCG 2T Assay Date I Inh A Assay Date I NT Assay Date PAPP A Assay Date FB hCG 1T Assay Date FILE FORMAT O Fixed length O Tab separated alph a Version 8 Use these buttons to configure Import Settings for Maternal Serum or Amniotic Fluid Items in the left hand column are available for selection Last name Forename s Hospital Number ve Date of birth Weight Ethnic group Previous NTD Previous Down s Age at prev preg I Interpretation I Smoker I Diabetes I IVF pregnancy Donor date of birth Click and drag items between the left and right columns to select or deselect them from the specification DATEFORMAT OPTIONS DM Comma separated M D Y O Y M D DOS Compatible Off NT levels to 2 d p H H H H H H FILE PATH Date of scan Machine Date of scan Number fetuses oR Figure 36 Import settings Items in the right hand column have been selected for the import specification 3 11 Integrated test options lf you use alpha to interpret Integrated Test results you ma
39. AF AFP Appendix H Definitions and abbreviations 95 confidence interval ah a b AC AChE AChE NTD band AF AFP Anencephaly BPD Clinical GA Combined Test CRL Dates GA Detection rate Double Test DVPI EDC EDD False positive rate GA HC hCG ID Code Integrated Test LMP MA MS MoM alph G Version 8 The range of values within which one can be 95 certain that the true value occurs If the same trial were repeated 100 times in 95 trials the confidence interval would include the true value and in 5 trials it would not a multiplied by b a raised to the power b Abdominal circumference Acetylcholinesterase The amniotic fluid electrophoretic gel band that migrates to the same position as cerebrospinal fluid and is inhibited by BW284C51 Amniotic fluid Alpha fetoprotein Anencephaly with or without spina bifida Biparietal diameter GA based on clinical examination Late first trimester 10 13 completed weeks test based on combining NT measurement with hCG PAPP A and maternal age Crown rump length GA based on time since the first day of LMP The proportion of affected pregnancies with positive screening results Early second trimester 14 22 completed weeks test based on the measurement of AFP and hCG together with maternal age Ductus venosus pulsatility index Expected date of confinement Expected date of delivery The proportion of unaffected pregnancies with positive screening r
40. COEFFICIENTS cc cceccceccceeeeceeeeseeeeeeeeeeeaeesseeeeeeeeseseaseeeeeeesssuaeaeeeeeeeesaaas 71 alph d Version 8 3 13 3 Adding NEW markers n nnnunnennnnessennnrosrnrrrrrrnrrrrsrnrrressnrrrersrnrerenrnrereosnnrrrrntnrrrennnnrrennnnne 71 3 13 3 1 Normal median equations Serum markers cceeeeeeeceeeeeeeseeeeeeeeeeeseeseeeeeeeeeeeeseaas 72 3 13 3 2 Normal median equations Ultrasound markers cccceceeeeceeceeeceeeeeeeeesseaeeeesaees 73 3 13 3 3 Weight adjustment eouatons 73 3 14 Message Lee de E 74 Sel AOS GC WO e r siesenepaademes E E E AE paaasddnadsninsena ieadunantoreenanincenugt in 15 316 Repon TOFMAL ne wiscevsccsneunaneneriricavarinesndalvanee donaunenaienirienviaones tute ssiaovedandRinieavtteusantererancPes 76 317 SOMES OCS IG eases neg oie cgrcatancencs ses E TEE O EEEE E OT aE E E E 77 3 18 onograpber cocdes nasisisi i aeiia inast 80 3 19 Titles and signature messages 80 O U Er ODIO eege 80 SS DNR et E EN 80 cee EIER deeg 81 3 20 3 Report export format selechon ne 81 3 20 4 Auto complete n annnaannnneannnnennnonrnnnsrnrrrsnrnnsrnrrrsnrrrorntrrsnrrronnrrnstrtrrantrrnntrrnnrennnnnrrnnnnen ne 81 3 20 5 XPS filename for reportmg 81 3 20 6 Patient Hrmtmg iiaiai ciiadind inaidai ndiaideiiiia ininda 81 3 20 7 Nuchal Translucency Monitor ccccccccccccseseeeeeeseeeeaeeeeeseaeeeesseseeeseeeeessaueeesseeeessaaeeees 82 3 20 8 Errorlog palh E 82 Sel S 2 oe E
41. DAT and EXPORTAF DAT Full details of the fields which can be exported are given in Appendix G Import Export Data transfer and Analyze it formats alph d version 8 2 tk EI Setup aah O alpha 8 0 Export settings Use these buttons to configure Export Settings for Maternal Serum or Amniotic Fluid Date of birth Last name LMP Forename s Weight Hospital Number Items in the left hand column are available for selection Previous Down s t hce em Mom Items in the right hand column have been selected for the export specification Ethnic group Ms AFP MoM Previous NTD uE3 MoM l Age at prev preg Inh A MoM Prev Pre eclampsia NT MoM I Interpretation PAPP A MoM smoker Fe hce am Mom Diabetes Down s prior risk I IVF pregnancy Down s risk post I Donor date of birth Date embryo transfer Date egg collection R i Click and drag items between the left and right columns to select or deselect them from the l Repairs specification GA by scan Doctor GA by scan On l GA by scan Number fetuses FILE FORMAT DATE FORMAT FILE PATH O Fixed length D M Y DOS Compatible exportdata txt Off Comma separated M D Y NT levels to 2 d p Off Tab separated O Y M D Figure 35 Export settings 3 10 Import settings Before importing data into alpha from text files you first need to define the forma
42. E E E 144 e Eet 147 5 12 Screening performance ssesesssseettnrrttttttrrtreessssttttnntttttttttttennrrrttnnnr Ettr Erteeeennnnnn nanne 148 D13 Ee 151 5 13 1 Setting up tabulations cc ceeececccccseseeceecceeeeeeeeceeeseeeeeseeeeeeeessseaeeeeeseeaeeeeesseaeeeeseaas 152 5 13 2 Restricting reports to specified doctors addresses of sonographers 153 5 13 3 Tabulation by gestational age 153 5 13 4 Tabulation by crown rump Jengih 155 5 13 5 Tabulation by weaht rtt rreenn enn 156 5 13 6 Serum markers and ethnic oroupe 158 6 Monitoring your Screening Programme ENEE 161 C MODO SACS EE 161 6 2 Monitoring the False Positive S sgetuguedeeetebekegka invedineistentsrdsvacdceiebasseninanddeeinneataninwediesdsien 161 6 3 Checking and updating the Median MOM Values 162 6 3 1 Monitoring estimate median MOM Values n ssnssnneennesnsrnnnsessrrrrenrrrtrrrsrnrrreerrnrrrnrnrrrrene 162 6 3 2 Specifying Sonographer Specific Medians for Nuchal Translucency cccccsseseeeeeees 162 oA E eil ef 163 L TROT ler 165 Appendix A Rules used in producing reports cceeeccceecsssseeeeecaeeeeceeesaeeeeeeeeeaeaeeeeeessaaeeeeeessaeeees 171 Appendix B Prompts and their meammgs 175 Appendix C Acceptable settings for poarameiers ne 184 Appendix D Equations used in calculations ccccccccecseeeeeeeeeeeeeceeeceeeeeeeeeesaaeeeesaaueeessaaeeseseeeeeensags 187 Appendix E Message addition Categories 190 Appendix F Con
43. E The detection rate and corresponding cut off value at fixed fixed positive rates m The false positive rate and corresponding cut off value at fixed detection rates Li fis 2 Statistics oO Select the condition for which the screening performance is required Cl alpha 8 0 Screening Performance PERFORMANCE FOR Test Select the marker combinations to use Timing cn ee Select whether the risk cut offs relate to the risk at term or at the time of test AGE DISTRIBUTION SE Select whether the age distribution is taken from the alpha database or Aipha database a from the distribution of maternities in England amp Wales Use markers for selection off E Specify that only those reports with the markers used in the screening test MATERNAL AGE RANGE are used to determine the age distribution Allages From O __ Select the maternal age range to use in the age distribution o REPORT DATE RANGE All periods F HHE gt S a Specify the date range used to select the reports to determine the age i distribution or if all reports should be used CODES lInclude all codes Specify that reports associated with selected report addresses doctors or sonographers be used to determine the age distribution See section 5 13 2 for further information Refresh results zo Press refresh to update the results Figure 110 Screening Performance alph d Version 8 The firs
44. Entered lt 7 strong 3 absent 4 pending 1 single PChE bands PChE band Integer Entered multiple absent maja pending 0 Result of AF e Oea tee te ete eO O O O Version 8 Page 222 Field name Date received Time received Lab number Spare Spare Spare Spare Spare Spare 6 Reports to ech lt oo gt NO T lt x at O Patient flag Date entered Date reported Repeat flag Version 8 Date sample received Time sample received Laboratory number sample reference number Spare field 1 Spare field 2 Spare field 3 Spare field 4 Spare field 5 Spare field 6 Not used Not used Date patient data first entered Date report made Shows if report is a first or repeat test Type of field Date Time Text 15 Text 100 ek TIT CO o SaS Tex Tex Text T Q Tex Text 10 _ esch CH i xe x xw O Date Date Text 1 T Ou N ur Leg st Ben Ur OU c ul Ben Fe vis Vv Vv Vv Amniotic Fluid Vv Vv wi wi wi wi wi wi Bn OH Ze g E O gt 2 x S maii o z os O O goe D x E E LC LL LL Entered Entered Entered Derived T Vv Ion Comment 1 initial test or broken match R repeat test means that pointers have changed since original report Page 223 Amniotic Fluid Type
45. Inhibin A 0 3095 Version 8 49 Unless stated otherwise First trimester Free B hCG 0 0763 EIN 0 0285 0 0048 0 0654 0 5401 0 7292 0 2852 PAPP A 0 28607 0 0269 0 1728 0 2776 0 0214 0 0127 0 0030 PIGF 0 14777 0 05470 0 0854 0 1509 Second trimester AFP 0 2473 0 1336 0 0722 0 1896 UE Total Free B g hCG hCG 0 1008 0 1089 0 8475 0 1083 0 4225 0 3957 Page 248 Correlation coefficients for the screening markers in unaffected pregnancies gestational age based on scan without adjustment for maternal weight First trimester Total hCG Free B hCG PAPP A PIGF DVPI Second trimester AFP UE Total hCG Free B hCG Inhibin A Version 8 49 Unless stated otherwise First trimester NT 10 weeks 0 0626 0 0334 0 0417 0 0093 0 0714 0 0097 0 0476 0 0556 0 0507 0 0414 NT 11 weeks 0 0753 0 0402 0 0503 0 0093 0 0714 0 0116 0 0573 0 0669 0 0610 0 0499 NT 12 13 weeks 0 0815 0 0436 0 0544 0 0093 0 0714 0 0126 0 0621 0 0725 0 0660 0 0540 Total hCG 0 7281 0 2795 0 1298 0 0572 0 7225 0 7258 0 3366 Free B hCG 0 1961 0 1526 0 0285 0 0736 0 0023 0 5858 0 7781 0 3179 PAPP A 0 28207 0 0269 0 2105 0 1533 0 1217 0 1186 0 0877 PIGF 0477 0 05477 0 08547 0 1509 Second trimester AFP 0 2219 0
46. MS or AF export data format then each time you create a final report Section 4 2 3 or a corrected or updated report Section 4 4 alpha will write selected information from the report to a text file By default the text file is called EXPORTMS DAT for MS reports and EXPORTAF DAT for AF reports You can specify your own names for these files if you wish New information is added to the end of the files if they exist new files are created if they do not exist To create the import data format highlight the fields in the left hand column of the Export Settings screen Figure 35 that you want to appear in the export file and drag it to the right hand column To remove a field highlight it in the right hand column and drag it to the left hand column Select the export file format fixed length comma separated or tab separated the date format d m y m d y or y m d If DOS compatible mode is selected the doctor code address code and sonographer code are taken to be four characters long If this is not selected the codes are taken to be eight characters long Also if DOS compatible mode is selected NT MoM values in twin pregnancies are exported separated by a If NT levels to 2dp is selected NT levels are exported with 2 numbers after the decimal point If this is not selected NT levels are exported with 1 number after the decimal point Enter the name for the export file or leave this field blank to use the default names EXPORTMS
47. NJ 2013 Allowing for ethnic group in antenatal screening for Down s syndrome J Med Screen 20 52 54 Huttly WJ Bestwick J and Wald NJ 2014 Effect of smoking status on inhibin A in second trimester prenatal screening for Down syndrome Prenat Diagn 34 406 407 Appendix A Rules used in producing reports A report may contain various items of information which are derived from a combination of the input data and the appropriate parameter and coefficient settings The main rules and considerations affecting this are outlined here Gestational age GA by Dates 1 If LMP and EDD estimated from LMP are both recorded LMP is used 2 If LMP EDD and GA by dates are both recorded the gestation derived from LMP EDD is used 3 Ifthe month of LMP or EDD is known but not the day of the month the 15 day is used in calculations Gestational age GA by Scan 1 If fetal measurement s biparietal diameter BPD crown rump length CRL or abdominal circumference AC and GA by scan are both recorded the gestation derived from the fetal measurement s is used 2 Fetal measurement s and GA estimated by scan take precedence over EDD estimated by scan 3 In atwin pregnancy if two fetus specific BPD CRL AC or HC measurements are recorded the mean of the corresponding gestations is used in calculating the MoM values for serum markers For ultrasound markers such as nuchal translucency a separate MoM value is calculated for each fetus b
48. Press e to transfer these values to the batch file L Patients Ik Enter or browse to the file containing Analyser Import Marker FileName gt MS AFPO J o alpha txt S os uE3 o alpha txt Total hCG o alpha txt Inhibin A o alpha txt FreeB hCG o first txt PAPP A o first txt Select the checkbox to import measurements for the marker Figure 67 Analyser Import File Selection eee ay 22 Patienss TE Analyser Import Number of imported results 8 rae ee rer ae S ees ee ess 2 cone v EK8690 137496561 36 24 36 24 2 31 2 31 42058 42058 171 5 17L5 MS AFP result already exists v k8691 131496559 30 47 30 47 3 17 3 17 48834 48834 258 0 258 0 MS AFP result already exists v EK3684 13TS01526 15 9 15 9 1733 1733 FreeB hCG result already exists v EK8685 137541111 67 5 67 5 10005 10005 FreeB hCG result already exists v amp K8686 13M024557 33 9 33 9 4314 4314 FreeB hCG result already exists v EK8687 137541108 83 9 83 9 5169 5169 FreeB hCG result already exists Al K 137541109 13 7 13 7 2113 2113 FreeB hCG result already exists EKSGSS emm mn 137541110 24 0 24 0 5059 5059 FreeB hCG result already exists Number of import errors 6 D Number of sample ID s without a matchs 398 Transfer Figure 68 Analyser Import Data Screen 4 6 Export The data stored in the records in a batch file can be exported to a text file This can be useful if the data entere
49. Saree ri S CLINICAL DETAILS uE3 ng mL 2 1 _ First day of LMP 10 09 13 hCG miu mL 21000 _Maternal weight kg oi Ihibin A pg mL 2101 Previous NTD f f None 2 BLOOD SAMPLE Date taken 07 01 14 1 BLOOD SAMPLE Date taken 0712 13 _PreviousDown s None RESULTS _PAPP A mg L DU o __Previous Pre eclampsia Noe DI measurement mm 12 Smoker No _Datetaken O7A2N3 Diabetic PN Oana Sonographer DR EVANS Figure 3 Screening requisition form Screening requisition forms are normally processed in batches The data are entered into the computer using the data entry screen See Figure 4 The data entry screen consists of a series of fields into which the data is entered and prompts which give the meaning of the fields alpha requires the following information in order to produce a report patient identification maternal age MS reports only at least one estimate of gestational age date of sample maternal serum marker or ultrasound marker MS reports or AF AFP level AF reports The data entered are checked and a screening report produced automatically The screening report produced by the data entered in is shown in Figure 5 You can enter more information if you wish for example gestational age by ultrasound scan additional screening markers ethnic group maternal weight and previous history of Down s syndrome or open neural tube defects A full list of the available items is given in Appendix B Prompts
50. Tabulation options 5 13 1 Setting up tabulations For each type of tabulation you can specify a number of options to select the data you want for example data relating to Caucasian women screened during 2013 In order to specify the date range over which to tabulate the data you can either select all periods which will include all eligible data in the database or you can specify start and end dates Records are included in the tabulation if the date of reporting falls within the requested period If you have included the Ethnic group prompt in your screen design you can choose to produce separate tabulations of maternal serum markers only for each ethnic group or for all women regardless of ethnic group See section 5 13 6 for an explanation of how alpha tabulates the data in this case Depending on the circumstances some reports may be excluded from tabulations automatically Reports for women who smoke for women with diabetes or a multiple pregnancy are excluded Repeat tests re interoreted reports and reports that have been deleted are also excluded Reports that have been corrected are also excluded however the correct version of the report will be included if it is otherwise eligible Reports that are uninterpretable for the purposes of the current tabulation are also excluded alph d Version 8 For tabulations with gestational age any reports that are based only on a clinical estimate of gestational age are excluded W
51. Version 8 Page 204 lt lt AS lt lt lt lt Maternal Serum Comment Fixed width format for import and export Entered or derived Type of l e Clinical GA for Clinical GA at 2nd sample second sample of Integer Integrated test j T Ou N c lt x Been Ur OU Le Ben Fe vis Derived Days H Screening result positive Screening result negative p A1 Derived T Increased risk of trisomy 18 negative for Down s S Increased risk of SLOS negative for Down s 3 Increased risk of Trisomy 13 negative for Down s U uninterpretable AL Positivity Positivity flag Text 1 Prior Downs risk Long ste mo p om ooo DE Prior Downs risk Long Down s prior unrounded unrounded pe lt risk has been trimmed gt risk has been capped pened Note if the data exported includes a twin pregnancy an additional field Down s risk flag twin 2 is exported This can be ignored Shows if Down s risk has been Text 1 trimmed or capped Down s risk flag wi wi wi wi wi In a twin pregnancy this is a pseudo risk and should be D Down s syndrome Long indicated as such ES risk right hand side Version 8 Page 205 Vv Maternal Serum Type of Letina LL tT E Down s risk LHS Down s syndrome Long py e fx x Derived unrounded risk left hand side panies ad Down s syndrome PONN S Sr BEE risk right han
52. a n a C The smoking adjustment factors are used from alpha version 7 0P for users who upgraded from the DOS to the Windows version of alpha These factors replace any smoking factors specified by the users in the DOS versions of alpha For users who have only used the Windows version of alpha these factors have always been used d Prior to version 7 1Q was 0 82 e The inhibin A smoking adjustment factor is Adjustment factor 1 0 1 016836 0 0169631 xGA 0 0000575 xGA The smoking adjusted MoM is calculated from SE Smoking unadjusted inhibin A MoM Smoking adjusted inhibin A MoM 22 _____W_ Adjustment factor rounded to two decimal places For gestational ages of 21 weeks and 1 day and higher the adjustment factor is fixed equal to 1 71 Prior to version 8 0 14120 22 was the smoking adjustment factor for inhibin A was 1 62 SEN s Appendix Q Suggested factors for adjusting MoM values for differences between ethnic groups Levels of the serum screening markers may differ on average in women of different ethnic groups Also average maternal weight may differ between ethnic groups alpha provides two methods for allowing for such differences the direct method and the adjustment method For further information on selecting the appropriate method for your screening service see Section 5 13 6 If you choose the adjustment method you need to specify adjustment factors that are used to co
53. a specified value 1 in x are printed as Less than 1 in x where x is between 20 000 and 1 000 000 Separate settings are provided for trimming the risk in Integrated Tests and non Integrated Tests You can also cap risk estimates that are judged to be very high Risks that are higher than a specified value x in y are printed as Greater than x in y where x in y represents a risk between 9 in 10 and 1 in 2 for the risk of Down s syndrome in Integrated Tests and between 4 in 5 and 1 in 5 for the risk of Down s syndrome in non Integrated Tests and for the risk of NTD or trisomy 18 Separate settings are provided for capping the risk of Down s syndrome in first trimester second trimester and Integrated Tests and for capping the risk of trisomy 18 in all tests The range of weeks in which a second trimester test can be interpreted are set with MS 2nd Trimester Interpretation Range The start of the range can be 14 or 15 completed weeks and the end of the range can be between 19 and 22 completed weeks If no values are set the interpretation range is between 14 weeks and 22 weeks 6 days The range of weeks in which AF AFP can be interpreted are set with AF AFP Interpretation Range Either 13 to 24 completed weeks or 15 to 21 completed weeks can be chosen If no values are set the interpretation range is 15 weeks to 21 weeks 6 days A graphical visualisation of the risk can be added with the Print Riskometer option If Pri
54. age distribution of England and Wales in 2006 to 2008 The screening performance table is shown in four columns Cut off The risk cut off Timing specifies if this is at term or time of test DR Detection rate with this cut off FPR False positive rate with this cut off OAPR Odds of being affected given a positive result at this cut off The screening performance can also be calculated using statistical parameters based on dates or scan gestation and with or without adjustment for maternal weight 2 kt Statistics Lt Screening Performance PERFORMANCE FOR Test Quadruple test New GESTATION Down s syndrome v Timing Term v WEIGHT AGE DISTRIBUTION Source England amp Wales 06 08 1 in 100 77 0 2 3 MATERNAL AGE RANGE 1in 150 81 0 3 3 All ages 1 in 200 83 6 43 _ From O years To 854 51 Refresh results 1 in 300 1 in 350 1 in 400 1 in 450 1 in 500 Cut off DR FPR OAPR lin 13 1in19 lin 23 lin 27 lin 31 1in35 1in 38 1in 41 1 in 44 DISPLAY Ak iwi Fixed Detection Rate Fixed False Positive Rate CG alpha 8 0 Select whether dates or scan gestation or with or without adjustment for weight is used to calculate the screening performance Select how the screening performance results are to be displayed Print the screening performance table Show the age distribution in the screened population At a risk
55. and insert it into a free USB port in the new computer see section 2 2 2 Please wait until the message Your new hardware is installed and ready to use is shown 10 11 2 11 2 On the new computer make a shortcut from the desktop to the file alpha exe in the Alpha subfolder of the folder copied in step 4 Start alpha from this short cut A message box stating Failure to connect to alpha database will be shown Press OK and the SQL Manager screen will be shown Figure 11 Enter the following details a In the Select server text box the name of the SQL server running on this computer b Under Log on credentials select the SQL server authentication mode Uncheck Windows authentication to select SQL server authentication and then enter the username and password for SQL server authentication c Under Connect to a database select Attach and then browse to the memory stick or drive containing the alpha 8 SQL server database MDB and log files LDB created in step 1 d Under Copy to browse to the location of the local Microsoft SQL server data folder and provide a file name for the database and log files when they have been copied to the new location e Under Database enter the database name SQL server will use for these files Press Test connection If this is successful press OK to complete the process g Alpha will start and confirm that the process has been successful
56. are exported as packeted information the principle is to split each item in the report into two parts an invariable first part for example Surname and a variable second part for example SMITH Some items consist of only one part for example 025 This is a repeat test In these items the second part is taken to be empty Each item has a unique code The codes and the items they correspond to are described in the following table Code First part of item 005 NEURAL TUBE DEFECT AND DOWN S SYNDROME SCREENING 006 AMNIOTIC FLUID AFP 010 This is a corrected version of the report produced on lt date gt 015 This is a reinterpretation of the report produced on lt date gt following the addition of further information 020 A repeat test was requested but no previous test for this pregnancy has been found It has therefore been interpreted as a first test 025 This is a repeat test 030 Surname 035 Forename s 040 Address 045 Phone number 050 ID Code 055 Date of birth 060 LMP 065 EDD based on LMP 066 EDD based on ultrasound 067 EDD if no other EDD entered 070 Date of sample first sample in integrated screening 071 Date of second sample in integrated screening only 075 Date received 080 Time received 085 Lab Number 090 Doctor 095 Report Address 100 Spare 1 105 Spare 2 110 Spare 3 115 Spare 4 116 Spare 5 117 Spare 6 120 Previous NTD 125 Previous Dow
57. associated with selected report addresses doctors or sonographers be included or excluded from the analysis You can monitor the effect of repeat testing and scan updates tests that are reinterpreted on the basis of ultrasound scan information added after the initial screening result by examining tables which show how the results changed following the second report When the Report Summary option is first selected the screen in Figure 106 is shown Once the options have been selected and the Refresh button pressed a screen similar to that in Figure 107 is shown 2 th Statistics O CO alpha 8 0 Report Summary Specify if the report summary is for maternal serum or amniotic fluid TEST All tests v lt ___________ Specify the tests to include in the report WOMEN TO INCLUDE All women regardless of race lt _ Restrict the analysis to women of a specified ethnic group or select all women REPORT DATE RANGE O All periods _ From 01 01 03 T i mom Specify the date range used in the median analysis or if all reports should To be used CODES Include all codes You can specify that data from reports associated with selected report addresses doctors or sonographers be included or excluded from the Refresh results analysis See section 5 13 2 for further information Figure 106 Options in Report Summary alph d Version 8 L ro e d alpha 8 0 Repor
58. be imported Press the Import button to save the data in a batch 21 Patients Tk O aipha 8 0 Import Import file name import txt o Browse Summary This shows a summary of the number of records read from the ee See Ee GE import file and the number of warnings errors and matches Details Record Errors Warnings Matches 1 0 0 This shows a list of the records imported indicating which have errors warnings or matches Select Import to import the selected gt records to a batch Import data ro Per Figure 66 Import data 4 5 2 Analyser import lf Analyser Import has been configured See section 3 4 Analyser import this option will be shown in the dropdown list for the Import 9 button When this option is selected the screen shown in Figure 67 is shown This allows you to select the filenames containing the marker measurements you wish to import Press t to import the measurements and to show the Data Screen Figure 68 This shows the field used for matching Sample Number in this example the marker measurements read from the import file and the matching patient s name and ID Code PatientID in this example in the alpha batch files together with the current marker measurements stored in the batch file if any The screen also shows any errors found when reading the import files and any lines in the import file for which matching record in the alpha batch files were not found
59. both are reported and a comment is added to the report indicating that the BPD based MoM was used for spina bifida screening kk Maternal age If age at EDD and date of birth are both given date of birth is used Where maternal age at EDD is calculated as less than 15 years the age specific risk at 15 years is used Maternal serum marker MoM value Adjustment is made for maternal weight when available Positive Screening Result At least one of i MS AFP MoM value cut off in twins and diabetics adjusted MS AFP MoM value cut off ii risk of Down s gt cut off in twins risk of Down s probably gt cut off lil previous NTD pregnancy provided gestational age gt 15 weeks iv previous Down s syndrome pregnancy v If interpretation for pre eclampsia requested risk of pre eclampsia gt cut off vi If interpretation for pre eclampsia requested previous pregnancy affected with pre eclampsia Positive Diagnostic Result One of i AF AFP MoM value GA specific cut off and AchE test not done ii AF AFP MoM value gt GA specific cut off and AchE NTD band present Ambiguous Diagnostic Result One of i AF AFP MoM value gt GA specific cut off and AchE NTD band absent ii AF AFP MoM value lt GA specific cut off and AchE NTD band present Uninterpretable Screening Result At least one of I in second trimester screening for Down e syndrome GA lt 14 weeks 0 days or gt 22 weeks 6 days ii in first t
60. changing the medians The median analysis screen provides options for printing the report and shows where coefficient changes took place 5 5 Missing information The Missing Information option provides a breakdown by doctor or report address of the proportion of reports for which information normally entered into the data entry screen is missing for a specified date range The table is useful for determining which doctors or centres routinely provide for example maternal weight and scan information alph d Version 8 When the Missing Information option is selected a screen similar to that in Figure 87 is shown This shows that 6136 tests were carried out in the specified period and that 15 19 of them were missing maternal weight These results are broken down by address code showing that for example 14 tests 14 38 were missing maternal weight in address code 102 Any field in the alpha data entry screen can be included in the report of missing information To include another field select it from the drop down list and press the Add button An example of this is shown in Figure 88 which shows that 14 6 of reports were missing LMP information Fields can be combined to show to show reports which were missing more than one piece of information For example in Figure 88 pressing the Add bution on the right of the screen will include another column showing reports which were missing both LMP and Ethnic Origin Pressing the button next to
61. code is found in the database This option may be helpful in settings where the D code field is used to record a permanent patient specific code such as a Health Service number Additionally alpha can automatically complete the first and second date of sample and the first and second sample receipt date and assay dates based on the last value entered This helps to avoid unnecessary repetitive data entry in situations where most or all of the samples in a batch tend to be drawn or received on the same day 3 20 5 XPS filename for reporting Each final reports can be written to a single XPS XML Paper Specification file This option allows the name of the file to be specified and it can be built from a combination of the patient s surname forenames and ID code and the report date 3 20 6 Patient Printing This option determines the appearance of the reports printed using the Print button on the Patients screen See Section 4 8 Different formats can be specified for Maternal Serum Amniotic Fluid and the Integrated test list See Section 3 11 For each case the columns which appear in the list the column on which they are sorted and column used to group separate sections can be chosen by pressing the button and selecting from the list of fields The default settings are shown in Table 6 Table 6 Default settings for Patient Printing Maternal Serum Surname Forename None None Date of birth and ID Code Amniotic Fluid Surname Fo
62. corrected for weight and y ethnicity but not twins IVF smoking or diabetic status Version 8 Page 203 wi wi Age at EDD decimal Single v v calculated with decimal fraction v v v v Maternal Serum Comment t and export OH sj o Oo ab E 2 2 D c O ES Been O O z e 2 x lt c LL impor Data transfer Type of Lu nceann fe fe fx LAS Derived ootan anazo if the MOM ig necative th or Export and Analyze it if the MoM is negative this Marker4MoM CL ls lx IS A8 Derived indicates that the MoM is less than the absolute value of Marker5MoM II Tv Lv X FAS Derived the number shown fas Dever ing MoM tien rodo or data transfer the corresponding MoM flag should be tv fy fe x AS Derived checked to see if the marker MoM 4 less Ver the value Ill x as Derived given Pe ee x fas Derived AS IS AS IS AS IS lt lt lt KR l gd AS IS IS LISIS LIKS lt lt Marker 10 MoM Te lv Jv x TAS Derived NT MoM values in twins are formatted according to Note 15 Varker TT MoM EE e as Derivo Varker T2 MoM E EECHER gt x ie pores pas first sample GA by dates for l pave aticeanne GAMERS Tine x ie oid ay sample GA by scan for Scan GA at 2nd sample second sample of Integer v v v I3 Derived Days Integrated test Dates GA at 2nd sample AA y CAE Integer v v v I3 Derived Days second sample of
63. cut off at term of 1 in 200 the detection rate is 83 6 with a false positive rate of 4 3 and odds of being affected given a positive result of 1 in 23 Figure 112 Screening performance table for quadruple test Figure 113 shows a screening performance table for the Integrated test using the age distribution from the screened population The screening performance at 10 11 12 and 13 weeks of gestation or as in this case the average gestation for the screened population can be displayed The number of tests carried out at each week of gestation is also shown Press the Print button for a printed copy of the Screening Performance The age distribution used for the screening performance table can be seen by pressing the Population u button See section 5 7 alph d version 8 L rr o aa O alpha 8 0 Screening Performance PERFORMANCE FOR SE Select the gestational week D r the aver ion for mm ee 3 or the average gestation fo Timing this population for which the Term screening performance table GESTATION WEIGHT WEEK is to be calculated Source FIRST TRIMESTER TEST DISTRIBUTION SECOND TRIMESTER TEST DISTRIBUTION Alpha database 1 Cut off DR FPR OAPR i Week 10 Week 14 markers for EO 1 in 100 89 6 16 1in5 W Lin 150 91 3 22 1in7 ee GE 1in 200 924 29 1in9 Wio Wies All ages 1 in 250 93 2 34 lin il Week 12 Week 16 From B 2265 BW 2864 O 1 in 300 938 3 9 1in 12 H To Week
64. database To copy the database to another location browse to the path where you want to copy the database files to for example a memory stick or another drive provide a filename and press the Copy button alpha will copy two files the SQL server database file with an MDF extension and SQL server log file with an LDF extension to the specified location Section 2 11 1 provides details of how to use this facility to move your copy of alpha to another computer alph d Version 8 UCLH and Whittington Database i 3 lu D 1 Setup AAA Windows ver 15 10 04 Ot alpha 8 0 Database Details Name alpha8new SQL Server version 11 00 3128 Location C Program Files Microsoft SQL Server MSSQL11 SQLEXPRESS MSSQL DATA copy mdf C Program Files Microsoft SQL Server MSSQL11 SQLEXPRESS MSSQL DATA copy It Size 2 608 MB 2 44 MB 0 168 MB Copy to location This operation can only be carried out from the same computer as the SQL server database Path Browse Figure 32 Database 3 Doctor codes Doctor codes provide a way of recording the names of doctors associated with reports using a code to represent each doctors name A similar facility is provided for recording the report addresses Section 3 3 Address codes and names of sonographers Section 3 18 Sonographer codes Using codes reduces data entry time and helps reduce errors The codes used may be up to eight characters long The Doctors screen Figur
65. defects Mean maternal serum AFP levels og MoM in singleton pregnancies with neural tube defects according to gestational age Pregnancy Mean Anencephaly 15 weeks 0 6412 16 0 7469 17 0 8110 18 0 8335 19 0 8144 20 0 7537 21 0 6514 22 0 5075 76 Open spina bifida 15 weeks 0 4554 0 6107 16 0 5522 0 7075 17 0 6024 0 7578 18 0 6060 0 7613 19 0 5630 0 7183 20 0 4734 0 6287 21 0 3372 0 4925 22 0 1544 0 3097 Closed spina bifida 0 0000 0 1553 t Unaffected mean set to 0 t Values in parentheses based on gestation estimated from biparietal diameter BPD measurement Standard deviation of AFP log MoM in unaffected pregnancies and pregnancies with neural tube defects Pregnancy Standard deviation Gestational age estimated by Dates scan Without weight With weight Without weight With weight adjustment adjustment adjustment adjustment Unaffected 0 1688 0 1649 0 1579 0 1468 eee 0 3335 0 3316 n a n a Open spina bifida 0 3378 0 3358 0 3324 0 3272 A iia 0 1688 0 1649 0 1579 0 1468 bifida alpha Version 8 Mean maternal serum AFP level log MoM in unaffected twin pregnancies and twin pregnancies with neural tube defects Pregnancy Mean Gestational age estimated by Other than BPD BPD Unaffected 0 3284 0 3284 ON NOC poo cepiay 0 8749 n a Open spina bifida 0 6435 0 7212 enotek GE spina 0 3284 0 4060 see note 6 Correlation coefficients of AFP logo MoM between first and repeat
66. dongle ccc eecccccseeeeceeecaeeeeeeeeceeeseceeeeeeeseeeeesseaseeeeeseeaeeeesessaeseeeeesaaees 17 SC NEE adi e t 18 2A COMMULAUOMN sirinin iniaeeai bedaine ada aa ahi haa iia aa ai binada inini tecenbdasadendsdaeeiers 19 25 SCrEGNING le 19 26 Navigating COV E 23 20 1 alpha SOCIOS E 23 26 2 ul ue dates I CUO A EE 24 2 6 3 Print preview EE 25 2 Files and the alpha database A 26 2 8 Processing a batch of tests sxcccseecssectcntansaseedchetsentandatienineccdentancctnmteensiendebiadnotaneddicedamasewetaeeddaetaesays 26 RK ae ae CH 27 2 10 Using alpha in the diagnosis of open neural tube defects cccccccececeeeeeeeeeeeeeeeeseeeeeseaees 28 2 10 1 Designing an AF data entry screen 29 2 10 2 Policy settings related to AF AFP 29 RIGS E aca un el e EE 29 dae WE ene 30 2111 Moving Reie ru T EE 30 2 11 2 Adding another computer to a multiuser configuration ccceeeeeeeeeeeeeeeeeeeeaeeeeeeeeeaaees 31 BU EE 33 Sil IP CRAPNC CNS eege 35 oi eg el Gelle ee Les E 36 3 1 2 Printing current and historical parameters n naannnnennnnennnnnnnnnnsnnnnnrnnrnsnrrnrnnrrnsnnrernnrrennne 38 3 1 3 Adjustment for ethnic group 39 3 1 4 Background prevalences A 39 alph d Version 8 3 1 5 Bhb Dcorrechontfachors 40 SAG UNIONS ebe 40 SN FOO OS EE 41 3 1 8 Median equation policies cccccccccccccssssecececeeeseceesceeseceesseeeeceeseeaaeeeeesseegeeeessseageeesessagess 41 3 1 9 Median reduction factors AF AFP
67. false match A previous pregnancy will not be presented as match in the following cases A previous pregnancy has been affected with Down s syndrome or open neural tube defects The current pregnancy is a twin pregnancy The previous pregnancy was a twin pregnancy The previous pregnancy was less than 10 months ago The previous pregnancy produced an uninterpretable screening result The woman was a smoker in one pregnancy but not in the other At least one of the markers measured in the current and previous pregnancy was the same pha versions See section 4 2 2 2 for further information 3 1 12 Scan update policy You use scan update policy to control the reinterpretation and reclassification of screening tests from screen positive for increased risk of Down s syndrome to screen negative after the addition of ultrasound scan information You can choose to reinterpret the test always or to do so only if the new scan estimate of gestation differs from the dates estimate by at least a specified number of days between 1 and 28 days Tests that are not reinterpreted because the difference in gestation is too small are reported with the same screening result screen positive as the original report with the addition of a message indicating that the original interpretation remains unchanged Restricting the reclassification of screening results in this way will help to avoid giving false reassurance to those
68. following screening It also provides estimates of the detection rates for Down s syndrome and neural tube defects in the screening programme To access the Screening Audit section click Screening Audit ON the icon in the side bar See Figure 95 EE EES The screening audit can be C Fem 01017980 4 20 10 2008 Include sglected SERIES restricted to report dates i Include seleclad dockors oriy screening tests or doctor or address codes C Ta kimene Ea Co rei a fe A tege Li C Integrated T bull screening audi rmai rbag EAR E toe Print in either a summary or a full screening audit With outcome Without outcome Tota a7 02 26977 99 8 27024 Diagnostic tests Ar 1 74 per 1000 Mone found performed REESEN sae ae Re l None found Hone found ina Bifida lopen of closed or with other omg o Anencophai Omm Abnormality statistics None found Figure 95 Outcome screening audit The full screening audit Figure 96 shows the information in far greater detail categorising the abnormality count according to the screening result positive negative uninterpretable For positive and uninterpretable screening results the number of affected pregnancies according to the reason for the positive or uninterpretable result is also shown The full report also categorises the diagnostic procedure in the same way The report also categorises the number of amniocenteses according to risk category shown in a table and
69. if you wish to interpret the Integrated Test Code between 1 and 9 identifying the ultrasound machine or type of machine used to perform the examination or the centre at which the examination is performed The code is used to select a machine or centre specific equation for estimating GA from ultrasound measurements In addition if the Type of Measure is 1 BPD it is used to select the appropriate BPD correction factor for the machine or type of machine see Section 3 1 5 Required if Date of scan is given Number seen at scan If left blank alpha assumes a singleton pregnancy Page 176 Type of Measure 1 Measurement 1 5 Measurement 2 5 RE EE re 1 Measurement 1 8 Measurement 2 8 Le e rm e e vm rm rm e rm rm em rm e rm rm e rm rm rm rm em mm 1 BPD 2 CRL 3 AC 4 HC Required if Date of scan is given Measurement mm on date of scan Required if Date of scan is given Second measurement if multiple pregnancy Not available if Number of fetuses is blank or 1 Optional if Number of fetuses is 2 1 BPD 2 CRL 3 AC Optional second ultrasound measurement Date of scan is taken to be the same for both measurements Measurement mm on date of scan Required if Type of measure is given Second measurement if multiple pregnancy Not available if Number of fetuses is blank or 1 Optional if Number of fetuses is 2 Estimated gestational age based on clinical examinatio
70. it The Analyse it option provides a powerful and flexible facility for users to analyze their MS and AF data It can be used to export data to a text file or directly to a Microsoft Excel spreadsheet Appendix G Import Export Data transfer and Analyze it formats gives the meaning and format of the fields exported using Analyse it When the option is selected a screen similar to Figure 76 is shown If you have already prepared an Analyse it query it can be selected from the list in the left hand side of the screen To create a new MS or AF query select either the New MS Query and New AF Query buttons Press the Save Query to save a new query To delete a selected query press the Delete query button Once selected the query can be run or modified Four tabs are available Options Output Criteria and Ordering The Options tab Section 5 2 1 is used to test and run the query and specify the type of results file and filename Output Section 5 2 2 to specify the fields to export Criteria Section 5 2 3 to specify the criteria used for selecting the fields and Ordering Section 5 2 4 how the results are ordered Sections 5 2 2 to 5 2 5 illustrate the features of Analyse it by means of a worked example The query will return a dataset from alpha that can be used to examine the median gestational age of all women screened with the Integrated test in a certain date range 5 2 1 Options The Options tab allows you to select results whethe
71. left hand side of the criteria is selected from the drop down list containing the field names in the alpha database See Figure 79 the operator from the drop down list containing the available operators and the right hand side entered into the text box Press the Add Criteria button again to add further criteria to build up the whole query See Figure 80 The alpha database fields specified in the Output tab Section 5 2 2 are included in the results if the criteria specified in Figure 80 are all satisfied Table 11 provides an explanation of the criteria used in this example s Je stattstics O Analyse lt Q alpha 8 0 New MS query New AF query Delete query er ee QO Median GA of IT women at second stage T R Sa Type est query Run query ve query Name Median GA of IT women at second stage Maternal Options Output Criteria Ordering The E button deletes the criteria at NULL this level Pointer forward Pointer back Delete status flag Update flag Version flag Age at EDD decimal MS AFP MoM uE3 MoM T hCG 2T MoM Free a hCG MoM FB hCG 2T MoM Inh A MoM NT MoM FB hCG 1T MoM PAPP A MoM The criterion is built up from the alpha database field The 7 button adds a criterion at this level You can combine the criteria at this level with other levels using the Add new criteria button names and operator from the dropdown list and a term entered in the text box Figure 79 Analyse it criteri
72. linear equation cccecceeeeeeeeeee 141 Figure 103 Comparison of log quadratic and log cubic equations for OF 142 Figure 104 Update medans Ettr Eent tatt Eneee nenn 143 Figure 105 Update sonographer specific medians cccccseeeceeeeeeeeeeeeeeeeeeeeeeeeaeaceeeeeeeeseaaaneeeeeeess 143 Figure 106 Options in Report Summary ccccccccsseseecceeeeeeeeeeseeeeeeeeeeeseeseeeeeeeessseaseeeeeeeessuaaeeeeeeees 144 IOUS 107 Repon SUMMA 145 Fig r 108 Report SUNNY asrine aiina na aeaa ria aE E ria ARENALES ARA EEE aE EERS 146 FOUE TOS REKAN YSI cenn a E A 147 Figure 110 Screening Performance ccccccccssssssessssssseeeecceeeeeeeeeeeeeaauaesasaeeeeeceeeeeeeeeeeeeesaaaaaaaagsnseesees 148 Figure 111 Specify markers to use for screening performance ole 149 Figure 112 Screening performance table for quadruple test 150 Figure 113 Screening performance table for Integrated rest 151 Sleeve leide 152 Figure 115 Code selechon nen 153 Figure 116 Tabulation of MS AFP by gestational age 154 Figure 117 Nuchal translucency tabulation cccccecceceeeeeeeeeeseeeeeeeeeeeaeeeeeeeeeeeeaaaaaceeeeeeeessaaageseeeeess 156 Figure 110 VV CICME tabula NON NEE 157 List of tables Table 1 Terms frequently used in oloha 17 Table 2 Sections in CUO EE 23 Table 3 Purpose of buttons in Print Preview screen 26 Table 4 Meaning of terms in Analyser Import screen 56 Table 5 Integrated test Options 22 2 cecccccs
73. loose matching the ID Code must be patient specific not pregnancy specific May be omitted if both Surname and Date of birth are included Patients address Patient s postcode Patient s telephone number Doctor s name in full or a code up to 8 letters or numbers for 50 character name Include this field if you want doctor specific summaries and Statistical tabulations If included Reports To must be omitted Alphanumeric code for address to send report codes for up to 4 lines of 50 characters Include this field if you want centre specific summaries and Statistical tabulations If included Reports To must be omitted Displays a pop up window in which the names or codes for up to three doctors can be entered together with their report address codes One copy of the final report is printed and addressed to each doctor The language for each report may also be specified If included Doctor and Report Address must be omitted Patient s date of birth May be omitted if ID Code Surname and Age at EDD are included Maternal age at expected date of delivery This field is only used when Date of Birth is not known In such cases alpha assumes the mid point of the specified year of age for example if 35 is entered 35 5 years in used in calculations Page 175 Gestational age estimation dates LMP 3x2 EDD from LMP 3x2 Certain 1 GA by Dates 4 On 3x2 First day of last menstrual period LMP If the exact da
74. measured in the same examination as CRL If CRL was not measured the date of NT must be specified 0 absent 1 present 2 not reported If absent or present nasal bone is recorded this is used to adjust the risk of Down s syndrome using the method of Cicero et al The nasal bone adjustment is not made when the sample gestational age is less than 11 weeks 0 absent 1 present 2 not reported Used to record the absence or presence of nasal bone in the second fetus in a twin pregnancy Not available for singleton pregnancies 0 No 1 Yes When screening for pre eclampsia and a previous pregnancy has been affected with pre eclampsia the result is classified as screen positive regardless of the levels of the screening markers Not used in an interpretation for Down s syndrome or open neural tube defects 0 Reverse or absent 1 Forward 2 Not reported Amniotic fluid AF related information First or repeat 1 Diabetes 1 Ethnic group 1 alph d Version 8 1 first AF AFP test this pregnancy 2 repeat sample If this field is used to indicate a repeat sample and the record is not subsequently matched to an earlier record relating to a previous sample in the same pregnancy a message to this effect appears on the report 0 none 1 insulin dependent diabetes mellitus Not used in the interpretation 1 black 2 non black 3 not known 4 group 4 5 group 5 6 group 6 Not used in
75. medians between the reference group and women of other ethnic groups When specifying coefficients for the first time it is best to avoid the use of medians in assay package inserts it is preferable to derive them by assaying samples possibly in parallel with another laboratory Preferably at least 50 samples are used per week of gestation as follows pha versions E For second trimester screening at least 50 samples per week in four gestational weeks with smaller numbers acceptable in other weeks m For first trimester screening at least 50 samples per week in three or more gestational weeks between 10 and 13 weeks The form of the median equations is given in Appendix D Equations used in calculations A choice of median equations is given for uE3 and inhibin A and the selection made can be on the basis of how well the equation fits data from your local population 3 2 1 2 Weight adjustment equations alpha uses weight adjustment equations to adjust the MoM values of serum markers for maternal weight The equations estimate the median MoM value in women of a given weight A woman s MoM value is divided by the expected median MoM given her weight to obtain the weight adjusted MoM and the adjusted MoM value is used in the interpretation Where the screened population includes women from different ethnic groups you can specify ethnic group specific weight adjustment equations to allow for differences in weight between wome
76. mg L miu L mm ug mL mg L kiu mL Miu L mmHg kilograms or pounds None print do not print never always if age gt x years never when positive or age gt x years never when positive when positive and print comment when negative never when positive when positive and print comment when negative never when increased AND Down s or trisomy 18 risk is increased when increased when increased and print comment when decreased Page 184 Parameter Print NTD risk Timing of Down s risk Timing of trisomy 18 risk Timing of trisomy 13 risk Trim printed risk non Integrated Tests Trim printed risk Integrated Tests Cap printed Down s risk first trimester Cap printed Down s risk Second trimester Cap printed Down s risk Integrated Test f Cap printed trisomy 18 risk Cap printed NTD risk MS 2 trimester interpretation range AF AFP interpretation range Print Riskometer Print Pre eclampsia risk Print Adjusted MoMs Cut offs Down s risk Second trimester Down s risk first trimester Down e risk Integrated Test with NT Down s risk Integrated Test without NT Trisomy 18 risk Second trimester Trisomy 18 risk first trimester Trisomy 18 risk Integrated Test Trisomy 13 risk SLOS risk Sequential testing first trimester risk NTD MS AFP NTD MS AFP diabetics NTD AF AFP 13 15 weeks NTD AF AFP 16 18 weeks NTD AF AFP 19 21 weeks NTD AF AFP 22 2
77. number of women and the median ultrasound marker measurement Then tabulate the data as shown in the example Excel spreadsheet shown in Figure 41 A C D Median CRL Number of Median NT CRL group mm mmm women measurement mn lt 40 38 0 3 1 00 40 47 0 4 1 15 50 55 2 142 1 30 DL 64 3 173 1 50 EE 95 1 70 61 6 Z 1 60 30 0 I 1 70 Figure 41 Derivation of normal medians for nuchal translucency The tabulated median data may then be entered directly into alpha s regression facility which derives the coefficients of the regressed median equation See section 5 9 1 Provided the fit is sufficiently good the coefficients derived in the regression may be entered into alpha See Section 3 2 Coefficients 3 13 3 3 Weight adjustment equations lf your maternal serum data entry screen includes a prompt for the maternal weight you will need to provide coefficients for the equations alpha will use to adjust MoM values of the new marker for maternal weight To derive the coefficients create a table consisting of maternal weight bands of 5 kilograms or 10 pounds Within each weight band record the median maternal weight the number of samples and the median marker level in MoM before adjustment for maternal weight The unadjusted MoM value for each sample is derived by dividing the observed marker level in concentration units by the expected marker level given the woman s gestational age The expected marker level is in turn de
78. or no influence on the median The MoM allows for the change in concentrations of the serum markers with gestation and from centre to centre Metres per second Nuchal translucency Neural tube defect Spina bifida with neural tissue either completely exposed or covered by a thin transparent membrane Oral contraceptives Pregnancy associated plasma protein A Pseudocholinesterase Placental growth factor Early second trimester 14 22 completed weeks test based on the measurement of AFP uE3 total hCG and inhibin A together with maternal age Red blood cells GA based on ultrasound examination Testing in which a first trimester test is performed for example the Combined test and the results interpreted immediately If this is positive a diagnostic test is offered but if it is not positive second trimester serum markers are measured and the first trimester markers reused to form an Integrated Test A variant of the Integrated Test using serum markers only PAPP A in the first trimester and the Quadruple Test in the second trimester Smith Lemli Opitz syndrome Spina bifida cystica or encephalocele without anencephaly Early second trimester 14 22 completed weeks test based on the measurement of AFP uE3 and hCG together with maternal age Unconjugated oestriol XML Paper Specification A file format in common use for the exchange of printable documents Page 236 Appendix Packet export report format When final reports
79. press CO If alpha has been configured for both MS AFP and AF AFP screening you will need to select Add MS from the drop down for MS data entry or Add AF for AF data entry To start data entry in an existing file either double click the name of the batch or the name of the patient you want to edit alpha displays the data entry screen showing the first record in the batch file or the record you specified If you are working with a new file a blank record is displayed An example of a data entry screen is shown in Figure 54 The appearance of your data entry screen depends on the prompts and screen layout you have selected see Section 3 17 Table 8 shows the meaning of the various items in the data entry screen 21 Patients th ei Q alpha 8 0 Search Aug 01 13 Last name VENABLES Date of scan 01 07 13 E ei Forename s Vanessa Seier E Manage Hospital Number Number fetuses D Date of birth Type of measure 2 CRL i coo Edit started 02 08 2013 12 28 12 Ethnic group 2 Caucasian v Integrated screening 1 Standard v 30f3 K lt Previous NTD 0 None v Sonographer ALL All sonographers Q Previous Down s 0 None v Sample number 1 12165 Age at prev preg Date of sample 01 07 13 E Prev Pre eclampsia mn we l Sample number 2 12198 Interpretation 1 Down s Syndrome and NTD Date
80. recommended for clinical obstetric practice Ultrasound 17 161 167 Wald NJ and Cuckle HS 1987 Recent advances in screening for neural tube defects and Down s syndrome Bailliere s Clinical Obstetrics and Gynaecology 1 649 676 Morris JK and Wald NJ 2007 Estimating the risk of Down s syndrome in antenatal screening and the gestation at which this risk applies J Med Screen 2007 14 5 7 J P Bestwick WJ Huttly and N J Wald 2010 Distribution of nuchal translucency in antenatal screening for Down s syndrome J Med Screen 17 8 12 NJ Wald AK Hackshaw and HS Cuckle 2000 Maternal serum alphafetoprotein screening for open neural tube defects revised statistical parameters British Journal of Obstetrics and Gynaecology 107 295 298 HP Robinson and JE Fleming 1975 A critical evaluation of crown rump length measurements British Journal of Obstetrics and Gynaecology 82 702 710 NJ Wald HS Cuckle 1982 Estimating an individual s risk of having a fetus with open spina bifida and the value of repeat aloha fetoprotein testing Fourth Report of the U K Collaborative Study on Alpha fetoprotein in Relation to Neural Tube Defects J Epid Comm Hlth 36 87 95 NJ Wald HS Cuckle J Boreham G Stirrat 1980 Small biparietal diameter of fetuses with spina bifida implications for antenatal screening Brit J Obstet Gynaecol 87 219 221 NJ Wald JK Morris J lbison T Wu and George 2006 Screening in early pregnancy for pre eclampsia using Down sy
81. regression to use with the option buttons Regression details A BxGA days Regressio Observed Ax pGA days axp GA days C A 0 07097723 B 1 034643 Update medians This represents a 26 9 increase in median uE3 per week 120 130 Gestational Age Days Observed nmol L Expected 2 02 2 289 2 76 2 906 3 59 3 565 4 725 4 373 5 9 5 55 SC 7 288 CO alpha 8 0 Regression details A BxGA days Regression Observed ax pGA days axp GA days C A 11 23494 B 0 9996379 C 170 82 Update medians 120 130 Gestational Age Days Observed nmol L 150 2 02 Samples Expected 2 021 844 2 76 2 815 3 59 3 635 4 725 4 573 5 9 5 783 7 25 7 242 8 489 Figure 103 Comparison of log quadratic and log cubic equations for uE 5 9 4 Updating median equation coefficients If you judge that the regression represents a satisfactory estimate of the median values or weight corrections in your population press the Update Medians button A window similar to the one shown in Figure 104 will be shown If ethnic group specific medians have been derived select the checkbox alongside the name of the group to update the coefficients for that group only Press the Update button to update the selected coefficients The new coefficients will be used from date and time on which they are updated The current and historical coefficients can be viewed using Coefficients in the Setu
82. samples before reporting the results Alternatively it may have arisen because of a change in the assay for example a new assay lot number or a change in laboratory conditions In such cases you could perform a regression of the tabulated data from the batch file and update the coefficients of the median equation to allow for the change in the assay provided of course that the regression is based on a sufficiently large number of samples and is judged to be satisfactory pha versions 5 Statistics screen The statistics screen provides facilities with which you can E Generate a wide range of tabulations graphs and summaries to help in monitoring the performance of your screening programme SG Perform regressions to obtain coefficients for equations used in estimating the median marker level for a given gestational age and in correcting serum marker levels for maternal weight E Extract records from the database for analysis by another software package The options available are Analyse it Section 5 2 provides a powerful facility for users to analyse data collected by alpha Data transfer Section 5 3 exports data collected by alpha to a text file Median Analysis Section 5 4 provides facilities for producing graphs of median MoMs with time Missing information Section 5 5 provides a facility for creating tables of information which was missing from patient records Nuchal Translucency monitor Section 5 6 provides
83. settings Current Click Print current to view the current coefficient settings Figure 28 This is helpful when you change one or more settings to verify that the new settings have been entered correctly Click Print historical o to view the historical list of coefficients This is similar to the list of current settings except that all the settings ever entered are listed along with the dates when changes were made This provides a useful record of changes to your coefficients settings over time alph d version 8 A table of equation numbers is given at the end of the coefficient listing Pa Current coefficient settings 21 05 2013 10 33 53 CH Median equation MS AFP GA Overall 4 396402 1 018981 1 01 01 1980 Median equation uE3 GA Overall 0 1632426 1 02475 1 01 01 1980 Median equation T hCG GA Overall 14129 23 6640 29 4 01 01 1980 Median equation Inh A GA Overall 214 7009 3 01 01 1980 Median equation NT CRL Overall 0 6947472 1 010547 1 01 01 1980 Median equation NT CRL ALL 0 6947472 1 010647 1 26 03 2013 Median equation PAPP A GA Overall 0 1073264 1 056131 1 01 01 1980 Median equation FB hCG GA Overall 1 11E 10 0 6499239 1 002375 2 01 01 1980 Weight adjustment MS AFP Overall 1 596285 0 992937 5 01 01 1980 Weight adjustment uE3 Overall 1 260027 0 996563 5 01 01 1980 Weight adjustment T hCG Overall 1 733906 0 992135 5 01 01 1980 Weight adjustment Inh A Overall
84. specific cut off values are used they must increase monotonically with gestational age Cut offs in the ranges 2 0 4 0 MoM 2 0 4 5 MoM 2 0 5 0 MoM and 2 0 5 5 MoM are accepted for 13 15 16 18 19 21 and 22 24 weeks respectively m Units for AF AFP see section 3 1 13 SG Median reduction factors for AF AFP see section 3 1 9 The relationship between median AF AFP and gestational age is known to be log linear for 15 24 weeks but at 13 and 14 weeks the observed median values may be overestimated by a log linear model You use this setting to specify the percentage reduction in median AF AFP for 13 and 14 completed weeks The reduction at 13 weeks must be greater than or equal to that at 14 weeks Reduction factors of 0 40 and 0 20 are accepted for 13 and 14 weeks respectively If the median AF AFP level at 13 or 14 weeks fits a log linear regression well specify a reduction factor of zero 2 10 3 AF AFP medians The coefficients of the equation describing the relationship between median AF AFP levels and gestational age are specified in Coefficients see section 3 2 The general principles are the same as those for maternal serum markers except that ethnic group specific medians are not required nor are medians specific to the method of estimating gestational age dates or scan pha versions Coefficients for the median equations may be derived initially by assaying AF AFP in your laboratory for at least 200 amniotic flui
85. syndrome pregnancy PNTD Previous NTD pregnancy bl olpha Version 8 Page 232 Raised AFP RAFP Increased risk of Down s syndrome IRDS Codes 16 through 63 correspond to positive screening results when the interpretation involves pre eclampsia ka Di oO c Raised AFP Previous NTD Previous Increased Previous syndrome eclampsia syndrome amp o Q E D O D Yes Yes Yes Yes Yes Yes Yes Yes Yes es Ys Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes pi ei N Q GU D alph G Version 8 Reason Previous Increased Previous Previous Raised Increased code pre risk Down s NTD AFP risk of eclampsia of pre syndrome Down s eclampsia syndrome mm mei jel el vs mn 1 el el el Yes e 1 el jel el Ver em 1 rel jel el Ver Reason codes for positive and uninterpretable results amniotic fluid Reason code A Uninterpretable test done too early Uninterpretable test done too late es Wel Positive raised AF AFP and AChE band present E Ambiguous raised AF AFP and AChE band absent Ambiguous AChE band present and AF AFP not raised Positive raised
86. taken to be 18 days longer than the time since embryo transfer If the date of embryo transfer is recorded this takes precedence over other estimates of gestational age Prior to version 7 0V this field was called Date of egg collection A six digit number or lt less than followed by a five digit number A seven digit number or lt less than followed by a six digit number A four digit number or in a twin pregnancy two four digit numbers separated by a Date field appearing after each serum marker Used in cases where the median or weight correction equations may have changed after the date of assay for example those relating to first trimester markers in the Integrated Test If specified the assay date is used to select the chronologically correct equations If left blank the date of the report is used instead Page 180 Date of NT 3x2 Nasal bone fetus 1 ui Nasal bone fetus 1 2 Previous pre 1 eclampsia Ductus venosus 1 blood flow Date field appearing after nuchal translucency NT Used in cases where NT is not measured in the same ultrasound examination as crown rump length CRL or where CRL was not measured If specified the date is used to estimate the CRL measurement corresponding to the date of measurement of NT for the purpose of calculating the MoM value The date is also used to specify the chronologically correct equations If left blank it is assumed that NT was
87. test is being used analyte values for second trimester markers are being imported and no matching sample ID is found using the field specified here then the Lab number field will also be tested for a matching value This allows laboratories which perform both integrated and second trimester screening to use the analyser import before being stored in the patient record this marker 3 4 2 Example An import file which has no header lines contains the following data in each line Sample ID inhibin A AFP uE3 hCG An example of a line in the file is BE gt 2004 0764 21 712 56 427 1000 alpha Version 8 The import file configuration would be as follows hCG Items Inibin A AER UES Headerlinesinfle JOO Lower assay limit OO S 0 Quotation character Leave blank Leave blank Leave blank 1 Leave blank Leave blank Ignore string Leave blank Leave blank Leave blank Leave blank Qualifying string Leave blank Leave blank Leave blank Leave blank o cc column column Fixed width result start column Fixed width result end column OO LD O OO sat me Deena start E KENNEN end number Round assay value Select as required Enter assay date Select as required 3 4 3 Test import file Test The file format specification can be tested by highlighting a marker row and the pressing the button on the Analyser Import screen Figure 30 The e Next and Previous Previous button can be used to re
88. the selection data transfer specification Previous NTD Previous Down s Age at prev preg Prev Pre eclampsia Interpretation Smoker Click and drag items between the left and right columns to select or deselect them from the specification Diabetes IVF pregnancy Donor date of birth Date embryo transfer Date egg collection Doctor J FILE FORMAT DATEFORMAT OPTIONS EXCLUSIONS Comma separated D M Y Field name header Deleted reports Updated results Exclude Bs siInclude Include Diabetic women Repeat tests Other options Include Include are selected Tab separated O M D Y O Y M D Multiple pregnancies Incorrect reports here Include S Include FILE PATH datatransfer txt Figure 31 Data transfer settings 3 6 Database Database provides a facility for making a copy of the alpha database to another location see Figure 32 It also provides details about the SQL server database name SQL server version being used and the location of the database files on the computer running SQL server and their size Important You can only use this facility to copy a database to another location when alpha and SQL server are running on the same computer This facility will normally be used when you want to move the alpha software and database to another computer In a multiuser configuration please contact your network administrator if you wish to move the alpha software and
89. the interpretation Page 181 Previous NTD Amnio reason AF appearance AF AFP AChE NTD band PChE bands Fetal cells RBC million ml alph d Version 8 0 none 1 one 2 two or more Not used in the interpretation 1 raised MS AFP 2 suspicion of NTD on ultrasound 3 previous suspicious AF AFP AchE 4 family history of NTD 5 increased risk of Down s syndrome 6 unrelated to NTD or Down s risk 7 advanced maternal age 8 abnormal ultrasound finding 9 increased risk of trisomy 18 Not used in the interpretation 1 clear 2 cloudy 3 frankly bloodstained 4 significantly discoloured If the amniotic fluid sample is bloodstained or significantly discoloured and the diagnostic result is positive raised AF AFP a message is added to the report indicating that the result may be a false positive due to blood contamination of the amniotic fluid A five digit number or lt followed by a four digit number 1 faint 2 strong 3 absent 4 pending Amniotic fluid acetylcholinesterase AchE is one of the two main biochemical diagnostic tests for open NTD the other is raised AF AFP A faint or strong AchE band together with raised AF AFP indicates a positive diagnostic result If the band is absent and AF AFP is not raised or if the band is present and AF AFP is raised the result is classified as ambiguous 1 single 2 multiple 3 absent 4 pending A comb
90. the segregation of inherited chromosome structural rearrangements in 1356 prenatal diagnoses Prenat Diagn 4 45 67 5 Cuckle H Wald N 1987 The impact of screening for open neural defects in England and Wales Prenat Diagn 7 91 99 6 Cuckle HS Wald NJ Thompson SG 1987 Estimating a woman s risk of having a pregnancy associated with Down s syndrome using her age and serum alpha fetoprotein level Br J Obstet Gynaecol 94 387 402 7 Wald NJ Cuckle HS Densem JW Nanchahal K et a 1988 Maternal serum screening for Down s syndrome in early pregnancy Br Med J 297 883 887 8 Wald NJ Cuckle HS Nanchahal JK 1989 Amniotic fluid acetylcholinesterase measurement in the prenatal diagnosis of open neural tube defects Second Report of the Collaborative Acetylcholinesterase Study Prenat Diagn 9 813 829 9 Cuckle HS Wald NJ 1990 Screening for Down s syndrome In Lilford RJ Ed Prenatal Diagnosis and Prognosis 67 92 Butterworth 10 Cuckle H Wald N Stevenson JD May HM et al 1990 Maternal serum alpha fetoprotein screening for open neural tube defects in twin pregnancies Prenat Diagn 10 71 77 11 Wald NJ Cuckle HS Wu T George L 1991 Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in twin pregnancies Implications for screening for Down s syndrome Br J Obstet Gynaecol 98 905 908 12 Wald NJ Kennard A Densem JW Cuckle HS Chard T Butler L 1992 Antenatal maternal serum screening for Do
91. to data mEouredi ceeeccceceeeceeceeeeeeseeeeeeeseeeeeeseneeeeeas 22 Figure 6 Navigating alpha USING the ICONS ccccccceccceeeceeeceeeceeeceeeceuecaueeeeeeeceueeseesaeeseeseeeseeeseeeees 23 Figure 7 The number of screens associated with a section is shown next to the con 23 Figure 8 Thumbnails show which screens are open and allow you to navigate and close them quickly Ee 24 Figure 9 neue 25 Figure 10 Example of print preview screen 25 Figure 11 Attaching a new database to alpha cecccccccseeeecceceseeeeeeeeeaeeseeeeeeaeeeeeeeessaaeeeessaaeeeeessaaaes 31 Figure 12 Installing alpha on another computer cceecccccseeeeeceeeeeeeeeeeeeeeeseeeseeeeeeeeeeeeeseeseeesseneeeeas 32 Fig re 13 SETUP EE CT EE 33 Figure 14 Parameters screen 36 Figure 15 Selecting a parameter value cccccccccsssseccecceesseceeceuaeseceeseeaueeeeseseaaeeeeeseaaeeeeessaageeeeessaaass 37 Figure 16 Recording the name of user and reason for change sssssssssssrnrrresrnnrrnerrnrrresrnrrreeernrnee 38 Figure 17 Current parameters settings E 38 Figure 18 Coefficients Screen ccccccccsssseecccceccceeeeseeeceeeeeeseeseeceeeeseeseeeseceeeeessaeeaeeeeeeeessaaaaeeeeeeeeessaas 47 Figure 19 Coefficients screen selecting option 48 Figure 20 Coefficients changing values cccceeececcceceeceseeeseeeeeeeeeeeeeseeceeeeeesaeeaeeeeeeeeessaeaaeeeeeeeeesaaas 49 Figure 21 Coefficient and Median equation POLIC
92. unrounded Trisomy 18 posterior risk See note 14 SLOS prior risk rounded Integer Integer Text 1 Integer Long Integer Integer Long Integer Integer j T Ou N Cc st Been Ur OU Le Ben Fe vis H wi wi wi wi wi wi wi Vv ES DD DD DD Bn O EES F H x PES O T e go 2a GC E A hi gt a on 12 CH 2 Ben Ou xe Ben O CH Ben j c LLI e E EH E gt risk has been capped The trisomy 18 risk can only be reported when it is above the screening cut off and should not be reported in twin or diabetic pregnancies Derived w Page 207 Maternal Serum Comment OH SEN Se g E O gt 2 x S maii o Be os O E 3 ESA D _ ZS E c IL ZE LLI _ T Ou N c st Been Ur OU Le Ben Fe vis Type of SLOS prior risk Long SLOS prior unrounded unrounded Shows if risk has SLOS risk flag been trimmed or Text 1 v capped e SLOS risk Long SE rounded SLOS risk RHS Speen unrounded Integer SLOS risk LHS SLOS risk left hand unrounded side Integer SLOS risk RHS SLOS risk right Long unrounded pane e Integer unrounded verea gt risk has been capped Derived The SLOS risk can only be reported when it is above the screening cut off and should not be reported in twin or diabetic pregnancies Derived ze ze NO
93. user User who started data es a Version 8 Page 210 wi wi wi wi wi wi wi wi wi wi Maternal Serum Comment t and export Been O sj o CH E 2 2 D c Le ES Been O O CH 2 gt x lt ic uw Data transfer impor user who made final report gt For corrections only the name of the user who made the correction is stored Type of entry and username of user who made final report Comment Text entered fa Text v v Entered correction or update 255 l Time patient data Doctor code or Doctor 2 nee Worse ane Text 50 v v Entered doctor to send report to Address code for Report address 2 second address to Text 8 v v Entered send report to Doctor code or Doctor 3 ees OPANG Text 50 v v Entered octor to send report to Address code for Report address 3 third address to Text 8 v v Entered send report to Language code for 1 English 2 German 3 Italian 4 French 5 Greek 6 Language 2 Language code for neger v v x x Entered 11 Slovak 12 Vietnamese 13 Romanian 14 Chinese Version 8 Page 211 Been OH EES ES O x SS O 35 ee xe OO ei LL Entered or derived H T Ou N c st Been Ur OU Le Ben Fe vis impor Maternal Serum Comment sl P At Derived For positive and un interpretable results only See note 16 Type of 8 l report of second doctor Language code for
94. values for parameters and coefficients relevant to your screening policy and your laboratory The parameters and coefficients that you specify will depend on your screen designs Parameters see section 3 1 are used to specify your screening policy including screening cut off levels when to report risk estimates concentration units for biochemical markers and ultrasound machine settings Coefficients see section 3 2 are used to define the relationships between E gestational age GA and expected median values of maternal serum markers and AF AFP E crown rump length CRL and expected median values of ultrasound markers such as nuchal translucency E maternal weight and maternal serum marker MoM values E biparietal diameter BPD crown rump length CRL head circumference HC and abdominal circumference AC measurements and GA You can customise alpha further with the options in Set up see section 3 For example you can choose the way gestational age is entered into alpha and printed on reports You can also specify your own comments that can be printed on the reports depending on the results of the test alpha checks that you have chosen suitable prompts for the screen designs in order for a report to be produced and that valid settings are available for all the required parameters and coefficients alpha displays a message whenever a required parameter or coefficient value has not been set 2 5 Screening Reports alpha is
95. when it reaches the end of the file it resumes searching from the beginning of the file the current record in the batch or all records in the batch This shows an interpreted report for the current record in the data entry screen The preview report allows you to check the interpretation and helps to detect data entry alph d Version 8 em Purpose S O Auto Save F Edit started 02 08 2013 12 28 12 12 1 164 16 5 When entering data 12 01 14 errors If a required item such as the sample date is missing or if the record contains invalid data for example the sample date is after the current date alpha prompts ou to correct the error This setting controls how patient data is saved when moving between patients in the data entry screen When AutoSave is not selected alpha will prompt the user to confirm that the data should be saved Otherwise alpha will automatically save the data By default this is set to the same value selected in Save patient data in data entry in User Options See section 3 20 1 This setting can be changed temporarily here to prevent an unwanted change from being automatically saved This shows when editing started The record navigator shows the record number and the total number of records in the batch It also provides buttons to allow navigation backwards forwards gt and to the beginning K and end gt l of the batch Press the to add a new record to the bat
96. 0 SETTINGS Use Alpha Settings PREVALENCES TIMING OF RISK CUTOFFS Figure 51 What if Open the Prevalences timing of risk or cutoffs expander to change the settings as required or you can select the settings used in alpha by clicking Use alpha Settings Changing the screening policy settings in What if has no effect on the settings used by alpha The last screening policy settings used in What if are stored and are loaded the next time you open What if So apart from the first time you use What if there is no need to specify the settings each time Of course you can change the settings at any time to see the effect this has on the interpretation What lf provides interpretations for first trimester second trimester and integrated screening tests olpha For first trimester screening tests enter a gestational age GA between 10 and 13 weeks and enter MoM values for first trimester screening markers only What uses the appropriate gestation specific parameters in estimating the risk of Down s syndrome For second trimester screening tests enter a GA between 14 and 22 weeks and enter MoM values for second trimester screening markers only Version 8 m For integrated screening tests enter MoM values for first and second trimester screening markers and enter either a first trimester 10 13 weeks and a second trimester 14 22 weeks GA What lIf uses the appropriate gestation specific parameters for the first trim
97. 0 Derivation of normal Medians for serum markerg 72 Figure 41 Derivation of normal medians for nuchal translucency 73 Figure 42 Message Addition screen 75 Figure 43 Page setup EE 76 Fig re 44 Report Format Seng E 77 alph d Version 8 Figure 45 Figure 46 Figure 47 Figure 48 Figure 49 Figure 50 Figure 51 Figure 52 Figure 53 Figure 54 Figure 55 Figure 56 Figure 57 Figure 58 Figure 59 Figure 60 Figure 61 Figure 62 Figure 63 Figure 64 Figure 65 Figure 66 Figure 67 Figure 68 Figure 69 Figure 70 Figure 71 Figure 72 Figure 73 Figure 74 Figure 75 Figure 76 Figure 77 Figure 78 Figure 79 Figure 80 Figure 81 Figure 83 Figure 82 Figure 84 Figure 85 Figure 86 Figure 87 Figure 88 Figure 89 Figure 90 Figure 91 Figure 92 Figure 93 Figure 94 Figure 95 Figure 96 alph d Version 8 Screen Design ccccccseeccccccceeseccccceesececccaeuseeeesseeaeeeeeseaeeeeeeseaaueceeesuaaeceeessaeeeeesseageeeesssaasss 78 Screen Design change prompt 79 Screen Design enter default value ccceccccccseeeeceeceeeeceeeceeeseeeeeseeaeceeeeeeaeeeeesseaeeeeessaaaes 79 Uar e E 82 BEE 83 Entering a NOW E 84 Un E EE 85 Window envelope setup ne 87 FSA SCPC ea E E E A A ye mtatomnsenmeleuaeiae 89 DATA CHIUY Ee ET 91 WSS TAC OG EE 94 FCS E 95 Recurrent false positive MALCMING ireuicratnanouceisivantnicnnnaccuaaacnsinnvsedaineuschianevadvereusanieiwawvinneaua elu 9
98. 1 gt 0 62 lt M9MoM1 gt lt D1PostL gt 1 lt D1PostL gt lt D1PostR gt 440 lt D1PostR gt lt record gt Figure 83 Analyse it XML format alph d Version 8 5 3 Data transfer The Data Transfer option allows selected fields from the MS or AF database to be exported to another software program Section 3 5 describes how to specify or change the fields to be exported and how to store them in a data transfer specification When the option is selected a screen similar to Figure 84 is shown The data transfer specification description can be selected from a drop down and the filename in which the results are to be stored specified You can select whether reports are to be exported from the MS or AF database and which tests first trimester second trimester integrated sequential or all tests should be included You can also select the date range for the report and screening reports associated with selected report addresses doctors or sonographers be included or excluded from the analysis See Section 5 13 2 Press the Transfer DG to start the transfer When the transfer is complete alpha asks if you want to open the data transfer file 2 IG Statistics d alpha 8 0 Specify if the report summary is for maternal serum or amniotic fluid Data Transfe Specify the tests to include in the report E Description aert daily set of results v All tests Select the data transfer description and Filename _ k quch v61a ENCRYP expo
99. 18 Coefficients screen alph d Version 8 2 tk 1 Setup AAA Q alpha 8 0 Coefficients This shows the selection of the MS AFP overall regression Clicking on the item leads to the next item on the branch Ome Ultrasound gestation BPD CRL AC and HC T J Weight Adjustment 3 ti Oi Setup AAA Q alpha 8 0 Coefficients Bak Median Equations AF AFP amp GA Current uE3 amp GA T hCG amp GA FA FB hCG amp GA Inh A amp GA E NT amp CRL GE 2 tk ei 1 Setup AAA Cl alpha 8 0 Coefficients Bade Median Equations gt MS AFP amp GA MS AFP Dates GA Ca MS AFP Scan GA pocceeneceencenccecencencnccecccses O Don t prompt GC for changes i DT E Figure 19 Coefficients screen selecting option alph d Version 8 2 Jk HI Setup oni d alpha 8 0 Coeffi cle nts This shows the adjustment of the MS AFP overall regression equations Sen _s gt MS AFP amp GA gt MS AFP GA MS AFP GA Overall 01 01 1980 Overall Expected median Ax pGA days Current non Black A A graph of the equation is shown here Group 4 Group 5 Evaluate Select the desired setting for the coefficients and Don t prompt for changes press save to save the values Black B 1 018981 Group 6 oO Median MS AFP LD 100 120 140 Gestational Age Days HISTORY The current setting and history of previous settings are shown here Median Equations gt MS A
100. 181 Pressing displays a calendar from which the date can be selected using the mouse alph d Version 8 KT The date separators are shown in the text box AJ SI and do not need to be entered Mo Tu We Th Fr Sa Su Pressing allows 4 2 31 L 3 4 the date to be chosen 3 Pos 30l from a calendar 12 13 14 15 16 D l 18 20 31 2 FM DE 2 7 38 Hw 4 1 2 3 4 5 6 7 amp Figure 9 Entering dates 2 6 3 Print preview screen Throughout alpha results which can be printed are presented in a common format Figure 10 li ei 2 Setup AAA CO alpha 8 0 Each page can be displayed by clicking on the thumbnails hy Current coefficient settings 02 08 2013 17 06 19 Zei MS AFR medians A B Eqn Sartanie Median equation MS AFP GA Overall 4 396402 1 018981 01 01 1980 Median equation MS AFP GA Caucasian 4 396402 1 018981 01 01 1980 uE3 medians A B Start date Median equation uE3 GA Overall 0 1632426 1 02475 01 01 1980 Median equation uE3 GA Caucasian 0 1632426 1 02475 01 01 1980 Total hCG medians A B Start date Median equation T hCG GA Overall 14129 23 6640 29 01 01 1980 Median equation T hCG GA Caucasian 14129 23 6640 29 01 01 1980 Inhibin A medians A 8 Start date Median equation Inh A GA Overall 214 7009 01 01 1980 Median equation Inh A GA Caucasian 214 7009 01 01 1980 Nuchsl medians A B Start date Median equation NT CRL Overall 0 6947472 1 010647 01 01 1980 Median
101. 2 3 Table 3 Purpose of buttons in Print Preview screen Button Purpose D Dem ooo zn View two pages of the report next to one another Close the preview screen 2 Files and the alpha database ace a ed TTT WW 8 Data relating to a batch of screening requisition forms are stored initially in a named file known as a batch file When you produce final reports for a batch of requests the data in the batch file together with the values calculated by alpha are automatically merged into the database and the batch file is deleted Separate databases are kept for MS and AF data but links are created between the two databases for MS and AF results that relate to the same pregnancy The database allows you to retrieve individual results easily and to produce statistics for monitoring In addition selected records from the alpha database can be exported to other software applications For example you might export screening data from alpha to a spreadsheet or statistics package for further analysis New batch files are created using Data Entry Section 4 1 or Import Section 4 5 When the batch is closed alpha prompts to save the batch and gives a batch file name based on the current date plus an extra letter For example the first file to be created on 11 April 2013 would have the name Apr 11 13 The second file would be Apr 11 13 A unless Apr 11 13 had already been deleted or reported in which case Apr 11 13 would be used
102. 3 Weight adjustment equations for maternal serum markers may be specified separately for different ethnic groups Figure 23 To choose a different regression equation select Change and make a selection from the options given Figure 24 alph d Version 8 Equations used to estimate gestational age from ultrasound measurements may be specified for up to nine ultrasound machines or centres Figure 25 To choose a different regression equation select Change and make a selection from the options given Figure 26 The first time you choose a setting for each coefficient it will be given a start date of 01 01 1980 Each time you change a setting the date and time of the change will be used as the start date You will need to enter acceptable values for all the required coefficients before you can create reports 2 tit i Setup oni Coefficients Bade Weight Adjustment gt MS AFP MS AFP Overall 01 01 1980 a Adjusted MoM Ax Bweight kg non Black Change A 1 596285 B 0 992937 Black Group 4 Group 5 Group 6 Press Change to use a different weight regression equation Use can use a log linear or linear reciprocal function o d Adjusted MoM 50 100 150 Maternal weight Kilograms HISTORY Weight Adjustment gt MS AFP Coefficient A Coefficient B Coefficient C Coefficient D Equation Start Date End Date User Name Comment 1 596285 0 992937 Log Linear Tuesd
103. 4 weeks Pre eclampsia risk i 2 3 4 NN m _ A M alph d version 8 Acceptable settings never always when positive term time of test 1 in 20000 1 in 1000000 1 in 20000 1 in 1000000 4in5 1in5 4in5 1in5 9 in 10 1 in 2 for the risk of Down s syndrome in Integrated Test 4in5 1in5 4in5 1in5 Range starts from 14 or 15 completed weeks finishes between 19 and 22 completed weeks 13 to 24 completed weeks or 15 to 21 completed weeks Yes or No Yes or No Default setting Do not adjust Default setting or Adjust 1 in 100 1 in 500 1 in 50 1 in 300 1 in 10 1 in 60 2 0 4 0 MoM 2 0 4 0 MoM 2 0 4 0 MoM 2 0 4 5 MoM amp 2 1 2 0 5 0 MoM amp 2 2 2 0 5 5 MoM amp 2 8 1 in 5 1 in 300 Page 185 Background prevalences for overall population and up to 5 specified ethnic groups Spina bifida ea 0 2 4 0 per 1000 Pre eclampsia 10 80 per 1000 BPD correction factors Ultrasound machine 1 9 1540 m s outer to inner edge of cranium 1540 m s outer to outer edge of cranium 1600 m s outer to inner edge of cranium 1600 m s outer to outer edge of cranium AF AFP median reduction factors 13 completed weeks 0 40 reduction 14 completed weeks 0 20 reduction Recurrent false positives Do not adjust strict matching loose matching 1 The value of x must be specified Values in the range 12 55 years are accepted 2 See Section 3 1 10
104. 500 are black and 500 are South Asian you might reasonably decide to use the direct method for Caucasian and black women For South Asian women the small number screened may make it difficult to obtain reliable estimates of the median marker levels especially over short periods of time In this case it might be preferable to use the adjustment method specifying the largest ethnic group Caucasian women as the reference group and providing correction factors to allow for differences in marker levels and weight between South Asian and Caucasian women A special case is the overall group This does not correspond to a real ethnic group but to the screened population as a whole Medians and weight correction equations for the overall group are derived by tabulating data for all women regardless of ethnic group In screening centres with an ethnically homogeneous population medians and weight correction equations need only be specified for the overall group Even if the population is ethnically mixed you still need to provide medians and weight correction equations for this group since these equations are used to convert marker levels to MoM values in women whose ethnic group is not recorded The direct method is always used for the overall group and you cannot specify the overall group as a reference group When tabulating serum marker data for an ethnic group that is a reference group for other groups corrected marker levels from the oth
105. 52 0 850000024 0 819999993 1 179999948 0 829999983 0 550000012 4 570000172 1 74000001 0 50999999 0 810000002 0 629999995 0 829999983 1 190000057 0 810000002 0 920000017 1 200000048 0 769999981 0 49000001 0 889999986 0 5 0 670000017 0 860000014 0 870000005 1 700000048 1 080000043 1 110000014 0 660000026 1 25999999 1 200000048 0 860000014 1 019999981 0 620000005 1 25999999 1 169999957 1 440000057 1 419999957 1 129999995 0 839999974 0 839999974 1 139999986 0 939999998 0 910000026 0 920000017 1 450000048 1 379999995 0 839999974 1 039999962 1 149999976 0 74000001 1 730000019 1 440000057 1 220000029 1 24000001 2 190000057 0 899999976 1 059999943 1 100000024 1 110000014 0 860000014 1 269999981 1 279999971 1 450000048 0 eigipigigioioioioioioioioicoioigoigoiscoigoioiso i f so o GALA HLH AL AL ALL 0 62 0 73 1 33 1 0 53 0 96 0 68 0 89 0 58 0 9 2 39 0 47 1 38 0 98 Ready 7 Figure 82 Analyse it Results in Excel lt record gt lt ReportDate gt 05 01 2004 00 00 00 lt ReportDate gt lt EDDAge gt 39 4 lt EDDAge gt lt IntegerEDDAge gt 39 lt IntegerEDDAge gt lt ScanGA1 gt 91 lt ScanGA1 gt lt ScanGA2 gt 118 lt ScanGA2 gt lt M1MoM1 gt 1 18 lt M1iMoM1 gt lt M2MoM1 gt 0 68 lt M2MoM1 gt lt M5MoM1 gt 1 54 lt M5MoM1 gt lt M6MoM1 gt 1 7 lt M6MoM1 gt lt M7MoM1 gt 1 26 lt M MoM1 gt lt M7MoM2 gt 0 lt M7MoM2 gt lt M7MoM2 gt 0 lt M7MoM2 gt lt M9MoM
106. 6 leen 97 Separating sequential tests 2 0 eeeeeecccccecceeeeeeeeeeeeeeeaeeeseeeeeeeeesuaeseeeeeeeeessseaaseeeeeeesseaasesss 98 Report exported in Standard Tomat 100 Part of report exported in packet format ccccccseeeeceeeeeeeeceeeeeeeeeeeeseeeeeeeeesesaaeeeeeseaeaseeees 101 SE DEE 102 Advanced search ME 103 EG TODO aaa E E E E E A 104 Report ee dee E 105 Jun eier Le EE 107 Analyser Import File Selection ccceccccccceesseeeeeceeeseeeecceauseceseseaaeeessesaaeeeeessuageeeeessaaass 108 Analyser Import Data Gcreen 108 Statistics screen showing Automonitor results 2 0 0 eeeeeeccecececaeeeeeeeeeeeeessaeeeeeeeeesessaeaeeees 112 Automonitor Markers A 112 Automonitor Report SUMMAPY cccccccssssesccceeeeceeeeseeeceeeeeeeeeeaeeeeeeeesseueeseeeeeeesessaaaaeses 113 Automonitor Test Specific SUMIMALY cccccccceeeeeeseeeseeceeeeeeaeeeeeeeeeeeeseaeeseeeeeeeeessaeaaeses 113 Automonitor Demographics nessenoeenenennensrrrensrnresrrrrrsrrresnrrersrnrersrrersrnrersnrersnrrersnreeene 114 Automonitor EE 114 Automonitor Nuchal Translucency 115 Analyse it e EEN 116 PANS OU eege 117 Analyse it Criterag 118 Analyse it criteria entering a criteria ccccccccccseeeeeeceeeeeecseeeeeeeeeeeeeeeegeeeseaeeeessaaseeesaaeeeeeas 119 Analyse it Complete ouerm 120 Pay SOM OGG CUMING E 121 Analyse it XML format ccccccccssecceceeeeeeeseeeeeeseeeeeeseeeeeeaeaeeeeseaeeeeseageeessaeeessaeeee
107. 63 Packeted report format 237 to Spreadsheet See Data transfer Export data to spreadsheet See Data Transfer False positive rate 235 Field 17 Final reports See Reports Final GA Clinical 177 235 Dates 176 235 Estimating from ultrasound measurements 45 See BPD CRL AC Precedence among GA estimates 172 Printing format 80 Scan 176 236 Gestational age See GA Graph medians AF AFP 30 HC 188 235 Import Analyser 55 Import data 13 26 27 106 Data import format 64 106 Installing alpha Initilisation 19 Software 17 Insulin dependent diabetes 13 178 MoM adjustment factor 70 MoM values in report 98 Integrated test 12 15 179 235 Serum 236 Intellectual property rights 2 15 244 In vitro fertilization See IVF IVF 13 780 MoM adjustment factor 70 MoM values in report 98 Laboratory information system See Exporting data Importing data Licence 34 67 Likelihood ratio 13 LMP 176 235 Log Gaussian model 13 Mailshots 62 Markers alpha fetoprotein AFP 14 Anomalous patterns 14 Assay date 180 Change names 68 Correlation coefficients 71 Data of sample 179 First trimester markers 14 inhibin A 14 Mean values in affected and unaffected 71 243 260 pregnancy associated plasma protein A PAPP A 14 Regression equation serum markers vs 187 Regression equation serum markers vs GA Coefficients 44 Regression equation serum markers vs GA from tabulated data See Tabulations Second trime
108. 7 Anomalous marker patterns in Down syndrome screening Prenat Diagn 27 185 186 Palomaki G Knight G Neveux L Pandian R Haddow J 2004 Maternal serum invasive trophoblast antigen ITA in first trimester trisomy 18 pregnancies Poster 2794 presented at The American Society for Human Genetics Annual Meeting 2004 Toronto Canada Wald NJ Bestwick JP Huttly WJ Morris JK and George LM 2006 Validation plots in antenatal screening for Down s syndrome J Med Screen 13 166 1771 Wald NJ Bestwick JP Huttly WJ 2008 Inhibin A concentrations between 14 and 22 weeks of gestation Prenat Diagn 2008 28 360 361 Bestwick JP Huttly WJ Wald NJ 2008 First trimester Down s syndrome screening marker values and cigarette smoking new data and a meta analysis on free beta human chorionic gonadotophin pregnancy assisted plasma protein A and nuchal translucency J Med Screen 15 204 206 70 71 12 73 14 19 76 T1 78 79 80 81 82 83 84 85 86 Wald NJ Cuckle HS Densem JW Nanchahal K Canick JA Haddow JE Knight GJ and Palomaki GE 1988 Maternal serum unconjugated oesiriol as an antenatal screening test for Down s syndrome British Journal of Obstetrics and Gynaecology 95 334 341 Lambert Messerlian G Palomaki GE and Canick JA 2009 Adjustment of serum markers in first trimester screening J Med Screen 16 102 103 Loughna P Chitty L Evans T Chudleigh T 2009 Fetal size and dating charts
109. 8 Wald NJ Watt HC Hackshaw AK 1999 Integrated screening for Down s syndrome based on tests performed during the first and second trimesters N Eng J Med 341 461 467 39 Wald NJ White N Morris JK Huttly WJ Canick JA 1999 Serum markers for Down s syndrome in women who have had in vitro fertilization implications for antenatal screening Br J Obstet Gynaecol 106 1304 1306 40 Wald NJ 2000 Neural tube defects In Wald N Leck Eds Antenatal and neonatal screening 63 Oxford University Press 41 Wald NJ Hackshaw AK George LM 2000 Assay precision of serum alpha fetoprotein in antenatal screening for neural tube defects and Down s syndrome J Med Screen 7 74 77 42 Hackshaw AK Wald NJ 2000 Revised distribution parameters for serum markers for trisomy 18 J Med Screen 7 215 43 Spencer K 2000 Screening for trisomy 21 in twin pregnancies in the first trimester using free B hCG and PAPP A combined with fetal nuchal translucency thickness Prenat Diagn 20 91 95 44 Hackshaw AK Wald NJ 2001 Repeat testing in antenatal screening for Down syndrome using dimeric inhibin A in combination with other maternal serum markers Prenat Diagn 21 58 61 45 Rudnicka AR Wald NJ Huttly W Hackshaw AK 2002 Influence of maternal smoking on the birth prevalence of Down syndrome and on second trimester screening performance Prenat Diagn 22 893 897 46 Morris JK Mutton DE Alberman E 2002 Revised estimates of the m
110. 8 risk lt 1 in 100 Comment Not in the high risk category for trisomy 13 risk lt 1 in 100 1 00 1 10 00 1 in 9 000 0 77 100 00 0 Down s pre NTD syndrome eclampsia A screen negative result does not exclude the possibility of Down s syndrome a neural tube defect or pre eclampsia because screening does not detect all affected pregnancies This is an Alpha report Figure 5 Screening report corresponding to data in Figure 4 alph d Version 8 2 6 Navigating alpha 2 6 1 alpha sections There are three principal sections in alpha Patients see Section 4 Statistics see Section 5 and Setup see Section 3 These are selected by clicking on the icons at the top of the screen Figure 6 2 Patients Im Statistics O Setup Click on the icon to select the required section Figure 6 Navigating alpha using the icons The principal features in each section are shown in Table 2 Table 2 Sections in alpha Prinicipal features 3 7 Patients Data entry reporting import search and corrections Statistics Tabulation median monitoring regressions D o Setup Configuration and setup features Additional screens will be opened as you navigate through alpha The number of screens open which are associated with each section are shown next to the corresponding icon Figure 7 L Patients Ik e Figure 7 The number of screens associated with a section is shown next to the icon This shows that one screen is o
111. 89999986 0 649999976 1 279999971 0 689999998 1 549999952 0 980000019 1 309999943 0 660000026 1 320000052 0 910000026 1 220000029 0 660000026 4 289999962 1 669999957 1 529999971 0 620000005 0 449999988 1 059999943 1 059999943 0 879999995 1 080000043 0 899999976 1 600000024 1 320000052 1 860000014 0 910000026 0 680000007 1 070000052 0 519999981 0 579999983 0 629999995 0 910000026 1 289999962 uE3 MoM FB hCG 2T MoM Inh AMoM NTMoM NT MoM 2 PAPP AN E 0 680000007 1 200000048 1 340000033 0 870000005 0 939999998 1 330000043 2 0 75 1 24000001 1 370000005 0 99000001 1 00999999 0 970000029 1 110000014 1 519999981 1 019999981 1 409999967 0 939999998 0 74000001 0 800000012 0 920000017 1 419999957 0 910000026 1 570000052 0 709999979 1 190000057 0 920000017 1 0 899999976 0 74000001 0 879999995 1 169999957 0 75 0 560000002 0 860000014 1 409999967 1 539999962 0 74000001 0 730000019 0 730000019 3 049999952 0 800000012 0 779999971 1 730000019 0 660000026 1 450000048 0 629999995 2 089999914 2 470000029 0 899999976 0 239999995 2 630000114 1 75999999 0 589999974 1 940000057 0 790000021 1 200000048 0 889999986 0 370000005 0 930000007 0 709999979 1 190000057 0 769999981 1 789999962 0 699999988 0 5 1 389999986 1 129999995 1 019999981 1 190000057 2 25999999 0 709999979 1 700000048 0 689999998 0 660000026 0 819999993 0 870000005 0 839999974 1 200000048 0 699999988 1 2999999
112. Correct and update options Section 4 4 You use Edit to change reports that have already been issued and to add information which was not available at the time of the original report for example ultrasound details or maternal weight A message is added to the corrected or updated report indicating that it is a revised version of a previously issued report The Search and print option Section 4 3 provides additional copies of reports which can be printed viewed on screen or exported 4 2 1 Test reports In order to start a Test Report select the batch file you want to work with and click Gi if necessary selecting Test report from the dropdown alpha verifies the data in each record and checks for potential matches with existing records in the database and with unreported results The verification step checks that each item of data is valid and that sufficient information is available for each record to create a report The matching process checks each record in the batch against records in the database to identify earlier reports that may relate to the same pregnancy or toa previous pregnancy in the same woman See section 4 2 2 Matching also checks each record against other unreported records to identify records that may have been entered twice in error If an error is found during the verification stage alpha indicates the type of error and offers you the choice of either editing the batch so that you can correct the error or a
113. EN Preferred Address 1 Preferred Address 2 Exclude 00000002 No 00000003 No 00000002 No 00000003 No Mailshot list provides an option for generating mailshot addresses Enter contact details if you wish Enter codes for up to two doctors who will receive copies of reports addressed to this doctor The report will be shown in the language selected Enter codes for up to seven addresses with which the doctor is associated Exclude this doctor from other lists Page 62 3 8 Ethnic groups With this option you can specify the names alpha uses to refer to different ethnic groups You can specify a short name and a long name for each ethnic group The long name up to 30 characters in length is printed on alpha reports and the short name up to 10 characters in length is used in menus and statistical summaries By default three ethnic groups are defined in alpha overall non black and black You can change the names used to refer to these three groups as well as defining up to three additional ethnic groups of your choice For each ethnic group defined you can specify separate ethnic group specific median equations weight correction equations anencephaly prevalences and spina bifida prevalences Please note that the group named by default overall and black are reserved for women whose ethnic group is not specified and for black women respectively 3 9 Export settings If you have created an
114. FP amp GA gt MS AFP GA Coefficient A Coefficient B Coefficient C Coefficient D Equation Start Date End Date User Name Comment 4 396402 1 018981 Log Linear Tuesday January 01 1980 SYSALPHA LMS Canag Figure 20 Coefficients changing values 3 2 3 Changing coefficients You can change coefficient settings by editing them in the Coefficients screen See Figure 20 alpha stores historical settings for each coefficient and the date on which each value was changed When reports stored in the database are reprinted or accessed for tabulations alpha ensures that the correct value is used for each coefficient by retrieving the values that were current at the date of the original report Coefficients can also be updated without being typed in using the Tabulation and Regressions options See Section 5 9 4 Not all coefficients will require setting and this will depend on your screen design A full description of the available coefficients is given in Appendix D Equations used in calculations For maternal serum markers coefficients for up to three normal median equations may be given for each ethnic group according to the median equation policy you have specified Figure 21 See section 3 1 8 Median equation policies for more information on specifying median equation policies If you wish to specify a sonographer specific regression equation relating NT to CRL select NT amp CRL press the Q Add Sonographer butto
115. For some markers more than one regression equation relating measurement to gestation age is available See Appendix D Equations used in calculations Users can choose which equation fits their data best Figure 103 shows a comparison of the log linear and log quadratic regression equations for uE3 Use the graph and the table of expected and observed values to examine the goodness of fit of the regression Large deviations between observed and expected values should be considered in relation to the number of women on which each value is based For regressions with maternal weight you can specify either a log linear regression 7 or alternatively a linear reciprocal regression Although there is little to choose between the two models some users may find that one model fits their data better than the other The log linear model is the one most widely used alph d Version 8 L re Regressions uE3 Gestational age MARKER UNITS nmol L PLOT OPTIONS O Logarithmic Y Axis OVERLAY SETTING No overlay v 2 Je Statistics Statistics 2 H Median uE3 nmol L Median GA Days 102 Q Regressions uE3 v Gestational age v MARKER UNITS nmol L PLOT OPTIONS Li Logarithmic Y Axis OVERLAY SETTING No overlay alph d Version 8 co On Median uE3 nmol L a Median GA Days 102 109 115 121 128 136 CO alpha 8 0 Select the
116. Head circumference Karyotype Birth weight Craniorachischisis Iniencephaly cm alaik Kg Ib oz Closed encephalocele Open encephalocele Encephalocele type of lesion unk Comments Outcome entered by Closed frontal encephalocele Wane el Open frontal encephalocele Frontal encephalocele type of lesi w Delete Save Close Figure 94 Outcome Data Entry Screen alph d Version 8 The Abnormality codes section lists all ICD and user defined codes for selecting in the abnormality inputs The user can enter abnormalities by either selecting the code form the list or by typing the code which will automatically find the code within the list Pressing lt Enter gt will select the code highlighted in the list Selecting the code 99999 allows the user to enter a custom abnormality description The Outcome details section allows the user to enter information regarding Details of any diagnostic procedures together with abnormalities diagnosed Delivery details Outcome details for 1 or more foetuses Sex Foetus outcome Up to three abnormalities present Head circumference cm Karyotype Birth weight kilograms or pounds and ounces Comments and the name of the person entering the record 5 7 4 Screening Audit The screening audit section is used for monitoring the proportion of screened pregnancies for which outcome information is available and the uptake of diagnostic procedures such as amniocentesis
117. PP A level 12 11 mg L INTERPRETATION Screening result Screen negative Risk of Down s 1 in 9 000 at term Risk of NTD 1 in 7 000 Risk of Pre eclampsia 1 in 60 Comment Down s risk due to maternal age alone is 1 in 720 Comment Not in the high risk category for trisomy 18 risk lt Comment Not in the high risk category for trisomy 13 risk lt A screen negative result does not exclude the possibility of Down s syndrome a neural tube defect or pre eclampsia because screening does not detect all affected pregnancies Figure 60 Report exported in standard format 4 2 6 2 Packet Export In Packet format each element of the report is defined by a packet number and the fixed and variable parts of the text are presented in a specified format Figure 61 shows part of the report in Figure 2 exported in Packet format Full details of Packet format are given in Appendix Packet export report format This format may be useful when a laboratory information system prepares a screening report in a bespoke format using the messages and details provided in the alpha screening report alph d Version 8 090 00 01 01 Dr Albert Brown MD 095 00 04 04 The Surgery 24 Park Lane LONDON NE3 ZA9 005 01 01 02 2 DOWN S SYNDROME NEURAL TUBE DEFECT AND PRE ECLAMPSIA SCREENING Report dated 08 Jan 14 030 01 01 02 Last name JONES
118. Pre eclampsia screening using first trimester PAPP A mean arterial pressure MAP and first and second trimester placental growth factor is now possible These markers were not previously available for pre eclampsia screening alpha 8 can calculate screening performance estimates for Down s syndrome trisomy 18 SLOS trisomy 13 and pre eclampsia Previously screening performance estimates for Down s syndrome only could be calculated Since version 8 0 14120 22 the detection rate at a fixed false positive rate and the false positive rate for a fixed detection rate are both calculated alpha 8 includes a gestation specific adjustment for inhibin A for women who smoke Prior to version 8 0 14120 22 the adjustment factor for inhibin A was not gestation specific Technical advances alpha 8 contains many advances which improve ease of use and user friendliness Simpler navigation o All features are grouped into one of three sections Patients Statistics and Setup o Easy to switch from one feature to another and back again You can return to the first feature and carry on from exactly where you left it Automonitor o Provides an overview in a single screen of the performance of your screening program o Highlights issues which require further investigation o Complements the existing statistical and monitoring features in alpha Statistical analysis o Calculations up to 30 times faster o Selection of date ranges for
119. T hCG 2T 2 tit HI Setup oni Q alpha 8 0 Parameters Bak Adjustment for Ethnic Group gt MS AFP Ge Black Don t prompt for changes Group 4 Group 5 2 tt HI Setup oni Q alpha 8 0 Parameters Bak Adjustment for Ethnic Group gt MS AFP gt Caucasian Search Current Select the desired setting for the parameter Adjustment Method Don t prompt for changes The current setting and history of previous settings are shown here HISTORY Adjustment for Ethnic Group gt MS AFP gt Caucasian Setting Start Date End Date User Name Comment Figure 15 Selecting a parameter value alph d Version 8 Save changes Caucasian Direct Method User s name John Smith Comment Initial setting Figure 16 Recording the name of user and reason for change 3 1 2 Printing current and historical parameters You can print or view a list of current parameter settings and a complete historical list of settings Current Click Print current to view the current parameter settings Figure 17 This is helpful when you change one or more settings to verify that the new settings have been entered correctly It also provides a summary of your current screening policy Pin Current parameter settings 20 05 2013 12 57 19 S Printing of risks Down s risk cap integrated test 4in5 01 01 1980 00 00 00 Trisomy 18 risk cap 1in2 01 01 1980 00 00 00 NTD risk cap lin2 01 01 1980 00 00 00 Print Pr
120. Use default Use default _ STANDARD DEVIATION _ Include date Select Grouping Select Grouping Select Grouping Filename lt Surname gt lt Forename s gt lt Hospital No gt xps Use default Use default Use default to Ke Sorting Select Sorting Select Sorting _ INCREASE PER WEEK to Re format of the XPS Re is given here Figure 48 User Options 3 20 8 Error log path The path used by alpha to store the error logs is shown here Your alpha distributor may ask you to send the error log files to help with the diagnosis of problems This folder is opened by pressing the Open folder button alph d version 8 3 21 Users This option allows the system administrator to manage the list of users who can access alpha by assigning usernames passwords password expiry dates security levels and the language in which the user s data entry screen appears See Section 4 1 and screening reports Figure 49 When New User is selected Figure 50 the new user s details and security levels can be entered alpha is supplied with one user account the SYSALPHA or system administrator account This account has security level 6 and it is the only account which can create modify or delete other user accounts Appendix F Controlling access using security levels gives details of the security levels available 2 te Gi Setup oni d alpha 8 0 Users Your account SYSALPHA This sel
121. Y ccceccccceccsseeeeeeeeseeeeeeeeseeeseeeeesseeeeeeessaeeeeeeesaaess 50 Figure 22 Select equation fOr UES 0 cceecccccccccceseseseeeeeeeceeeesseeeeeeeessaeeeseeceeeessseeaeeceeeeessaeaaeeeeeeeeesaaas 50 Figure 23 Selecting weight adjustment equations ccccccccecceeeeeeeeceeeeseeeeeseaeeeeeeessaaseeeessaeeeeeeeesaaees 51 Figure 24 Select weight adjustment equation cccccccccsseseeeceeeeeeeseeeseecceeeeesseeaeseceeeeessuaaseeeeeeeeseaas 51 Figure 25 Equations for estimating GA from fetal measurements nnnnnoannnnnnennnnnnnnnnnnnnnnnnneneennnne 52 Figure 26 Select NEW ultrasound eguaton 52 Figure 27 Evaluate coefficients cccccsssccccsseeccseseecceeuseccseeseeeceaueeessaaeeecseuueeessageeessageeessegseesssaeeeeees 53 Figure 28 Current coefficients ccccccccccccsesseccecceesecececeesseceeeceeaseeeesseaaeeeessaaaeeeeessuaaeeeeessaageeeeessaaass 54 Figure 29 Addresses ecreen nenen 55 Figure 30 Testing the analyser Import le 58 Figure 31 Data transfer settings ccccccscccccssseeeceeseeeceeseecseeuceeceaeeecsagsceeseseeessageeessegeeessegeeesssaseeeeas 60 Foure RE 61 Figure 33 Doctors screen 62 PUIG D e Ee e CLO E 62 leift elle SNC e E E E N E E 64 Figure 36 Import settings A 65 Figure 37 Integrated test options ccccccccsssseccceceeeseceeeceesseceeeeaaseeeeseeaaeceesseaaeeessesaaeeeeessaaeeeeeesaaass 66 Fig re 38 e Nee E 67 EE Tele 68 Figure 4
122. a column will remove it from the report LI lu 1 Statistics o Select a field from this d aipha 8 0 dropdown and press add to include it in the missing PERR information results Missing Information GROUP BY Scan GA at 1st sample Add Combine with Dates GA at 1st sample Add By Report Address v Total tests Weight 6136 15 19 REPORT DATE RANGE O All periods Report address Total Tests Weight Select a field from this gn 00000001 1014 20 5 dropdown and press add to a ombine it with the field to the e Ge SS SE Ze Ge missing dee results 00000103 25 12 0 00000104 20 0 0 00000106 8 0 0 00000107 49 14 3 This shows the number and percentage of reports which E 30 8 were missing maternal weight 00000110 33 15 2 00000108 50 2 0 00000111 1 0 0 00000112 60 3 3 00000113 13 23 1 00000114 31 16 1 00000115 5 0 0 00000116 17 11 8 00000117 13 7 7 00000119 27 11 1 00000120 18 0 0 00000121 10 0 0 00000122 1 0 0 00000123 7 8 00000124 12 5 00000125 0 0 Figure 87 Missing information alph d Version 8 2 Jr Statistics LE CO alpha 8 0 Missing Informatio GROUP BY LMP Add Combine with By Report Address hl Total tests Weight LMP 6136 1519 2 1460 REPORT DATE RANGE All periods Report address Total Tests Weight LMP Select a field from this dropdown From NGO o ek Lo and press add to combine it with L
123. a entering a criteria alph d Version 8 2 tr Statistics O O alpha 8 0 New MS query New AF query Delete query na Median GA of IT women at second stage Test query Run query Save query Name Type Median GA of IT women at second stage Maternal Options Output Criteria Ordering TE 6 DO OG Monte satus tan vr Ys E ER PO Ye Minesrtessceenno ER DR O e DECH ER FOR x Gw The query is built up from separate criteria combined with the AND and OR operators Figure 80 Analyse it Complete query Table 11 Explanation of criteria used in Analyse it example Criteria Meaning o Z o Oo SS O PointerForward NULL Do not include corrected records Delete Status Flag NULL Do not include deleted records MS AFP MoM lt gt NULL Include records where the MS AFP MoM is specified Number of fetuses lt gt 2 Include records where the number of fetuses is not equal to 2 Integrated Screening 1 Include records when the Integrated test was performed Date reported 2 1 1 04 Include records where the report date was on or later than 1 January 2004 Date reported lt 1 7 04 Include records where the report date was before 1 July 2004 5 2 4 Ordering The order in which the results are exported are specified on the Ordering tab See Figure 81 In this example reports will be ordered using the alpha report date field alph d Version 8 2 hh7 Statistics OB d alpha 8 0 New MS query New AF query Del
124. a facility for monitoring sonographer specific nuchal translucency medians Outcome Section 5 7 provides a facility for entering pregnancy outcomes and for the complete validation of your screening programmes Population Section 5 8 shows the maternal age distribution in your screened population Regressions Section 5 9 provides facilities for deriving regression equations for the expected marker median levels Report summary Section 5 10 provides a breakdown of reports according to the screening results Risk analysis Section 5 11 provides a facility for investigating the cut off required for a given screen positive rate Screening performance Section 5 12 provides facilities for calculating the expected screening performance for any screening test Tabulations Section 5 13 provides facilities for monitoring the variation of marker levels with gestational age or CRL Tabulated data can then be used in the regressions facility Section 5 9 to calculate new values for the regression equation coefficients 5 1 Automonitor Automonitor provides an overview in a single screen of the performance of your screening programme when the Statistics screen is shown Figure 69 It provides an immediate warning of any issues which may need further investigation and complements the other statistical and monitoring features provided by the Statistics options pha versions Automonitor automatically selects a date to start monitori
125. a from the alpha database combined with data from the outcome database To access the Data Transfer section click Data Transfer onthe icon on the side bar There are three different export file options of an Excel spreadsheet comma delimited or tab delimited text files To transfer data from alpha Outcome select the file options the fields you wish to export and then select run to compute the data transfer For large amounts of data this may take some time 5 8 Population The Population option shows the maternal age distribution expected prevalence of various conditions Down s syndrome trisomy 18 trisomy 13 SLOS and pre eclampsia distribution of ethnic groups and prevalence of smoking diabetes previous NTD IVF previous Down s and previous pre eclampsia in the screened population Selected tests first trimester second trimester integrated sequential or all tests and women of selected ethnic groups can be included in the report You can select the date range for the report and whether screening reports associated with selected report addresses doctors or sonographers be included or excluded from the analysis see section 5 13 2 for further information Figure 100 shows an example of the Population screen The results can be printed with the Print button 2 thi Statistics BO d alpha 8 0 Population EE All periods From 7 CODES lInclude all codes v MATERNAL AGE RANGE 15 20 25 30 35 40
126. again When using Data Entry to create a batch file you can choose an alternative to the default batch file name if you prefer You can also use Data Entry and Import to add records to an existing batch file by choosing the file you want to work with from a file selection window some of the options in alpha automatically create another file based on the data in an existing batch file For example if you have chosen to export the final reports for a batch of requests instead of printing them alpha will create an export file In such cases the name of the file created consists by default of the batch file name plus an extension For example alpha might give the name MAR1206A EX1 to an exported report file for the batch file MAR1206A You can choose another name for the file if you prefer 2 8 Processing a batch of tests For most day to day purposes you will only need to use a few of the facilities and options available in alpha namely those relating to the production of reports for the given batch of tests pha versions The information relating to a batch of tests must first be entered into a file The information for each batch is usually stored in a new file but it is possible to add further tests to an existing batch file You can add data to a batch file in one of the following ways m You can enter each item of data manually using the Data entry options E You can import some or all of the data from another computer syste
127. ailable on the Tabulations screen will depend on the screening markers installed in alpha See Figure 114 alph d Version 8 L ro O O aipha 8 0 Tabulations MARKER Select the marker required for the tabulation TABULATE BY Gestational age lt Select whether tabulation by gestational age or maternal weight is required GA MEASUREMENT Scan if available dates otherwise lt Specify the estimates of gestational age to be included in the tabulation Use dates specific and scan specific tabulations if your policy is to use Leste le leeds separate medians according to whether gestational age is estimated by Al women regardless of ra Y ultrasound or other means Use overall medians Off Restrict the tabulation to women of a specified ethnic group or select all EE women Use ethnic group specific tabulations if your policy is to use ethnic O All periods group specific medians and weight correction medians SE To 01 01 05 F Se 01 01 05 E Use overall medians or ethnic group specific medians for all women CODES lInclude all codes Include reports from a specified period or all reports You can specify that data from reports associated with selected report addresses doctors or sonographers be included or excluded from the Satterpot_ d tabulation Refresh results Display the graph as a scatter plot or a box plot DISPLAY GRAPH AS Figure 114
128. alpha Antenatal screening software for Down s syndrome open neural tube defects and pre eclampsia For use in first trimester second trimester and Integrated screening for Down s syndrome and pre eclampsia and second trimester screening for open neural tube defects Version 8 User manual aloha is a product of Logical Medical Systems Ltd 29 30 Newbury Street LONDON EC1A 7HU United Kingdom Tel 44 0 20 7600 3193 Fax 44 0 20 7606 0506 email aloha Imsalpha co uk www Imsalpha co uk 0088 Logical Medical Systems Ltd 2014 No part of this publication may be reproduced or transmitted in any form or by any means without the prior permission of Logical Medical Systems Ltd Manual Issue 2 alph d Version 8 WELCOME TO alpha 8 We at Logical Medical Systems Limited seek to produce the best possible screening software Our priority is to make screening as effective and safe as possible introducing regular improvements to the software so that scientific advances in screening are available as soon as possible We also aim to provide the means to regularly monitor a screening service so that users are able to check the performance and quality of their screening programmes We hope that you find this manual helpful We would welcome any comments and suggestions on how it might be improved Please email us with your comments to alpha Imsalpha co uk This manual is for use with alpha version 8 0 14136 23 and later
129. alpha 8 0 Pag C setu L d nd Styles You can specify the paper size margins and line spacing for up to four page styles Page setups Print styles A4 Top margin Bottom margin Left margin Right margin Units i Test report For each type of EE Pe printed output select a print style form the Search and print drop down list Tabulation List This selects the paper size and margins for the selected page setup Gei ee The line spacing setting determines the amount of space between lines ened ae Ke The value is a percentage of the normal spacing used The heading skip setting determines the space alpha leaves blank at the top of each page before printing The value is given in the same units as the margin This can be used to leave space for a pre printed letter heading or logo You can also use if to provide space for the doctor s address when using window envelopes Figure 43 Page setup The Report format option Figure 44 allows you to choose the report definition files RDF to use for MS and AF reports An RDF contains a description of the report layout for example the position size and font for each item in the report alpha is supplied with a standard RDF ALPHA8 RDF which is designed to produce standard format alpha reports on any printer on the screen or in export files The report layout can be modified by installing an alternative RDF To install an RDF type the name of the file i
130. an NT measurement in mm in each CRL ensures that chronologically correct median equations are selected when recalculating MoM values E The median NT measurement in MoM values in each CRL group MoM values are recalculated using the specified estimate of gestational age where necessary alpha Since there may be systematic differences in NT measurement between sonographers it is important to specify sonographer specific or centre specific NT medians for those sonographers or groups of sonographers at the same centre who have made a sufficiently large number of NT measurements say at least 100 200 measurements This helps to reduce the variance of NT MoM values leading to an improvement in screening performance 49 Sonographer specific NT medians may be derived by limiting the tabulation to one sonographer or group of sonographers using the Include selected sonographers option in the Tabulation screen see section 5 13 2 The estimated standard deviation of the logo NT MoM derived from the tabulations can be compared with published estimates see Appendix J Statistical parameters Down s syndrome as an indication of whether the measurements of an individual sonographer or group of sonographers are suitable for use in screening Further information on sonographer specific medians can be found in Sections 5 6 and 6 3 2 Press the Print button for a printed copy of the tabulation or the Regression button for a regression of the tabu
131. an reduction factors AF AFP Printing of Risks Select the parameter you want to Recurrent False Positives change from this list Scan Update Policy Units Figure 14 Parameters screen 3 1 1 Changing parameters Parameters are grouped in a branching tree structure as shown below Figure 15 Clicking on the sub branches will lead to a place to enter a value for the selected parameter Some parameters for example cut offs require a numerical value alpha will prompt you to enter a value as required The first time you set a parameter it will be given a start date of 1 January 1980 Each time you change a setting the date and time of the change will be used as the start date and time for the new value If you change a parameter more than once on the same date the last setting will be used When a change has been made to a parameter alpha displays a window in which you can record your name and a brief comment Figure 16 There are no default settings for the parameters in alpha You need to explicitly set a value for each required parameter alph d Version 8 2 bk HI Setup oni Q alpha 8 0 Pa ra mete TC This shows the selection of the adjustment method for the Caucasian group for MS AFP sack C Clicking on the item leads to the next item on the branch Current 2 bk o SESE oni Q alpha 8 0 Parameters Click on the back button to go to the previous screen f pare uE3 Don t prompt for changes
132. and the Refresh button pressed a screen similar to that in Figure 86 showing a graphical summary of the reported median MoM value 2 IE Statistics d alpha 8 0 Median Analysis MARKER Nuchal e EE Specify the marker to use in the analysis SUMMARISE BY O Day O Week 1 Specify whether the data is to be summarised by day week month or Month quarter O Quarter WOMEN TO INCLUDE All women regardless of race lt Restrict the analysis to women of a specified ethnic group or select all women REPORT DATE RANGE All periods E O Specify the date range used in the median analysis or if all reports should Oo be used CODES Include all codes You can specify that data from reports associated with selected report addresses doctors or sonographers be included or excluded from the analysis See section 5 13 2 for further information OPTIONS Exclude Smokers On lt lt Include or exclude smokers from the analysis Refresh results Figure 85 Options in Median Analysis alph d Version 8 L ee Series oO d alpha 8 0 Median Analysi MARKER 1 25 uE3 KR Dotted lines indicate the dates on which the normal median equations were changed 6 Changes SUMMARISE BY Day Month Click on the orange and purple Quarter lines with the mouse to move them horizontally WOMEN TO INCLUDE All women regardless of race
133. and their meanings and further information about data entry is given in Section 4 1 alph d Version 8 A Last name Forename s Hospital Number Date of birth LMP Weight Ethnic group Previous NTD Previous Down s Age at prev preg Prev Pre eclampsia Interpretation Smoker Diabetes IVF pregnancy Donor date of birth Date embryo transfer Date egg collection Doctor Report address GA by scan On Number fetuses Scan measure Patients i amp New batch JONES Jenny 1342ZYC 02 11 81 22 05 13 0 None 0 No v 4 Down s NTD and pre ecam Y 0 No v 0 None 0 No v 00000001 Dr Albert Brown Q 00000001 The Surgery 24 Q Machine Number fetuses Type of measure CRL 1 mm CRL 2 mm Integrated screening Sonographer Sample number 1 Date of sample Sample number 2 Date of 2nd sample MS AFP ng mL uE3 ng mL T hCG 2T miu mL Inh A pg mL NT mm PAPP A mg L FB hCG 1T ng mL Nasal bone fetus 1 Nasal bone fetus 2 Expected date of delivery Gestational age weeks and days at the date of sample date of second sample for the integrated test and on today s date alph d Version 8 Figure 4 Data entry screen corresponding to Figure 3 55 4 1 Standard ALL All sonographers Q 52413 20 08 13 52601 Q alpha 8 0 Gestational age corresponding to fetal measurement Edit started 20 09 2013 12 00 01 K lt
134. and vertically by holding the right mouse key down and moving the mouse Moving the mouse with the mouse wheel held down will select an area to zoom into when the mouse wheel is released 250 300 Risk Cut off 1 in Total tests Risk cutoff Count Percent E Se a SE Ee ae Puce Os ye Figure 109 Risk Analysis alph G version 5 12 Screening performance With the Screening Performance option alpha can calculate estimates of the expected screening performance given the age distribution of the screened population With this option you can monitor differences between the observed and expected median values When this option is selected the screen in Figure 110 is shown The screening performance for Down s syndrome trisomy 18 trisomy 13 SLOS and pre eclampsia can be calculated The age distribution used can either be that of the screened population or from maternities in England and Wales for selected years If the age distribution of the screened population is used then there are additional options provided for selecting the age range the range of report dates to use to provide the age distribution and whether reports associated with selected report addresses doctors or sonographers be included or excluded from the analysis The age distribution is not used when calculating the screening performance for pre eclampsia The results can be displayed as m The detection rate and false positive rate achieved at fixed cut off values
135. ard Export A report in the Standard format is a copy of the printed report written to a text file Text formatting such as boldening and underlines and the riskometer are not included in this format Figure 60 shows the report in Figure 2 exported in Standard format This format may be useful when a laboratory information system needs to store the full text of the report alph d Version 8 Dr Albert Brown MD The Surgery 24 Park Lane LONDON NE3 ZA9 DOWN S SYNDROME NEURAL TUBE DEFECT AND PRE ECLAMPSTA SCREENING Report dated 08 Jan 14 Last name JONES Forename s Jenny Hospital Number 1342ZYD Date of birth 02 03 82 10 09 13 EDD 20 06 14 Date of sample 07 12 13 Date of 2nd sample 07 01 14 Sample number 1 52413 Sample number 2 52601 CLINICAL DETAILS AND TEST RESULTS Previous NTD None Previous Down s None Prev Pre eclampsia No Insulin dependent diabetes None Smoker No Maternal age at EDD 32 years Scan measurement CRL 55 4 mm on 07 12 13 Gestation at date of Lat sample 12 weeks 4 days by dates 12 weeks 1 days by CRL scan Gestation at date of 2nd sample 17 weeks 0 days by dates 16 weeks 4 days by CRL scan Gestation used Scan estimate CRL Weight 65 2 kg Ethnic group Caucasian MS AFP level 30 1 ng mL uE3 level 2 1 ng mL Total hCG level 21000 miu mL Inhibin A level 210 1 pg mL Nuchal measurement 1 2 mm PA
136. as a screening marker in alpha you need to specify the coefficients of at least one equation that alpha will use to estimate the expected median NT measurement for a given crown rump length CRL measurement Such equations should be derived from a regression of historical NT and CRL measurements made by the sonographer s who will provide NT measurements in your screening service Each regression should be based on at least 100 NT and CRL measurements preferably evenly distributed across at least three gestational weeks between 10 and 13 weeks For individual sonographers who have made at least 100 NT and CRL measuremenis it may be possible to derive sonographer specific regressions Tabulate each sonographer s NT and CRL measurements as described in section 5 13 4 and examine the regressions obtained Provided the regressions fit the observed median NT values reasonably well and the rates of increase of NT are as expected about 15 25 per gestational week you may decide to specify sonographer specific medians for those sonographers To do so first print a copy of the regression and then select the Coefficients option on the System menu Click NT amp CRL then click Add sonographer and then select the sonographer from the list Enter the coefficients A and B from the printed regression and click Add to assign those coefficients to the selected sonographer If there are too few historical measurements initially to provide sonographer sp
137. ased on the corresponding fetus specific CRL measurement or estimated CRL measurement where CRL is not recorded Gestational age GA by crown rump length CRL In screening tests that include the measurement of nuchal translucency NT a CRL measurement will normally have been made at the same ultrasound examination This is the preferred approach since the NT MoM value may then be based directly on the CRL at the time of NT measurement In cases where a CRL measurement is not made in the same ultrasound examination the NT MoM is based on an indirect estimate of CRL derived according to the following rules 1 If no CRL measurement is available the CRL corresponding to the best alternative estimate of gestational age other ultrasound measurement if available dates otherwise is estimated from the equation derived from 7 CRL mm 0 1223 x gestational age days 2 8046 2 Ifa CRL measurement is available but was made on a different date from the NT measurement the CRL corresponding to the date of NT is estimated from the equation used to estimate gestational age for a given CRL measurement see Section 3 2 1 3 Equations used to estimate gestational age from fetal ultrasound measurements pha versions As stated above the preferred approach is to record an NT and a CRL measurement made at the same time alpha includes such NT measurements in tabulations of NT with CRL and therefore they contribute to the monitor
138. aternal age specific live birth prevalence of Down s syndrome J Med Screen 9 2 6 47 Palomaki GE Bradley LA Knight GJ Craig WY Haddow JE 2002 Assigning risk for Smith Lemli Opitz syndrome as part of 2 trimester screening for Down s syndrome J Med Screen 9 43 44 48 Wald NJ Rish S Hackshaw AK 2003 Combining nuchal translucency and serum markers in prenatal screening for Down syndrome in twin pregnancies Prenat Diagn 23 588 592 49 Wald NJ Rodeck C Hackshaw AK Walters J Chitty L Mackinson AM 2003 First and second trimester antenatal screening for Down s syndrome the results of the Serum Urine and Ultrasound Screening Study SURUSS J Med Screen 10 56 104 50 Wald NJ Huttly WJ Rudnicka AR 2004 Prenatal screening for Down syndrome the problem of recurrent false positives Prenat Diagn 24 389 392 51 Wald NJ Rodeck C Hackshaw AK Rudnicka AR 2004 SURUSS in perspective Br J Obstet Gynaecol 111 521 531 52 53 54 55 56 OG 08 59 60 61 62 63 64 65 66 67 68 69 Cicero S Rembouskos G Vandecruys H Hogg M Nicolaides KH 2004 Likelihood ratio for Trisomy 21 in fetuses with absent nasal bone at the 11 14 week scan Ultrasound Obstet Gynaecol 23 218 223 Wald NJ Rodeck C Rudnicka AR Hackshaw AK 2004 Nuchal translucency and gestational age Prenat Diagn 24 150 151 Morris JK Wald NJ 2005 Graphical presentation of distributions of risk in sc
139. atically Different messages can be printed depending on the type of report and the test results The table below lists the different categories of message and the circumstances in which they will appear on the report if enabled Locally defined comments are preceded by the Message addition system title The Header message and Footer message are used for messages that you wish to appear on all reports Some of the messages require one or more cut off values before they can be enabled Cut off values are indicated by x and yin the table MATERNAL SERUM Single category messages Message addition system title Header message Footer message Missing weight Missing diabetes Missing ethnic group Missing previous Down s Missing previous NTD Clinical gestation only Twin pregnancy Age at EDD gt x years specify x Increased risk of trisomy 18 Test at 14 weeks Weight gt x kg specify x Increased risk of SLOS LMP based gestational age Multiple category messages Screen negative Screen positive NTD Screen positive Down s MS AFP x MoM specify x alph d version 8 First test Repeat test Raised AFP first test with scan Raised AFP first test without scan Raised AFP repeat test Previous NTD Increased Down s risk first test with scan Increased Down s risk first test without scan Increased Down s risk repeat test Previous Down s syndrome First test with scan First test without scan Re
140. ay January 01 1980 SYSALPHA Figure 23 Selecting weight adjustment equations Select new equation iaxpweight kg MoM ai _ E eM ania Figure 24 Select weight adjustment equation alph d Version 8 Cl alpha 8 0 Current Evaluate Don t prompt for changes 2 tk 1 Setup Coefficients Back AAA AC and HC gt Crown rump length Crown rump length Ultrasound machine 1 Ultrasound machine 1 Ultrasound machine 2 GA days A Bxx Cxx2 Dxx2 Change J A 38 59628 B 1 307924 c 0 0111987 D 5 17E 05 Ultrasound machine 3 Ultrasound machine 4 Ultrasound machine 5 Ultrasound machine 6 Ultrasound machine 7 Ultrasound machine 8 Ultrasound machine 9 Press Change to use different regression equations to estimate gestational age from fetal measurements HISTORY Ultrasound gestation BPD CRL AC and HC gt Crown rump length Start Date End Date Tuesday January 01 1980 Coefficient A Coefficient B Coefficient Coefficient D Equation 38 59628 1 307924 0 0111987 5 17E 05 Cubic Ci alpha 8 0 Current 01 01 1980 Evaluate S Don t prompt for changes z KA LG Kl Si lt 80 E 2 a bi yn ki CH 50 Measurement mm User Name Comment SYSALPHA Figure 25 Equations for estimating GA from fetal measurements Select new equation O Au Bach EN 2 _ A B xt Cxx ei A tBx
141. b is selected An Analyse it query consists of a number of criteria A criterion is a rule which needs to be true for the record to appear in the results The criterion consists of a left hand side an operator and a right hand side The left hand side is one of the alpha database field names the operator one of the terms in Table 10 and the right hand side a constant such a text string number or date The following are examples of criteria MS AFP MoM gt 2 0 True if the MS AFP MoM value is greater than 2 0 Date Reported lt 01 01 2013 True if the report date is on or earlier than 1 January 2013 Criteria can be combined with the logical AND and OR operators to create complex queries You can enter NULL in the right hand side to denote an empty database field alph d Version 8 Table 10 Analyze it operators Operator 1 Meaning S Equals eS ps essa Less than Searches for a specified pattern For example JON matches all fields starting with JON In Matches a field to one of a series of values Specify the values to match on as a series of values separated by commas 2 th Statistics LE CO alpha 8 0 Analyse lt Ne HE E Tpaere geet Query name New Query Test query Run query Save query Name Type New Query Maternal serum Options Output Criteria Ordering Add new criteria Figure 78 Analyse it Criteria Press the Add Criteria button to add a new criterion to the Analyse it query The
142. bandoning the test reports If you choose to edit the batch alpha opens the data entry screen and displays the record containing the error You can then edit the record in the usual way When you close the data entry screen alpha continues with the test reports Having verified the data and checked for potential matches alpha displays a preview of the report as shown in Figure 55 See Section 2 6 3 for further information about using the preview screen 21 Patients Tk O aipha 8 0 H alpha sorts the reports according to the result type See section 3 20 2 Click on the thumbnail to view the report and hover over the thumbnail to view the patient s name To i i my e Maternal serum 02 Aug 13 del ji IO Last name SMITH Forename s Sally Hospital Number V123891239 Date of birth 02 02 83 LMP 02 03 13 EDD 03 12 13 Date of sample 02 07 13 Sample number 1 X907121 Previous NTD None Previous Down s None Prev Pre eclampsia No Insulin dependent diabetes None Smoker No Maternal age at EDD 30 8 years Scan measure Other than BPD alone 18 weeks 0 days on 02 07 13 Gestation at date of sample 17 weeks 3 days by dates 18 weeks 0 days by scan Gestation used Scan estimate eight 6 2 kg Ethnic group Caucasian MS AFP level 15 ng mL uE3 level 1 ng mL Total hCG level 24102 miu mL Inhibin A level 300 pg mL Screening result SCREEN POSITIVE Reason Increa
143. between median AF AFP and gestational age is known to be log linear for 15 24 weeks but at 13 and 14 weeks the observed median values may be overestimated by a log linear model alpha allows you to specify the percentage reduction in median AF AFP for 13 and 14 completed weeks alpha increases the proportional reduction daily from 15 weeks and 2 days to 14 weeks and 3 days using the 14 week parameter value and from 14 weeks and 2 days to 13 weeks and 0 days using the 13 week parameter value 3 1 10 Printing of risks The following options are available for controlling the printing of risk estimates for Down s syndrome open NTD pre eclampsia trisomy 18 trisomy 13 and Smith Lemli Opitz syndrome SLOS on maternal serum reports E For the age specific and test specific risks of Down s syndrome you can choose separately for reports which are positive and those which are not whether to print the risk in all cases never to print the risk or to print the risk only if the woman s age at her expected date of delivery is equal to or above a specified age You can also choose to print a message comparing the risk estimate with the age specific risk E For NTD you can choose to never print the risk always print the risk or only print the risk when the screening result is positive E For trisomy 18 and trisomy 13 you can choose to never print the risk or to print the risk when it is equal to or above a specified cut off risk see sectio
144. biochemistry in first trimester screening for Down s syndrome Prenat Diagn 17 821 829 29 Wald NJ Kennard A Hackshaw A McGuire A 1997 Antenatal screening for Down s syndrome J Med Screen 4 181 246 30 Wald NJ Hackshaw AK Huttly W Kennard A 1997 Empirical validation of risk screening for Down s syndrome J Med Screen 3 185 187 31 Schuchter K Wald N Hackshaw AK Hafner E Liebhart E 1998 The distribution of nuchal translucency at 10 13 weeks of pregnancy Prenat Diagn 18 281 286 32 Wald NJ Watt HC Haddow JE Knight GJ 1998 Screening for Down syndrome at 14 weeks of pregnancy Prenat Diagn 18 291 293 33 Canick JA Rish S 1998 The accuracy of assigned risks in maternal serum screening Prenat Diagn 18 413 415 34 Bradley LA Palomaki GE Knight GJ et al 1999 Levels of unconjugated estriol and other maternal serum markers in pregnancies with Smith Lemli Optiz RSH syndrome fetuses Am J Med Genet 82 355 358 pha versions 35 Morris JK Wald NJ Watt HC 1999 Fetal loss in Down syndrome pregnancies Prenat Diagn 19 142 145 36 Tul N Spencer K Noble P Chan C Nicolaides K 1999 Screening for trisomy 18 by fetal nuchal translucency and maternal serum free B hCG and PAPP A at 10 14 weeks of gestation Prenat Diagn 19 1035 1042 37 Wald NJ Huttly WJ 1999 Validation of risk estimation using the quadruple test in prenatal screening for Down syndrome Prenat Diagn 19 1083 1084 3
145. btain an estimate of the expected number of Down e syndrome term births in the screened population in the absence of screening and therapeutic abortion this can be compared with the total number of Down s syndrome pregnancies identified For further information on monitoring your screening programme refer to Section 5 2 Analyse it section 5 10 Report summary section 5 4 Median Analysis section 6 Monitoring your Screening Program 1 6 Choice of screening markers alpha version 8 contains the statistical parameters means standard deviations and correlation coefficients used in screening with the serum markers alpha fetoprotein AFP unconjugated oestriol uE3 total and free B human chorionic gonadotrophin hCG and inhibin A in second trimester screening between 14 and 22 weeks of pregnancy and with total and free 8 hCG pregnancy associated plasma protein A PAPP A placental growth factor PIGF nuchal translucency NT and ductus venosus pulsatility Index DVPI in first trimester screening between 10 and 13 weeks of pregnancy pha versions First and second trimester screening markers may be used in combination to provide a single estimate of risk in the Integrated Test see Section 1 8 The Integrated Test Sequential testing can also be performed in which early completion of screening is allowed for women with very high risk pregnancies identified in the first trimester Nearly all women proceed to the f
146. ch Q Forename s Last name Date of birth Search results Patients ename s Reports 1 result s found Jenny In batches 1 result s found AA Enter the search terms here 0 amp IB i F Global All periods Batches Recent 13 weeks WY A Reports Last name Date of birth Date reported Comment JONES 02 05 1981 21 05 2013 EES Se The details of the patients found are shown here Reported patients matching the search criteria are shown under Reports and unreported patients shown under In Batches Select the desired action on the record selected o e CO alpha 8 0 Actions Delete Print Q Edit You can specify that records are searched for globally in the alpha database and in batches in batches only or as reports i e in the alpha database In addition the report date range can be specified so that all periods i e without restriction on date recent reports reports made within a specified number of weeks or in a specified date range Any field in the alpha data entry screen can be added as a search field To do this select the dropdown to the right of the search field and a list of the available search fields will be shown If you wish to add further search fields press the ES button Fields can be deleted with the SS button Records found in the alpha database are shown under the Search Results heading Reports and records which have not yet been reported are shown under the
147. ch The meaning of each of these fields can be ascertained by hovering over them In this case the first field 12 1 is the gestational age at the date of the first sample the second field 16 4 is the gestational age at the date of the second sample the third field 16 5 the gestational age today and the fourth field the expected date of delivery The gestational age at the sample dates are shown in red if the sample has been drawn too early or too late In non integrated tests only one sample gestation is shown m Surnames are always displayed in upper case First names are displayed with the first letter of each name capitalised E For fields with coded values such as IVF pregnancy or Previous NTD you can either enter the required code directly or select the code from a drop down list SG A date field appears to the right of each serum marker field This field may be used to record the date of assay This can be helpful in situations where the medians or weight correction equations may have been updated between the date of assay and the date of the report for example in centres that provide the integrated test If the assay date is specified alpha bases the MoM value on the equations in effect on the date of assay If the assay date is left blank the current equations are used m If the screen includes nuchal translucency NT a date field appears to the right of the NT field This field may be used to record the date of NI measureme
148. d The following equation can be selected for gestational age when head circumference is derived from measurements of biparietal diameter and occipital frontal diameter _ 0 010611 HC 0 000030321HC 0 43498 x 107 HC 1 848 Gestational age days 7 Xe where HC head circumference measured in mm Ultrasound gestation FASP The following equation recommended by the UK Fetal Anomaly Screening Program FASP can be selected GA days 8 052 x 1 037 x CRL mm 23 73 a For maternal serum markers only separate median equations may be provided for Non scan GA scan GA Separately for overall population and up to 5 Best GA specified ethnic groups The ethnic group specific medians are needed only if the Ethnic group prompt is included in the MS screen design Separate medians for non scan and scan GA are needed only if the corresponding median equation policy is to use separate equations see Section 3 1 8 b Separate equations are available for each of the nine ultrasound machines selected by the Machine prompt c Separate equations relating median NT to CRL can be provided for individual sonographers d This equation can also be expressed Expected inhibin median A x 1 000884123 4 x 1 000532269 4 120 x 9 999990723 64 120 Where GA is the gestational age in days Appendix E Message addition categories Message addition can be used to add locally defined comments to MS or AF reports autom
149. d marker level Derived Derived Version 8 Page 213 Maternal Serum Type of field t and export ntered or derived specitiest tre T0 X x x Derived marker marker Tam x v x x Derived Contains lt if the MoM value was below the value shown MoM was below the Ten x v x x Deet Treat x v x x Derived n Trent x v x x Derived Tea x v x x Deeg Version 8 Page 214 Bn O E Bn O Us lt Ee gt O a LL j T Ou N c lt x Been Ur OU Le Ben Fe vis el py x x py x x vy x x py x x py x x vy x x py x x py x x vy x x py x x impor LLI Derived Derived Derived Derived Derived Derived E D E EE Text Text 1 i D x lt J s s D O xX Xx A A i D x lt i D x lt i OD x lt J 4 OD Ke Im l gg AS lt lt re lt d OD Ke RN S lt lt Comment t and export e j S Oo D E gt Ban 2 O oS ES Been O Gi Se D D Q ZS c D Wu impor Maternal Serum ESCHER x x Derived x fx Derived x x Derived x x Derived single x v x x Derved MoM including Singe x v x x Derived Adjusted serum marker MoM includ
150. d Trisomy 13 risk superseded Version 8 Trisomy 18 risk unrounded Field E see comment SLOS risk unrounded Field superseded see comment Pre eclampsia risk unrounded Field superseded see comment Trisomy 13 risk unrounded Field superseded see comment Bn O EES ES H x lt 2 O 35 go 2a ii E Data transfer j T Ou N c st Comment CH Ou 2 Ben Ou xe Ben O CH Ben Ou _ Cc LLI Derived Derived Derived Derived Page 217 Field name Record number oi SS Surname Forename s ID code Address 1 Address 2 Address 3 Postcode Phone number Doctor Report address Date of birth Age at EDD Version 8 Database record number Patient s surname Patients forename identification code Patient s phone number Doctor s name or doctor code Address code Patient s date of birth Age at expected date of delivery in data entry screen Type of field Integer Text Text 5 4 OD x lt t O1 x Text Text Text Text Ql 2l alala Sl IL l Text a 2 Text 50 8 Text Date Integer T Ou N Cc st Ben Ur OU c ul Ben Fe vis el pe x fe pv v fe Marre le fe vty fe eee ely fe Vv Vv Vv Vv wi wi wi wi Vv Amniotic Fluid O a Zen ES H x PES w O SS gt go
151. d in the interpretation Date OC stopped 2x2 Month and year patient stopped using oral contraceptives Not used in the interpretation however women in whom oral contraceptive use is recorded within 60 days of conception may be excluded from certain tabulations a These prompts allow a second set of ultrasound measurements to be entered If chosen they should follow the primary prompts previous item b Linked prompts if the first is chosen the others are included automatically c The units chosen as parameters see Appendix C Acceptable settings for parameters are automatically displayed with these prompts d These prompts can only be chosen for maternal serum tests and provided Date of scan and the associated prompts are chosen too e These numbers may contain a decimal point and will be printed on the reports as entered f This prompt is no longer required and is included for compatibility with previous versions of alpha 9g Alternative names may be given to the six groups if desired However code 3 is reserved for women of unknown ethnic group and should only be used for this purpose N B Dates apart from Date OC stopped are entered as six digits two each for day month and year The order of the day month and year is determined by your computer s regional settings Appendix C Acceptable settings for parameters Parameter Median equation policies MS AFP uE3 For overall total hCG free B population amp
152. d into alpha needs to be reviewed elsewhere for example for quality control The export button will only be present if a file ExportFieldsMS txt for MS batches or ExportFieldsAF txt for AF batches is present in the folder containing the alpha software This file contains a list of the database table column names which are to be exported When this button is pressed you will be prompted for a filename and the specified data for the currently selected batch will be exported 4 7 Delete Unreported and reported records can be deleted from the Patients screen alph d Version 8 4 7 1 Unreported records An unreported record can be deleted by selecting it on the Patients screen and dragging it to the Delete button Unreported records can also be deleted in the data entry screen See Table 8 4 7 2 Reported records To delete a record first find it using the search features See Section 4 3 and then press the Delete button All records in a report series related to the selected record will be deleted See Section 4 4 Deleted records remain in the database but are no longer available for search correct and update and they are also excluded from all tabulations and summaries 4 8 Print The Print button changes its behaviour depending on the context in which it is selected Following a search Section 4 3 a report stored in the alpha database can be retrieved and shown in the preview screen by pressing the print button If y
153. d samples preferably evenly distributed across three or four gestational weeks between 13 and 24 completed weeks After tabulating the data according to gestational week use the AF AFP GA option in Regressions to derive the coefficients see section 5 9 1 If in your judgement the regression overestimates the median AF AFD level at 13 or 14 weeks select the option Exclude AF AFP values before 15 weeks 3 days and generate the regression again The ratio of the expected regressed median AF AFP level to the observed level at 13 or 14 weeks indicates the appropriate median reduction factor for each week see section 2 10 2 For example if the observed median AF AFP level at 13 weeks is 200 miu L and the regressed level after excluding AF AFP values before 15 weeks 3 days is 250 miu L the appropriate median reduction factor to specify for 13 weeks is 20 1 200 250 Once you have interpreted a sufficiently large number of AF samples with alpha you can use AF AFP GA in the Tabulations and Median Analysis options to monitor median AF AFP MoM values and to revise your estimates of the gestation specific AF AFP levels should this be necessary see section 5 9 4 2 11 Computers All computers running alpha must conform to the specification in Appendix R 2 11 1 Moving computer When alpha is running in a single user configuration you can move alpha to another computer with the following procedure You may require administrator rights on t
154. d side Long v v Derived unrounded unrounded Integer Down s syndrome Down s risk post posterior risk See v A12 Derived note 14 KE NTD prior risk Long NTD prior unrounded NTD prior risk ong fe fe x x f Derived Shows if risk has NTD risk flag been trimmed or Text 1 v v Derived capped NTD risk right hand Long al l NTD risk right hand Long NTD risk RHS side uraunded ie x NTD risk left hand Long NTD risk LHS unrounded gp J is LL x X NTD risk right hand Long NTD risk RHS unrounded Sige Ges Imeger Version 8 Page 206 Comment Fixed width format for import and export CH Ou gt Ou xe Ben O CH Ben Ou _ Cc LLI Data transfer _ A N c lt x lt risk has been trimmed gt risk has been capped Derived Derived Derived Maternal Serum Field name NTD risk post Trisomy 18 prior risk Trisomy 18 prior unrounded Trisomy 18 risk flag Trisomy 18 risk LHS Trisomy 18 risk RHS Trisomy 18 risk LHS unrounded Trisomy 18 risk RHS unrounded Trisomy 18 risk post SLOS prior risk Version 8 NTD posterior risk See note 14 Trisomy 18 prior risk rounded Trisomy 18 prior risk unrounded Shows if risk has been trimmed or Capped Trisomy 18 risk left hand side Trisomy 18 risk right hand side rounded Trisomy 18 risk left hand side Trisomy 18 risk right hand side
155. designed to interpret i Maternal serum MS and ultrasound markers used in screening for Down s syndrome ii MS and history of a previous pregnancy with pre eclampsia in screening for pre eclampsia iii MS alpha fetoprotein in screening for open neural tube defects iv Amniotic fluid alpha fetoprotein and acetyl cholinesterase AChE results used in the diagnosis of open neural tube defects Clinical information and test results are used to produce reports This information is stored in a database which you can access in order to review a woman s test results and to monitor the performance of the screening and diagnostic programme You can tailor alpha to suit your individual requirements alpha is primarily intended for situations in which the information relating to each sample is either available on a screening requisition form or can be accessed from a data file produced by another computer system for example a laboratory information system Alternatively you can use a combination of these two approaches An example of a serum screening requisition form is shown in Figure 3 DOWN S SYNDROME AND OPEN NEURAL TUBE DEFECT SCREENING _Consultant or GP PR BROWN ULTRASOUND SCAN Please use CRL to calculate gestation where possible Do not use femur PATIENT length measurement _Sumame i ONES Ultrasound measurement 3 4mm ooe Forename ___JENNY Number of fetuses EE EE Hospital Mute 1242ZYD I BLOOD EE SEH Caucasian RESULTS
156. determining the age specific risk of Down s syndrome 777 and modifying it in the light of the screening marker levels using a multivariate log Gaussian model derived from published parameters The log Gaussian model is used to generate a likelihood ratio LR which is used to modify the age specific risk according to the levels of the different screening markers as follows Test specific risk as an odds ratio Age specific risk as an odds ratio x LR The marker levels are expressed as multiples of the median MoM in unaffected pregnancies of the same gestational age thereby allowing for changes in the normal median with gestational age and for systematic differences between laboratories and between assay reagents The MoM values may be adjusted to allow for other factors that affect the normal median value such as maternal weight ethnic group insulin dependent diabetes mellitus multiple pregnancy 10 11 48 97 in vitro fertilization and smoking pha versions By using MoM values in this way alpha is independent of the assay reagents used alpha provides a wide range of statistical facilities that enable you to monitor the normal medians and to change them if necessary for example to correct for drift in the normal medians or if you decide to change the assay reagents used alpha can also identify cases where a single marker has a very large influence on the risk estimate In the
157. drome is not recorded If potential matches are found alpha displays them See Figure 57 If there is more than one matching pregnancy the most recent is shown as the default match Earlier matching pregnancies are also shown in case the most recent match is a false match because of inaccurate recording Further information describing the method used to select patients for matching is given in section 3 1 11 Current pregnancy Section 4 2 2 1 and previous pregnancy matches are shown on the same Matching screen alph G version Matching Previous Pregnancy Match tor Recurrent False Positive Adjustment Alpha has found a possible match in the Alpha database for this patient in a previous pregnancy The current patient is highlighted and the possible matches are in the following lines Select the match to the current patient Select Surname Forename IDCODE Date of Birth JONES ie e 04061551 03 07 1973 3 3 JONES 04061551 03 07 1973 Continue Figure 57 Recurrent false positive matching 4 2 2 3 Unreported records As well as checking for matches with previously reported tests alpha checks for matches with records in the same batch file and in other batches which have not yet been reported This feature is helpful for identifying patients who have been entered twice in error If this occurs you should abandon the test report and delete one of the duplicate records before proceeding with test reports Alternatively if the duplica
158. e 33 provides facilities for viewing editing and deleting stored doctors and adding new doctors A new doctor can be created with the New button and an existing entry modified with the Edit button When these options are selected a window similar to the in Figure 34 is shown which shows all the information which can be stored with the doctor code m The report will be shown in the Language specified for the doctor This setting overrides the language selected by the user See section 3 21 E The First Copy and Second Copy are the Doctor codes which are automatically selected when the Doctor is specified in the data entry screen prompt Reports To See Appendix B Prompts and their meanings The Preferred Addresses are the addresses which are shown for this Doctor when the amp button is selected in the Data Entry screen See section 4 1 The first Preferred Address is automatically used as the address when the Doctor is specified in data entry screen prompt Reports To See Appendix B Prompts and their meanings E The Exclude setting will exclude the doctor s name from being displayed elsewhere in alpha This prevents lists of doctors shown in alpha becoming unnecessarily long Use the Mailshot lists option to create a text file of doctors names and addresses suitable for generating mail shot letters labels or envelopes Only doctors who are linked to one or more address codes are included in the mail shot file You can choose to
159. e Eclampsia risk always 01 01 1980 00 00 00 Down s risk cutoff 2nd trimester 270 01 01 1980 00 00 00 Down s risk cutoff 1st trimester 270 01 01 1980 00 00 00 Down s risk cutoff integrated test with NT 100 01 01 1980 00 00 00 Down s risk cutoff integrated test without NT 100 01 01 1980 00 00 00 SLOS risk cutoff 100 01 01 1980 00 00 00 Trisomy 18 risk cutoff 2nd trimester 100 01 01 1980 00 00 00 Trisomy 18 risk cutoff 1st trimester 100 01 01 1980 00 00 00 Trisomy 18 risk cutoff integrated test NTD MS AFP cutoff Pre Eclampsia risk cutoff NTD MS AFP cutoff diabetics Spina bifida prev Overall Anencephaly prev Overall Pre Eclampsia prev Overall Pre Eclampsia prev non Black Pre Eclampsia prev Black Pre Eclampsia prev Group 4 Pre Eclampsia prev Group 5 Pre Eclampsia prev Group 6 BPD correction ultrasound machine no 1 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 01 01 1980 00 00 00 Figure 17 Current parameters settings Click Print historical oz to view the historical list of parameters This is similar to the list of current settings except that all the settings ever entered are listed along with the dates when changes were made This provides a useful record of changes to your screening
160. e Security Weight maternal 73 177 Adjustment 13 45 50 158 MoM values in report 98 Regression equation model 188 Linear reciprocal 45 141 Log linear 45 141 Regression equation MoM vs weight Coefficients 44 from untabulated data 140 Tabulation of observed median MoM Values See Tabulations What if 84 Page 273
161. e from the scientific literature including SURUSS the Serum URine and Ultrasound Screening Study SURUSS is the report of a large collaborative study designed to identify the safest and most effective method of antenatal screening for Down s syndrome using nuchal translucency and first and second trimester biochemical markers together with maternal age in various combinations alpha is licensed to interpret the Integrated Test 38 The Integrated Test providies safer and more effective Down s syndrome screening than ever before There are also technical improvements that make alpha more flexible and easier to use than ever before No other software of its kind offers such a wide range of facilities or quality control features 1 2 Getting started Your alpha software will be installed by an approved installer who will E help you set up the software according to your needs provide training in the use of alpha Only operators who have received training in the use of alpha from an approved installer should use alpha He or she will assist you in setting up alpha for you to use You will find more information on the steps involved in setting up alpha in the following sections of this manual Section 2 General Principles E Section 3 Set up 1 3 Data entry and reporting As well as entering data manually using a form which you can design yourself data can be imported from files generated by other software Assay r
162. e original report EE C correction of a non updated report modification of Text 1 Derived S scan update re or correction l s correction of scan update any other change Report has been Correct update flag 2 corrected or Text 1 v v Derived Copy of Correct update flag 1 in the later test updated Report has been corrected updated meser P y Derived Record number of corrected report or repeat test or is the initial test H preceded by M if report is MS AF or A if AF AFP of a repeat test Version 8 Page 202 Correct update flag 1 Pointer forward hom O Q gt lt xe Cc bel 0 MS Derived 1 AF 2 NTD only Maternal Serum D rved Record number of previous report preceded by M if report is MS AF or A if AF AFP 0 MS Derived 1 AF e D record deleted a ES A Type of l Pointer forward type DEER Integer v report Report is a Pointer back correction update Integer v or a repeat test Pointer back type i iii Integer v Delete flag If set record is not OH bell o Oo ab E gt 2 D c O ES Been Oo O a D D g x lt c iL Wu j T Ou N c st Been Ur OU Le Ben Fe vis impor wi wi Vv aa Delete status flag included in Text 1 v statistical tabulations Update fag Age at expected date of delivery v v Derived Derved Years and decimal fraction v Serum marker MoMs are
163. e regression curve and coefficients of the regression as shown in Figure 102 The expected regressed median values in the table are also updated automatically as you enter or add data The coefficients displayed are those relating to maternal weight in kilograms and these are the ones required by alpha If you have chosen to enter weight in pounds alpha will automatically convert to kilograms for the purposes of the regression even though weights are printed in pounds on the reports 2 J Statistics eee ON Regressions uE3 v Regression details Regression Maternal weight alpha plots the observed AFP Observed MoM J O EE EE MoM yellow circles and the AxBweight kg expected AFP MoM blue line SS from the regression equation acs nmol L d _ Logarithmic Y Axis A 1 205427 OVERLAY SETTING alpha calculates B 0 9972445 No overlay 3 the coefficients in 5 Update medians Zo the regression equation for this marker 20 40 60 80 100 120 140 160 180 200 Maternal weight Kilograms Median Weight Kilograms Samples Observed MoM Expected 42 49 1 199 1 074 47 5 198 1 14 1 057 52 9 441 1 059 1 042 These are the 57 718 oe SS results transferred pe ee men L from the tabulation 67 668 0 97 1 002 72 468 0 97 0 988 Figure 102 Regression of uE3 MoM with maternal weight log linear equation 5 9 3 Changing the equation used in the regression
164. e tasks are described in the following three sections 2 10 1 Designing an AF data entry screen When designing an AF data entry screen the same general principles apply as to the MS data entry screen see section 3 17 for more details As a minimum your AF screen design must include the following prompts E Surname and ID code Surname and Date of birth or ID code and Date of birth to serve as identification fields E An indication of the woman s age either Date of birth or Age at EDD Date of sample E Amniotic fluid AFP level AF AFP This is used in classifying the diagnostic result as positive negative ambiguous or uninterpretable see Appendix A Rules used in producing reports E Atleast one estimate of gestational age GA You may wish to include other fields as appropriate for example Doctor and Report address or alternatively Reports to SG AchE NTD band This is used in classifying the diagnostic result as positive negative ambiguous or uninterpretable see Appendix A Rules used in producing reports Amnio reason E AF appearance 2 10 2 Policy settings related to AF AFP The policy settings that relate to AF AFP are specified in Parameters see section 3 1 The following settings are required m AF AFP cut offs see section 3 1 6 You can either specify the same cut off level in MoM for all gestational weeks or gestation specific cut offs for 13 15 16 18 19 21 and 22 24 weeks If gestation
165. earch the alpha database for the patient record using the Search database tab in the Search section See Section 5 7 2 On finding the patient and pregnancy record within the database the outcome data entry can be opened by double clicking on the patient listing When another user is editing the outcome record other users can still open the outcome record in a read only mode The data Entry screen is split into Patient details Outcome details and Abnormality codes See Figure 94 The Patient details lists information from the alpha report for the pregnancy This should always be checked to make sure the correct patient pregnancy has been selected This information cannot be changed Outcome Data Entry MCGREGOR 40016006 Patient details Outcome details Entered 24 10 2006 Surname MCG REGOR Diagnostic procedure bk yes Date of fi 9 10 2005 performed procedure S LINDSEY Forename Diagnostic procedure D Amniocentesis E 40016006 de Abnormality diagnosed DOWN Down s syndrome Date of bith 27 09 1977 Date of delivery Method of delivery Number of fetuses Downs risk fi in 200 dy x Report address oooo0001 d Fetus1 gt Sex Outcome P Female D D SE Abnormalities present code and description Description DOWN Down s syndrome yndrome Down s syndrome Unknown moo Free text code Ee None Not reported Anencephaly and similar malformat Anencephaly
166. eating and editing of outcome data see Section 5 7 3 5 7 2 2 List Pregnancies without Outcome This tab is used to list all pregnancies for which an outcome has not been entered See Figure 92 This can be filtered by the screening result report date or by doctor and address codes Clicking on the Change button next to the doctor and address code options allows the selected doctors and address codes to be changed Refresh results Allpregnancies Screen postive pregnancies Screening result filter Ge All periods f All doctor and address codes f Expected date of delwery f Date of latest sample C Include selected addresses only 01 01 1980 e 20 1 02006 C Include selected doctors only Doctor and address filter Figure 92 Pregnancies without Outcome Once this list has been compiled it can be printed in by clicking the print button on the side bar The user can either choose to simply print the list or an Outcome request sheet can be created containing details of the patient and spaces for details on the outcome to be filled in 5 7 2 3 List Pregnancies with Abnormalities This tab is used to list all pregnancies for which an outcome containing an abnormality has been entered This can be filtered by the report date or by doctor and address codes To list pregnancies with abnormalities requires the selection of up to seven different abnormality codes For example in the case of Down s syndrome this a
167. ecific regressions a reasonable approach would be to pool the measurements from all sonographers in a single regression and assign the coefficients of the regression equation to the Overall NT medians To do SO first print a copy of the regression and then select the Coefficients option on the System menu Double click NT amp CRL then double click Overall and enter the coefficients A and B from the regression Once a sufficiently large number of NT measurements have been made by individual sonographers sonographer specific medians could be specified As time progresses and you accumulate NT measurements in your alpha database you can monitor each sonographer s measurements individually using Median Analysis see section 5 4 and Tabulations see section 5 13 4 Use these facilities to identify systematic differences in NT measurement between sonographers and potential problems in NT measurement for example rates of increase that fall outside the expected range of 15 25 per week or standard deviations that differ markedly from published estimates 6 4 Changing Assays If you intend to change an assay you will need to establish normal medians for the new assay by assaying a sufficiently large number of routine samples in parallel with the old assay Preferably the new medians will be based on at least 50 samples per week in four gestational weeks Use the Regression option to calculate median equation coefficients for the new as
168. ect one of the marker combinations used to calculate screening performance tables See Section 5 11 It shows a summary of reports which used this marker combination Report Summary and the expected screening performance derived from the maternal age distribution of the population who were screened using this marker combination Expected Performance This allows you to easily compare the observed positive rate with the expected false positive rate in your screening programme r Quadruple 7 Positive KK False positive rate Negative KK Detection rate Uninterpretable o OAPR Total Figure 72 Automonitor Test Specific Summary 5 1 4 Demographics Demographics Figure 73 shows for each ethnic group the number of women screened their median weight and median age Overall White Black Asian Oriental Other Figure 73 Automonitor Demographics 5 1 5 Markers Markers Figure 74 shows for each serum marker the number of measurements taken and the median MoM for all groups and each ethnic group separately FB hCG Inh A Figure 74 Automonitor Markers 5 1 6 Nuchal Translucency Nuchal Translucency Figure 75 shows for all sonographers and for each sonographer the number of measurements and the median NT MoM alpha Version 8 Page 114 All lis LGH 00025004 00065763 00078104 00108648 Figure 75 Automonitor Nuchal Translucency 5 2 Analyse
169. ects the language in which the user s data nglish v 2 entry screen and reports will appear Password expires No date set Other Users Select New user to create a new user Edit user to edit an existing user and Delete user to delete an existing user User name Security level Expires No date set No date set The available user names their security levels and password expiry dates are given here Figure 49 Users alph d Version 8 3 22 What if New user Username Password Verify password Expiry date 01 01 2014 Language English ki Security level i All data entry facilities amp What If Reporting facilities except Correct and Update All statistics facilities Edit doctor s sonographer s and address codes Correct and Update Some setup options Modify Coefficients and Parameters Modify Users Figure 50 Entering a new user Enter the username and password Enter the password expiry date Enter the user s language Use the slider to specify the security level The selected security level is summarised here What if is an educational tool in antenatal screening for open neural tube defects and Down s syndrome What if can be helpful in understanding how changes in a patient s clinical details and test results and changes in the screening policy can affect the interpretation of screening tests What if provides similar interpretations to those provid
170. ed by alpha but the information entered is not stored in the database What If is not intended for use in a screening service to interpret and report patient results it should not be used in this way When you open What if alpha displays a screen in which you enter information about the pregnancy and screening test results See Figure 51 Provided that sufficient information has been entered age at EDD at least one estimate of gestational age and at least one screening marker level and that the screening policy settings have been specified see below an interpretation is displayed The interpretation is updated immediately to reflect any changes you make in the pregnancy details test results or screening policy alph d Version 8 2 th 1 Setup AAA Ge What If CLINICAL DETAILS Age at EDD MARKER LEVELS IN MoM 35 Years 6 Months MS AFP 1 Previous NTD 0 None v uE3 Previous Downs 0 None T hCG 2T Non Diabetic Inh A Number of fetuses NT Number of BPD if twins PAPP A Weight adjusted FB hCG 1T Non smoker Non IVF GESTATIONAL AGE GA GA measured by Non BPD scan GA 15 Weeks 3 Days RISKS Risks rounded Age specific risk Down s risk NTD risk T18 risk SLOS risk 1 in 350 at term 1 in 5 800 at term 1 in 5 400 1 in 66 000 at term 1 in 480 000 SCREENING RESULT Screen negative COMMENT Down s risk due to maternal age alone is 1 in 350 Cl alpha 8
171. ed on the medians for the overall group This provides a method of checking the accuracy of the overall group medians If the checkbox Use overall medians is not selected in the Tabulation options scfeen the MoM values shown in the tabulation will be based on the medians for each ethnic group This provides a method of checking how accurate the individual ethnic group medians are 6 Monitoring your Screening Programme lt is important to monitor your screening programme on a regular basis especially to ensure that the normal median equations accurately reflect the median levels of the screening markers at different gestational ages for your population This chapter provides you with helpful notes on some of the routine monitoring tasks you need to perform when using alpha 6 1 Monitoring Usage lt is often useful to know how many reports have been provided in any given time period This is easy to determine using the Report Summary options See Section 5 10 Report Summary provides tables of first tests updated tests and repeated tests for both MS and AF over a specified time period The first test tables are subdivided into the number of reports with each type of screening or diagnostic result positive negative ambiguous or uninterpretable with further subdivisions indicating the reasons for positive ambiguous or uninterpretable tests The update and repeat test tables allow you to monitor the number of tests being updated or r
172. ed or updated reports the settings on the date of the original report are used Repeat Tests Clinical information including gestational age maternal weight date of previous amniocentesis previous Down s syndrome or NTD pregnancy and diabetes from an earlier report may be used in producing the repeat test report Where there is a discrepancy between the information provided with the earlier test and the later test priority is given to the most recent information pha versions Appendix B Prompts and their meanings Prompt Surname Forename s ID Code Address 1 Address 2 Address 3 Postcode Phone number Doctor Report Address Reports to Date of Birth Age at EDD alph d version 8 Maximum characters 50 50 50 50 50 50 10 15 50 N A 3x2 Meaning of input and notes Patient s surname May be omitted if both ID Code and Date of birth are included Patient s forename s If initials are entered they should be separated by a space or A patient specific or pregnancy specific identification code Sample specific codes e g lab numbers specimen numbers must not be used in this field since it is used in identifying potential repeat samples in the same pregnancy ID Code may also be used to identify records relating to screening in a previous pregnancy to help avoid recurrent false positives see Section 3 1 11 If your policy is to match such records strict matching or
173. eecceceeseceeceseceeceeeeeeceeseeeeseueceeseeeeesseecessaaecesseaeeeessaeeeessaeees 66 Table 6 Default settings for Patient Prmtmg 81 Table 7 Purpose of the buttons in the Patients ecreen 89 Table 8 Meaning of items in the data entry screen 91 Table 9 Print and export options available in final reporting ccccccceeececceeececceeeceeseeeceeseeeeeeeseaeess 97 Table 10 AnalyZe it operators cccccccccsssseceecceeeeceeeceeeseceeeseaaseeeeessauseceeeseeaeeeeessaaseceeessaaseseessaagseeess 118 Table 11 Explanation of criteria used in Analyse it example n0annnannnannnnnnnoennnnnnnnnnnonnnnnnnnnnnnennnenne 120 Table 12 Columns in Tabulation ccccccccccccessseccceeeesseceeecaeseeceeeseesseceeeseuaeeceeeseeaeeeseeseaeeesssaaaneeess 154 Table 13 Columns in NT vs CRL tabulation wacinticticacensepcwavdntccintvieenrsteedicameuinanvtiniccaaaunetietinnadeacurs 155 Table 14 Columns in weight tabulation cc cccccccccssseceeeceeseeceeecaeeeceeeceeaeceeeeeeseeeeeseanseceseeaaaseeess 157 alph d version 8 1 Introduction 1 1 About alpha version 8 Welcome to alpha the leading interpretive software for use in antenatal screening for Down s syndrome open neural tube defects NTDs and pre eclampsia alpha was the first software of its kind originally developed in 1987 by Professor Wald and Professor Cuckle and it is still the standard against which most others are compared It is based on publis
174. efore attempting to set up alpha in a multi user configuration Each alpha workstation will require i the ability to read write create and delete files in the alpha folder on the server li a separate licensed dongle security key alpha database files normally reside in the default folder specified by SQL Server Your database administrator should ensure that all alpha users have SQL Server Security database roles db_datareader and db_datawriter on the SQL Server database used by alpha Please consult your network administrator for further information Display Screen alpha will work satisfactorily with most display screens however we recommend a display with a diagonal size of at least 19 inches 48 25 cm and a resolution of at least 1280 x 1024 pixels To avoid eye strain ensure that you adjust the brightness and contrast settings of your screen to a comfortable level that the lighting in your work area is suitably adjusted to avoid screen reflection and that you take regular breaks during long periods of work at your computer Backups You should make frequent backups of alpha and the SQL server database used by alpha SEN e Appendix S Advances in alpha Scientific advances alpha 8 can be used for Down s syndrome screening using first trimester placental growth factor as a marker This marker was previously not available in alpha alpha 8 includes the latest statistical parameters for pre eclampsia screening
175. ents 3 14 Message addition Message addition allows you to add your own locally defined messages depending on the screening or diagnostic result The messages are defined in the Message Addition screen Figure 42 alph d version 8 Li IP ei 1 Setup Message addition is turned on by selecting the checkbox next to d alpha 8 0 the MS message addition description and entering a message MessageAddition Use these buttons to configure Message Addition for Maternal Serum or Amniotic Description Message Details been omitted v MS message addition London Medical Centre Header message Footer message v Missing weight Including the patient s weight can improve the accuracy of the screening result E Different messages can i dinpetes be printed depending SE on the type of report and v Missing race Including the patient s race can improve the accuracy of the screening result GE the test results For Missi cis Down issing previous Down s example you might _ Missing previous NTD choose to print a v Clinical gestation only Gestation from an ultrasound scan can improve the accuracy of the screening result message similar to this if C Twin pregnancy the patient s weight has Screen negative first test Screen negative repeat test Screen positive NTD raised AFP first test with scan Screen positive NTD raised AER first test wi
176. epeated and also to see to what extent screening results are being reclassified following updates and repeat tests In addition to using Report Summary you can use Missing Information section 5 5 to determine the number of reports requested from each report address However this will only be informative if you have selected Report address as one of the prompts To determine the distribution of reports by gestational week tabulate a maternal serum marker or AF AFP by gestation and the number of reports at each week will be displayed section 5 13 3 6 2 Monitoring the False Positive Rate The screen positive rate is a close approximation to the false positive rate since true positives are relatively rare To determine your screen positive rate you can use either the Report summary table See Section 5 10 or the Risk Analysis See Section 5 17 The report summary will tell you what percentage of reports were initially classified as positive In addition the tables of updates and repeats allow you to calculate a final positive rate after reclassification The Risk Analysis can in addition be used to select a Down s risk cut off that will achieve a specified screen positive rate The expected Down s syndrome false positive rate given the age distribution of screened women is obtained by tabulating the Screening Performance See section 5 11 If the observed screen positive rate is markedly different from the expected false positive ra
177. equation NT CRL 00000001 0 6947472 1 010647 01 01 1980 Median equation NT CRL ALL 0 6947472 1 010647 26 03 2013 PAPA medians A E Start date _ Median equation PAPP A GA Overall 0 1073264 1 056131 01 01 1980 Median equation PAPP A GA Caucasian 0 1073264 1 056131 01 01 1980 Free hCG medians A B S Start date Median equation FB hCG GA Overall 111E 10 0 6499239 1 002375 01 01 1980 Median equation FB hCG GA Caucasian 111 10 0 6499239 1 002375 01 01 1980 _MS AFP weight corrections A B Cc Start date Weight adjustment MS AFP Overall 1 596285 0 992937 01 01 1980 Weight adjustment MS AFP Caucasian 1 596285 0 992937 01 01 1980 VE weight corrections A B Start date _ Weight adjustment uE3 Overall 1 260027 0 996563 01 01 1980 Weight adjustment uE3 Caucasian 1 260027 0 996563 01 01 1980 Total hCG weight corrections A B Start date Weight adjustment T hCG Overall 1 733906 0 992135 01 01 1980 Weight adjustment T hCG Caucasian 1 733906 0 992135 01 01 1980 Inhibin A weight corrections A B E Start date Weight adjustment Inh A Overall 2 060995 0 9891762 01 01 1980 Weight adjustment Inh A Caucasian 2 060995 0 9891762 01 01 1980 I TACE T aaa E S SES E l E P P P FP P PR WW po Figure 10 Example of print preview screen alph d Version 8 Table 3 gives the purpose of the buttons at the bottom of the Print Preview screen In some circumstances the buttons have additional uses See Section 4
178. er ethnic groups will be pooled with the levels from the tabulated group Referring to the screened population in the example above selecting Caucasian in the Tabulation screen would result in a tabulation comprising data from all Caucasian women as well as data from South Asian women corrected using the adjustment factor you specified Median marker levels derived from the tabulation could be used to calculate MoM values in Caucasian and after adjustment in South Asian women Selecting South Asian in the Tabulation screen would give a tabulation comprising data from South Asian women only If your screening policy were to change such that the direct method was used in South Asian women for example because the volume of screening tests increases to the point where a sufficiently large number of South Asian women are screened you could use the tabulation to derive initial medians for South Asian women Selecting All women regardless of ethnic group in the Tabulation screen would result ina tabulation comprising data from eligible screening tests in women of all ethnic groups as well as in women whose ethnic origin was not specified Median marker levels derived from a regression of the tabulated data could then be used to calculate MoM values in women whose ethnic group is not specified the overall group If the checkbox Use overall medians is selected in the Tabulation screen the MoM values shown in the tabulation will be bas
179. er levels MoM in twin diabetic and IVF pregnancies and in smokers relative to singleton non diabetic and non IVF pregnancies and non smokers Twin IVF Serum marker pregnancies Diabetic pregnancies pregnancies Smokers Not Adjusted or weight used Second trimester 14 22 weeks AFP D3 0 88 gt 0 777 n a 1 05 uE 1 67 0 95 0 92 4 0 943 0 96 total hCG 1 841 n a n a 1 14 orr m free B hCG 1 90 n a n a 1 14 0 80 inhibin A 1 99 n a n a n a see note e First trimester 10 13 weeks 0 81 PAPP A 1 86 n a n a 0 917 0 94 free B hCG 2 10 n a n a n a 0 80 total hCG 1 87 n a n a n a t alpha adjusts MoM values in a twin diabetic and IVF pregnancies see Tor in a smoker by dividing by the corresponding value in the table t alpha adjusts uE3 total hCG and free B hCG MoM values in an IVF pregnancy by multiplying by the reciprocal of the corresponding value in the table rounded to 1 decimal place 1 1 0 9 0 9 for uE3 total hCG and free B hCG respectively n a No adjustment made a These adjustment factors were introduced in alpha version 7 0V b Prior to alpha version 6 4AB the following adjustment factors were used for diabetic pregnancies Serum marker Diabetic pregnancies Not Adusted aduste for weight Second trimester 14 22 weeks AFP 0 82 0 77 UE 0 94 0 92 4 total hCG n a n a inhibin A 0 91 0 88 First trimester 10 13 weeks PAPP A n a n a total hCG n
180. ersion 8 3 13 Markers The markers section allows you to change the names alpha uses for the screening markers to review the statistical parameters used for each marker and to add new markers See Figure 39 2 Ih EI Setup aan Markers Change names of the markers used by Alpha uE3 Total hCG Free B hCG Inhibin A Nuchal PAPP A FreeB hCG Total hCG ADD MARKERS Alpha supports up to a maximum of 12 different screening markers Once a marker has been added it cannot be removed You will need to call your Alpha distributor to complete this process The following markers can be added to Alpha DVPI Y Add Marker 3 13 1 Changing marker names Q alpha 8 0 The marker names can be changed here Information for uE3 General Adjustment Factors Statistics Correlation Coefficients Marker number Type Serum ne This section shows the statistical Second parameters and adjustment factors for Predictor each marker Gestational age Expected change with gestational age Increasing Expected change with maternal weight Decreasing Truncation limits MoM 0 40 to 2 00 New markers can be added to alpha here Figure 39 Markers With this option you can change the names alpha uses to refer to the installed screening markers The name of AF AFP cannot be changed You can specify a long name up to 20 characters in length and a short name up to 10 cha
181. es 3 Matching with a report from an earlier pregnancy alpha checks to see if there are reports from a previous pregnancy for the same woman If there is and if the user chooses to alpha will then adjust the serum marker levels to avoid the problem of recurrent false positive pregnancies 50 59 see section 3 1 11 lt is important to match reports if the second relates to a repeat sample This is because interpreting a repeat sample without taking into account the marker levels in the previous sample will yield a risk estimate that is incorrect alpha takes account of the levels in the previous sample when interpreting repeat samples alpha also allows you to match AF reports to MS reports for the same pregnancy After you create the test reports and correct any errors the next step is to select the Final report option This creates and prints the final reports and then merges the data into the database The other options you are likely to use on a regular basis are Search and print used to search for and print copies of already reported results Correct and update used to create corrected reports or to reinterpret reports following the addition of extra information such as an ultrasound estimate of gestational age 2 9 Types of reports Amniotic fluid AF reports are used in the diagnosis of open neural tube defects Maternal serum MS reports are used in screening for Down s syndrome pre eclampsia and for open neural t
182. ester screening markers in estimating the risk of Down s syndrome 3 23 Window envelope With this option you can control the position of the doctor s name and report address on the report in order to use window envelopes when dispatching reports as shown in Figure 52 The address window can contain up to 10 lines of 30 characters and may include the doctor and address information any of the spare fields blank lines and a single line of fixed text To select fields for the address window click and drag the field from the left column to the right column If you select Add Fixed text alpha prompts you to enter the text to use To remove a field click and drag the field from the right column to the left column To specify the position of the address window enter the offsets from the left edge and top edge of the printable area of the page The offsets can be measured in either cm or inches The offsets are measured from the position of the left hand margin and top margin and are independent of the Heading skip settings See Section 3 15 It is possible to position the address window so that it overwrites part of the alpha report text You can avoid this by either of the following methods position the address window in an unused area of the report for example to the right of the PATIENT DETAILS section E Position the report text below the address window using the Heading skip setting in Page setup alph d version 8 3 l
183. ests first trimester second trimester integrated sequential or all tests should be included in the analysis You can also select the date range for the report and screening reports associated with selected report addresses doctors or sonographers be included or excluded from the analysis See Section 5 13 2 The results in Figure 109 show that 5645 tests were carried out in the period selected and that 292 5 17 had a risk greater than the cut off 1 in 250 The cut off can be changed by moving the orange line on the graph and the results are automatically updated The results can be printed by pressing the Print button They are presented as a table which cut offs from 1 in 10 to 1 in 500 in risk bands of 1 in 10 You can use this table to examine the screen positive rate corresponding to different risk cut off levels and to determine the risk cut off required to yield a given screen positive rate 2 thi Statistics O CO alpha 8 0 Risk Analysis RISK OF TEST All tests Selected Cutoff REPORT DATE RANGE O All periods The blue line shows the cumulative _ From 01 01 04 Hm percentage of results with risks ee 01 01 05 greater than that corresponding risk cut off CODES w Include all codes v Click and drag the orange line to change the risk cut off and update the results Percentage a You can zoom in and out of the graph with the mouse wheel and move the graph horizontally
184. esults Gestational age This is usually reported in weeks and days and grouped in completed weeks For example 16 completed weeks includes 16 weeks to 16 weeks 6 days Head circumference Human chorionic gonadotrophin A unique personal identifier Medicare No Hospital No National Health Service No The use of screening markers measured in the first and second trimester of pregnancy integrated into a single test result Unless otherwise qualified Integrated Test refers to the integration of NT measurement and PAPP A in the first trimester with the Quadruple Test in the second First day of last menstrual period Maternal age Maternal serum Multiple of the median value of a screening marker in unaffected pregnancies of the same gestational age measured in the same laboratory or in the case of ultrasound measurements at the same centre or by the same sonographer It Page 235 m s NT NTD Open spina bifida OC PAPP A PChE PIGF Quadruple Test RBC Scan GA Sequential Testing Serum Integrated Test SLOS Spina bifida Triple Test uE XPS alph G Version 8 is therefore the observed concentration divided by the expected concentration where the expected is the median The median is often calculated using measurements from all pregnancies not just unaffected pregnancies this makes little or no difference to estimating the MoM value because affected pregnancies are rare and therefore have little
185. esults can be transferred automatically from your laboratory equipment to alpha You can export screening data from alpha to other systems and to your spreadsheet or database software The manual and automatic methods of data entry are fully interchangeable and they can be combined in a way that suits the way you work For example you could import part of a patient s record from a laboratory information management system LIMS then manually enter other data such as ultrasound information which may not be available on the LIMS and then merge this automatically with test results from your analyser For more information on the different methods of data entry available in alpha refer to E Section 4 1 Data Entry E Section 4 5 Import Our philosophy is that patient reports should be simple informative and clear and alpha s reports achieve this Reports are stored in a database allowing you to reprint a copy of any report If changes or additions are made to a report alpha retains both the original report and all modified versions so a full report history is available for every woman screened For more information on creating and modifying reports in alpha refer to the following sections of this manual E Section 4 2 Reporting E Section 4 3 Searching E Section 4 4 Edit reports 1 4 Test interpretation and risk estimation The method which alpha uses to estimate the risk of a woman having a Down s syndrome pregnancy is based on
186. ete query SONY nae QO Name Typ Test query Run query Save query Median GA of IT women at second stage Maternal Options Output Criteria Ordering A Date reported WW Date entered lA Repeat flag The results from this query are ordered using the date on which the report was made LA Correct update flag 1 LA l Correct update flag 2 A Pointer forward A Pointer back lA Delete status flag A Update flag A Version flag Age at EDD decimal A MS AFP Mom A Lu Mom A T hCG 20 Mom A Free a hCG MoM A FB hcG 27 MoM A inh a Mom A NT Mom A Fe hce an MoM A PAPP A MoM A over Mom A Scan GA at 1st sample Figure 81 Analyse it Ordering 5 2 5 Query results To test the query press the Test Query button This will show the number of rows of data it will return To run the query and write the data to the type of file and filename specified press the Run Query button Selected results from the query prepared in the previous sections are shown exported to an Excel file Figure 82 and to XML format Figure 83 alph d version 8 Page Formulas Data Review View Developer am u A ER Ewo oee RH ee a ra E JE J a A CEE EZ a TEE ER 9 lt 8 00 Conditional Format Cell Insert Delete Format Sort amp Find amp Formatting 7 as Table Styles lt 2 Clear Filter Select Page Layout Median GA of IT women at second stage l _2 Date re
187. f Pre eclampsia 1 in 35 Comment Down s risk due to maternal age alone is 1 in 430 Comment Since a BPD was recorded anencephaly has been excluded and the risk of NTD given is for spina bifida alone Figure 65 Report correction When you create a corrected or updated report alpha prompts you to enter a comment You might choose to use this feature to record further details of the correction or update such as what prompted it The comment is optional however if you enter a comment it is stored in the alpha database The name of the user who made the change is also recorded in the database These comments can be reviewed in the list of patients in the Patients Screen You can also access them by exporting the Comment field with Analyze It Section 5 2 alpha treats reports for each pregnancy as a series Most report series consist of a single report However where repeat tests are matched to previous tests or a corrected or updated report is issued the report series consists of two tests Further repeat tests corrections or updated reports can increase the number of reports in a series alpha only allows you to work with the latest report in a series SO any corrections or updates are made to the last report in a report series alph a Version 8 4 5 Import 4 5 1 Import from text file You can use Import to create a batch file or add records to an existing batch file from an external text data file without having to ente
188. f sonographer codes is given in Sections 5 6 and 6 3 2 3 19 Titles and signature messages The Titles option allows you to add change or remove the screen and report title i Screen title The screen title is displayed when you start alpha You can enter up to two lines of 80 characters Edit the text as required To remove the screen title delete the text ii Report title The report title is printed at the top of each final report You can enter up to four lines of 80 characters Edit the text as required To remove the report title delete the text Extra blank lines after the report title are not printed on the report You can specify a Signature message of up to 80 characters to be printed at the end of all reports The signature message consists of the words Reviewed by or the equivalent in the selected report language followed by your own message You can also specify the position of the signature message relative to the left margin of the page by entering an offset between 0 and 50 characters 3 20 User options alpha provides a variety of options for data entry and reporting These are accessed from User options Figure 48 and are described below 3 20 1 General Hide all AF options Use this option to hide menu options that relate to amniotic fluid AF tests You can show the AF menu options by selecting this option again If you never use the facilities provided by alpha for interpreting AF tests you may pre
189. fer to hide them GA Format Selects comma or plus as the separation character between weeks and days when alpha prints or displays a gestational age GA For example a gestational age of 15 weeks and 4 days would appear as 15 4 or 15 4 depending on the setting you choose Save patient data in data entry This setting controls how patient data is saved when moving between patients in the data entry screen When Manual is selected alpha will prompt the user to confirm that the data should be saved When Automatic is selected alpha will automatically save the data pha versions 3 20 2 Print Order Group Screening Results Group final reports together which are positive uninterpretable and negative Additionally order by Within the grouped categories above final reports can also be ordered by Date entered Surname ID Code Patient s address Doctor report address or Date of birth Print alpha logo on reports Specify whether the alpha logo es and the message This is an alpha report appear on screening and diagnostic reports 3 20 3 Report export format selection These options select whether reports should be available for export in standard and or packet format See Section 4 2 3 3 20 4 Auto complete If you prefer alpha can automatically complete the woman s name address post code phone number date of birth and ethnic group based on the ID code you type in the data entry screen if a woman with the same ID
190. first time 44 Combined test 235 Correct and Update See Edit Report Correct and update report 27 93 See Report Series CRL 235 Regression equation GA vs CRL 45 188 Coefficients 44 alpha Version 8 Regression equation NT vs CRL See NT Crown rump length See CRL Data entry 13 26 27 90 AE AED 28 29 Assay date field 92 180 Auto complete 81 Default values 78 Import data 64 106 NT date field 92 181 Reports to 175 Search 91 Data Entry Save patient data 80 Data transfer 59 Data Transfer 123 Database 17 Dates used in reports for parameters and coefficients See Report Detection rate 235 Diabetes See Insulin dependent diabetes Doctor codes 61 175 in Tabulations See Tabulations Dongle Purpose 18 USB 18 Double test 235 Down s syndrome Age at previous pregnancy 178 Interpretation of test for 28 179 Previous 178 Down s syndrome See Risks DVPI 14 180 235 EDD 235 Edit Report 104 Ethnic group Adjustment for 13 39 44 63 158 184 188 Adjustment method factors 39 158 266 Anencephaly prevalence 39 63 Change names 63 158 Default groups 63 778 Direct method separate median equations 39 158 in Tabulations See Tabulations by ethnic group Median equation policy 42 Overall group 63 159 Screen design 39 Spina bifida prevalence 63 Weight adjustment 45 50 63 Export Format selection 81 99 Export data 13 Export data format 63 EXPORTAF DAT 63 EXPORTMS DAT
191. for maternal serum markers and AF AFP Except for AF AFP you specify in the Tabulations screen the gestational age estimate alpha should use for tabulating the data If you use or intend to use a single median equation for all women regardless of the method of estimating gestational age choose Scan if available dates otherwise If you use separate median equations for gestational age estimated by dates and by scan you will need two tabulations one using Dates only and the other Scan only Select the options you require and press the Refresh button to begin the tabulation alpha displays a preview of the tabulation as shown in Figure 116 L ro Statistics BO A Q alpha 8 0 Tabulations Lal D MARKER Gestational age MS AFP v Completed weeks Median days Level iu mL MoM Print 14 102 0 150 21 90 1 030 TABULATE BY 15 109 0 854 25 50 1 051 Gestational age v 16 115 0 29 25 1 067 Regression ily 121 0 822 34 00 1 089 GA MEASUREMENT 18 128 0 413 38 30 1 061 Scan if available dates otherwise 19 136 0 269 46 30 1 129 20 143 0 154 55 70 1 171 EN 149 0 81 55 70 1 055 All women regardless of race v 22 156 0 24 73 75 1 198 Use overall medians 1 072 On 10th centile 0 692 90th centile 1 694 SD log10MoM 0 157 WOMEN TO INCLUDE REPORT DATE RANGE All periods From 01 01 04 The table shows median MoM values without adjustment for maternal weight Median MoM value
192. grapher code are taken to be four characters long and the fixed length formats are A15 A4 and 14 4 respectively See also section 15 3 13 Importing data for the Integrated test When importing data for the integrated test using the import data format it is necessary to send all the data relating to both the samples in one record Once imported a record cannot be updated with subsequent information using this method For this reason the demographic and first sample data should be held on the host system until the second sample data are available after which all the data can be sent to alpha When only demographic information and first trimester data have been imported into alpha using this method and this data is held in a batch file and so not yet final reported the second trimester results may be imported into alpha using the analyser import feature Section 3 10 14 Risks post Export only For comma separated and fixed length export posterior risks are reported in the format lt left hand side of risk gt lt right hand side of risk gt The table below shows examples of how the risk is exported Risk on screening Value in export report file 1 in 100 1 100 Greater than 9 in 10 Less than 1 in lt 1 1000000 1 000 000 For tab separated format a tab character is always used as the separator between the left and right hand side of the posterior risks 15 NT MoM values 15 1 Data transfer For twin
193. gt Dr Albert Brown MD The Surgery 24 Park Lane LONDON NE3 ZA9 DOWN S SYNDROME NEURAL TUBE DEFECT AND PRE ECLAMPSIA SCREENING Report dated 08 Jan 14 Last name Forename s Hospital Number Date of birth LMP EDD Date of sample Date of 2nd sample Sample number 1 Sample number 2 CLINICAL DETAILS AND TEST RESULTS Previous NTD Previous Down s Prev Pre eclampsia Insulin dependent diabetes Smoker Maternal age at EDD Scan measurement CRL Gestation at date of 1st sample Gestation at date of 2nd sample Gestation used JONES Jenny 1342ZYD 02 03 82 10 09 13 20 06 14 07 12 13 07 01 14 52413 52601 32 years 55 4 mm on 07 12 13 12 weeks 4 days by dates 12 weeks 1 days by CRL scan 17 weeks 0 days by dates 16 weeks 4 days by CRL scan Scan estimate CRL Weight 65 2 kg Ethnic group Caucasian MS AFP level 30 1 ng mL 0 77 MoM uE3 level 2 1 ng mL 0 75 MoM Total hCG level 21000 miu mL 1 27 MoM Inhibin A level 210 1 pg mL 0 96 MoM i e a SE Nuchal measurement 1 2mm 0 96 MoM EE PAPP A level 12 11 mg L 1 10 MoM a graphical visualisation of the risk INTERPRETATION S Risk 1 in MS AFP MoM Screening result Screen negative i g Risk of Down s 1 in 9 000 at term Risk of NTD 1 in 7 000 Risk of Pre eclampsia 1 in 60 1 Comment Down s risk due to maternal age alone is 1 in 720 D Ge Comment Not in the high risk category for trisomy 1
194. h d Version 8 The estimates of the 10 and 90 centiles and the observed standard deviation of the MoM values transformed to logarithms to the base 10 are also shown F in Figure 116 A standard deviation that differs markedly from published estimates see Appendix J Statistical parameters Down s syndrome may indicate an assay problem and prompt further investigation Press the Print button for a printed copy of the tabulation or the Regression button for a regression of the tabulated data The regression provides the coefficients needed to update the median equations should you wish to do this see Section 5 9 for more information on regressions 5 13 4 Tabulation by crown rump length Tabulation according to crown rump length CRL is available for the ultrasound marker nuchal translucency NT The principle is the same as for tabulation by gestational age see section 5 13 3 except that the data are tabulated by 5 mm CRL bands and not by completed gestational weeks Also there is no option for ethnic group specific tabulations and you do not need to specify which estimate of gestational age to use Figure 117 shows an example of a tabulation of nuchal translucency according to crown rump length There are five columns in the tabulation and these are labelled A to E in Figure 117 and described in Table 13 Table 13 Columns in NT vs CRL tabulation B The median CRL in each group Z o gt SSS O D The medi
195. hCG inhibin A P gt PAPP A PIGF specified ethnic groups Adjustment for ethnic group MS AFP uE3 total hCG free Forupto5 B hCG inhibin specified ethnic A PAPP groups A PIGF Reinterpretation of screening result Units Maternal serum markers Nuchal translucency AF AFP MAP Maternal weight Ductus venosus pulsatility index Footnotes MS screen positive message MS screen negative message Printing of risks Down s risk positive Down s risk not positive Prior risk of Down s positive Prior risk of Down s not positive Down s risk comparison Print trisomy 18 risk Print trisomy 13 risk Print SLOS risk alph d version 8 Acceptable settings single equation separate equations for GA by scan and for GA by dates or clinical examination Direct method alpha will expect to find a median equation and a weight correction equation for the specified ethnic group Adjustment method in women of the specified ethnic group alpha uses the median equation and weight correction equation for a specified reference population adjusting the MoM value using two correction factors that allow for differences in the normal median and in maternal weight between the specified ethnic group and the reference group See section 5 13 6 for further information Always reinterpret Reinterpret only if scan and dates GA differ by at least n days N lt 28 ng mL ug L iu mL kiu L iu L nmol L miu mL pg mL
196. he new computer to follow this procedure 1 First you must copy the alpha database to another location such as a memory stick or external disk drive To do this select the Database function in the Setup section See also section 3 6 Browse to the path where you want to copy the database to and provide a filename When you press Copy alpha will copy the SQL server database MDB and log files LDB to the location specified 2 Make a note of the location of the folder containing the alpha software which is shown in the About tile of the alpha Setup section This will usually be the folder C Program Files Logical Medical Systems 3 Close down alpha 4 Copy the folder identified in step 2 to the Program Files folder on the new computer It may be necessary to first copy the folder to a memory stick or external disk drive and then copy from here to the new computer 5 Locate the alpha 8 installation CD or the MSI file used to install alpha 8 The name of this file will be of the type SetupAlpha8 0 xxxxx yy msi Contact your alpha distributor if you are unable to find this 6 On the new computer navigate to location of the alpha 8 MSI file and start the installer by double clicking on the MSI file name 7 A screen similar to that in Figure 12 will be shown Select Components and this will install the components necessary to run the alpha software Press Close when it has finished 8 Remove the dongle from the original computer
197. heading In Batches Double clicking on the poatents name will show the screening report for a report in the alpha database or show the data entry screen for unreported patients Press x to clear the search results 4 4 Edit reports Correct and update You use Edit reports Correct and update to create MS or AF reports that are either corrections or reinterpretations updates of existing reports alpha classifies each report generated with this option as either a correction or an update The new report carries a heading indicating that it is a correction or an update of a previous report MS reports are classified as updated reports after the addition of ultrasound scan AF reports are classified as updated after the addition of ultrasound scan AchE or PchE results Any other change is classified as a correction A report cannot be corrected and updated at the same time alpha will use the settings of the coefficients and parameters on the date of the original report for the corrected or updated report To edit a report you first search the database for the original report as described in section 4 3 and then select The data entry screen for the original report is now shown and can be modified as required Figure 64 AAA Make any desired changes for example changing the patien s date of birth 01 08 13 E O alpha 8 0 i OG Correct amp Update Last name ATKINS 2 1 Patients g a a Date of scan
198. hed scientific data on antenatal screening and diagnosis and is regularly updated in the light of new scientific advances See Section 7 References alpha has been used in screening over 9 million women in 49 countries alpha uses a woman s age the concentration of serum markers for Down s syndrome and NTDs and other information about the pregnancy to estimate the woman s risk of having a pregnancy with either of the two disorders 7 The ultrasound markers nuchal translucency and ductus venosus pulsatility index the presence or absence of fetal nasal bone and the use of ductus venosus blood flow as a categorical marker can also be used in estimating the risk of Down s syndrome if desired alpha also uses the concentration of first trimester mean arterial pressure and the first and second trimester serum markers to estimate the risk of the pregnancy developing pre eclampsia 80 8993 94 You can choose to print the risk of trisomy 18 Edward s syndrome DIS trisomy 13 82 83 84 or Smith Lemli Opitz syndrome SLOS 77 if they are high alpha is suitable for first trimester second trimester and integrated screening for Down s syndrome lt also interprets amniotic fluid AF alpha fetoprotein and acetyl cholinesterase AChE results used in the diagnosis of open neural tube defects alpha version 8 is a major step forward incorporating the latest medical and scientific advances in antenatal screening for Down s syndrom
199. hen tabulating with gestational age estimated by dates LMP dates classed as uncertain are also excluded Dates are regarded as uncertain when they are recorded as such or when oral contraceptive use is recorded less than 60 days before the first day of the LMP or when only the month and not the exact day of the LMP or EDD is recorded 5 13 2 Restricting reports to specified doctors addresses of sonographers If you want to restrict the tabulation to specified doctors addresses or sonographers select the appropriate option in the Codes section of the Tabulation screen and select the Change button to specify the doctor address or sonographer codes you want to include or exclude A screen similar to the one in Figure 115 is shown for doctors and similar screens are shown for addresses and sonographers Code selection lt Unsaved list gt v Code Details E Code Details 00000001 Dr Albert Brown MD 00000001 Dr Albert Brown MD 00000002 Dr Colin Dexter 00000003 Dr Egdar Fox Use the left and right arrows to move the doctors between the two This is the list of doctors This is the list of which can be selected selected doctors GI 00000004 Dr Gareth Hills These buttons allow you to clear the list of selected doctors and to save it to filename Figure 115 Code selection 5 13 3 Tabulation by gestational age The Tabulations screen provides tabulations according to gestational age
200. here are six columns in the tabulation and these are labelled A to F in Figure 118 and described in Table 14 Table 14 Columns in weight tabulation B The median weight in each group Z o gt SSS O D The median unstandardised MoM in each group E The median standardised MoM in each group The standardised MoM values are derived by dividing the unstandardised MoM values by the overall unstandardised median MoM to correct for any systematic shift in unadjusted MoM values The MoM values adjusted for weight in each group alph d Version 8 The expected adjusted median value for each weight group is 1 0 MoM The unadjusted MoM values will tend to be high in lighter women gt 1 0 MoM and low in heavier women lt 1 0 MoM This is because the volume of interstitial fluid increases with maternal weight and this will influence the concentration of maternal serum markers The overall medians for adjusted and unadjusted MoM values should both be close to 1 0 MoM the aim of weight correction being to adjust each MoM to be the equivalent value for a woman of the median weight in the screened population Patterns of deviation in the adjusted MoM values such as being consistently high or low or starting high and ending low or vice versa would indicate that the weight adjustment coefficients should be recalculated Press the Print button for a printed copy of the tabulation or the Regression button for a regression of the tabulated da
201. ich can be carried gt 1 patients 1 to be test reported 3 Delete out in the Patients screen Queries SC MS to the right of the batch name means the Stage One batch contains records for Maternal Serum Medians 1 patients 1 to be test reported screening and AF indicates the batch contains Test report 1 patients 1 to be test reported records for Amniotic Fluid AFP screening This shows a list of batches Each batch contains patients who have not been reported The selected batch Aug 01 13 has a darker background Sa Dati Figu ire 53 Patients screen The purposes of the buttons next to the search box are given in Table 7 Table 7 Purpose of the buttons in the Patients screen Button Purpose SSS ae Show the advanced search screen Section 4 3 Refresh the list of patients d Show a list of patients having the integrated test which are ready to report Section 3 11 ts Show a list of patients having the integrated test who are not yet ready to report with 7 their ideal second sample date Section 3 11 alpha Button Purpose Wee a Show a list of patients having the integrated test whose second sample is now due i Section 3 11 Ob Show a list of patients having the integrated test whose second sample is now overdue Section 3 11 address code This grouping will also be used when a batch listing is made See Group the patients according to the date when they were entered or the docto
202. in which the normal median MoM level of the marker changes with increasing maternal weight 3 13 2 1 6 Truncation limits Specifies the lower and upper MoM limits known as the truncation limits of the range of values for which the distribution of logo MoM values of the marker is judged to be Gaussian normal For the purpose of risk estimation if a MoM value falls outside this range the value at the corresponding truncation limit will be used instead 3 13 2 2 Adjustment factors 3 13 2 2 1 Twin pregnancies This specifies the median MoM value of the marker in unaffected twin pregnancies In screening for Down s syndrome in twin pregnancies MoM values are divided by the corresponding median values in unaffected twin pregnancies and the risk of Down s syndrome estimated as in singleton pregnancies This policy will yield a false positive rate which is in expectation similar to that in singleton pregnancies Although estimating the risk in this way is a valid way of judging whether a result is positive it is not the woman s true risk Neither the true risk nor the corresponding detection rate can be estimated because the distribution of the serum markers in twin pregnancies with Down s syndrome is not known See Appendix P Factors used for adjusting MoM values 3 13 2 2 2 Pregnancies in women with insulin dependent diabetes mellitus This specifies the median MoM value of the marker in unaffected pregnancies in women with insuli
203. ination of an AchE NTD band and multiple PchE bands is consistent with a neural tube defect abdominal wall defect intrauterine death or blood contamination of the amniotic fluid and a message to this effect is added to the report Result of AF Kleihauer test Fetal blood contamination of amniotic fluid can be a cause of false positive amniotic fluid AFP and AchE results Not used in the interpretation Concentration in amniotic fluid Contamination of amniotic fluid with fetal not maternal blood can cause AchE false positives especially if there are more than about 60 million fetal red cells per ml of amniotic fluid Not used in the interpretation Page 182 Other Lab number 15 Any string Spare 1 50 Any string Spare 2 50 Any string Spare 3 50 Any string Spare 4 50 Any string Spare 5 50 Any string Spare 6 50 Any string Femur length 1 SS 3 Measurement mm on date of scan l Not used in the interpretation Femur length 2 3 second measurement if multiple pregnancy Not used in the interpretation Date received 3x2 Date sample reached laboratory Not used in the interpretation Time received 4 Hours 2 digits followed by minutes 2 digits Not used in the interpretation Date 2 sample 3x2 Date 2 sample reached laboratory integrated screening only received Not used in the interpretation Time 2 sample 4 Hours 2 digits followed by minutes 2 digits integrated received screening only Not use
204. include all linked addresses for each doctor or the first linked address only The text file contains the doctor s full name and the four lines of the doctor s address separated by tab characters The first record in the file contains the field names Doctor Address 1 Address 2 Address 3 Address 4 also separated by tab characters 2 th Et Setup oni Doctors alpha Search Dr Albert Brown MD Dr Colin Dexter Dr Egdar Fox Dr Gareth Hills Search for a doctor by entering a search term here Edit doctor 00000001 Title r Doctor Code First name Albert Last name Brown Qualifications MD Dr Albert Brown MD English v Preferred addresses 00000001 The Surgery Q Address 3 Q REH Address 5 Q Ci LJ Full name Language Address 1 Address 7 Q Exclude Version 8 Mailshot list Email 020 Y6001 3193 020 76001 0506 A Brown Surgery com 00000001 6001 3193 020 76001 0506 C Dexter Sur ery com 00000002 00000001 00000001 Edit an existing doctor create a new doctor or delete a doctor with these buttons Figure 33 Doctors screen 020 76001 3193 Fax 020 76001 0506 e mail A Brown Surgery com First copy 00000001 Dr Albert Bro Q Second copy 00000002 Dr Colin Dexter Q Address 2 00000002 Charterhouse Q Address 4 Address 6 Figure 34 Edit a doctor Cl alpha 8 0 o R doctor codes from lists of doctors E
205. ing corrections for adjustments lt E single x v x x Dervea Single x x Derived Down s syndrome risk rounded Field p Derived jaa Beie Deprecated field NTD risk rounded This field exports risks no greater than 1 2 NTD risk Superseded Field superseded v Derived see comment Version 8 Page 215 Analyze it heidi oe Data transfer lt lt is Dok Down s risk superseded Maternal Serum Field name Trisomy 18 risk Superseded SLOS risk Superseded Pre Eclampsia risk Superseded Trisomy 13 risk Superseded Unrounded Down s risk Superseded Unrounded NTD risk Superseded Version 8 Trisomy 18 risk rounded Field superseded see comment SLOS risk rounded Field superseded see comment Pre eclampsia risk rounded Field superseded see comment Trisomy 13 risk rounded Field superseded see comment Down s syndrome risk unrounded Field superseded see comment NTD risk unrounded Field superseded see comment Type of field j T Ou N c st Been Ur OU Le Ben Fe vis O EES ES H x lt 2 O 35 go 2a ii E Comment CH Ou Ben Ou xe Ben O CH Ben Ou _ Cc LLI Page 216 Maternal Serum Type of EM Unrounded Trisomy 18 risk superseded Unrounded SLOS risk superseded Unrounded Pre Eclampsia risk superseded Unrounde
206. ing of NI measurement Exceptionally if no CRL measurement is available or if the CRL is measured at a different time from the NT alternative estimates may be used however such NT measurements are excluded from tabulations and monitoring of NT measurement will be incomplete Gestational age GA by Clinical This is taken to be the recorded number of completed weeks plus three days Precedence among GA estimates If more than one estimate of gestation is available the one adopted is determined by the purpose for which the estimate is to be used The following table shows the order of precedence for different uses Use Gestational age based on BPD CRL Other Dates Clinical Ultrasound Measure Screening markers 1 Acceptable time for test 2 1 2 3 4 2 Maternal age at EDD 2 1 2 3 4 3 MoM calculation 2 1 2 3 4 Down s syndrome Screening 4 M 1 2 2 3 4 oM calculation open NTD Screening AF AFP 1 Acceptable time for test 1 1 1 2 3 2 MoM calculation and cut off selection a BPD gestation less than dates 3 1 1 2 4 b Otherwise 1 1 1 2 3 Those tested too early are rescheduled to return at 16 weeks for second trimester screening or 10 weeks for first trimester screening using same priority and consequently the type of parameter used for risk calculation T If MoM values based on BPD and CRL measurements both lie on the same side of the AFP cut off only the CRL based MoM is reported If they lie on opposite sides of the cut off
207. ing the separator For example 16 weeks 3 days is entered as 16 3 For the comma separated variable file format the separator must be used 11 NT levels 11 1 Data transfer For twins the levels corresponding to the marker number for NT will be expanded to a separate field for each fetal measurement 11 2 Analyze it For NT the level is given as a 3 digit number followed by a slash x xx or for a twin pregnancy two 3 digit numbers separated by a slash x xx y yy 11 3 Import Export NT levels are imported and exported according to the setting of the Import NT levels to 2 dp mode on the Import Data Format screen and Export NT levels to 2 dp mode on the Export Settings screen Section 3 9 Import Export NT Fixed length format wasto Zapmode fn NOT SET A6 The NT level is a 3 digit The NT levels are two 3 number between 0 1 digit numbers between and 9 9 0 1 and 9 9 without In fixed length formata separators e g 1 61 2 value is entered for example as 1 6 followed by three spaces The NT level is a 4 digit The NT levels are two 4 number between 0 01 digit numbers between and 9 99 0 01 and 9 99 without In fixed length formata separators e g value is entered for 1 651 25 example as 1 65 followed by four spaces 12 Import Export Format DOS Compatibility mode lf DOS compatible mode is selected in the MS Import Data Format or MS Export Data Format screen the doctor address code and sono
208. ing up alpha 18 Set up 33 SLOS 12 See Risks Smith Lemli Opitz syndrome See SLOS Smith Lemli Optitz syndrome See Statistical parameters Smoking 179 MoM values in report 98 Sonographer Codes 179 in Tabulations See Tabulations Specific medians See NT Sonographer Specific NT Medians NT Monitor 127 Updating 143 Spina bifida 236 Open 236 Prevalence 186 Statistical parameters Down s syndrome 243 260 NTD 255 Pre eclampsia 262 Smith Lemli Optitz syndrome 261 Trisomy 13 259 Trisomy 18 257 Statistics 111 SURUSS 12 Tabulations 151 95 confidence interval 154 AF AFP 30 by selected doctor address or sonographer 153 156 by selected Ethnic group 152 158 Data excluded 152 observed MoM values by Weight 156 observed NT MoM values by CRL 151 155 observed serum markers by gestational age 153 alpha Version 8 Print 155 156 158 Report summary 144 Selecting data required 152 153 Standard deviation of MoM values 156 Updating Medians 155 156 158 Test reports See Reports Test Titles screen 80 Triple test 15 236 Trisomy 13 12 See Statistical parameters Trisomy 18 12 See Statistical parameters See Risks Twins 13 171 Chorionic sacs 179 MoM adjustment factor 70 MoM values in report 98 Ultrasound markers See NT Nasal bone Ultrasound measurements AC See AC BPD See BPD CRL See CRL Machine number 40 189 Nasal bone See Nasal bone NT See NT Units 44 184 Username Se
209. ion 4 If there is a previous Down s syndrome pregnancy of unknown type it is taken to be non inherited 5 MS AFP uE3 hCG first and second trimester NT and PAPP A MoM values are used where available to estimate the risk of trisomy 18 MS AFP uE3 and total hCG MoM values are used where available to estimate the risk of and Smith Lemli Opitz syndrome SLOS Inhibin NT hCG and PAPP A MoM values are used to estimate the risk of trisomy 13 6 Risks are rounded as follows 1 in 20 1 in 99 to the nearest 5 1 in 100 1 in 999 to the nearest 10 1 in 1 000 1 in 9 999 to the nearest 100 1 in 10 000 1 in 99 999 to the nearest 1 000 1 in 100 000 1 in 999 999 to the nearest 10 000 7 Risk estimates higher than a specified value x in y are reported as greater than x in y See Section 3 1 10 Printing of risks for acceptable values for x and y 8 Risk estimates lower than a specified value 1 in x are reported as less than 1 in x See Section 3 1 10 Printing of risks for acceptable values for x and y Parameters and Coefficients When more than one setting is available for a parameter or coefficient the chronologically correct setting is used The date the report is produced is used when selecting the correct setting except where the date of assay is specified when the date of assay is used instead When more than one setting is available for the date of report or date of assay the later setting is used For correct
210. ion of observed median values See Tabulations observed NT MoM values by CRL NT Monitor 127 NTD 236 See Statistical parameters Interpretation of test for 179 Prevalence 39 Page 271 Previous 178 Nuchal translucency See NT OC 183 236 Open NTD diagnosis of 28 See AF AFP Operating environment 267 Outcome 128 Abnormality code 128 Abnormality codes 133 136 Data entry 132 Data transfer 128 137 List pregnancies with abnormalities 131 List pregnancies withtout outcome 130 Risk analysis 128 134 Screening audit 128 133 Search 128 130 Validation plot 135 Overall group See Ethnic group Parameters 19 35 Current settings 38 Historical settings 38 Printing 38 53 Statistical See Statistical parameters See Statistical parameters Password See Security Patients Delete 90 Move 90 Selecting a group 90 Patients screen Purpose of symbols 89 Patients Screen 89 Pre eclampsia See Statistical parameters Previous 181 Screening 12 14 28 41 42 67 173 179 185 Preferences 19 Pregnancy Outcome recording See Outcome Prompt 17 Prompts 78 Quadruple test 15 236 Record 17 Recurrent false positives 43 95 Loose matching 43 Strict matching 43 References 165 Regression equations Coefficients See Coefficients Updating See Tabulations Updating coefficients 143 Regressions 138 CRL 140 GA 140 Weight 140 Repeat sample See Matching in same pregnancy Report AF AFP 27 28 Cap r
211. isks 43 Correct and update See Correct and update alpha Version 8 Dates for parameters and coefficients used 174 Final 27 93 96 Merging 26 Footnotes 41 184 Format 76 Message addition 190 MoM values See MoM values printed in reports MS 28 Page setup 34 75 Printing of risks 42 184 Reinterpretation amp reclassification 44 Risk cut off levels See Risks cut off levels Riskometer 43 Rules used in producing 171 Signature message 80 Test 27 93 Title 80 Trim risks 42 Window envelope 86 Report series 105 Reporting Additionally order by 81 Group results 81 XPS filename 81 Request card 19 26 Risk Analysis 147 Riskometer See Reports Riskometer Risks Age specific risk of Down s syndrome 243 260 Capping 43 Cut off level for given screen positive rate 147 Cut off levels 40 185 Estimation 13 Printing 42 Rules for calculating estimates 174 Timing 42 Trimming 42 Scan update policy 44 Screen design 19 34 77 Screen positive Observed rate See Tabulations Report summary Rules for positive result 172 Screening markers See Markers Screening Performance 148 Screening result Positive 173 Uninterpretable 173 Screening test Reinterpretation amp reclassification 184 Search 27 101 in Batch See Data entry Search Security 18 192 Modify user list 34 83 Sequential testing 15 41 98 179 236 Serum integrated test 15 Page 272 Serum markers See Markers Sett
212. l MoM value lies outside the 95 confidence interval around 1 0 MoM There may be some fluctuation and you should not place too much emphasis on median MoM values which are based on small numbers of observations as is frequently the case for earlier or later gestational ages Look for patterns in the median MoM values by week or crown rump length interval Consistently high or low values or trends from high to low or vice versa will need some attention If you need to recalculate the median equations use the Regression option and update the coefficients in the usual manner section 5 9 Remember to use the Evaluate coefficients option to examine the new expected medians as a safety check see section 3 2 4 You should examine the tabulations for each screening marker and for AF AFP as appropriate If separate median equations are used for women of different ethnic groups you will need to examine the tabulations for each ethnic group as well as for the overall population lf separate median equations are used for gestation estimated by scan and gestation estimated by other means you will need to examine the tabulations using scan based and dates based estimates of GA When you tabulate the data you should choose a suitable time period Too long a period for example a year may mask recent changes in median levels whereas too short a period for example a month may provide insufficient data to truly represent the long term picture One sol
213. l report for an Integrated Test A C credit is used each time you produce a final report in which a pre eclampsia risk is calculated The appropriate credits are also charged for repeat tests see section 4 2 2 1 Updates corrections test reports and reprints do not use credits alpha will notify you when the licence is about to expire with one of the following messages alpha usage is approaching the current licence limit alpha displays this message when less than 10 of the previous allocation of A credits remains The licence to use alpha is due to expire on lt date gt alpha displays this message when the expiry date is within 30 days of the current date 2 te HI Setup oni d alpha 8 0 Licence Licence number 11077 A Credits Ge Geier ae alpha displays the expiry date credits 1191 22 April 2014 7167 remaining total credit usage and your B Credits licence number Level Expiry date Usage 4632 22 April 2014 4836 The expiry date credits remaining and C Credits credit usage are shown separately for Level Expiry date Usage A B amp C credits 4378 22 April 2014 1089 CO Last allocation of credits was A 5000 B 5000 C 5000 To renew your licence please phone your Alpha distributor Quote Code Verify Code Enter Unlock Code 82272 63371 iz Seb ate ba Rd To renew your licence contact your Local alpha distributor quoting the number O UK displayed here Figure 38 Licence screen alph d V
214. lated data The regression provides the coefficients needed to update the median equations should you wish to do this see Section 5 9 for more information on regressions L ro Statistics OB O alpha 8 0 Tabulations Lal MARKER Crown rump length mm Number Nuchal v CRL group Median CRL Level mm S lt 20 Q Print REPORT DATE RANGE 20 All periods 25 Regression _ From 01 01 04 30 GA 35 To 01 01 05 if 45 50 Include all codes X 55 CODES 60 65 DISPLAY GRAPH AS m 80 Refresh results 85 90 95 10th centile 90th centile SD log10MoM The following categories are excluded updated results repeat tests and multiple pregnancies Median NT MoM Figure 117 Nuchal translucency tabulation 5 13 5 Tabulation by weight The Tabulations screen provides tabulations according to maternal weight for maternal serum marker MoM values You can choose whether to tabulate maternal weight in kilograms or in pounds As with tabulations by gestational age you can tabulate data for specified ethnic groups and you can specify doctors addresses or sonographers to include or exclude from the tabulation You can also specify a date range over which to tabulate the data Press the Refresh button to begin the tabulation alpha displays a preview of the tabulation as shown in Figure 118 alph d Version 8 2 thi Statistics OB d alpha 8 0 Tabu
215. lations 4 D D B MARKER Maternal Weight kg Median uE3 MoM uE3 v Group Median Unadjusted for weight Adjusted for weight Print Unstandardised Standardised TABULATE BY 42 00 49 1 260 1 199 1 151 Maternal weight 47 50 198 1 198 1 140 1 123 Regression 52 90 441 1 112 1 059 1 056 57 00 718 1 088 1 036 1 052 Kilograms 62 00 856 1 037 0 987 1 016 67 00 668 1 018 0 970 1 018 72 00 468 1 019 0 970 1 035 All women regardless of race 77 00 288 1 042 0 992 1 082 Use overall medians 82 00 234 1 036 0 986 1 090 off Bess 87 00 133 1 012 0 964 1 091 91 70 92 1 032 0 983 1 127 SS 97 00 58 1 004 0 956 1 111 penads 102 00 29 1 017 0 968 1 141 ga From 01 01 04 107 00 21 0 986 0 939 1 125 re 01 01 05 112 00 15 0 961 0 915 1 126 116 80 T 1 028 0 978 1 220 CODES 126 00 17 0 867 0 826 1 098 64 00 4292 1 050 1 049 Include all codes v Median standardised unadjusted MoM values are derived by dividing the median unstandardised MoM in each weight group by the overall median unstandardised MoM When using the regression facility to derive coefficients for weight adjustment the Refresh results standardised MoM values should be used TABULATE WEIGHT IN WOMEN TO INCLUDE REPORT DATE RANGE alpha plots the median MoM with maternal weigth to provide a visual method of checking that the median values are correct across the range of weights Median uE3 MoM Figure 118 Weight tabulation T
216. lence of pre eclampsia used to estimate the risk of developing a pregnancy with pre eclampsia 3 1 5 BPD correction factors Ultrasound machine numbers or types for up to nine machines or types of machine can be specified for users who wish to enter fetal biparietal diameter BPD crown rump length CRL and abdominal circumference AC measurements directly rather than the estimates of gestational age derived from the scan examination When fetal ultrasound measurements are entered directly the machine number must be given The machine number is used to select the equations for calculating gestational age from the fetal measurements section 3 2 1 3 It is also used to select a correction factor needed to adjust BPD measurements for the sound velocity assumed 1540 or 1600 m s and whether the measurement is made outer to outer cranial edge or outer to inner When a BPD measurement is recorded alpha makes an adjustment according to the value of the BPD correction factor you specify for the corresponding ultrasound machine see Appendix C Acceptable settings for parameters and Section 3 1 5 The BPD correction factor allows for differences in the estimated gestational age arising from different methods of BPD measurement outer to inner or outer to outer edge of the cranium and the sound velocity assumed 1540 or 1600 m s The standard measurement is made outer to inner cranial edge with an assumed sound velocity of 1540
217. level first test with scan MS AFP gt specified level first test without scan MS AFP gt specified level repeat test MS AFP lt specified level first test with scan MS AFP lt specified level first test without scan MS AFP lt specified level repeat test MS AFP between specified levels first test with scan MS AFP between specified levels first test without scan MS AFP between specified levels repeat test Increased risk of T18 Test at 14 weeks Weight gt specified weight Increased risk of SLOS Page 239 Code First part of item 385 AF message addition Header message 390 Footer message 395 Negative 400 Positive AFP 405 Positive AFP and positive AChE 410 Ambiguous AFP and negative AChE 415 Ambiguous WY AFP and positive AChE The second part is Report dated lt date gt Format of packeted items An item with code N appears in the exported file of reports as a string the packet header oN nl nzn followed by n3 lines of maximum length 80 characters terminated by a carriage return and line feed n1 lines being the first part of the item and the next n2 lines the second part Each line of the first part is delimited by and each line of the second part by The numbers n1 n2 and n3 are two digits packed with a leading zero as necessary For example S050 201 01 02 Surname SMITH Multiple patients in a batch scree
218. ll markers set to 0 Birth prevalence of trisomy 18 is taken to be one tenth of the age specific prevalence of Down s syndrome SEN e Appendix M Statistical Parameters Trisomy 13 Means standard deviations and correlation coefficients og MoM for unaffected and trisomy 13 pregnancies and truncation limits MoM for serum markers and nuchal translucency NT Marker Unaffected Trisomy 13 pregnancies pregnancies MEAN 2 trimester Inhibin 0 0000 0 2068 1 trimester Free B hCG 0 0000 0 3279 PAPP A 0 0000 0 5850 NT 0 0000 0 3263 STANDARD DEVIATION 2 trimester Inhibin 0 2078 0 2714 1 trimester Free B hCG 0 2651 0 2743 PAPP A 0 2495 0 1986 NT 10 weeks 0 1550 0 3014 NT 11 weeks 0 1275 0 3014 NT 12 13 weeks 0 1105 0 3014 CORRELATION COEFFICIENTS UNAFFECTED PREGNANCIES First trimester NT NT NT Free B PAPP A 10 weeks 11 weeks 12 13 hCG weeks First Trimester Free B hCG 0 0325 0 0391 0 0423 PAPP A 0 0429 0 0516 0 0559 0 1395 Second trimester Inhibin 0 0415 0 0499 0 0540 0 2937 0 0237 CORRELATION COEFFICIENTS AFFECTED PREGNANCIES NT Free B PAPP A hCG First Trimester Free B hCG 0 1541 PAPP A 0 1418 0 1476 Second trimester Inhibin 0 0 0 SEN e All pregnancies TRUNCATION LIMITS 2 trimester Inhibin 0 5 2 0 17 trimester Free B hCG 0 3 1 35 PAPP A 0 2 0 5 NT 0 9 2 5 The age specific live birth prevalence of trisomy 13 is give
219. llows for all associated codes to be listed in a single screen See Figure 93 Search database List pregnancies without outcome List pregnancies with abnormalities l Codes E SEI oam a St Abnormlity codes Easy access to common codes e All pernod Expected date of delivery SE Quick selection of codes on 0171480 Multiple congenital malformation ai to Other specified congenital malto Congenital malformation unspe Trisomy 21 meiotic nondigunction Trizomy 21 mosaicism mitotic ri Screening Result Palen MT Ton E Lei Date of sa a Figure 93 Outcome List pregnancies with abnormalities On entering a new code into the textbox a popup list appears showing all codes available to the user Clicking on a code or pressing lt Return gt will select it whilst lt Esc gt will hide the list Once the codes have been selected press refresh to perform the search alph d Version 8 Once this list has been compiled it can be printed by clicking the print button on the side bar 5 7 3 Outcome Records This section describes how to create edit and delete outcome records You can create and outcome record from an individual pregnancy only if one or more maternal serum screening reports relating to the pregnancy have already been created using alpha 5 7 3 1 The Outcome Data Entry Screen As every outcome record is linked to an individual pregnancy the user is required to first s
220. m Information you enter whether manually or from a computer file is automatically checked Invalid data are not accepted and you will be asked to confirm extreme or implausible values The next step is to create reports This is a two stage procedure First you create test reports and check the reports for data entry errors Errors are corrected using the Data entry option Once you are satisfied that the data are correct you can produce final reports and print them or export them Once final reports have been created the data are automatically merged into the database Any changes must be made using Correct and update see section 4 4 When you create test reports three other procedures are automatically applied to the data 1 Data Validation alpha verifies that the data entered are valid and that there are sufficient data present to create each report If any problems are encountered you can edit the data at that point and continue 2 Matching with a report from the same pregnancy alpha checks to see if there are previous reports from the same pregnancy that can be matched to any of the tests being reported see section 4 2 1 lf potential matches are found you can select whether or not the new report should be linked to any existing previous report Matches are only offered to reports for the same woman if the previous test was performed in the last 13 weeks This avoids the possibility of matching tests across different pregnanci
221. m s in which case alpha makes no adjustment correction factor of 1 0 When other techniques are used for measuring BPD alpha reduces the BPD measurement before using the adjusted BPD measurement in estimating gestational age For BPD measured outer to outer cranial edge with an assumed sound velocity of 1540 m s or outer to inner cranial edge with an assumed sound velocity of 1600 m s the BPD measurement is reduced by 4 correction factor of 0 96 For BPD measured outer to outer cranial edge with an assumed sound velocity of 1600 m s the BPD measurement is reduced by 7 correction factor of 0 93 If you are unsure about which adjustment factor is appropriate in your setting you may wish to discuss this with your ultrasound department 3 1 6 Cut offs Cut off levels must be specified for the risk of Down s syndrome and trisomy 18 in second trimester screening and for the risk of SLOS and trisomy 13 A cut off MS AFP MoM level must be specified for open neural tube defects If you intend to use alpha for first trimester screening you will also need to specify Down s syndrome and trisomy 18 risk cut offs for first trimester screening pha versions If you intend to use alpha for screening with the Integrated Test you will also need to specify a trisomy 18 risk cut off for integrated screening a Down s syndrome cut off for integrated screening tests that include nuchal translucency NT measurement and a Down s sy
222. men who undergo in vitro fertilisation IVF and those who conceive naturally This can lead to differences in the false positive rate among the different groups screened at a fixed risk cut off For example the screen positive rate among IVF pregnancies screened with the Quadruple Test is about twice that in naturally conceived pregnancies for a risk cut off of 1 300 To avoid this alpha adjusts MoM values in twin diabetic and IVF pregnancies and in women who smoke using the adjustment factors given in the table below Since women with insulin dependent diabetes mellitus tend to be heavier than those without this condition two adjustment factors are given one used when a diabetic woman s MoM values are weight adjusted and the other when they are not There are too few data in which two or more of these circumstances twin diabetic IVF pregnancies and women who smoke apply in the same pregnancy In these cases an adjustment factor can be derived by multiplying the adjustments factors for each circumstance For example the adjustment factor for uE3 for a woman who smokes and is diabetic adjusted for weight is 0 96 X 0 95 0 912 Other factors are derived in a similar way This is the approach used in alpha The table below also indicates by a superscript letter when the adjustment factor value was first used in alpha If there is no indication the adjustment factor has always been used in the Windows version of alpha Median mark
223. ment for ethnic group NTD amp pre eclampsia background prevalences BPD correction factors cutoffs footnotes median equation policies AF AFP median reduction factors if AF AFP options are activated printing of risks matching for recurrent false positives scan update policy units of measurement alpha stores historical settings for each parameter together with the dates on which settings were changed When reports stored in the database are reprinted or are accessed for statistical tabulations alpha ensures that the correct setting is used for each parameter by retrieving the setting that was current on the date of the original report The parameters are described in more detail below and a complete list of the parameters and their acceptable settings is given in Appendix C Acceptable settings for parameters You may not need to set all the parameters depending on your screen design alpha displays a warning message if any required parameters are missing alph G Versions 2 lu o j Setup AAA Ci alpha 8 0 Pa ram ete CS Enter a search term for the parameter gt you wish to see and press Search Back Search Adjustment for Ethnic Group Current Select this button to print the current or SE on t promp EE historical parameter settings Lee BPD correction factors Pa ER If this option is checked then the user is Footnotes not prompted to give the reason for a parameter change Median Equation Policies Medi
224. n dependent diabetes mellitus Separate adjustment factors are given according to whether or not the MoM value has been corrected for maternal weight or not The use of separate adjustment factors allows for the difference in weight on average between diabetic and non diabetic women In screening for Down s syndrome in pregnancies in women with insulin dependent diabetes mellitus MoM values are divided by the corresponding median value in unaffected diabetic pregnancies and the risk of Down s syndrome estimated as in non diabetic pregnancies This policy will yield a false positive rate which is in expectation similar to that in non diabetics See Appendix P Factors used for adjusting MoM values 3 13223 Women who smoke This specifies the median MoM value of the marker in women who smoke See Appendix P Factors used for adjusting MoM values 3 13 2 2 4 IVF pregnancies This specifies the correction factor for adjusting MoM values of the marker in women who have become pregnant through in vitro fertilization IVF In IVF pregnancies the levels of some serum markers differ on average from those in non IVF pregnancies and the screen positive rate may as a result be higher or lower than expected Correcting the MoM values should yield a screen positive rate similar to that seen in non IVF pregnancies See Appendix P Factors used for adjusting MoM values 313225 Recurrent false positive slope This specifies the slope of the e
225. n s 126 Age at previous pregnancy affected by Down s syndrome 127 Previous pre eclampsia 128 Ductus venosus blood flow 130 Insulin dependent diabetes mellitus 131 Smoker Code First part of item 132 IVF pregnancy 133 Date of egg collection 134 Date of embryo transfer 135 Maternal Age at EDD 136 Donor age at EDD 140 Reason for amniocentesis 145 Ultrasound Scan 150 Scan Measurement 155 Scan Measure 160 Gestation at Date of Sample non Integrated Test 161 Gestation at date of 1 sample integrated screening only 162 Gestation at date of 2 sample integrated screening only 165 Weight 170 Ethnic group 175 Sample Appearance 180 Fetal cells 185 RBC million ml 187 Fetal Nasal Bone 190 Marker 1 MS AFP 195 Marker 2 uE3 200 Marker 3 total hCG 201 203 Markers 4 6 The identities of the markers can be determined from the 4 5 and 6 entries in the Markers screen Section 3 13 205 AF AFP Level 206 209 Markers 7 10 The identities of the markers can be determined from the 7 g 9 and 10 entries in the Markers screen Section 3 13 210 AChE NTD Bands 211 212 Markers 11 12 The identities of the markers can be determined from the 11 and 12 entries in the Markers screen Section 3 13 215 PChE Bands 220 lt is no longer possible to reprint this report in full because links with other reports were changed as a result of the correction on lt repor
226. n 3 1 6 Cut offs A message can also be printed when the trisomy 18 or trisomy 13 risk is below the cut off E For SLOS you can choose to never print the risk to print the risk only if it is equal to or above the specified cut off or to print the risk if it is equal to or above the specified cut off and the risk of Down s syndrome or trisomy 18 is equal to or above the relevant specified cut off A message can also be printed when the SLOS risk is below the cut off E For pre eclampsia you can choose to always or never print the risk The options for controlling the printing of Down s syndrome open NTD pre eclampsia trisomy 18 trisomy 13 and SLOS risk estimates are described in Appendix C Acceptable settings for parameters For Down s syndrome trisomy 18 and trisomy 13 you can specify whether the risk printed is the risk at term or at the time of the test Second trimester risks are approximately 23 higher than term risk for Down s syndrome and 70 higher for trisomy 18 on account of the selective fetal loss of Down s syndrome and trisomy 18 pregnancies In the first trimester the risk of Down s syndrome is approximately 43 higher than at term For trisomy 13 second trimester risks are approximately 42 higher than term risk and first trimester risks 49 higher on account of the selective fetal loss of trisomy 13 pregnancies You can trim risk estimates that are judged to be very low Risks that are lower than
227. n alpha s data entry screens and also to define import export worksheet and report formats see section 3 17 Titles and signature messages specifies the title that appears in the alpha screen the top of the screening report and a signature message for the report See section3 19 User options provides options to further configure alpha according to your requirements See section 3 20 With Users you can manage the list of users who can access alpha by assigning a username password and security level to each user see section 3 21 You can also use Users to change the password used to log in to alpha Once a password is assigned to a user only the user may change the password see section 3 21 What if is an educational tool which allows you to see the effect of changing patient details on the screening result See section 3 22 Window envelope configures the position of an address on the screening report See section 3 23 Wipe locks removes any locks put on patient records in batches in cases where alpha has closed unexpectedly during final reporting pha versions 3 1 Parameters You use parameters in alpha to specify your screening policy You can use the Parameters screen Figure 14 to E Change the setting of any parameter D View the current and historical settings for a parameter E Print current and historical settings for all parameters The parameters in alpha fall into the following categories adjust
228. n and select the sonographer from the list The coefficients for this sonographer can then be entered alph d Version 8 2 kk EI Setup 44 Cl alpha 8 0 Coeffi CIE nts Serum marker GA if you have specified SE Median Equations gt MS that a single median equation will be used regardless of the method of estimating gestational age this median equation will be MS AFP Dates GA for all women MS AFP Scan GA a Serum marker dates GA if you have specified that separate median equations will be used for gestational age estimated by dates and gestational age estimated by other Don t promo means this equation will be used for women Lo changes j whose gestational age is not based on an ultrasound scan MS AFP GA Current Serum marker scan GA if you have specified that separate median equations will be used for gestational age estimated by scan and gestational age estimated by other means this equation will be used for women whose gestational age is based on an ultrasound scan Figure 21 Coefficient and median equation policy There is a choice of regression equations for the median equations for UES or inhibin A To choose the equation select the item you wish to change and press the Change equation button and select the new equation from the options given Figure 22 Select new equation e A BxGA days Ax pGA days Axpl GA days C Figure 22 Select equation for uE
229. n by 1 r prevalence 1 0253 325 Ee EE The risk of an individual woman having a pregnancy affected with trisomy 13 1 risk Sea TT 9 53 3 25 L e033Aa8e 380 l e SS Fetal Loss Rates The fetal loss rates for tests carried out in the first trimester 12 weeks gestation and second trimester 18 weeks gestation are taken to be 49 and 42 respectively SEN s Appendix N Statistical parameters Smith Lemli Optitz syndrome SLOS Means standard deviations and correlation coefficients log10 MoM for unaffected and SLOS pregnancies and truncation limits MoM for each serum marker Serum marker Unaffected pregnancies SLOS pregnancies MEAN AFP 0 1427 UE 0 6778 hCG 0 1192 STANDARD DEVIATION AFP 0 1527 0 1465 UE3 0 1351 0 3501 hCG 0 2260 0 3159 CORRELATION COEFFICIENTS AFP uE3 0 3140 0 3760 AFP hCG 0 0950 0 2230 UE3 hCG 0 2150 0 3960 All pregnancies TRUNCATION LIMITS UE 0 3 1 0 hCG 0 3 1 5 t All measured between 14 and 22 weeks of pregnancy Personal communication July 2001 from Foundation for Blood Research Unaffected means for all markers set to 0 The birth prevalence of SLOS is taken to be 1 in 20 000 4 SEN s Appendix O Statistical parameters Pre eclampsia Means standard deviations and correlation coefficients log10 MoM for unaffected and pre elampsia pregnancies and truncation limits for serum markers Marker MEAN 1 trimester
230. n in completed weeks only Women in whom GA by clinical is the only available estimate of GA are excluded from certain tabulations Date to which GA by clinical relates Screening MS related information First or repeat 1 Weight 5 Weight units 1 Date weighed 3X2 alph d version 8 1 first screening sample this pregnancy 2 repeat sample If this field is used to indicate a repeat sample and the record is not subsequently matched to an earlier record relating to a previous sample in the same pregnancy a message to this effect appears on the report Woman s weight The units kilograms or pounds may be specified in Weight units if it is included in the screen design If not or if Weight units is left blank the units are taken from the parameter settings see Section 3 1 13 0 kilograms 1 pounds If given the value entered overrides the default weight units specified in the parameter settings see Section 3 1 13 If chosen this prompt should follow Weight Not used in the interpretation Page 177 Previous Down s Age at previous pregnancy Previous NTD Diabetes Ethnic group alph d version 8 0 none 1 non inherited 2 inherited translocation 3 type unknown Type of previous pregnancy if any affected with Down s syndrome If 3 type unknown is entered 1 non inherited is assumed by default When a previous affected pregnancy is recorded a recurrence risk of 0 34 if n
231. n of different ethnic groups Alternatively you can allow for such differences by specifying a weight adjustment equation for the majority ethnic group the reference group and correction factors that are used to allow for differences in weight between the reference group and women of other ethnic groupe With alpha you can specify one of two different regression models for weight adjustment the log linear model or the linear reciprocal model In general there is little advantage in using one model over the other and the log linear model is the one most commonly used However you may wish to choose which model to use on the basis of how well each model fits the observed weight specific MoM values in your own population You can specify the model used for each serum marker The equations for the log linear and the linear reciprocal models are given in Appendix D Equations used in calculations 3 2 1 3 Equations used to estimate gestational age from fetal ultrasound measurements These equations are used to estimate gestational age from ultrasound measurements of biparietal diameter BPD crown rump length CRL head circumference HC and abdominal circumference AC You can specify equations for each of nine machines as specified by the ultrasound machine prompt See Appendix D Equations used in calculations for more information When a BPD measurement is recorded alpha makes an adjustment according to the value of the BPD c
232. n the appropriate position in the Report formats screen Click on a browse button kal to locate an RDF using the standard file browser window Click OK to save your changes Please contact your alpha distributor for information on obtaining customised RDFs alph d Version 8 2 Jk Hi Setup oni Q alpha 8 0 Report Formats Use these buttons to configure Report Formats for Maternal Serum or Amniotic Fluid Test reports Print alpha8 rdf Enter the name of the RDF you wish Final reports to use for each type of report Print alpha8 rdf Standard export alpha8 rdf Packeted export alpha8 rdf Search reports Print alpha8 rdf Standard export alpha8 rdf Packeted export alpha rdf Figure 44 Report Format Settings 3 17 Screen design You can choose which prompts appear on the data entry screens and specify the layout on the screen A separate set of prompts is chosen for maternal serum and amniotic fluid tests The prompts and blank lines can be arranged in up to five columns The MS screen design screen is shown in Figure 45 The left hand column lists all of the fields you can use in the MS data entry screen and the columns on the right show the fields that have been added to the screen design You add and remove fields by clicking and dragging the items between these columns alph d version 8 2 i Screen design Amniotic Fluid Valid screen design Empty row Address 1 Address 2 Address 3 j Pos
233. n the interpretation is for Down s syndrome only Interpretations for pre eclampsia are only given for second trimester tests The number of amniotic sacs in a twin pregnancy Not used in the interpretation The number of chorionic sacs in a twin pregnancy Used as an indication of zygosity in screening tests that include NT measurement Dichorionic twins are assumed to be dizygous Monochorionic twins are taken to be monozygous If left blank the pregnancy is assumed to be dichorionic O No 1 Standard integrated Combining the results of the first and second trimester markers 2 Sequential testing Only women who have a negative first trimester test proceed to the full Integrated test This field must be included in the screen design if you wish to interpret the Integrated Test If included the type of test Integrated or standard Integrated or Sequential testing must be specified for each woman screened This field should preferably precede Date of sample and Date of second sample in the screen design Code up to 8 letters or numbers identifying the sonographer who made the nuchal translucency NT measurement Required in Integrated Tests which include NT O No 1 Yes alpha adjusts MoM values of certain serum markers in smokers to allow for differences in the levels between smokers and non smokers If left blank patient is assumed to be a non smoker See Section Appendix P Factors used for adjusting MoM values for more info
234. nd sample 17 weeks 0 days by dates 16 weeks 4 days by CRL scan 270 01 01 02 Gestation used Scan estimate CRL 165 01 01 02 Weight 65 2 kg 170 01 01 02 Ethnic group Caucasian 190 01 01 02 MS AFP level alph a Version 8 30 1 ng mL 0 77 MoM 195 01 01 02 UE3 level 241 ng ml 0 75 MoM 200 01 01 02 Total hCG level 21000 miu mL 1 27 MoM 202 01 01 02 Inh hibin A level 210 1 pg mL 0 96 MoM 203 01 01 02 Nuchal measurement 1 2 mm 0 96 MoM 206 01 01 02 PAPP A level 12 11 mg L 1 10 MoM 225 01 01 02 Screening result Screen negative 245 011 01 02 Risk of Down s 1 in 9 000 at term e200 01 01 02 Risk of NTD 1 in 7 000 255 01 01 02 Risk of Pre eclampsia 1 in 60 240 01 01 02 Comment Down s risk due to maternal age alone is 1 in 720 240 01 01 02 Comment Not in the high risk category for trisomy 18 risk lt 1 in 100 240 01 01 02 Comment Not in the high risk category for trisomy 13 risk lt 1 in 100 275 00 03 03 A screen negative result does not exclude the possibility of Down s syndrome Ja neural tube defect or pre eclampsia because screening does not detect all affected pregnancies alph a Version 8 Appendix J Statistical parameters Down s syndrome The age specific live birth prevalence of Down s syndrome is given by 1 r prevalence 14 6733 421 jee ee The ri
235. ndrome Quadruple test markers Prenat Diagn 2006 26 559 564 A Borrell V Borobio JP Bestwick and NJ Wald 2009 Ductus venosus pulsatility index as an antenatal screening marker for Down s syndrome use with the Combined and Integrated tests J Med Screen 16 112 118 JP Bestwick WJ Huttly and NJ Wald 2013 Screening for trisomy 18 and trisomy 13 using first and second trimester Down syndrome screening markers J Med Screen 20 57 65 GM Savva K Walker JK Morris 2010 The maternal age specific live birth prevalence of trisomies 13 and 18 compared to trisomy 21 Down syndrome Prenat Diagn 30 57 64 JK Morris GM Savva 2008 The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18 Am J Med Genet A 146 827 832 JP Bestwick WJ Huttly and NJ Wald 2012 Unconjugated estriol values between 14 and 22 weeks of gestation in relation to prenatal screening for Down syndrome Prenat Diagn 32 299 301 NJ Wald JP Bestwick and A Borelli 2012 Adding ductus venosus blood flow as a categorical variable to the Combined and Integrated tests in Down s syndrome screening J Med Screen 19 49 50 87 88 89 90 91 92 93 94 95 96 97 WJ Huttly and NJ Wald 2012 The estimation of gestational age of pregnancy for use in screening for Down s syndrome using ultrasound measurements and embryo transfer date Prenat Diagn 32 1008 1009 NJ Wald JP Bestwick and WJ Huttly 2013 Improvements in antena
236. ndrome cut off for integrated screening tests that do not include NT measurement Different risk cut offs are needed for different screening tests because a given risk cut off Say 1 in 250 may yield different false positive rates according to the screening test used For example if you provide first trimester and second trimester screening and you wish to achieve a 5 false positive rate for both types of screening using the same risk cut off for both tests may not yield the desired results If you intend to use alpha with sequential screening you will also need to specify a first trimester risk cut off to identify those women with very high risk pregnancies who will not proceed to the Integrated test A high risk cut off is used for the first trimester test so there is a low false positive rate The allowed range of risks for the cut off is 1 in 10 to 1 in 60 If you intend to use alpha for screening for pre eclampsia you will need to specify a pre eclampsia risk Cut off You only need to set the four gestation specific AF AFP cut offs if you intend to produce AF reports 3 1 7 Footnotes You can choose to add a standard message to the bottom of the screening reports The standard footnote for screen positive reports Is A screen positive result indicates an increased risk of having a pregnancy with Down s syndrome or a neural tube defect Most women with positive screening results will not have an affected pregnancy The standard fo
237. nformation system can be imported into alpha and the measurements from the file stored with the corresponding patient record in an unreported batch file Each qualifying line of the file must contain one or more analyte measurements together with a code such as a sample ID which is used to identify the patient from whom the measurements were taken When the file is imported into alpha the patient record containing the same code is identified and the analyte measurements added to that record The Analyser Import screen provides a facility which describes the format of these files for each of the analytes which can be entered into alpha The files are read into alpha using the Import facility described in section 4 5 The meaning of each of the items in the Analyser import screen is given in Table 4 Table 4 Meaning of terms in Analyser Import screen File path and mask Path and filename of file containing the measurements If required a mask can be used to specify the name of the file to be used The default import filename is given by replacing the mask characters in the following way Mask character Replaced by H DD Dayrnumber S Examples Masked filename Filename presented as default AFP lt gt B TXT If the last filename matching the mask is AFP04B TXT AFPO05 TXT UE3 lt DDMMYYYY gt A TXT If the date is 22 May 2013 UE322052013A TXT Header lines in file Number of header lines in the file before the star
238. ng S y Derived hand side Integer The trisomy 13 risk can only be reported when it is above Integer Page 209 Maternal Serum Comment Type of 8 l Trisomy 13 risk LHS Trisomy 13 risk left Long unrounded hand side Integer Trisomy 13 risk Trisomy 13 risk RHS right hand side Bn O Se g E O gt 52 S Z d fs d Ze H Oo ESA D pr ZS E c IL LLI _ T Ou N c st Been Ur OU Le Ben Fe vis Vv Long unrounded rounded Integer Trisomy 13 Trisomy 13 risk post posterior risk See 12 Derived note 14 increased risk of trisomy 18 trisomy 18 risk below threshold increased risk of trisomy 13 trisomy 13 risk below threshold increased risk of SLOS SLOS risk below threshold Derved MoMs are corrected for weight and ethnicity but not twins IVF smoking or diabetic status 1 first trimester Derived 2 second trimester 3 integrated test 0 kg enicred Format is lt Username of user who started data entry gt lt username of wi Trisomy 18 flag Trisomy 18 flag Text v Trisomy 13 flag Trisomy 13 flag Text v SLOS Flag SLOS Flag Text AFP MoM for NTD AFP MoM for NTD screening screening Shows which A A Vv 1 1 1 1 1 A5 v Single v trimester this 4 OD Ke Lamm Trimester flag 1 v measurement was taken in Units in which the Ke AR weight was entered Megs Username of
239. ng so that at least 250 reports are analysed from the selected date to today It analyses the reports in this date range and presents the results in a number of sections on the Automonitor screen which are summarised below 2 ib Statistics Q AAA O aipha 8 0 Monitor from 01 09 20 Last completed 9 27 2013 11 00 57 AM Took 1 7 sec Analyse It MS AFP uE3 T hCG 27 FB hCG Inh A NT Advanced export data from sipha repo x EIN Median weight of 740kg for 0 A 0 Back women is out ot line with 1 expected 66 0eg Data Transfer SSUES issues Loes issues issue Export data trom alpha reports Median Analysis Loot for trends in marker cata Test Increased risk Missing Information Analyse messing field data Negateve Nuchal Translucency Monitor View and analyse Nuchal Transiucency data Uninterpreteble Total Outcome Record the outcome of pregnancies Population Look af the age distribution in al screened patients Regressions Create new marker coetticents MS AFP 3 u3 3 034 00064991 Report Summary Analyse a reports in alpha TG 0 o 00085767 mae 0 0 0 OTH Risk Analysis Inh A 3 L 00023957 Analyse reported moks in all screened patients FB hCG 4652 103 V OS oO D PNE Screening Performance PAPP A 4652 099 03 0 00031713 View detection and false positive rates for a specific test Tabulations Analyse marker data Figure 69 Statistics screen showing Automonitor results 5 1 1 Marker MoM Automonitor displays a tile fo
240. ngs Patient import settings 1 parameter change s made s The events log records parameter amp Integrated test options coefficient changes relicensing upgrades Configure options to assist with the identifying patients SS 4 fartheliagatdtea Installed version 8 0 14120 22 and events chosen by the user Licence Installed version 71R You can search the events log or specify the Renew licence and view current licence details S i S i starting date from which entries are made Markers All marker information and add new markers Message Addition User defined messages to add to screening reports Page setup Change margins and page sizes Parameters View and adjust screening parameters Report formats settings Cian item T1 OH CR Anen CAFO T Figure 13 setup screen You use Parameters to define your screening policy and the way risks are reported See section 3 1 and Appendix C Acceptable settings for parameters The equations for expected medians weight adjustment and ultrasound gestational ages are defined in Coefficients See Section 3 2 1 and Appendix D Equations used in calculations About provides contact details for Logical Medical Systems and information concerning accreditations Address codes doctor codes and sonographer codes provides a way of allocating codes to addresses doctors and sonographers to facilitate data entry See sections 3 3 3 6 and 3 18 Analyser import allows you to set up ho
241. ning reports are normally processed in a batch containing many patients In this case the packeted export file will contain the results of all the patients with each new patient starting with the 005 packet Example of report in Packet Format The following shows the report in Figure 5 in Packet Export Format 5090 00 01 OL Dr Albert Brown MD 5095 00 04 04 The Surgery 24 Park Lane LONDON NE3 ZA9 005 01 01 02 DOWN S SYNDROME NEURAL TUBE DEFECT AND PRE ECLAMPSIA SCREENING Report dated 08 Jan 14 030 01 01 02 Last name JONES 035 01 01 02 2 Forename s Jenny 2050 01L 01 02 Hospital Number 1342ZYD 055 01 01 02 Date of birth 02 03 82 060 01 01 02 LMP 10 09 13 067 01 01 02 EDD 20 06 14 070 01 01 02 Date of sample 07 12 13 071 01 01 02 Date of 2nd sample 07 01 14 085 01 01 02 Sample number 1 524137 100 01 01 02 Sample number 2 52601 120 01 01 02 Previous NTD None 125 01 01 02 Previous Down s None 2127 01 01 02 Prev Pre eclampsia No 5 L300 01 01 02 Insulin dependent diabetes None 131 01 01 02 Smoker No 135 01 01 02 Maternal age at EDD 32 years 150 01 01 02 Scan measurement CRL 55 4 mm on 07 12 137 161 01 02 03 Gestation at date of lst sample 12 weeks 4 days by dates 12 weeks 1 days by CRL scan 162 01 02 03 Gestation at date of 2
242. nt if this is not the same as the date of crown rump length CRL measurement If CRL was not measured the date of NT must be specified If CRL was measured and the date of NT is left blank it is assumed to be the same as the date of CRL measurement alph d version 8 Page 92 A lookup button H appears next to the Doctor Report Address and Sonographer fields Click the lookup button to access the list of doctors addresses or sonographers See Sections 3 3 3 6 and 3 18 for more information on working with the doctor address and sonographer lists 4 2 Reporting The production of reports in alpha is a two step process Firstly you create test reports When you create test reports alpha checks each record for invalid data and ensures that each record contains sufficient data to create a report alpha also looks for previous reports that may relate to the same pregnancy or an earlier pregnancy in the same woman and gives you the option to match such records together Test reports give you an opportunity to review the results and to correct any data entry errors or suspect data before issuing the final report When you are satisfied with the test reports you create the final reports which can either be printed or exported When you create the final reports the batch of records is automatically merged into the database Once the final reports are created any further changes to each report may only be made using the Edit
243. nt adjusted MoMs is set to Adjust the MoM values on the report will be adjusted in twin pregnancies IVF pregnancies for women who smoke and for diabetic women See Section 4 2 4 3 1 11 Recurrent false positives Women who have had a false positive screening result in one pregnancy are much more likely to have a one in a subsequent pregnancy than women in general TT alpha can help to avoid this by adjusting serum marker levels in women who have been screened in a previous pregnancy and who have not had a previous pregnancy with Down s syndrome You use the recurrent false positives parameter setting to control how alpha identifies such women Selecting Do not adjust specifies that screening in a previous pregnancy is not taken into account in the interpretation Selecting Strict matching specifies that women screened in a previous pregnancy are identified on the basis of a matching surname ID code and date of birth Strict matching will go a long way to avoid false matches but may mean that such women are not identified in situations where the surname date of birth or ID code is not always recorded accurately Selecting Loose matching specifies that women screened in a previous pregnancy are identified on the basis of a matching surname and ID code a matching surname and date of birth or a matching date of birth and ID code Loose matching will increase the chances of identifying such women but will also increase the chance of a
244. nteger Date of first Date of sample sample Date Date of last amniocentesis Date Previous amnio performed or attempted in this pregnancy PENE Date sample Time received Time sample Time Vv Version 8 Page 197 Maternal Serum Type of field Comment Field name Entered or derived Bn O E Bn O Us lt Ee gt O a LL import and export j T Ou N c lt x Been Ur OU Le Ben Fe vis el received Laboratory number Lab number sample reference Text 15 v number Entered Entered Entered el ke L 100 D x lt mp CH i 100 T eleje ag 1 Down s syndrome and NTD 2 NTD only Specifies the type of interpretation v required Not used Amniotic sacs amniotic sacs ina Text 1 twin pregnancy chorionic sacs ina Integer 3 Down s syndrome only 4 Down s syndrome NTD and pre eclampsia 5 Down s syndrome and pre eclampsia Vv Entered Vv Version 8 Page 198 Maternal Serum Comment t and export CH Ou 2 Ben Ou xe Ben O CH Ben Ou _ Cc LLI Type of l Bn O E Bn O Us lt Ee gt O a LL j T Ou N c lt x Been Ur OU Le Ben Fe vis el impor wegen ER E MS AFP level Text eg Text 7 Date of second Date
245. o the measured data but to suppress this behaviour for example to facilitate comparisons between different sonographers select Fixed Axis Range on The graph can be printed by pressing the button The Analyse Codes button prepares a report showing the number of measurements median MoM standard deviation and increase per week for all sonographers or address code for the time period selected The Audit Code button prepares a report for the selected sonographer or address code showing the number of measurements median MoM standard deviation and increase per week for the two preceeding years alph d Version 8 2 Iu Statistics Q AR The number of measurements Q alpha 8 0 median MoM standard deviation and increase per week is displayed Nuchal Translucency Monitor REPORT DATE RANGE Count O All periods PAT 713 C ion for Overall o SE Medion MoM SE 1 14 CODES Standard Deviation CH Sonographers 0 085 Report Addresses Code Description Increase per week OTH Other 16 61 Lo in Analyse Codes AUDIT CODE am jt Median Nuchal mm PLOT OPTIONS This shows the NT CRL plot for the Y Axis selected sonographer or address code Logarithmic The measured values are shown as green EE circles and the red line shows the fitted Off regression equation The orange line shows the current regression for this songrapher Refresh results 40 50 60 70 Crown Rump Length CRL mm Figu
246. of pens anneal C correction of a non updated report modification of Text 1 Derived S scan update ire or correction s correction of scan update any other change Report has been Correct update flag 2 corrected or Text 1 v v Derived Copy of Correct update flag 1 in the later test updated Report has been corrected updated iene P S Derived Record number of corrected report or repeat test or is the initial test H preceded by M if report is MS AF or A if AF AFP of a repeat test Type of corrected Sp Pointer forward type ee Integer v v Derived 1 AF p 2 NTD only Report is a l Record number of previous report preceded by M if report Pointer back correction update Integer v v Derived is MS AF or A if AF AFP or a repeat test Type of previous a Pointer back type report Integer v v Derived 1 AF Delete flag If set ecord Is ne Text 1 v v Derived D record deleted included in statistical Version 8 Page 224 H TE K E o gt 5 S S X 2 Comment g 5 gt s 5 2 D x 2 m E c iL E LLI Data transfer T Ou N ur c lt Correct update flag 1 Pointer forward Delete status flag Field name Update flag Version flag AF AFP MoM Scan gestation days Dates gestation days Clinical gestation days Positivity User Comment Time entered Doctor 2 Version 8 AF AFP Positivity flag Username of user who started data entry and u
247. of 2nd sample 01 08 13 JI Smoker 0 No v Diabetes 62 None a MS AFP ng mL 30 IS IVF pregnancy 0 No vl uE3 ng mL 2 LI EE Donor date of birth T hCG 2T miu mL 12000 tt Date embryo transfer Inh A pg mL 210 Date egg collection S NT mm Se S __ actor 00000001 Dr Albert Brown Q PAPP A mg L 1100 J fs Report address 00000002 Charterhouse Su Q Se BS ng m GA by scan RS Nasal bone fetus 1 On Nasal bone fetus 2 D Number fetuses Scan measure 12 1 164 16 5 12 01 14 Figure 54 Data entry screen Table 8 Meaning of items in the data entry screen hem Purpose S O This closes the batch If you have not opened an existing batch file alpha prompts you for a name for the new file The default name is based on the current date See section 2 7 Type a new name if you wish to change the name of the file If the batch file contains more than one record you can click Search to search through the file for the record you want For example to search for a record with surname SMITH place the cursor on the Surname field and then click Search alpha prompts you for the surname to search for Click Search again to start the search and find the first record with surname SMITH If the file contains more than one record with surname SMITH you can find the next one by clicking Search again You can use the same method to search on any field alpha uses a circular search
248. of 2nd sample sample for Date integrated test Integrated if NT levels are formatted according to Note 11 s For import export and analyze it the first character is lt if v AG Entered the measurement is less than the number following the lt pv A6 Entered For data transfer the lt is removed and the corresponding level flag should be used to check if the level is less than the value given jae fea O No P P v IH Entered 1 Standard integrated Combining the results of the first and second trimester markers 2 Sequential testing Only women who have a negative Version 8 Page 199 a N v v Vv Integrated screening Integer screening _ N gg Maternal Serum Field name Sonographer IVF pregnancy Weight units Date 2nd sample recd Time 2nd sample recd Smokers Donor date of birth Version 8 Date second sample received for integrated test Time second sample received for integrated test Smoker donor s date of birth in an IVF pregnancy in which the egg is donated Analyze it EE CH k D O Gu HI ap TTT Fixed width format for import and export on or derived OAR 8 Entered Tu ren Jk a Comment first trimester test proceed to the full Integrated test Code up to 8 letters or numbers identifying the sonographer who made the nuchal translucency NT measurement For impo
249. on inherited or 10 if inherited is added to the age specific risk at term In addition the result is classified as screen positive regardless of the levels of the screening markers MoM values from any previous pregnancy will not be taken into account see Section 3 1 11 for further information Not available if Previous Down s is none If known the age at which a previous pregnancy was affected with Down s syndrome is used to calculate the Down s syndrome recurrence risk above the maternal age related risk If left blank the adjustment described in Previous Down s is made 0 none 1 one 2 two or more Number of previous pregnancies if any affected with open NTD If a previous affected pregnancy is recorded the result is classified as screen positive regardless of the AFP level In the case of a single previous pregnancy affected with NTD Alpha will multiply the NTD prevalence by ten if the total NTD prevalence is 0 005 or more and by 15 if less than 0 005 For two or more previous pregnancies affected with NTD the resulting prevalences are doubled 0 none 1 insulin dependent diabetes mellitus In women with insulin dependent diabetes mellitus MoM values of serum markers may adjusted before being used in the interpretation If left blank patient is assumed to not be diabetic See Section Appendix P Factors used for adjusting MoM values for more information 1 black 2 non black 3 not known 4
250. or be shut down incorrectly while alpha is in use data entered but not saved should be regarded as suspect and re entered alpha should only be used by operators who have received training in its use IMPORTANT Regular backup of alpha data is essential Backups should be made weekly as a minimum and preferably after each day s use of alpha The use of regularly updated anti virus software is recommended Failure to follow these recommendations could lead to the irretrievable loss of data for which Logical Medical Systems accepts no responsibility alph d Version 8 1 PVE CTS WN EE 12 Tet ADOUVGIDNG versio E Ded rensittabereheikensiaiediensDeieceinbeedsceivalhnedisinddenneia 12 1 2 Getting Stared a crass ga tesserae ant eseine vance cece tend ncaneneno se a ia aaria ee iere aai 12 1 3 Data entry and reportng 13 1 4 Test interpretation and risk estimation cccccecccccseeeeeeseeeeeeeeeeeeeeeaeeeeseaseeesaaueeessaeeeeesaeeeenaaes 13 1 5 Monitoring screening performance ss sssssssseserrresrrrrsrrrrrrnrrrsrrrrorrrresrrrrnsnrrentrrrnnnreesrrrennnrrene 14 1 6 Choice of screening markerg 14 Tied TE Ee Ce E E Piesaueteriamereovuncesanieineguais 15 1 8 The Integrated TSU sce necaesse soc ceseeneencaeiedcceseenacetchenescnesenwseneaeadeceseennaatsecescesenase sesame adeavouoreceteeesaccoss 15 2 General eene 17 2 1 Terms used IN this manual 17 GC UE Le EE 17 2 2 1 Installing the software 17 2 2 2 Installing the alpha
251. orrection factor you specify for the corresponding ultrasound machine see Appendix C Acceptable settings for parameters and Section 3 1 5 BPD correction factors The BPD correction factor allows for differences in the estimated gestational age arising from different methods of BPD measurement outer to inner or outer to outer edge of the cranium and the sound velocity assumed 1540 or 1600 m s 3 2 2 Overview of Coefficients Screen You access the Coefficient screen Figure 18 from the Set up screen Section 3 Like the parameter settings coefficients are grouped in a branching tree structure Figure 19 Clicking on the sub branches will lead at the end of each branch to the individual equations with their coefficient settings Figure 20 The example shows the coefficients A and B of the equation that alpha uses in estimating the expected median level of MS AFP given a woman s gestational age GA The table at the bottom of the screen shows the different values assigned to the coefficients over different time periods You can use the Coefficient Settings screen to E Change the values of the coefficients of any equation E For uE3 and inhibin change the type of median equation See Appendix D Equations used in calculations Record details of the change who changed the coefficients and the reason for the change m View current and historical values for the coefficients of an equation E Print current and historical value
252. orrelation coefficients between logio MoM values of NT and the biochemical markers in unaffected pregnancies 3 13 3 Adding new markers Appendix J Statistical parameters Down s syndrome gives a list of all the markers which can be used with alpha A maximum of twelve of these markers can be installed for use with alpha If you wish to install a marker not currently used in your alpha installation select the marker in the ADD MARKERS section and press the ADD MARKER You will need to enter an unlock code provided by your alpha distributor to complete the installation Once the marker has been added it cannot be removed from alpha Once the marker has been added you will need to E Add the marker to the data entry screen See Section 3 17 Screen design m Decide the median equation policy to use See Section 3 1 8 Median equation policies E Specify normal median equations and weight regression equations See Section 3 13 3 1 below E Specify the units of measurement See Section 3 1 13 Units SG Update the import and export formats if required See Section 3 10 Import settings and Section 3 9 Export settings The above process would also be followed if you were to start using a marker which was already installed in alpha but not previously used pha versions 3 13 3 1 Normal median equations Serum markers For new serum markers you will need to provide the coefficients for the equations which are used to calc
253. otnote for screen negative reports is A negative screening result does not exclude the possibility of Down s syndrome or a neural tube defect because screening does not detect all affected pregnancies These footnotes will help to ensure that those reading the screening reports do not confuse positive with affected or negative with unaffected The footnotes are altered accordingly if the screening result is for Down s syndrome only or for open neural tube defects only or for Down s syndrome and pre eclampsia see section 2 9 3 1 8 Median equation policies For serum markers you can specify that alpha use either a single median equation regardless of the method of estimating gestational age or separate median equations for gestational age estimated by ultrasound scan and for gestational age estimated by dates LMP or otherwise In situations where most pregnancies are dated by one method or the other a single equation could be used Where both methods are used in a significant proportion of women separate median equations are preferred This is because there may be systematic differences in gestational ages estimated by the two methods which could lead to differences in the expected median levels at a given gestational age pha versions This policy can be specified for each marker and each ethnic group in the screened population 3 1 9 Median reduction factors AF AFP The relationship
254. ou select more than one report from the search all the reports selected will be shown in the preview screen when the print button is pressed If a batch is selected and the print button pressed a summary of the data in the batch is shown in the preview screen Also following a search Section 4 3 a summary of the records found in batches can be shown in the preview screen by pressing the print button The records identified using the Integrated test options Section 3 11 can also shown in the preview screen by pressing the print button For the summary of data in the batch and the Integrated test list the columns shown the column used for sorting and the column used for grouping records can be selected See Section 3 20 6 4 9 Medians As well as tabulating median values for reported results See Section 5 2 you can also examine tabulations of the medians in a batch of unreported results using the Medians len in the Patients screen In large screening programmes with sufficiently large batch sizes this can be helpful in identifying assay problems and in correcting any problems identified before a batch of screening results is reported If the overall median MoM for a batch of results is significantly high or low outside the 95 confidence interval around 1 0 MoM this may indicate an assay error The appropriate corrective action in such cases might be to identify the cause of the error and having corrected it re assay the batch of
255. p screen See section 3 2 Update medians Not Specified _ Caucasian Select the _ Afro Caribbean checkbox alongside each of the South Asian coefficients you _ Oriental wish to update WW Other Update Close Figure 104 Update medians Sonographer specific medians can be updated from a regression made from a tabulation according to crown rump length CRL for nuchal translucency When the Update Medians button is pressed a window similar to that in Figure 105 is shown Open the Sonographer Specific section and select the checkbox alongside the sonographer whose medians you wish to update Press the Update button to update the selected coefficients The new coefficients will be used from date and time on which they are updated Update medians Not Specified Sonographer specific OTH Other PAJ PAL PAN PAT PEB PEL PER O O DO S O UO UO U Figure 105 Update sonographer specific medians 5 10 Report summary The Report summary option helps you to monitor the number of screening and diagnostic tests processed in a specified time period It provides a breakdown of the number of reports according to the screening or diagnostic result Selected tests first trimester second trimester integrated sequential or all tests and women of selected ethnic groups can be included in the report You can select the date range for the report and screening reports
256. peat test Page 190 MS AFP lt x MoM specify x First test with scan First test without scan Repeat test MS AFP gt x MoM and lt y MoM specify First test with scan x and vi First test without scan Repeat test AMNIOTIC FLUID Single category messages Message addition system title Header message Footer message Negative Positive raised AFP AChE not done Positive raised AFP AChE band present Ambiguous AFP raised AChE band absent Ambiguous AFP not raised AChE band present 1 These messages can be either off always on or only on if other messages appear 2 These messages are for singleton pregnancies only Appendix F Controlling access using security levels Security level 1 alph d Version 8 Can access All data entry facilities What if All level 1 facilities All reporting facilities except Correct Update reports All statistics facilities Doctor and address codes All level 1 and 2 facilities Correct Update reports All level 1 2 and 3 facilities Access to all system menu options except i add coefficients ii add parameters iii database check iv modify user list All level 1 2 3 and 4 facilities Add coefficients Add parameters All level 1 2 3 4 and 5 facilities Database check Modify user list Page 192 Appendix G Import Export Data transfer and Analyze it formats Maternal Serum H T Ou N Cc st Been a Les Ben Fe
257. pendent diabetes mellitus the prevalence of both anencephaly and spina bifida is taken as 5 per 1000 Appendix L Statistical parameters Trisomy 18 Means standard deviations and correlation coefficients log MoM for unaffected and trisomy 18 pregnancies and truncation limits MoM for serum markers and nuchal translucency NT Marker Unaffected pregnancies Trisomy 18 pregnancies MEAN 2 trimester AFP 0 1871 UE 0 3665 hCG 0 4437 free B hCG 0 4252 1 trimester hCG 0 4290 free B hCG 0 6293 PAPP A 0 5541 NT 0 2977 STANDARD DEVIATION 2 trimester AFP 0 1688 0 1980 UE 0 1391 0 2938 hCG 18 0 2401 0 3772 free B hCG 0 2508 0 4302 die D 0 2127 0 3259 E e deeg Se 0 2978 0 3142 C 0 3127 0 2309 g 0 1325 0 2943 CORRELATION COEFFICIENTS 2 trimester AFP uE3 0 2459 0 2466 AFP hCG 0 0859 0 0612 AFP free B CG 0 0843 0 1644 uE hCG 0 2122 0 0944 uEs free B hcG 0 1770 0 1770 17 trimester free B hCG PAPP A 0 004 0 420 0 0570 0 4164 NT free B hCG NT PAPP A hCG PAPP A 0 0000 0 0927 0 0050 0 4490 SEN s All pregnancies TRUNCATION LIMITS 2 trimester AFP 0 33 2 0 uE 0 4 1 5 CG 0 2 2 5 free B hCG ee 1 trimester hCG ee hd 0 2 1 0 free B hCG 0 2 0 7 PAPP A 08 22 NT l t First trimester markers measured between 10 and 13 weeks of pregnancy second trimester between 14 and 22 weeks R Unaffected means for a
258. pened within patients If you allow the mouse to hover over the icon it will show a thumbnail of the screens which are open Clicking on a thumbnail will open that screen Figure 8 The screen can also be closed by clicking the red cross on the thumbnail You can close the screen by clicking on L Patients Ib the red cross Data entry Apr 30 1 positive 1 patients Ready for final reporting Select the thumbnail to navigate to the desired screen Figure 8 Thumbnails show which screens are open and allow you to navigate and close them quickly Screens are usually closed by pressing the button at the top left hand corner of the screen Pressing this will return you to the previous screen Navigating within each of the screens is generally by selecting the option required from the list shown by clicking on the button or item required 2 6 2 Entering dates in alpha Dates are entered in the same way throughout alpha Figure 9 The date separators are automatically provided and only the numbers of the date need to be entered The day month and year are all entered as two digits so for example the 2 of the month is entered using the digits 02 The date is entered in the format specified by your local computer setting Also the date separator displayed is the one specified by your local computer setting When the date format is day month year a date such as 2 January 1981 would be entered by typing 020
259. plot No pregnances found with Closed Spina Bifida t b No pregnancies found with Spina Bifida open or closed or with other malformations or Anencephaly ables Abnormality Uptake of prenatal diagnosis PND Type of diagnostic procedure Uptake of different prenatal diagnostic procedures among women with positive negative and uninterpretable screening results Positive SO risk of Downs 20 egative sd CVS Chorionic villus sampling FBS Fetal blood sampling Amnio distribution with Risk Table and plot of amniocentesis distribution with risk Invasive testing rate 1 in 10 1in 100 1 in 10 1in 104 1 in 10 Risk Page 1 Figure 96 Outcome full screening audit Studies have shown that the risk of Down s syndrome predicted by alpha is in close agreement with the observed prevalence of Down s syndrome in the absence of screening alpha outcome allows alpha users to perform this analysis themselves provided a sufficiently large number of women have been screened To access Risk Analysis section click Risk Analysis on the icon in the side bar On selection of a screening test alpha outcome displays a summary showing the number of Down s syndrome pregnancies in each of several predicted risk categories Figure 97 alph d Version 8 Predicted risk category Median No of Down s sin fq d 1in5 hun d lind41 fiso 2 1in191 550 3 Less than 1 in 550 3 All 16 Figu
260. policy over time alph d version 8 3 1 3 Adjustment for ethnic group Serum marker levels may differ on average between women of different ethnic groups If the screened population is ethnically mixed alpha can allow for such differences in the marker levels as well as for differences in weight between women of different ethnic groups Doing so will help to ensure that the false positive rate is similar in each group screened See section 5 13 6 for further information on adjusting for differences between ethnic groups For each serum marker you can choose the direct method or the adjustment method to allow for differences in the concentration of the marker between different ethnic groups lf the direct method is chosen alpha will expect to find a separate ethnic group specific normal median equation and weight correction equation for the selected ethnic group If ethnic group specific normal median equations are used it is important to derive weight correction equations from the same population because median weights can differ between ethnic groups lf the adjustment method is chosen you will need to specify a reference population whose normal median equation and weight correction equation will be used to calculate MoM values in women of the selected ethnic group You will also need to specify adjustment factors to allow for differences in the marker levels and in maternal weight between the selected ethnic group and the reference
261. ported Age at EDD de Age at EDD calcul Scan GA at 1st sample Scan GA at 2nd sample MS AFP MoM 2 Ke 6 K 8 9 10 EI 12 13 14 E 16 azi 18 19 EM Z i E E E E 28 29 30 31 32 33 EI 35 36 37 38 WM AEN 05 01 2004 05 01 2004 06 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 07 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 08 01 2004 09 01 2004 09 01 2004 09 01 2004 09 01 2004 09 01 2004 09 01 2004 39 40000153 28 89999962 41 70000076 37 90000153 39 59999847 29 60000038 40 33 5 33 90000153 33 59999847 29 79999924 29 70000076 39 59999847 18 10000038 23 60000038 37 29999924 39 70000076 23 20000076 38 40000153 32 34 09999847 35 79999924 30 70000076 34 29999924 29 28 60000038 32 59999847 37 20000076 27 89999962 37 33 20000076 39 90000153 32 29999924 40 20000076 34 20000076 38 09999847 2013 08 12 1 39 28 41 37 39 29 40 33 33 33 29 29 39 18 23 37 39 23 38 32 34 91 86 87 82 77 89 86 87 75 118 120 118 115 120 121 107 101 123 116 117 112 120 120 118 115 aay 133 104 125 115 143 120 103 122 116 106 127 111 107 136 1 179999948 0 959999979 1 070000052 1 3
262. quation relating MoM values in the current pregnancy to a previous pregnancy This adjustment can reduce the false positive rate by adjusting the MoM values in the current pregnancy for values in a previous pregnancy pha versions 3 13 2 3 Statistics 3 13 2 3 1 Means This specifies the mean logo MoM value usually estimated from the median for the marker in affected and unaffected pregnancies For unaffected pregnancies the expected mean logio MoM value is 0 0 by definition For first trimester markers this specifies the estimated biochemical marker median and NT median in affected pregnancies with gestational age 3 13 2 3 2 Standard deviations This specifies the standard deviations of logo MoM values of the marker in affected and unaffected pregnancies Standard deviations are specified separately for gestational age estimated from dates and ultrasound scan each with and without adjustment for maternal weight For NT the standard deviation in unaffected pregnancies at specific gestations is specified 3 13 2 4 Correlation coefficients This specifies the coefficients of correlation between logio MoM values of the marker and other markers in a single maternal serum sample for affected and unaffected pregnancies Correlation coefficients are specified separately for gestational age estimated from dates and ultrasound scan each with and without adjustment for maternal weight This also specifies at specific gestations the c
263. r each maternal serum and ultrasound marker Figure 70 When the median MoM value is outside the 95 confidence interval for the marker it will be indicated as an issue an item which requires your attention When the median weight is 5kg different or 10 pounds different if the weight units chosen are pounds from the weight for which the MoM weight adjustment factor is 1 0 see section 3 2 1 2 it will also be indicated as an issue Separate issues will be shown when appropriate for each ethnic group for whom a direct median equation has been specified see section 3 1 3 If more than one issue is indicated for a marker then the issues are shown by hovering over the tile MS AFP uE3 T hCG FB hCG Inh A Roll over for more information The Median MoM for Oriental The Median MoM for White on these issues women of 0 83 is outside the ik 0 0 women of 1 09 is outside the expected range 0 85 1 17 expected range 0 95 1 05 Issues Issues Issues Figure 70 Automonitor Markers 5 1 2 Report summary The Report summary section Figure 71 gives the number and percentage of reports which are screen positive screen negative and uninterpretable for Down s syndrome screening for all the tests carried out alpha Interpretations for all tests Positive Negative Uninterpretable Total Figure 71 Automonitor Report Summary 5 1 3 Test specific summary The Test specific summary section Figure 72 allows you to sel
264. r or the section 4 8 Unreported patients can be moved to an existing batch a new batch or deleted from the Patients screen To do this select the record by clicking on it and then dragging and dropping it on to the batch name the button or the button respectively A consecutive group of patients can be selected by clicking on the first record holding the shift key down on the keyboard clicking on the last record and then dragging them to the desired location without releasing the shift key A non consecutive group of patients can be selected by clicking on the first record holding the ctrl key down on the keyboard clicking on the other desired records and then dragging them to the desired location without releasing the ctrl key The columns shown on the Patient screen can be selected by right clicking on the title row and selecting the desired columns A different set of columns can be chosen for the Integrated test list Section 3 11 by pressing one of the Integrated test list buttons to shown an Integrated test list right clicking on the title row and selecting the desired columns 4 1 Data entry You use data entry to manually enter information from new screening requisition forms and to edit records in an existing batch which has not been fully reported When entering new screening requisition form information you can either enter them into a new batch or add them to an existing batch To start data entry in a new batch file
265. r the data manually with Data entry You can import all or part of the information for each record The information you import is defined using the Import settings option Section 3 10 To import data press the Import on the Patients screen if necessary selecting MS Import or AF Import from the drop down In the import screen select the file to import and press the Next button A screen similar to that shown in Figure 66 will be shown When alpha imports data it checks each item of data for errors Errors are classified either as severe errors or warnings and alpha will display the number of each type of error found For example a sample date in the future or an invalid date such as 31 September would be classified as a severe error An implausible entry such as a weight of 220 kg or an LMP date less than 8 weeks in the past would be classified as a warning alpha will also check if the imported data matches any records which have not yet been reported This prevents any records being unnecessarily reported more than once alpha shows the number of records which have been read in the import file and indicates the number of warnings errors and matches Details of the warnings and errors can be found by double clicking on the record The details of any match found are shown with the record A check box is used to indicate if the record is to be stored in the batch By default all records except those with errors and matches are set to
266. r the results are written to an Excel spreadsheet a comma or tab separated text file or into an XML format The results filename is specified in the Output File Path text entry box To test the query press the Test Query button This will show the number of rows of data it will return To run the query and write the data to the type of file and filename specified press the Run Query button See Section 5 2 5 3 IE EEN OB O alpha 8 0 Analyse tt ee Use these buttons New MS query New AF query Delete query y to test run and Name Test query Run query Save query Type save the query Median GA of IT women at second stage Maternal Options Output Criteria Ordering Marker values less than the specified value entered using lt Select the operation required from Exclude E th i L Select a saved query from the ese four tabs list shown here OUTPUT FORMAT Excel spreadsheet xlsx e are rm Comma separated Boe y the type of output format S required Tab separated XML emt OUTPUT FILE PATH Browse Enter the name of the output file Figure 76 Analyse it Options 5 2 2 Output The Output tab specifies the database fields to include in the output See Figure 77 The left hand column shows the database fields which can be selected and the right hand column the fields in the selected query Click and drag the fields between the two columns to add and remove them from the query alph d Ve
267. racters in length for each marker The long name appears in alpha reports The short name is used in menus on the data entry screen and in statistical summaries The identity of a marker does not change when you rename it For example alpha will always interpret MS AFP as the level of aloha fetoprotein in maternal serum regardless of any alternative name you give to the marker alph d Version 8 3 13 2 Reviewing marker details This allows you to review the statistical parameters adjustments factors and other details associated with each marker To use this select the information tab next to the marker 3 13 2 1 General 3 13 2 1 1 Marker Type Specifies whether the screening marker is E aserum marker E an ultrasound marker 3 13 2 1 2 Trimester Specifies whether the screening marker is used in m the first trimester of pregnancy between 10 and 13 weeks E the second trimester of pregnancy between 14 and 22 weeks 3 13 2 1 3 Predictor for medians Specifies the predictor variable i e the x axis variable or independent variable which is used to derive normal median values of the screening marker The following predictor variables are used E gestational age E crown rump length E none 3 13 2 1 4 Expected change with gestational age Specifies the direction in which the normal median level of the marker changes with advancing gestation 3 13 2 1 5 Expected change with maternal weight Specifies the direction
268. range the risk is estimated for the corresponding limit Adjustment for recurrent false positive screening results The expected MoM in current pregnancy Previous Pregnancy MoM p Values of the exponent b are given in the following table First trimester b PAPP A 0 42 Free B hCG 0 49 Second trimester b AFP 0 41 UES 0 26 Total hCG 0 42 Free B hCG 0 42 Inhibin A 0 40 Correlation coefficients for the screening markers in unaffected pregnancies gestational age based on dates without adjustment for maternal weight Total hCG First trimester Free B hCG 0 7023 PAPP A 0 2067 PIGF DVPI 0 0000 Second trimester AFP 0 1085 Total hCG 0 7050 Free B hCG 0 6968 Inhibin A 0 3295 Version 8 49 Unless stated otherwise First Trimester Free B hCG 0 1315 EIN 0 0285 0 0571 0 0479 0 5667 0 7494 0 3094 PAPP A 0 28607 0 0269 0 2461 0 2820 0 0816 0 0692 0 0652 PIGF 0 1477 7 0 0547 0 08547 0 1509 Second trimester AFP 0 2595 0 1781 0 1168 0 2293 UE Total Free B 3 hCG hCG 0 0825 0 0904 0 8607 0 0876 0 4412 0 4122 Page 247 Correlation coefficients for the screening markers in unaffected pregnancies gestational age based on dates with adjustment for maternal weight Total hCG First trimester Free B hCG 0 6953 PAPP A 0 1490 PIGF DVPI 0 0000 Second trimester AFP 0 0481 UE 0 0162 Total hCG 0 7010 Free B hCG 0 6967
269. rch all date fields for a matching date Records found in the alpha database are shown under the Search Results heading Reports and records which have not yet been reported are shown under the heading In Batches Double clicking on the patient s name will show the screening report for a report in the alpha database or show the data entry screen for unreported patients Press x to clear the search results 2 Patients T Q S Enter the search term here OP alpha 8 0 o 0o f j i i FY Search results i Actions BS Forename s Last name Date of birth Date reported Comment Delete p Jenny JONES 02 05 1981 21 05 2013 1 result s found Print ft ee The details of the patients found are shown here ek 1 result s found Q a Reported patients matching the search criteria are shown under Reports and unreported patients shown under In Batches Select the desired action on the record selected Figure 62 Search alpha 4 3 2 Advanced search Press to show the advanced search screen Figure 63 The advanced search screen allows you to specify search terms for any of the fields in the database You can use wildcards for any field allowing text entry The wildcard matches any number of characters including none For example if you type BROWN into the last name field alpha will find all records where the last name begins with BROWN for example BROWN BROWNING 2 Patienss DW Advanced Sear
270. re 89 Nuchal Translucency Monitor 5 7 Outcome alpha outcome may be used to enter and store information on the outcome of pregnancies and on any diagnostic procedures carried out among screened women The presence or absence of neural tube defects Down s syndrome and other birth defects can be recorded using the 10 edition of the international classification of diseases ICD codes A range of screening audit facilities provides statistical information useful in monitoring screening performance Each pregnancy screened using the alpha software can have an outcome associated with it containing all data on the outcome of the foetuses This data can then be used to analyse the screening performance using the various sections in alpha Outcome 5 7 1 Outcome Sections The various features of Outcome are accessed from a menu to the left of the screen Figure 90 alph d Version 8 This section is used for searching for patients in the main reported database and listing pregnancies already containing outcome data and with abnormalities Many of the functions of alpha Outcome creating editing and searching for Outcome records are accessed though the search section Gy Alpha Outcome pn am a Transfer data entered in outcome combined with data entered in alpha except data transfer fas Enter search Figure 90 Outcome sections alpha outcomes can be entered for both Maternal Serum MS and Amniotic Fluid AF sc
271. re 97 Outcome risk categories You can change the predicted risk categories if you wish by editing the upper limit of each risk category The number of Downs s cases will be adjusted automatically Each category should preferably contain 10 or more pregnancies with Down s syndrome with approximately equal numbers in each category Risk analysis cannot be performed if the outcome database contains too few cases less than 10 You can insert and delete categories by clicking on the corresponding buttons on the toolbar Refresh will revert any changes you have made to the risk categories When you have specified the predicted risk categories click Plot on the toolbar alpha outcome will then complete the table and plot the results in a validation plot The validation plot Figure 98 includes a line of identity a straight diagonal line representing perfect risk estimation overlaid with the median predicted risk plotted against the observed prevalence This plot can be used to evaluate the performance of screening programmes and the accuracy of risk estimation67 The screening performance can be assessed by looking at the range of risk covered by the points in the validation plot A better screening performance is shown by m The greater the range of risk estimation the more discriminatory the test m The closer all the points are to the line of identity E Forn risk categories a greater risk range between the n 1 th and the nth points
272. re available Database The alpha database is stored in Microsoft SQL Server SQL Server 2005 SQL Server 2008 or SQL Server 2012 In a single user configuration Microsoft SQL Server must be installed on the users PC or on a server accessible to the PC In a multi user configuration SQL Server must be installed on a server accessible to the client PC Hardware You should ensure that your computers have the minimum hardware specification recommend by Microsoft for the operating system and or version of SQL Server you are using alpha should run satisfactorily on a computer with this minimum specification A USB port and CD ROM drive are required Single user configuration In a single user standalone configuration all alpha program files reside in a single folder on your computer s hard disk usually C Program Files Logical Medical Systems Ltd Alpha alpha files must not be placed in the root C folder alpha database files normally reside in the default folder specified by SQL Server You can also store your alpha files on another drive or on a network server if you prefer Multi user Configuration alpha can be used in a multi user network configuration on most computer networks eg Novell Netware Windows networks To use alpha in a multi user configuration all the alpha files must be placed in a shared folder on a file server You should consult your network administrator and your alpha distributor b
273. re replaced by the name of the corresponding marker used in alpha 3 Date and time formats The date format is as specified in the import export or data transfer format specification dd mm yy mm dd yy or yy mm dd Time format is hh mm ss For importing data if the file format is comma separated or tab separated the date should be provided with separators and leading zeroes For example 9 April 2010 in Day Month Year format would be imported as 09 04 10 If the file format is fixed length the date should be provided in 312 format For example 9 April 2010 in Day Month Year format would be imported as 090410 4 Text x Data is imported and exported as text with the maximum number of characters given by x Imported data greater than x characters length is truncated to x characters 5 Integer amp Long Integer Data is exported as an integer value between 32 768 and 32 767 Data is exported as a long integer between 2 147 483 648 and 2 147 483 647 6 Single Data is exported as a floating point number 3 402823E38 to 1 401298E 45 for negative values 1 401298E 45 to 3 402823E38 for positive values and 0 7 blank values Comma separated and tab separated file formats lf there is no value for a field the corresponding field in the data transfer import or export file is blank A blank field is shown by one field separator immediately following another For example if the fields field1 field2 Geld are expor
274. reening programmes The symbol us in the bottom left of the outcome screen shows the screening programme outcome is currently using Risk analysis is not available in AF outcome analysis 5 7 2 Search When alpha Outcome first starts the first screen to appear is the search screen as shown in Figure 91 fa To return to the Search section click on the Search icon on the side bar Alpha Outcome Sele search database List pregnancies without outcome List pregnancies with abnormalities Fe Search Sumame Procedure Abnormakty Entered in Forename diagnosed last daps ID code m Bec Eir Date of bth Search List All ah Outcome database fields Alpha database fields B Data Transfer Search results Number of search results appears here Print data fis Enter seagh Figure 91 Outcome search The Search section consists of three tabs for searching the alpha database and listing pregnancies with different filters Double clicking on any patient in any of the open tabs will open their outcome details or allow the user to create new outcome details for that pregnancy 5 7 2 1 Search Database Search database enables the user to list all reported patients in the alpha database and enter outcome data or view previously entered data for those patients filtered on the patient details or by some outcome details The Search database is the main section used to select the patient for the cr
275. reening J Med Screen 12 155 160 Morris JK Mutton DE Alberman E 2005 Corrections to maternal age specific live birth prevalence of Down s syndrome J Med Screen 12 202 Wald NJ 2005 Which gestational age estimate to use in AFP screening for spina bifida Prenat Diagn 25 623 Wald NJ Rish S 2005 Prenatal screening for Down syndrome and neural tube defects in twin pregnancies Prenat Diagn 25 740 745 Wald NJ Rodeck C Hackshaw AK Walters J Chitty L Mackinson AM Bestwick JP 2006 Correction to SURUSS report J Med Screen 13 51 52 Wald NJ Barnes IM Birger R Huttly W 2006 Effect on Down syndrome screening performance of adjusting for marker levels in a previous pregnancy Prenat Diagn 26 539 544 Huttly W Rudnicka A Wald NJ 2004 Second trimester prenatal screening markers for Down syndrome in women with insulin dependent diabetes mellitus Prenat Diagn 24 804 807 Morris KJ Mutton DE Alberman E 2005 Recurrences of free Trisomy 21 analysis of the data from the National Down Syndrome Cytogenetic Register Prenat Diagn 25 1120 1128 Watt HC Wald NJ Huttly WJ 1999 Inhibin A regression Prenat Diagn 19 893 894 Altman DG and Chitty LS 1997 New charts for ultrasound dating of pregnancy Ultrasound Obstet Gynecol 10 174 191 Wald NJ Rudnicka AR and Bestwick JP 2006 Sequential and contingent prenatal screening for Down s syndrome Prenat Diagn 26 769 777 Wald NJ Bestwick JP Barnes IM Kellner LH 200
276. reening marker and each ethnic group you can choose either the direct method or the adjustment method to allow for differences between ethnic groups see section 3 1 3 If you choose the direct method for a given marker and a given ethnic group alpha uses median and weight correction equations that are specific to that ethnic group to convert marker levels in women of that ethnic group into MoM values If on the other hand you choose the adjustment method then you need to specify a reference group and two correction factors alpha uses the reference group s median equation and weight correction equation to derive the MoM value in the first instance It then uses the first correction factor to correct the MoM value for differences in marker levels between the specified ethnic group and the reference group Lastly alpha uses the second correction factor to further correct the MoM value for differences in weight between the specified ethnic group and the reference group lt is appropriate to use the direct method for a given ethnic group when the screened population contains a sufficiently large number of women who belong to that group to allow you to derive and maintain ethnic group specific medians and weight correction equations The adjustment method is more suitable for ethnic groups that are represented in smaller numbers in the screened population For example if you screen 5 000 women per year of whom 3 000 are Caucasian 1
277. rename None None Date of birth and ID Code alph a Werona Integrated test list Surname Forename Date of birth ID Code Second sample due date GA Now and Batchname 3 20 7 Nuchal Translucency Monitor The Nuchal Translucency Monitor option is used together with the Analyse Codes feature in Nuchal Translucency Monitor See section 5 6 It allows a range to be specified for median NT MoM standard deviation of logi9 NT MoM and rate of increase of NT per week Sonographers in the list prepared by the Analyse Codes feature who have measurements outside of this range are indicated by the Q symbol 2 bk EI Setup oni User Options General Print order Report export format selection Hide all AF opti _ Hide all AF options Group screening results _ Standard export GA F t Se Additionally order by Date of birth _ Packeted export Save patient data in data entry Print Alpha logo on reports Manual Ce alpha 8 0 Auto complete _ Patient details COMPLETE DATES ON ENTRY E Sample date _ Date received _ Sample date 2 C Date received 2 Il Assay dates XPS filename for reporting Patient Printing Nuchal Translucency Monitor Elementi Surname MATERNAL SERUM AMNIOTIC FLUID INTEGRATED TEST LIST C MEDIAN MOM Use default Use default Use default Element2 Forename s Ss Select fields Select fields Select fields to Element3 Hospital No M Use default
278. rimester screening for Down s syndrome GA lt 10 weeks 0 days or gt 13 weeks 6 days UN in integrated screening for Down s syndrome GA at first sample lt 10 weeks 0 days or gt 13 weeks 6 days and GA at second sample lt 14 weeks 0 days or gt 22 weeks 6 days iv in screening for open NTD GA lt 15 weeks 0 days or gt 22 weeks 6 days v triplets or more fetuses vi an amniocentesis has been attempted during pregnancy prior to the sample date Uninterpretable Diagnostic Result One of i GA lt 13 weeks 0 days li GA gt 24 weeks 6 days 1 Or the MS 2 trimester interpretation range selected see Appendix C Acceptable settings for parameters Or the AF AFP interpretation range selected see Appendix C Acceptable settings for parameters pha versions Risk Estimates 1 If a BPD is recorded anencephaly can be excluded and the risk of open NTD given is for spina bifida only 2 In second trimester screening if the test is a repeat maternal serum MoM values from both the test being reported and the previous test are used to estimate the risk provided i both results are interpretable and ii the second MoM value is not more than twice or less than half the first MoM value for each marker Ifthe second MoM is not within this range a message is printed on the report 3 If there is a previous Down s syndrome pregnancy with an inherited translocation it is taken to be a non homologous maternal translocat
279. rived from the median equation for the marker and the gestational age Consider the following example Gestational age GA 15 weeks 3 days 108 days AFP level 32 6 iu mL AFP median equation Expected AFP level A x B amp 4 ays where A 2 674144 and B 1 020815 The expected AFP level is 2 674144 x 1 0208151 8 24 7 iu mL The AFP MoM value before adjusting for maternal weight is simply the observed AFP level divided by the expected level that is 32 6 24 7 or 1 32 MoM Repeat this calculation for each sample and summarise the data as described above You can use a spreadsheet or other software to automate this calculation Having summarised the data enter the values from the table into alpha s regression section to obtain the coefficients See Section 5 9 2 If weight adjustment data are not available for the new marker you can enter coefficients that will allow you to collect weight data without adjusting for maternal weight The values to use will depend on whether you specify the log linear model or the linear reciprocal model for adjusting the marker for maternal weight see Section 3 2 3 For the log linear model enter the value 1 0 for both coefficient A and coefficient B For the linear reciprocal model enter the value 1 0 for coefficient A and the value 0 0 for coefficient B Once sufficient data have been collected you can use the Tabulation option in alpha to derive the appropriate weight adjustment coeffici
280. rmation Page 179 IVF pregnancy Donor date of birth Donor age at EDD Date of egg collection Date of embryo transfer MS AFP and uE P Other serum markers and DVPI CG Nuchal translucency Assay date serum markers only alph d version 8 3X2 3x2 3x2 3x2 O No 1 Yes alpha adjusts MoM values of certain serum markers in IVF pregnancies to allow for differences in the levels between IVF and naturally conceived pregnancies If left blank it is assumed to not be an IVF pregnancy See Factors used for adjusting MoM values see Appendix P for more information The donor s date of birth in an IVF pregnancy in which the egg is donated This is used instead of the pregnant woman s date of birth to determine the age specific risk of Down s syndrome The donor s age at the estimated date of delivery in an IVF pregnancy in which the egg is donated and the donor s date of birth is not known This will be used instead of the pregnant woman s age to determine the age related risk of Down s syndrome In an IVF pregnancy using a frozen embryo the date of egg collection oocyte retrieval The mother or donor s age at EDD used for the Down s syndrome risk calculation will be her actual age at EDD less the number of days the embryo was frozen which is taken to be the time between the date of embryo transfer and the date of egg collection In an IVF pregnancy the date of embryo transfer Gestational age is
281. rrect for differences between the majority ethnic group and other groups The adjustment factors may be derived from your own screening data or from the scientific literature The table below provides published adjustment factors that could be used to allow for differences in four second trimester serum markers in black and South Asian women compared with Caucasian women Factors for adjusting for differences in serum marker levels and maternal weight in black and South Asian women compared to Caucasian women Ethnic Group Serum Marker Adjustment for Adjustment for differences in marker differences in levels maternal weight Black women 1 trimester Free B hCG 1 06 PAPP A 1 55 2 trimester AFP 1 10 1 05 uE3 0 96 1 02 Total hCG 1 15 1 03 Free B hCG 1 07 1 05 Inhibin A 0 95 1 03 South Asian women 1 trimester Free B hCG 0 95 0 94 PAPP A 1 14 0 89 2 4 trimester AFP 1 01 0 94 uE3 1 14 0 97 Total hCG 1 12 0 95 Free B hCG 0 99 0 94 Inhibin A 1 11 0 95 Oriental women 1 trimester Free B hCG 1 17 0 91 PAPP A 1 31 0 82 2 trimester AFP 1 10 0 92 uE3 1 16 0 96 Total hCG 1 30 0 91 Free B hCG 1 23 0 89 Inhibin A 1 14 0 94 Appendix R Operating environment Operating System alpha runs under the Windows XP service pack 3 Windows 7 recommended or Windows 8 recommended operating systems Microsoft NET framework 4 is required We recommend you configure your PC to download all the latest updates from Microsoft when these a
282. rsion 8 2 thi Statistics O d alpha 8 0 New MS query New AF query Delete query SONY nA Median GA of IT women at second stage Name Type Test query Run query Save query Median GA of IT women at second stage Maternal Options Output Criteria Ordering Address 1 Date reported l Record number Age at EDD decimal f j fi 1 l Date entered Age at EDD calculated I Repeat flag Scan GA at ist sample Correct update flag 1 Scan GA at 2nd sample Correct update flag 2 vs Ap MoM I Pointer forward uE3 MoM Pointer back _ Fe hcc 2m Mom Delete status flag Inh A MoM Update flag NT MoM Version flag PAPP A MoM Free ahCG MoM i l Down s risk LHS i FB hCG M Mom Down s risk RHS over mom L Dates GA at Ist sami Items in the left hand Items in the right hand column l Clinical GA at Ist sa column are available for have been selected for the Dates GA at 2nd sa selection data transfer specification Clinical GA at 2nd sample Positivity i 1 Down s prior risk Click and drag items between the left and right l NTD prior risk columns to select or deselect them from the ro Wb analyse it output Trisomy 18 prior risk Figure 77 Analyse it Output 5 2 3 Criteria The Criteria tab shows the criteria used to select the records in the results Before any criteria have been added a screen similar to that in Figure 78 will be shown when ta
283. rt UCHLIST TXT 2 the filename for the results REPORT DATE RANGE All periods Specify the date range used to select the reports to determine the age To 01 01 05 F EE S op distribution or if all reports should be used Transfer CODES Include all codes v Specify that reports associated with selected report addresses doctors or sonographers be used to determine the age distribution Figure 84 Data Transfer 5 4 Median Analysis The Median Analysis option provides a graphical and tabular summary of the reported median MoM values for the screening markers and for AF AFP by day week month or quarter during the requested time period Women of selected ethnic groups can be included in the analysis and reports associated with selected report addresses doctors or sonographers be included or excluded from the analysis Smokers may be included or excluded from this analysis alpha Version 8 Page 123 This option is useful for monitoring long term trends and short term fluctuations in the marker levels Restricting the summary to specified sonographers can be useful in monitoring differences in NT measurements made by different sonographers If differences are identified you may wish to consider specifying sonographer specific medians for NT measurement See Section 5 6 When the Median Analysis option is first selected the screen Figure 85 in is shown Once the options have been selected
284. rt and export See note 12 Mandatory import field for the Integrated test O No 1 Yes Years 12 years lt age lt 55 years Page 200 Maternal Serum Comment Fixed width format for import and export Entered or derived Analyze it Type of l of delivery in an IVF Sg the egg is donated and the donor s date of birth is not Known Date embryo transfer pregnancy the date Date of embryo transfer S Nasal bone status The age at which a previous pregnancy was affected with Down s syndrome In an IVF Jee 0 absent I1 Entered 1 present 2 not reported 0 absent I1 Entered 1 present 2 not reported Version 8 Page 201 Age at prev preg Integer v pregnancy using a Date egg collection frozen embryo the date of egg collection Date lt ee ce Sot Maternal Serum Comment O Ska eS 8 Es x c OH O OC a 5 CH SS D x E E Le IL LLI Data transfer Type of 8 SCH eclampsia Eves Ductus venosus blood Ductus venosus E Reverse or absent A Integer v v v wv it Entered 1 Forward flow blood flow 2 Not reported a EE a a Date entered Date patient data Date 312 Derived first entered Date reported Date reported Date report made Date report made made EE Derived Shows if report is a a test or broken match Repeat flag EE EE Text Derived repeat test H means that pointers have changed sinc
285. s the MoM values corresponding to the marker number for NT will be expanded to a separate field for the NT MoM value for each fetus 15 2 Analyze it For twins the MoM values corresponding to the marker number for NT will be expanded to a separate field for the NT MoM value for each fetus 15 3 Export Fixed Length Comma separated Tab separated fom eieiei Singleton and Twin Twin A10 Real number with Ina twin Real number with Ina twin two digits after the pregnancy if two two digits after the pregnancy if two decimal point NT measurements decimal point NT measurements are recorded two followed by a are recorded the MoMs are blank field ie an MoMs are exported each ina additional tab exported as two fixed field of five character real numbers characters for separated by a tab example If NT MoMs are each with two 1 10 0 96 not calculated two digits after the blank fields decimal point separated by a tab are exported In DOS compatible mode the MoMs in a twin pregnancy are exported as two real numbers separated by a TT each with two digits after the decimal point 16 Reason codes for positive and uninterpretable results maternal serum Reasoncode Meaning SSCS A Uninterpretable test done too early IRDS IRDS IRDS IRDS IRDS IRDS IRDS IRDS Codes F through T correspond to positive screening results and show the possible combinations of reasons for a positive result PDS Previous Down s
286. s been final reported 2 2 Installation 2 2 1 Installing the software Your computer should conform to the recommendations in Appendix R Operating environment alpha 8 is supplied on a compact disk CD The files are stored in a special compressed format and should not be copied to your computer If you are a new alpha user your alpha distributor will help you install alpha on your computer and set it up according to your requirements If you are upgrading from an earlier version of alpha your alpha distributor will help you with the upgrade Please do not try to install or upgrade alpha without assistance from your distributor If you need to re install alpha for example because of a computer failure please contact your distributor for help Access to the internet is required when alpha is being installed 2 2 2 Installing the alpha dongle The USB dongle provided by your distributor Figure 1 must be inserted into to a spare USB port on your computer pha versions The dongle prevents the use of unauthorised copies of alpha and maintains a record of the alpha credits assigned their date of expiry and the number of credits used See Section 3 2 5 alpha will not start if the dongle is not attached to your computer It has no effect on the operation of your computer and it can be used in conjunction with dongles supplied by most other software manufacturers If you plan to install alpha on a server you need to in
287. s for all coefficients E Evaluate the expected values yielded by an equation given its current coefficient values prints a table showing the expected marker level for a given GA the expected MoM value for a given weight or the expected GA for a given CRL BPD HC or AC measurement E Specify sonographer specific medians for ultrasound markers such as nuchal translucency to allow for systematic differences that may exist between sonographers Appendix D Equations used in calculations shows the equations alpha uses in calculations Use the Regression options see section 5 9 to obtain values of the coefficients for a regression equation corresponding to a given set of observed values As with parameters you may not need to set all the coefficients depending on your screen design and parameter settings alpha displays a warning message if any required coefficients are missing There are no default settings for the coefficients you need to specify the values of all required coefficients alph d version 8 2 tk eh Setup AAA Ol alpha 8 0 Coefficients e l ae SZ Median Equations Select this button to print the current or j Ultrasound gestation BPD CRL AC and HC historical parameter settings T Select the parameter you want to change from this list Don t prompt If this option is checked then the user is H for changes not prompted to give the reason for a parameter change Weight Adjustment Figure
288. s in the table may therefore o To 01 01 05 differ from those based on reported values The following categories are excluded updated results repeat tests multiple pregnancies and smokers CODES Include all codes v Observed median DISPLAY GRAPH AS Scatter plot Refresh results Median MS AFP MoM 130 Gestational Age Days alpha plots the median MoM with gestational age to provide a visual method of checking that the median values are correct across the range of gestational ages Figure 116 Tabulation of MS AFP by gestational age There are five columns in the tabulation and these are labelled A to E in Figure 116 and described in Table 12 Table 12 Columns in Tabulation B The median gestation in days for each group D The median maternal serum marker in concentration units for each group E The median maternal serum marker in MoM values for each group MoM values are recalculated using the specified estimate of gestational age where necessary alpha ensures that chronologically correct median equations are selected when recalculating E MoM values If the overall MoM value lies outside the 95 confidence interval around 1 0 MoM then this will be indicated by the symbol Oo as in the example in Figure 116 MoM values that are consistently higher or lower than the expected value 1 0 MoM may indicate that the current estimates of the gestation specific medians are not accurate and need revising alp
289. s to women who have not attended for the second stage For more information on the setup needed monitoring and management features available for the Integrated Test refer to E Section 3 1 6 Cut offs E Section 4 1 Data entry Section 3 11 alph d version 8 m Integrated test options alph d Version 8 2 General Principles This section provides you with background information on using the alpha software It also outlines what you will need to do to get started The facilities mentioned briefly in this chapter are described in greater detail in other chapters of the manual If you are viewing this manual as a PDF file using Adobe Reader where you see the hand icon you can click on the link to jump to the relevant place in the manual 2 1 Terms used in this manual some of the terms frequently used in alpha are given in Table 1 Table 1 Terms frequently used in alpha Term Meaning gt measurements from each patient can be entered reviewed or modified 2 The location in a record in the alpha database where information is stored of the data is the prompt Batch file Data on a number of patients taken for example from request cards entered together are stored in a batch file or batch Each patient in a batch file or in the alpha database is referred to as a record The screening interpretation and results obtained from processing the patient record Each report is added to the alpha database when the record ha
290. saaeeeesaags 122 Analyse it Results in Excel 0 122 Daa EA EE 123 Options in Median Analysis ccccccccccccceeeseecceeeeeeeeeeeeeeceeeeeeesaeeeeeeeeeeeseaeaseeeeeeeeessaaaaeses 124 Median Analysis for UE gasssriieinruriscresirtonnsisarec eninin kn sienna iaren erak estira irea 125 Missing information E 126 Missing information adding additional fields cccccececcceceseseeeeeeceeeeeceeeeaeeeeeeeeeaeeeeees 127 Nuchal Translucency Monitor EE 128 ITC ONE E ON eae EEE EE E eee 129 IC ONS Se IG D 130 Pregnancies without OUTCOME ccccccceeeeeccceeeeceseeseeeceeeeeceaeeeeseeeeeesessaaaseeeeeeesssuaaeeseeeeees 131 Outcome List pregnancies with abnormalities ccc cccccseeeeceeeceseeeeeeseeeeeeeeeeeeeeseeeesaaees 131 Outcome Data Entry Screen n nnnneannnnnnennnennnennnossrnnrnnrennrrnnrrnreessrnnrrnrrenennnrrrrennennnreenee 132 OUTCOME screening auct eniai i iiaa Tinie eniad 133 Outcome full screening audit eee ccccccceeeeseeeeeeeeeeeaeeeeeeeeeeeeeeseeeeeseeeeeeessaeaseeeeeeeeessaanaeses 134 Figure 97 Outcome risk categories cceeeeececceeeceeeeeeeeeeeeeceaaeasceeeeeeeesaaaeaeeeeeeeeseaeaceeeeeseessaaneeeeeeess 135 Figure 98 Outcome Validation Plot 136 Figure 99r Ufo gee 0 2 eee ene ee en ee en ae ee EE S AEON EAEE EE 136 Figuro TOO Ir OO E 138 Figure 101 Regression of MS AFP with gestational age 139 Figure 102 Regression of uE3 MoM with maternal weight log
291. say On the day you wish to start interpreting results using the new assay add the new coefficients in the Coefficients section You may also need to change the concentration units in the Parameters section When you are tabulating data in alpha you will need to remember when you changed to a new assay a historical listing of the coefficients will indicate the dates when the normal medians were changed You can examine tabulated median MoM values over different assays as alpha always uses the correct median equation when calculating the MoM values However care should be taken when examining the combined unit values for more than one assay as they will probably not be suitable for deriving new median equations alpha allows you to restrict the tabulations to specified date ranges SO you Can avoid tabulating data from more than one assay 7 References 1 Report of UK Collaborative Study on Alpha fetoprotein in relation to neural tube defects 1977 Maternal serum alpha fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy Lancet June 1977 1323 1332 2 Wald NJ Cuckle H Boreham J Stirrat GM Turnbull AC 1979 Maternal serum alpha fetoprotein and diabetes mellitus Br J Obstet Gynaecol 86 101 105 3 Hook EB Cross PK Schreinemachers DM 1983 Chromosomal abnormality rates at amniocentesis and in live born infants JAMA 249 2034 2038 4 Boue A Gallano P 1984 A collaborative study of
292. screening requisition form Appendix B Prompts and their meanings shows the complete set of possible prompts You can choose your own names for the prompts by double clicking on a selected prompt The Field information screen is shown where you can enter an alternative name for the prompt Figure 46 You can give a prompt any name up to 50 characters long The meaning of the prompts does not change when you rename them For example alpha will continue to interpret data entered in the Date of sample prompt as the date on which the blood or amniotic fluid sample was taken regardless of any alternative name you may give the prompt If you wish alpha can automatically complete specified fields in the data entry screen as you move the cursor over them to save unnecessary repetitive data entry For example you could have alpha automatically complete the Ethnic group field with the code corresponding to the majority ethnic group The value entered automatically can be overridden if necessary Different default values can be used for maternal serum and amniotic fluid AFP screening if required The default values are also entered in the field information screen See Figure 47 alph d Version 8 Field information Surname Please take care when changing the user defined name to ensure the definition of the field is retained Figure 46 Screen Design change prompt Field information Ethnic group Please take care when changing the user
293. se cases alpha will notify the user of the anomalous marker and give them the opportunity of removing it from the risk estimate in the screening report Women who have had a false positive screening result in one pregnancy are much more likely to have a one in a subsequent pregnancy than women in general 7 alpha can help to avoid this by adjusting serum marker levels in women who have been screened in a previous pregnancy and who have not had a previous pregnancy with Down e syndrome The methodology underlying risk estimation has been validated empirically Studies have found that the risk of Down s syndrome predicted by alpha is in close agreement with the observed risk gt 67 The method alpha uses to estimate the risk of a woman developing pre eclampsia is based on modifying the pre eclampsia prevalence in light of the screening marker levels together with the history of a previous pregnancy with pre eclampsia using a multivariate log Gaussian model derived from published parameters 0893334 1 5 Monitoring screening performance alpha provides a range of valuable monitoring features to help you achieve the best screening performance For example with alpha you can E examine and correct drift in the normal median values of the screening markers E obtain estimates of the expected screening performance given the age distribution of your population you can then compare this with the screening performance observed in practice E o
294. sed risk of Down s syndrome Risk of Down s 1 in 65 at term Risk of NTD 1 in 8 100 Comment Down s risk due to maternal age alone is 1 in 900 Figure 55 Test Report If after creating and checking the test reports for a batch file you change one or more records in the file or add records to the file you must create and check test reports again before you can create the final reports When this happens alpha will ask whether you want to create test reports for all the records in the file or just the records that were changed or added 4 2 2 Checking for matches alpha will check for matches with reports for the same patient in the current pregnancy and previous pregnancies and also with unreported patients in all batches 4 2 2 1 Current pregnancy Repeat tests The check for matches is made on the basis of the woman s surname ID code and date of birth Any previously reported records with matching information in two or more of these fields will be considered to be potential matches if reported in the previous 13 weeks When potential matches are found alpha displays the Matches window See Figure 56 showing the record in the batch file being reported and all potential matches found alph d Version 8 lt is important to match records that relate to repeat samples because estimating the risk correctly in a repeat sample requires that the marker levels in the previous sample be taken into account17 44 If you do no
295. sername of user who made final report correction or update first entered Doctor code or name for second doctor to send Type of field Single Text 50 Text 255 Time Text 50 T Ou N ur c lt Ben Ur OU c ul Ben Fe vis Vv Vv Vv Vv wi wi wi wi Vv Amniotic Fluid Vv O a Zen E S H x PES w O SR gt go 2a GC E 5 CH Ben Ou OH Ben O CH Ben _ Cc LLI Sp positive negative U uninterpretable Format is lt Username of user who started data entry gt lt username of user who made final report gt For corrections only the name of the user who made the correction is stored Page 225 Field name Report address 2 Doctor 3 Report address 3 Language 1 Language 2 Language 3 Reason code t Reali GC be em EDD calculated Version 8 Address code for second address to send report to Doctor code or name for third doctor to send report to Address code for third address to send report to Language code for report of first doctor Language code for report of second doctor Language code for report of third doctor Reason for positive or un interpretable result Expected date of delivery calculated Type of field T Ou N ur c lt Ben Ur OU c ul Ben Fe vis Text 8 Text 50 Text
296. sions option is selected a blank table is provided into which this information is entered Once the table contains three or more complete rows of data gestational age observed median and number of samples if known alpha displays the regression curve and coefficients of the regression as shown in Figure 101 The expected regressed median values in the table are also updated automatically as you enter or add data Use the graph and the table of expected and observed values to examine the goodness of fit of the regression Large deviations between observed and expected values should be considered in relation to the number of samples on which each value is based The slope of the regression line derived from the tabulated measurements is a further indication of suitability for use in screening NT measurements tend to increase with gestational age usually at a rate of about 15 25 per week Standard deviations and slopes that differ markedly from the usual values may be a prompt for further investigation alph d Version 8 When deriving a regression of AF AFP with gestation you have the option of excluding AF AFP levels before 15 weeks 3 days from the regression This is because a log linear regression may overestimate the observed AF AFP values before 15 weeks8 If you choose to exclude values before 15 weeks they are not used in deriving the regression equation but alpha prints the expected AF AFP levels at 13 weeks 3 days and at 14 weeks
297. sk of an individual woman having a pregnancy affected with Down s syndrome is given by r 1 risk 146733421 Le 0 281 Aage3773 Where age is the woman s age in years at the expected date of delivery Median screening marker levels og MoM in Down s syndrome pregnancies according to gestational age Gestational Median age 91 ihi Week Day NT JI EA ae TT Appen ue 10 0 0 4027 0 4689 0 0171 0 2105 n a n a n a n a 1 0 3962 0 4593 0 0050 0 2182 2 0 3897 0 4496 0 0072 0 2259 3 0 3833 0 4400 0 0193 0 2335 4 0 3768 0 4303 0 0314 0 2412 5 0 3703 0 4207 0 0436 0 2489 6 0 3639 0 4110 0 0557 0 2566 11 0 0 3574 0 4014 0 0678 0 2643 0 0403 n a n a n a 1 0 3509 0 3917 0 0799 0 2719 0 0507 2 0 3444 0 3821 0 0921 0 2796 0 0610 3 0 3380 0 3724 0 1042 0 2873 0 0714 4 0 3315 0 3628 0 1163 0 2950 0 0817 5 0 3250 0 3531 0 1285 0 3027 0 0921 6 0 3186 0 3435 0 1406 0 3103 0 1025 12 0 0 3121 0 3338 0 1527 0 3180 0 1128 n a n a n a 1 0 3056 0 3242 0 1649 0 3257 0 1232 2 0 2992 0 3145 0 1770 0 3334 0 1335 3 0 2927 0 3049 0 1891 0 3411 0 1439 4 0 2862 0 2952 0 2012 0 3487 0 1543 5 0 2798 0 2856 0 2134 0 3564 0 1646 6 0 2733 0 2759 0 2255 0 3641 0 1750 13 0 0 2668 0 2663 0 2376 0 3718 0 1853 n a n a n a 1 0 2604 0 2566 0 2498 0 3795 0 1957 2 0 2539 0 2470 0 2619 0 3871 0 2061 3 0 2474 0 2373 0 2740 0 3948 0 2164 4 0 2410 0 2277 0 2862 0 4025 0 2268 5 0 2345 0 2180 0
298. specific SUMMALY cece cccecceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeaaaeeeeeeaaaeeeeesaeaeeeesseaaeeeseesaaaeeeeeeaas 113 5 1 4 Demograpbce eee eeeeeeeeaeeeeeeeeaeeeeeeeeaeaeeeeeeaaaeeeeeessaaeeeeesaeeeeseesseneeeeeesas 113 a EE d S osassa Ra a An ea OE A sedini Te ean ER 114 5 1 6 ein Che ler Te 114 lee EE 115 SeA OPOS e E 115 SEA TEE 116 e E ed 117 Sere ae D 60 Ee WE 120 525 012 A DEE 121 is WVU ST EE 123 54 Median E 123 55 Missing OMAN ON DEE 125 56 N chaltranslucency une e EE 127 SY OUO gt meet nee mene oe E eon mr E eee 128 ol 0 10 10 Ee te E 128 oT de ee a ne nee ee ee eee eee 130 NEE e Data Ase eenaa EEA EE EAEE EEE 130 5 7 2 2 List Pregnancies without QUICOIMC senges gege SERGE 130 5 7 2 3 List Pregnancies with Abnormalities ccccccseeeeeeeeeeeeeeeeeeeeeeeeeeeeeaeaeeeeeeeaeneeeeeeeas 131 SS Outcome RECO EE 132 5 7 3 1 The Outcome Data Entry Gcreen i aneia akaba 132 alph G Versions 5 4 Ee En Wuere TE 133 E RT AE 134 a76 Een E e ee 136 led Doa e O ET 137 Se ee e EE 137 DS TSO RSS en eera A E E E E E A E E E T 138 5 9 1 Regressions with gestational age or crown rump Jength 138 5 9 2 Regressions with weight ENNER 140 5 9 3 Changing the equation used in the regression ccccceeecceceeeceeceeeeceecaeeceesseeeeesseeeeeeseaes 141 5 9 4 Updating median equation coefficients cccecccccceeeeceeeeeeeeeeeeeeeaaeaceeeeeeeeesaeaseeeeeeeeeeaaas 143 Sech REPO N ee a ER E
299. stall a dongle on each workstation on which alpha will be used You do not need to install a dongle on the server Figure 1 USB dongle To install the USB dongle m Plug the dongle into an available USB port on your computer It is important to wait for the message Your new hardware is installed and ready to use before starting alpha 2 3 Starting alpha alpha will have been installed on your computer by an approved installer and you will have received training in its use The installer will assist you in the initialisation of alpha which must be performed before reports can be produced The initialisation procedure is described in section 2 4 Configuration Start alpha by selecting it from the Programs menu or clicking on your Windows desktop You will then be prompted for your username and password See Figure 2 Enter your username and Username PY password in the login dialog Sconce TT box and press Enter or Click OK Close Figure 2 Entering username and password The System Administrator can create a username and password for you if you do not already have one see section 3 21 2 4 Configuration Before you use alpha you will need to configure the software to suit your requirements Your alpha installer will help you to configure alpha First use Screen Design see section 3 17 to select the prompts for the maternal serum MS and amniotic fluid AF data entry screens You will then need to specify
300. ster Free B hCG 0 5115 PAPP A 0 1330 PIGF DVPI Second trimester AFP 0 1416 UE 0 1656 Total hCG 0 6809 Free B hCG 0 5605 Inhibin A 0 2618 Version 8 49 Unless stated otherwise First trimester Free B hCG 0 0456 0 0651 0 0000 0 1063 0 3446 0 4695 0 7675 0 3031 PAPP A 0 04247 0 0000 0 1945 0 4586 0 1761 0 2484 0 1282 PIGF 0 2692 0 0056 0 3058 0 0053 Second trimester Total Free B SE uE hCG hCG 0 0017 0 2121 0 3796 0 2060 0 4172 0 8160 0 1976 0 2989 0 4296 0 4394 Page 251 Correlation coefficients for the screening markers in Down s syndrome pregnancies gestational age based on dates with adjustment for maternal weight Total hCG First trimester Free B hCG 0 4929 PAPP A 0 0749 PIGF DVPI Second trimester AFP 0 0879 UE 0 1921 Total hCG 0 6758 Free B hCG 0 5551 Inhibin A 0 2442 Version 8 49 Unless stated otherwise First trimester Free B hCG 0 1112 0 0651 0 0000 0 0554 0 3646 0 4418 0 7494 0 2824 PAPP A 0 04247 0 0000 0 1211 0 4671 0 2487 0 3170 0 1879 PIGF 0 2692 0 0056 0 3058 0 0053 Second trimester Total Free B An uE hCG hCG 0 0288 0 1725 0 4008 0 1738 0 4366 0 8046 0 1661 0 3182 0 4148 0 4284 Page 252 Correlation coefficients for the screening markers in Down s syndrome pregnancies gestational age based on scan without adjustment for maternal
301. ster markers 14 Standard deviations 71 alpha Version 8 Tabulation of observed median serum marker levels vs GA See Tabulations total human chorionic gonadotrophin hCG 14 unconjugated oestriol uE3 14 used in alpha 14 243 260 Matching 94 See Report Series Duplicated patient entries 96 In previous pregnancy 95 In same pregnancy 27 94 174 177 Breaking matches 96 To avoid recurrent false positives See Recurrent false positives Maternal serum See MS Median Analysis 123 Median equations 44 72 187 See Regression equations Coefficients See Coefficients Policy 41 49 184 188 Medians Establishing 72 Expected See Coefficients Evaluate Graph See Graph medians Monitoring See Median Analysis Observed See Tabulations Tabulating See Tabulations Updating See Tabulations See Tabulations See Tabulations Message Addition 74 190 Missing information 125 MoM 13 Value printed in reports 43 Values printed in reports 98 Monitoring Screening performance 14 MS Report See Report MS Multiple pregnancy See Twins Multiples of the median See MoM Multi user 15 See Installing Alpha Additional workstations Nasal bone 15 181 Neural tube defects See NTD Normal medians See Medians NT 180 Centre specific medians 155 Date field 181 MoM calculation when no CRL is available 171 Regression equation vs CRL 187 Coefficients 44 Sonographer specific medians 46 155 Standard deviation 155 Tabulat
302. t 4 GIN Weeks days eg 17 4 Date on which GA from LMP Date v v v v 312 Entered estimated EDD from scan Expected date of Date v v v v 312 Entered delivery from scan Text DO Wecedes eg 1714 Date on which GA from scan Date v v v v 312 Entered estimated Number of fetuses 1 BPD in singleton fetus 2 one BPD in twins Integer v v v v H Entered 3 _ both BPDs in twins 4 other Version 8 Page 194 oe E o gt 5 S F A a 2 Comment fs a H S g CH Ban D g x lt c iL LLI Data transfer impor Type of ultrasound measurement for GA by scan Maternal Serum Type of Date of ultrasound D end pate fv v v v ae emera number Number of fetuses from ultrasound Integer v v v v II Entered scan 1 BPD 2 CRL 3 AC 4 HC Integer v v v wv II Entered 10 mm lt BPD lt 110 mm 5 mm lt CRL lt 100 mm 30 mm lt AC lt 400 mm 80 mm lt HC lt 320 mm measurement measurement V Type of extra 1 BPD Type of measure ultrasound Integer v v wv it Entered 2 CRL measurement 3 AC Version 8 Page 195 Comment O Ska E5 8 Es 2 x c OH O z a 5 CH SS D x E E a WL LL Data transfer Type of ultrasound measurement Maternal Serum Comment Type of 8 Ra l Bn O am se 3 o x Ve O Ben 2E H o goe D x 2 E E C iL E LLI _ T Ou N c st
303. t Summary Amniotic Fluid TEST 5726 reports generated in requested period Print All tests H Type of report Number Percent Maternal serum tests 5665 98 9 WOMEN TO INCLUDE Repeat Maternal serum tests 45 0 8 SS e A Updated Maternal serum results 16 0 3 women regardless of race Total 5726 100 0 If any reports were corrected after 01 01 2005 the tables take account of any changes and do not include the original reports REPORT DATE RANGE O All periods From Z To 369 positive tests 6 5 of first tests Reason CODES Increased risk of Down s syndrome Raised AFP Include all codes v S Previous Down s only Previous NTD only 5665 first tests 98 9 of total tests 13 uninterpretable tests 0 2 of first tests Refresh results 5283 negative tests 93 3 of first tests Increased risk of trisomy 18 was reported in 14 first tests 0 2 Tests according to type 49 tests reported in the requested period and subsequently repeated 17 tests reported in the requested period and subsequently updated Report Address Code Summary Doctor Code Summary Figure 107 Report Summary The Report Summary screen gives an overview of the screening report The detail of each section can be seen by opening the expander by pressing on the next to the title and can be hidden by pressing H When the Print button is pressed a report similar to that in Figure 108 is shown The figure shows the meaning of the tables presented alph d
304. t date gt 225 Screening result 230 Diagnostic result 235 Reason 240 Comment 245 Risk of Down s 255 Risk of pre eclampsia 250 Risk of NTD 260 PREVIOUS REPORTS REPORT SAMPLE TEST RESULT NOTES 265 Fixed text portion of window envelope 270 Gestation used 275 Positive and negative footnotes 280 Title for MS message addition system 285 MS message addition Header message 290 Footer 295 Missing weight Code 300 305 310 315 320 325 330 335 340 345 350 355 360 365 370 375 380 385 390 395 400 405 410 415 420 425 430 435 440 445 380 alph G Version 8 First part of item Title for AF message addition system Missing diabetes Missing ethnic group Missing previous Down s syndrome Missing previous NTD Clinical gestation only Twin pregnancy Screen negative first test Screen negative repeat test Screen positive NTD raised AFP first test with scan Screen positive NTD raised AFP first test without scan Screen positive NTD raised AFP repeat test Screen positive NTD previous NTD Screen positive Down s increased Down s risk first test with scan Screen positive Down s increased Down s risk first test without scan Screen positive Down s increased Down s risk repeat test Screen positive Down s previous Down s syndrome Age at EDD gt specified level MS AFP gt specified
305. t match the samples the repeat test is interpreted as if it were a first test and the risk estimate will be less accurate Current pregnancy and previous pregnancy matches Section 4 2 2 2 are shown on the same Matching screen Matching Current Pregnancy Match Alpha has found a possible match in the Alpha database for this patient in the current pregnancy The current patient is highlighted and the possible matches are in the following lines Select the match to the current patient Select Surname Forename IDCODE Date of Birth Type Sample Date GA days ATKINS Anne A127126 02 04 1978 fv ATKINS Anne A12 126 02 04 1978 MaternalSerun 05 08 15 119 Cancel Continue Figure 56 Repeat test 4 2 2 2 Previous pregnancy Recurrent false positives Depending on the policy selected under section 3 1 11 alpha may also check for previous reports that may relate to an earlier pregnancy in the same woman Women who have had a false positive screening result in one pregnancy are much more likely to have a one in a subsequent pregnancy than women in general alpha can help to avoid this by adjusting serum marker levels in women who have been screened in a previous pregnancy and who have not had a previous pregnancy with Down s syndrome If you use this facility alpha attempts to match each record in the file you are currently reporting with records in the database that may relate to the same woman provided a previous pregnancy with Down s syn
306. t of the data Field number for sample ID Field number in the file that holds the sample ID The position of the sample ID in each line of the file If the sample number is the first field this value should be set to 1 or if the second field that value should be set to 2 and so on Field number for result Field number in the file that holds the sample ID The position of the result in each line of the file If the result is the first field this value should be set to 1 or if the second field that value should be set to 2 and so on ASCII code for field separator The ASCII code that defines the character that separates items of data in each line of the file Set this value to zero for one or more spaces 6 99 For example 44 for a comma Decimal separator Decimal separator For example or Result scaling factor The factor by which analyte results in the file are multiplied before saving in the batch For example 100 0 or 0 01 Numeric results in the file are scaled by this number Lower assay limit If the analyte result is less than this value the limit is entered into the patient record preceded by lt For example if the assay limit is 1 0 and the value read from the file 0 9 the value stored in the patient record is lt 1 0 Quotation character If the specified character delimits a sample ID or result in the file it is removed For example if the value is and the sample ID in
307. t of the import file When you select an Import data format option alpha displays the prompts chosen in Screen design To create the export data format highlight the fields in the left hand column of the Import Settings screen Figure 36 which appear in the import file and drag them to the right hand column To remove a field highlight it in the right hand column and drag it to the left hand column Select the import file format fixed length comma separated or tab separated the date format d m y m d y or y m d and the full path and filename of the file containing the data to import In fixed length records each field in the record occupies a fixed number of characters and there are no separators between fields In addition dates do not contain separators In comma separated and tab separated records the length of each field is variable fields are separated with commas or tabs and dates contain separators lf DOS compatible mode is selected the doctor code address code and sonographer code are taken to be four characters long If this is not selected the codes are taken to be eight characters long If Import NT levels to 2dp is selected NT levels are imported with 2 numbers after the decimal point If this is not selected NT levels are imported with 1 number after the decimal point alph d Version 8 Full details of the fields which can be exported are given in Appendix G Import Export Data transfer and Analyze it formats
308. t time you use the Screening Performance option the only screening test for which performance estimates are available is Maternal Age Alone To obtain estimates of screening performances for other tests for example the quadruple test you need to select the markers to use for each test To do this press the New button and the window in Figure 111 containing a list of the available screening markers will be shown Select the markers required and if necessary whether the test is an Integrated or Sequential test Repeat this procedure for each test for which you require estimates of screening performance The Edit button allows the marker combination to be edited and Delete will delete it Edit performance table TEST NAME MS AFP uE3 Total hCG Inhibin A Nuchal PAPP A Enter a descriptive name for the combination MARKERS MS AFP Click on the check boxes to select the markers you want to include in the Total hCG marker combination In this example the Integrated test markers Inhibin A have been selected uE3 Free B hCG KI LJ i Kl Kl Nuchal FreeB hCG Total hCG For tests involving first and second trimester markers select if the test is an Integrated or Sequential test Figure 111 Specify markers to use for screening performance table Select the name of the marker combination from the Test dropdown and press Refresh o to show the selected screening performance table See Figure 112 for the
309. ta The regression provides the coefficients needed to update the median equations should you wish to do this see Section 5 9 2 for more information on weight regressions 5 13 6 Serum markers and ethnic groups Provided your maternal serum MS screen design includes the Ethnic group prompt when you tabulate the levels of an MS marker with gestational age or with maternal weight you can choose to tabulate data either for a specified ethnic group or for all women regardless of ethnic group This section explains why this option is provided and how alpha tabulates the data in each case NOTE You can change the term alpha uses to refer to ethnic group if you prefer see section 3 17 You can also change the names alpha uses for individual ethnic groups see section 3 8 Levels of the serum screening markers may differ on average in women of different ethnic groups Also average maternal weight may differ between ethnic groups For example second trimester AFP levels tend to be higher in black women than in Caucasian women and South Asian women tend to be lighter than Caucasian women Correcting for these differences can yield a small but worthwhile improvement in screening performance as well as helping to ensure a similar screen positive rate in different ethnic groups If your screened population is ethnically mixed you may wish to correct for these differences and alpha allows you to do this in one of two ways For each sc
310. tabase if it is printed or exported It is not sufficient to simply to view the report Before you review the revised report you can create a new match by pressing Match If the report was already matched you can break the match by pressing Break Match Patients In ei Q alpha 8 0 Dr Gareth Hills Charterhouse Surgery The Square LONDON EC2B HU8 penp y a e DOWN S SYNDROME NEURAL TUBE DEFECT AND PRE ECLAMPSIA SCREENING Report dated 06 Aug 13 This is a corrected version of the report produced on 06 08 13 A message is added Last name ATKINS to the revised report Forename s Anne e A De Hospital Number A127126 to indicate that itis a Date of birth 02 04 79 EDD 13 01 14 Date of sample 05 08 13 interpretation ofa Sample number 1 2391897 previous report CLINICAL DETAILS AND TEST RESULTS Previous NTD None Previous Down s None Prev Pre eclampsia No Insulin dependent diabetes None Smoker No Maternal age at EDD 34 years Scan measurement BPD 35 2 mm on 01 08 13 Gestation at date of sample 22 weeks 2 days by dates 17 weeks 0 days by BPD scan Gestation used Scan estimate BPD Weight 65 4 kg Ethnic group Caucasian MS AFP level 40 2 ng mL uE3 level 2 9 ng mL Total hCG level 10121 miu mL Inhibin A level 210 1 pg mL INTERPRETATION Screening result Screen negative Risk of Down s 1 in 12 000 at term Risk of NTD 1 in 17 000 Risk o
311. tabulation directly from graphs of median MoM values E Live Screens o Screens showing statistical results are updated immediately when the settings are changed E Latest computing technology o Uses Microsoft SQL Server Windows Presentation Foundation and NET framework SEN s Abdominal circumference See AC AC 235 Regression equation GA vs AC 45 188 Coefficients 44 Address codes 54 175 in Tabulations See Tabulations Adjustment factors 264 AF AFP 181 235 AFP cut offs 29 Data entry See Data entry Exclude AF AFP values before 15 weeks 3 days 30 140 Graph medians 30 Hide options 28 80 Median reduction factor 29 42 186 Medians 29 Regression equation vs GA 29 Report See Report AF AFP Tabulations 30 153 Units 29 Age Specific risk of Down s syndrome See Risks See Risks Amniocentesis 28 Previous 179 Amniotic fluid AFP See AF AFP Analyser Import See Import Analyser Anencephaly 235 Prevalence 39 186 See Ethnic group Anomalous marker paterns See Markers anomalous patterns Backups 3 Batch 26 Medians 109 Processing 26 Batch file 17 Biparietal diameter See BPD BPD 235 Correction factors 40 186 Regression equation GA vs BPD 45 188 Coefficients 44 Coefficients 33 46 49 AC See AC AF AFP See AF AFP BPD See BPD Changing amp setting 19 44 140 CRL See CRL Current 46 53 Evaluate 46 52 Historical 46 53 NT See NT serum markers vs GA See GA Specifying for
312. tal screening for Down s syndrome J Med Screen 20 7 14 NJ Wald JP Bestwick LM George T Wu and J Morris 2012 Screening for pre eclampsia using serum placental growth factor and endoglin measurement with Down s Syndrome Quadruple test markers J Med Screen 19 60 67 JM Elwood J Little and JH Elwood 1992 Maternal illness and drug use in pregnancy In JM Elwood J Little and JH Elwood Eds Epidemiology and control of neural tube defects Oxford University Press NJ Wald JP Bestwick LM George and W J Huttly 2012 Antenatal Screening for Down Syndrome Using Serum Placental Growth Factor with the Combined Quadruple Serum Integrated and Integrated Tests Plos ONE 7 e46955 Wald NJ Densem J Stone R Cheng Raymond 1993 The use of free beta hCG in antenatal screening for Down s syndrome Br J Obstet Gynaecol 100 550 557 Akolekar R Syngelaki A Sarquis R Zvanca M Nicolaides KH 2011 Prediction of early intermediate and late pre eclampsia from maternal factors biophysical and biochemical markers at 11 13 weeks Prenat Diagn 31 66 74 Akolekar R Syngelaki A Poon L Wright D Nicolaides KH 2013 Competing risks model in early screening for preeclampsia by biophysical and biochemical markers Fetal Diagn Ther 33 8 15 Leck Epidemiological clues to the causation of neural tube defects In Dobbing J Ed Prevention of Spina Bifida and other Neural Tube Defects 155 182 Academic Press London 1983 Bestwick JP Huttly WJ and Wald
313. tcode Phone number Age at EDD EDD from LMP Certain GA by dates On EDD from scan Type of measure Measurement 1 Measurement 2 l Femur length 1 Femur length 2 l GA by clinical On Date OC stopped First or repeat Items in the left hand column are available for Q Setup AAA Cl alpha 8 0 Use these buttons to configure Screen Design for Maternal Serum or Amniotic Fluid Last name Forename s Hospital Number Date of birth uve Weight Ethnic group Previous NTD Previ Type of measure Measurement 1 Measurement 2 Date of scan Machine Number fetuses Integrated screening Sonographer Lab number Date of sample Spare 1 Date of 2nd sample Click and drag items between the left column and Age those on the right to select or deselect them from Prev the screen design Interpretation Smoker Diabetes IVF pregnancy i Donor date of birth in Empty row Date embryo transfer Date egg collectio Doctor Items in these columns have been selected for the screen sal bone fetus Select Add Column to add another column to the screen design selection Report address design GA by scan On Number fetuses Scan Spare 2 measure Spare 3 Spare 4 i SE Figure 45 Screen Design You will find data entry is easier if the order of the prompts on the screen is the same as the order on the
314. te you should in the first instance check that the observed medians at each week of gestation are reasonably close to 1 0 MoM Use Median Analysis section 5 4 and the Tabulation options section 5 2 to check these For markers in which low values are associated with Down s syndrome for example AFP uE3 and PAPP A persistently low observed median MoM values will lead to an increase in screen positive rate Similarly for markers in which high values are associated with Down s syndrome for example hCG inhibin A and nuchal translucency persistently high observed median MoM values will lead to an increase in screen positive rate 6 3 Checking and updating the median MoM Values 6 3 1 Monitoring estimate median MoM Values You should regularly examine observed median MoM values How often you do this will depend partly on the number of tests you perform but you should check them at least every three months The Median Analysis option is useful in obtaining a long term picture of fluctuations in reported MoM values section 5 4 To examine the medians use the options for tabulation with gestation or crown rump length on the Tabulations screen section 5 2 The tabulations show the observed median MoM at each week of gestation or crown rump length interval and the overall median MoM In expectation the median MoM is 1 0 for each week or crown rump length interval and also overall The tabulation will indicate whether the overal
315. te is not known enter 00 for the day of the month e g 00 12 2005 In such cases alpha uses the 15 day in calculations Expected date of delivery based on LMP 1 LMP EDD certain 2 LMP EDD doubttul If chosen the field must follow LMP and or EDD from LMP Women whose LMP is recorded as being doubtful may be excluded from certain statistical tabulations Estimated gestational age based on LMP in completed weeks and days separated by or Date to which GA by Dates relates Required if GA by Dates is given Gestational age estimation ultrasound EDD from scan 3x2 GA by scan A On EE Number of fetuses 1 Scan measure d pas dacant T 3xe Machine 1 Number of fetuses e 1 alph d version 8 Expected date of delivery based on ultrasound scan Estimated gestational age based on ultrasound scan in completed weeks and days of gestation separated by or Date to which GA by scan relates Required if GA by scan is given Number seen at scan If left blank alpha assumes a singleton pregnancy 1 BPD in singleton fetus 2 one BPD in twins 3 both BPDs in twins 4 other 5 not known Required if GA by scan is given lf Number of fetuses is blank or 1 options 2 and 3 are not allowed If Number of fetuses is 2 option 1 is not allowed Date of ultrasound scan This prompt together with the following five linked prompts must be included in the screen design
316. te record genuinely relates to a repeat sample the earlier sample should be processed before the later one Repeat samples cannot be processed in the same batch file The record for the initial sample must be moved to another file and reported before processing the repeat sample 4 2 2 4 Breaking and making matches after creating test reports When you create a test report and potential matches are identified between one or more records in the batch file and previously reported results alpha prompts you to select whether or not to accept of each potential match alpha remembers your selections and does not prompt again if you create the test report again for example if you later identify and correct data entry errors in the batch file This avoids having to repeatedly accept or reject matches when test reports are created more than once If you subsequently need to change one of your selections for example because you accepted the match in error you can force alpha to prompt you again by editing the corresponding record To do this open the batch file and locate the record for which you want to break or make a match Change the contents of any field for example the woman s name highlight any other field then move back to the field you changed and change it back to its correct value Then close the batch and create the test report again alpha will prompt you to accept or reject the match for the record you edited 4 2 3 Final reports
317. ted with values value1 blank value value3 the file will contain when the separator is a comma value1 value3 8 Regional settings using as the decimal separator and as the thousands separator 8 1 Data transfer lf the data transfer field separator is a comma numbers are exported with as the decimal separator lf the data transfer field separator is a tab or the file is in fixed width format numbers are exported with as the decimal separator Exported numbers do not use a thousand s separator 8 2 Import and Export If the import or export format field separator is a comma numbers are imported and exported with as the decimal separator lf the import or export format field separator is a tab or fixed length format is used numbers are imported or exported with as the decimal separator Imported and exported numbers do not use the thousand s separator 9 Excel cell formats for Analyze it The fields are exported to Excel cells with the following formats Export field Excel cell format Integer long integer and single General Numbers will be formatted using the regional settings used in Windows Text x General x is the maximum number of characters in the text string Date and time Date Dates will be formatted according to the regional settings used in Windows NULL Blank cell 10 Gestational age format The gestational age is entered in weeks and days includ
318. tests in unaffected pregnancies and pregnancies with neural tube defects Pregnancy Correlation coefficient Gestational age estimated by Dates scan Without weight With weight Without weight With weight adjustment adjustment adjustment adjustment Unaffected 0 7698 0 7345 0 7487 0 6727 REES 0 9394 0 9301 n a n a Open spina bifida 0 9407 0 9331 0 9339 0 9254 SE SE 0 7698 0 7345 0 7487 0 6727 n a Not applicable Notes 1 When calculating the NTD risk estimate the truncation limits applied to the AFP MoM value are 1 0 to 5 0 2 The birth prevalence of neural tube defects in twin pregnancies is taken to be 2 28 times the prevalence in singleton pregnancies 3 The open spina bifida prevalence is taken to be 0 84 times that of spina bifida 4 When a BPD measurement is supplied anencephaly is excluded and the NTD risk is given for spina bifida alone 5 When calculating the anencephaly risk and a scan measurement other than BPD is supplied the Statistical parameters for gestational age estimated by dates are used N J Wald personal communication 6 The mean AFP values in spina bifida twin pregnancies with GA estimated from BPD are derived from the non BPD means by assuming that i Only one fetus in affected twin pregnancies is affected li In expectation the GA estimated is based on the means of the two BPDs iii AFP levels in spina bifida fetuses where gestation is measured by BPD are 43 higher 7 In women with insulin de
319. the file alph G version ABC123 then the value used to identify the patient record is ABC123 Ignore string lf a sample ID or result in the file contains the specified string it is removed For example if the value is ID and the sample ID in the file is IDABC 123 then the value used to identify the patient record is ABC123 when importing data column the line where the sample ID starts column the line where the sample ID ends the line where the result starts the line where the result ends Database sample ID sub string alpha database sample ID start character for matching sample ID start read from file If zero the whole alpha database sample ID is used for matching Sample IDs from the file are matched with sample IDs in the alpha database If a substring of the alpha database sample ID is to be used for matching a non zero value is specified here Database sample ID sub string alpha database sample ID end character for matching sample ID end read from file If zero the whole alpha database sample ID is used for matching Data entry field for sample The field in the data entry screen used to match the sample ID number read from the file The choices are the data entry screen fields with prompts Lab number ID Code Spare 1 Spare 2 Spare 3 Spare A Spare 5 and Spare 6 These fields may have been renamed by the user Note If the Integrated
320. thout scan m Screen positive NTD raised AFP repeat test Screen positive NTD previous NTD Screen positive Down s increased Down s risk first test with scan Screen positive Down s E increased Down s risk first test without scan Screen positive Down s C increased Down s risk repeat test m Screen positive Down s Figure 42 Message addition screen The Message addition screen displays each of the categories of message in the left hand column A check box next to each category indicates whether it is currently on or off Enable messages for a particular category by selecting the check box and then enter or edit the text of the message in the middle column In some categories you can choose to print only under certain circumstances For example for the header message you can choose to print the message always or to print it only if other messages appear Appendix E Message addition categories lists each of the report categories which can generate a message for maternal serum reports 3 15 Page setup You use Page setup Figure 43 to specify up to four Print Styles A B C and D that you can associate with the various types of printed output produced by alpha for example patient reports statistical tabulations listings and error reports A Print Style controls the paper size margins and line spacing used for each type of printed output alph d Version 8 2 th Hi Setup aah Cl
321. tients can be separated into another batch for final reporting see section 4 2 3 as shown in Figure 59 Other patients continue to the full Integrated test and remain in the batch until the second trimester samples are available The Integrated test options See section 0 can be be used to set up reminder lists of patients whose second Integrated Test sample is overdue Separate patients for sequential test 2 sequential tests have been performed Positive in first trimester 1 Aua 01 13 positive T Continuing to Integrated test OU Aua 01 13 Non sequential tests 3 Aua 01 13 OK Cancel Figure 59 Separating sequential tests If hCG is measured in both the first trimester and second trimester of sequential testing the first trimester hCG measurement is not reused in the calculation of the Integrated test risk estimate The report summary see Section 5 10 can be used to monitor the number of sequential tests that were completed at the first trimester and how many proceeded to the full Integrated test 4 2 6 Export Report Formats In addition to exporting results to a text file when the final report is made see Sections 3 9 and 4 2 3 alpha can export the reports to a file in either Standard or Packet Export format Reports can be exported in these formats when a final report is made see Section 4 2 3 and Table 9 or after a search has retrieved the report from the alpha database see Section 4 3 4 2 6 1 Stand
322. trolling access using security levels cece ee cece eee e eee eeee reese eeeaaaaeeeeeeeeeeaaaeees 192 Appendix G Import Export Data transfer and Analyze it formats snoeennnnneennnnenennnneenn rennene 193 Appendix H Definitions and abbreviations cccccseeecccecceesseceeeceesseceeeceeeeeeeseseeseceesssaeeeeesssaaeeeess 235 Appendix Packet export report Le ge EE 237 AppendixJ Statistical parameters Down s SYNCrOMGE cceccecceeeeeeceeeeeeeeeeeeeeeaaeeesaeeeeesnaeeeenaees 243 Appendix K Statistical parameters Neural tube detects 255 Appendix L_ Statistical parameters Trisomy 18 257 AppendixM Statistical Parameters Trisomy 172 259 Appendix N Statistical parameters Smith Lemli Optitz syndrome GO 261 Appendix O Statistical parameters Hre eclampeig 262 alph d Version 8 Appendix P Factors used for adjusting MOM values 264 Appendix Q Suggested factors for adjusting MoM values for differences between ethnic groups 266 Appendix H Operating environment 267 Appendix S Advances in alph a ccccecccccsececeesceceeeeceaeeeceueecseeessaeeessaeeesaueeesaeessaueessaeeessueeeseaeeess 269 List of Figures Foue elei Le VE 18 Figure 2 Entering username and password sannss1nnsennornrnsnrrourronnrnnnnrrunrrnnrrnnrronnrrnnrrnnnrrnnennnnrnnnne 18 Figure 3 Screening FEQUISITION Tom 20 Figure 4 Data entry screen corresponding to Figure 2 21 Figure 5 Screening report corresponding
323. ts either printed or in export file format using the Search option See section 4 3 4 2 4 MoM values printed on reports Maternal serum MoM values appearing on alpha reports include adjustment for weight in cases where the woman s weight is recorded alpha may make certain other adjustments to the MoM values for example in twin pregnancies diabetic women women who conceive by IVF women who smoke and women screened in a previous pregnancy See Appendix P Factors used for adjusting MoM values While these adjusted MoM values are used in estimating the risk of having an affected pregnancy and in classifying the result as screen positive or screen negative the reported MoM values do not include these other adjustments unless the parameter Print Adjusted MoMs is set If Print Adjusted MoMs is set to Adjust the MoM values on the report will be adjusted in twin pregnancies IVF pregnancies for women who smoke and for diabetic women 4 2 5 Sequential testing alpha can be used to interpret sequential testing which allows early completion of screening with very high risk pregnancies identified in the first trimester A high risk cut off is set for the first trimester test See section 3 1 6 for further information Nearly all women proceed to the full Integrated test After a batch has been test reported and the close button on the preview screen selected tests that were positive in the first trimester are automatically identified These pa
324. tween the data fields in the export file In the tab separated formats a tab character appears between the data fields in the export file If you select the option Include Field name header the first row of the export file contains the names of the fields in the order they appear in the file separated by either commas or tabs according to the format you selected The supported formats are compatible with a wide range of statistics database and spreadsheet software Please consult the manual for your software if you are not sure which format to use You can also select the categories of record you want to exclude from the exported data You can export all records rows in the database or you can restrict the exported rows by excluding deleted and incorrect reports women with insulin dependent diabetes mellitus multiple pregnancies updated results and repeat tests The filename and path for the exported data can also be specified alph d version 8 Li iu o 1 Setu p AAA Select an existing specification from this list O alpha 8 0 Data tra nste SETLI ng S Create a new specification or delete or rename a specification with these buttons Maternal Serum Serum Ampjotit fluid Description New specification New Delete LMP Last Name Weight Forename s Ethnic group Hospital number Items in the left hand Date of birth Items in the right hand column column are available for have been selected for
325. u o 1 Setup AAA Q alpha 8 0 Window Envelope Add blank line Add Fixed text Sample number 2 Doctor Report address Click and drag items between the left column and those on the right to select or deselect them from the window envelope specification Window position Left SES Reeg Select the window envelope position This is an offset from the left hand and top margin position Top 1 00 Figure 52 Window envelope setup alph d Version 8 4 Patients screen The Patients screen Figure 53 shows a list of batch files together with a summary of the patient records contained in each batch This screen provides facilities for adding patient records to batches editing existing records importing data into batches and printing information from batches The Patients screen also provides facilities for test and final reporting batches searching for patient records in the alpha database and if necessary correcting these records LI Patients Im ei AAA see Table 7 for a description of these d alpha 8 0 Items Sock o l o l o o a ol F Batches Patients l l l l Actions EE This shows a list of patients in Aug 01 13 EE the selected batch Aug 01 13 H Add MS d Ee Click the column header to order Sally SMITH 02 02 1983 the results by that field Q Import MS 3 patients 3 to be test reported Aug 01 13 A Vanessa VENABLES 04 05 1975 1 patients 1 to be test reported NEQAS l This shows the actions wh
326. ube defects Pregnancies at increased risk of trisomy 18 trisomy 13 or Smith Lemli Opitz syndrome SLOS can also be identified if you wish In cases where the karyotype of the fetus is already known as a result of an earlier diagnostic procedure such as chorionic villus sampling you can request an interpretation for open NTD only provided the Interpretation prompt is included in the MS screen design Note however that screening results are regarded as uninterpretable in cases where an amniocentesis has been performed or attempted on or before the date of the blood sample This is because amniocentesis sometimes causes feto maternal transfusion which can increase the maternal serum AFP level If the gestational age is less than 15 completed weeks or an AFP result is not entered for an individual woman the test is interpreted for Down s syndrome only In addition you can request an interpretation for Down s syndrome only using the Interpretation prompt When an interpretation for pre eclampsia is required the Interpretation prompt must be included in the MS screen design An interpretation for Down s syndrome and pre eclampsia or Down s syndrome open neural tube defects or pre eclampsia can be requested An additional comment is printed on the report when the interpretation is for Down s syndrome or open neural tube defects only 2 10 Using alpha in the diagnosis of open neural tube defects As well as interpreting markers
327. ulate the normal median value of the marker at different gestational ages The number of equations you provide will depend on D whether the maternal serum data entry screen includes a prompt for the woman s ethnic group SG the median equation policies you have specified See Section 3 1 8 Median equation policies Median equations for the overall population must always be provided If the maternal serum data entry screen includes a prompt for the woman s ethnic group you may also provide median equations for women of different ethnic groups For each ethnic group you should provide either a single median equation or two separate median equations according to the median equation policy specified Normal medians should be established by assaying in your laboratory samples drawn between 14 and 22 completed weeks of pregnancy for second trimester markers or between 10 and 13 completed weeks for first trimester markers A minimum of 50 samples per week in four gestational weeks is recommended Group the samples by completed week of gestation Then for each group determine the median gestational age in days the number of samples and the median marker level in concentration units and tabulate the data as in the example Excel spreadsheet shown in Figure 40 A C D Gestational age Median gestational Number ol Median ut 1 completed weeks age days samples level ng mL 14 102 0 Z 194 15 108 5 144 202 16 115 0 258 3 58 17
328. ull Integrated test See section 4 2 5 Sequential testing alpha version 8 can interpret the ultrasound finding of present or absent fetal nasal bone and use ductus venosus blood flow as a categorical marker in estimating the risk of having a pregnancy affected with Down s syndrome N B There are intellectual property rights covering the use of some screening markers and screening tests e g the Integrated Test and users need to ensure that they have the legal right to use them 1 7 Multi user version alpha is available in a basic single user configuration or with multi user access With multi user access more than one user can access the alpha database simultaneously from different workstations on a local area network LAN Benefits of multi user access include E increased throughput several users can enter data simultaneously at different workstations greater convenience reports can be viewed or printed from any location on the network alpha is compatible with most Windows based LAN systems Multi user access Is available for a small increase in the license fee Please let us know if you would like a multi user license for alpha 1 8 The Integrated Test The Integrated Test and the Serum Integrated Test can be used with alpha including variants of these tests for example with Triple Test markers in the second trimester instead of the Quadruple Test markers The software provides a full audit trail including alert
329. until the message Your new hardware is installed and ready to use is shown 6 Start alpha from the shortcut ie Alpha Setup Choose Setup Type Choose the setup type that best suits your needs Components Installs dongle components only Complete Installs all program files Figure 12 Installing alpha on another computer alph a Version 8 3 Set up The set up screen provides you with the options you need to configure alpha to your requirements See Figure 13 Note Setup is only accessible to users with security level 4 or higher Users is only available at security level 6 The following options are offered e alpha 8 0 Li ln ei Set AAA The tiles show useful status information about alpha Pap including the version number and licence status About alpha Licence Parameters Coefficients Version 8 0 14120 22 Licence number 11077 Last updated Last updated Data base Select the option Si 01 05 2014 11 08 51 25 07 2011 00 00 00 Database operations i X Alpha amp SV Development 25 03 2015 Setting Setting ate d te by Alpha etc AlphaWpf B credits 4931 Print Adjusted MoMs Median equation DVPI None Doctor Codes clicking it with the AlphaWpfbin Debug i 25 03 2015 Overall Alpha exe C credits 4834 Add or modify doctor codes mouse 25 03 2015 Ethnic Groups Ethnic group names Events Log Export settings Patient report export settings E Y Entries from 09 12 2012 NMEA Import setti
330. used in screening for Down s syndrome and open neural tube defects alpha interprets amniotic fluid aloha fetoprotein AF AFP and acetyl cholinesterase AchE results used in the diagnosis of open neural tube defects NTDs Most users will use alpha to interpret screening tests and the major part of this manual is devoted to its use in screening This section is intended to give an overview of the issues relating to its use in the diagnosis of open NTDs Facilities in alpha that relate to screening are designated as MS for maternal serum and those relating to diagnostic testing as AF for amniotic fluid Many of the facilities in alpha are provided for both MS and AF For example Screen Design provides options for designing both MS and AF data entry screens In most cases the same general principles apply to the MS and AF options Where there are differences or special considerations that apply to the AF options these are discussed below Users who do not wish to use the AF options in alpha can disable them by selecting Hide all AF options in the General section of User Options see Section 3 20 1 To re enable the AF options select the same menu item again Before using alpha to interpret diagnostic tests you need to complete the following setup steps E Design an AF data entry screen E Specify policy settings relating to the diagnosis of NTD E Provide estimates of the gestation specific median AF AFP levels for your laboratory Thes
331. ution is to tabulate for both the previous month and previous three months Comparison of these should provide some idea of stability in the median MoM values The Median Analysis option provides a quick way to in which to do this 6 3 2 Specifying Sonographer Specific Medians for Nuchal Translucency There may be systematic differences in nuchal translucency NT measurement made by different sonographers With alpha you can allow for these differences by specifying sonographer specific normal medians for NT Doing so removes a source of variability in NT measurement tightening the overlapping distributions of NT MoM values in affected and unaffected pregnancies and leading to improved screening performance If you interpret screening tests that include NT for example the Combined Test or the Integrated Test you should include the Sonographer field in your MS screen design for the Integrated Test you must include this field This field can then be used to identify the sonographer who makes each NT measurement in the case of the Integrated Test the sonographer must be identified Even if you do not use sonographer specific medians you should record the identity of the sonographer Doing so will mean that you can monitor NT measurements according to sonographer See sections 5 2 and 5 13 4 for further information Sonographers are identified by means of sonographer codes see section 3 18 When you begin using NT measurement
332. view the whole file to confirm that the sample ID and analyte result are identified correctly Each line of the file is displayed and the sample ID and result shown in red Test Previous Next Import file line number 1of 22 fo jp fz Jb Js Js Iz t_Jb Ie _b fe fe tt bib Je Ie Ie Ie ie Jo_fo_lo_ acter a D j e VC ou Sr ey e j oo oy S eat EN j o w j e j ea o FE bl GGG a Glib GG Gaia Gi KEG a aif Sample ID 08 585 Result 21 Figure 30 Testing the analyser Import file 3 5 Data transfer settings alph d version 8 With Data transfer settings Figure 31 you can select fields from the MS or AF database which are to be exported to another software program such as a database or spreadsheet for further analysis Appendix G Import Export Data transfer and Analyze it formats gives the meaning and format of the fields exported using Data Transfer Once selected here the chosen fields are exported using the Statistics function Data Transfer See Section 5 3 The fields you select can be saved as a data transfer specification If you use data transfer regularly for example to export weekly statistics you only need to specify the fields once on subsequent occasions you simply select the saved specification The following data transfer file formats are available E Comma separated with or without field names E Tab separated with or without field names In the comma separated formats a comma character appears be
333. w alpha interprets files read from an analyzer See section 3 4 Data transfer settings allows you configure the fields you would like to export from the alpha database See section 3 5 Database allows you to copy the alpha database to another location See section 3 6 Ethnic groups allows you to specify the names alpha uses to refer to different ethnic groups See section 3 8 Export settings configures the files which contain data exported from alpha when a final report is made See section 3 9 Import settings configures the files which contain the data imported into alpha See section 3 10 Integrated test options sets up the features which assist with the management of patients having the Integrated test See section 0 Use Licence to view your alpha licence details or renew your licence See Section 3 12 Markers allows you to review the statistical parameters used in alpha change the marker name and add a new marker See section 3 13 Message addition allows customised messages to be specified which appear on the alpha report See section 3 14 Page setup is used to specify settings paper size font size line spacing and margins for four different page styles that can be associated with different alpha printouts see section 3 15 Report format settings allows you to specify the report format files to use for your screening reports See section 3 16 Screen design allows you to select which fields are used i
334. wei ght 49 Unless stated otherwise First trimester Second trimester NT TotalhCG FreeB hCG PAPP A DVPI AFP UE hos Free B hCG First trimester Total hCG 0 0804 Free B hCG 0 1063 0 5272 PAPP A 0 1420 0 1894 0 0004 PIGF 0 0134 0 0651 0 0424 DVPI 0 3855 0 0000 0 0000 Second trimester AFP 0 0744 0 1627 0 1250 0 1580 0 2692 uE3 0 0679 0 1410 0 3387 0 3788 0 0056 0 0670 Total hCG 0 0451 0 6960 0 4869 0 1552 0 2276 0 3540 Free B hCG 0 1454 0 5803 0 7955 0 2293 0 3058 0 2294 0 4106 0 8279 Inhibin A 0 1818 0 2668 0 3117 0 1217 0 0053 0 2069 0 3035 0 4319 0 4485 Page 253 Version 8 Correlation coefficients for the screening markers in Down s syndrome pregnancies gestational age based on scan with adjustment for maternal wei ght Unless stated otherwise First trimester Second trimester NT Total hCG p E PAPP A DVPI AFP uE Total hCG dien P First trimester Total hCG 0 0819 Free B hCG 0 1080 0 5053 PAPP A 0 1506 0 1284 0 0692 PIGF 0 0134 0 0651 0 04247 DVPI 0 3855 0 0000 0 0000 Second trimester AFP 0 0809 0 1075 0 0697 0 0660 0 2692 UE 0 0695 0 1741 0 3666 0 3712 0 0056 0 1093 Total hCG 0 0466 0 6912 0 4598 0 2295 0 1920 0 3808 Free B hCG 0 1471 0 5735 0 7797 0 3004 0 3058 0 1981 0 4356 0 8178 Inhibin A 0 1854 0 2493 0 2909 0 1842 0 0053 0 1770 0 3276 0 4197 0 4384 Version 8 Page 254 Appendix K Statistical parameters Neural tube
335. wn s syndrome results of a demonstration project BMJ 305 391 394 13 Wald NJ Cuckle HS Densem JW Kennard A Smith D 1992 Maternal serum screening for Down s syndrome the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight Br J Obstet Gynaecol 99 144 149 14 Wald NJ Cuckle HS Densem JW Stone RB 1992 Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in pregnancies with insulin dependent diabetes Implications for screening for Down s syndrome Br J Obstet Gynaecol 99 51 53 15 Wald NJ Densem JW 1994 Maternal serum free B human chorionic gonadotrophin levels in twin pregnancies implications for screening for Down s syndrome Prenat Diagn 14 319 320 16 Wald NJ Densem JW Smith D Klee GG 1994 Four marker serum screening for Down s syndrome Prenat Diagn 14 707 716 17 Hackshaw AK Densem J Wald NJ 1994 Repeat maternal serum testing for Down s syndrome screening using multiple markers Prenat Diagn 15 1125 1130 18 Hackshaw AK Kennard A Wald NJ 1995 Detection of pregnancies with trisomy 18 in screening programmes for Down s syndrome J Med Screen 2 228 229 19 Palomaki GE Haddow JE Knight GJ Wald NJ ef al 1995 Risk based prenatal screening for trisomy 18 using alpha fetoprotein unconjugated esiriol and human chorionic gonadotropin Prenat Diagn 15 713 723 20 Pandya PP Snijders RJM Johnson SP de Lourdes Brizot M
336. women with affected pregnancies who have been given a positive screening result based on dates 3 1 13 Units You will need to specify the units of measurement for maternal serum markers ultrasound markers AF AFP and maternal weight for those variables that you have included in the screen design 3 2 Coefficients 3 2 1 Equations Coefficients specify the equations mathematical functions that define the relationships between E gestational age GA and the expected median values of maternal serum markers and AF AFP E crown rump length CRL and the expected median values of ultrasound markers such as nuchal translucency maternal weight and the MoM values of maternal serum markers E biparietal diameter BPD crown rump length CRL head circumference HC abdominal circumference AC measurements and GA 3 2 1 1 Median equations alpha uses median equations to estimate the expected median value in the units of measurement e g ng mL of serum markers ultrasound markers and AF AFP for a given gestational age Where the screened population includes women from different ethnic groups you can specify ethnic group specific median equations to allow for differences in serum marker levels between women of different ethnic groups Alternatively you can allow for such differences by specifying a median equation for the majority ethnic group the reference group and correction factors that are used to allow for differences in
337. x C xx24 D xy FASP Equation OK Cancel Figure 26 Select new ultrasound equation 3 2 4 Evaluating coefficients Each time you change coefficient values select Evaluate coefficients Evaluate O check that the changes you made are acceptable This produces a table Figure 27 showing expected values for the coefficients entered Examining these tables is a useful safeguard against entering incorrect values for the coefficients of median or weight adjustment equations and for equations used to estimate GA from fetal ultrasound measurements alph d version 8 This shows an evaluation of the coefficients in the regression Pn Evaluate coefficients equation for total hCG 21 05 2013 10 24 44 Bei Tage medians Expected median A B e C GA days D Overall A 14129 23 B 6640 29 Gestation Median TotalhCG Days Weeks amp Days Overall non Black Black Group 4 Group 5 Group 6 98 14 0 21963 56 101 14 3 20242 59 105 15 0 18521 10 108 15 3 17556 33 112 16 0 16591 28 115 16 3 16050 44 119 17 0 15509 44 122 17 3 15206 25 126 18 0 14902 97 129 18 3 14733 00 133 19 0 14562 98 136 19 3 14467 70 140 20 0 14372 39 143 20 3 14318 97 21 0 14265 54 150 21 3 14235 60 154 22 0 14205 65 157 22 3 14188 86 160 22 6 14175 76 Figure 27 Evaluate coefficients 3 2 5 Current and historical coefficient values You can print or view a list of current coefficients and a complete historical list of
338. y find the Integrated test options useful See Figure 37 When the Integrated test options are configured the icons W H and a are also shown on the Patients screen and can be selected to show lists of patients meeting the criteria specified See Table 5 and Table 7 Table 5 Integrated test options Description An Integrated test is deemed to be ready to report when the markers specified have been measured T Second sample planner The ideal gestational age at which the second trimester sample in the Integrated test should be provided added to the reminder list added to the overdue reminder list Q alpha 8 0 gg 2 th i Setup aah Integrated test options Ready to report Select required second trimester markers uE3 Total hCG M Si Si Ei Inhibin A Second sample planner Ideal gestational age for second sample days equivalent to 16 week s 3 day s Reminder list H Sample due at days equivalent to 17 week s 3 day s O Overdue reminder list Sample overdue at 143 days equivalent to 20 week s 3 day s Figure 37 Integrated test options 3 12 Licence You use this option Figure 38 to examine the status of your alpha licence or to renew your licence The licence status is also shown in the Setup screen Figure 13 An A credit is used each time you produce a final report for a non Integrated Test An A credit and a B credit are used each time you produce a fina

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