Screen-positive Cases Research Articles

A Canadian Provincial Screening Program for Lynch Syndrome.

Manitoba implemented the first Canadian provincial program of reflex screening through mismatch repair immunohistochemistry (MMR-IHC) for all colorectal cancers diagnosed at age 70 years or younger in December 2017. We evaluated compliance to universal reflex testing and for referrals to Genetics for individuals with MMR-deficient tumors. We searched the provincial pathology database with "adenocarcinoma" in the colorectal specimen pathology reports between March 2018 and December 2020. We cross-referenced with paper and electronic records in the Program of Genetics and Metabolism to determine whether patients with MMR-deficient tumors had been referred for Genetic assessment and what proportion of patients and first-degree relatives accepted an appointment and genetic testing. We performed logistic regression analysis to identify predictors of testing. We identified 3,146 colorectal adenocarcinoma specimens (biopsies and surgical resections) from 1,692 unique individuals (mean age 68.66 years, male 57%). Of those aged 70 years or younger (n = 936), 89.4% received MMR-IHC screening. Individual pathologists (categorized by the highest, average, and lowest screening rates) were the biggest predictors of MMR-IHC screening on multivariable analysis (highest vs lowest: odds ratio 17.5, 95% confidence interval 6.05-50.67). While only 53.4% (n = 31) of 58 screen-positive cases were referred by pathologists for genetic assessment, other clinicians referred an additional 22.4% (n = 13), resulting in 75.8% overall referral rate of screen-positive cases. Thirteen (1.4%) patients (1.1%, aged 70 years or younger) were confirmed to experience Lynch syndrome through germline testing, and 8 first-degree relatives (an average of 1.6 per patient) underwent cascade genetic testing. The first Canadian Lynch syndrome screening program has achieved high rates of reflex testing.

Colposcopic Findings for Detecting Pre-invasive Lesion of Cervix Among Visually Inspected Acetic Acid Positive Cases

Background: Cervical cancer-a preventable disease, is the second most commonly diagnosed cancer among women of developing countries. Paps smear is the gold standard screening method worldwide. But a low-cost test, visual inspection of cervix with acetic acid (VIA) has been emerged as an alternative for use in lowresource settings. VIA is simple and easy to perform by auxiliary health professionals. Colposcopy is an essential procedure in the evaluation of screen positive cervix though it requires considerable training and experience. Objective: The objective of this study was to evaluate the VIA positive cases by colposcopy, colposcopy guided biopsy and histopathological examination. Methods: This was a cross sectional observational study conducted among 100 VIA positive cases attended at GOPD of Dhaka Medical College Hospital from July 2014 to December 2014. Colposcopy was performed in all VIA positive cases. Subsequent biopsy and histopathological examinations were done for those with colposcopic abnormal findings. Results: The mean age of the study population was 37.9±9.3 years. Among VIA positive cases 66.0% had complaints of whitish vaginal discharge. Among the study population, colposcopically 46.0% had healthy cervix (normal) and 54.0% had abnormal findings. Colposcopy guided biopsy was taken from those with abnormal findings. Histopathological findings were normal in 38.9% cases, chronic cervicitis in 20.37% cases, squamous cell metaplasia in 3.7% cases, CIN I in 16.7%, CIN II in11.11%, CIN III in 5.6% and 3.7% cases were carcinoma cervix. True positive value was 20, false positive value 34 and positive predictive value of colposcopy was 37.03%. Conclusion: This study concluded that VIA is effective in detection of CIN and invasive carcinoma of cervix. It also suggests the role of colposcopy in the evaluation of CIN and other cervical diseases in screen positive cases. VIA can be used as a screening tool in low and middle income countries like Bangladesh, not only in rural areas and small health centres, but also in hospitals, cancer institutes, and other health facilities with better resources. Bangladesh Med Res Counc Bull 2022; 48(1): 27-32

Fiberoptic endoscopic validation of a clinical screening test of swallowing function in critically ill patients performed within 24 h after extubation

BackgroundA bedside screening tool of swallowing dysfunction (SD) (BSSD) after extubation would be useful to identify patients who are at risk of SD. We aimed to evaluate the accuracy of our BSSD in comparison with fiberoptic endoscopic evaluation of swallowing (FEES) in critically ill patients after extubation. MethodsWe conducted a 1-year prospective monocentric study to evaluate the accuracy of our BSSD to diagnose SD following endotracheal intubation in comparison with FEES (gold standard). Patients intubated for longer than 48 h were included. Both tests were assessed within 24 h after extubation. Primary endpoint was the accuracy of the BSSD. Secondary endpoint was to assess risk factors of SD. ResultsSeventy-nine patients were included in the study. Thirty-three patients (42%) presented with a SD. The BSSD showed a sensitivity of 88% (95% CI 0.72–0.97) and a specificity of 91% (95% CI 0.79–0.98), a positive predictive value of 88% (95% CI 0.72–0.97) and a negative predictive value of 91% (95% CI 0.79–0.97). The AUC reached 0.83 (95% CI 0.74–0.92). ConclusionOur study describes an accurate clinical screening tool to detect SD after extubation in critically ill patients. Screening-positive cases should be confirmed by instrumental tests, ideally using FEES.

Biochemical Serum Markers Influencing Maternal Age Risk for Down's Syndrome in Quadruple Marker.

Objective: Maternal age is the primary risk factor associated with Down syndrome (DS) in the fetus. Biochemical serum markers in maternal screenings have improved DS detection rates in prenatal screenings. However, there is a dilemma regarding which age group should undergo preliminary noninvasive screening before undergoing invasive diagnostic procedures. Based on recommendations, all pregnancies are at risk of chromosomal abnormalities. While all women should be offered screenings, those over 35 are mainly offered an invasive diagnostic procedure, and serum screening tests are of little benefit for this age group. This study evaluated the maternal serum screening population and the significance of the final screen positivity rate in the risk group aged above 35 years.Method: An observational retrospective study was conducted on a cohort of pregnancies in the second trimester (14-20 weeks and 6 days of gestation) over a period of one year. The quadruple test consisted of serum alpha-fetoprotein (AFP), free beta hCG, unconjugated estriol e3 (Ue3), and inhibin-A. The risk for DS was calculated using software with corrections for ethnicity, smoking, weight, and age. We compared the age risk for DS with the biochemical risk. Statistical analysis was done using McNemar’s test to test the proportion of screen-positive (SP) cases between the two calculation methods, i.e., age alone versus final risk calculation with biomarkers.Results: The proportion of SP cases from age risk and final risk were 56.3% and 12.6%, respectively. The computed McNemar’s chi-square test statistic was 97.959 (p < 0.001), which showed a significant reduction in SP cases when biomarkers were added to screen for trisomy 21 women aged >35 years.Conclusion: The age risk of DS increased with increasing maternal age. Notably, the final biochemical risk in this population was significantly lower. Consequently, we proposed that a noninvasive serum screening be used to screen all age groups to rule out negative screen cases before subjecting them to invasive procedures.

Cancer screening in the COVID-19 pandemic; Development of early diagnostic strategies

Aim:Early diagnosis is very important in some cancers such as breast, cervical and colorectal. However, the COVID-19 pandemic has severely disrupted cancer screening programmers in many countries. In this study, it is aimed to contribute to the literature on this subject by reviewing the status of local cancer screenings during the pandemic period.Methods: This retrospective study includes the 114.727 people in the risky group for cancer screening determined in Bolu, Turkey as two groups. During 2017-2019 years was determined as pre-pandemic group while the year of 2020 was the pandemic group. Data about patients’ results of smear / HPV (Human Papilloma Virus), fecal occult blood test (FOBT) and mammography had analyzed and compared with chi-square test.Results:For all of the screening strategies, smear / HPV, FOBT and mammography, mean of screening cases, positive cases and biopsies had significantly decreased (p&lt;0.05),but there was no statistically difference for mean of definitive diagnoses about all of these cancers even if it has been decreased between two groups.Conclusion: The results of our study show that cancer screening processes are significantly disrupted during the pandemic period. Therefore, it is important to develop new screening strategies for the uninterrupted execution of cancer screening programs, especially during pandemic periods. However, we believe in the necessity of supporting studies with larger patient groups.

Mesonephric-like Endometrial Carcinoma: Results From Immunohistochemical Screening of 300 Endometrial Carcinomas and Carcinosarcomas for This Often Overlooked and Potentially Aggressive Entity.

Mesonephric-like endometrial carcinoma is a rare but frequently misclassified and aggressive malignancy. KRAS mutations, limited estrogen receptor (ER) expression, and TTF-1, GATA3, and luminal CD10 expression are described in these tumors, but an immunohistochemistry-based screening approach has not been studied. We assessed 300 endometrial carcinomas/carcinosarcomas to ascertain the specificity of TTF-1/GATA3/luminal CD10 expression with or without ER staining for this diagnosis. Next-generation sequencing and morphologic review were performed on screen-positive cases. In all, 3% (9/300) were TTF-1+; 2 coexpressed GATA3. No cases expressed luminal CD10 or GATA3 in isolation. Two TTF-1+/ER- cases, one of which was also GATA3+, were reclassified as mesonephric-like based on morphology and molecular results (KRAS mutations without mismatch repair deficiency, TP53 mutations, or PTEN mutations): these represented 0.7% of all cases (2/300). The reclassified cases were originally diagnosed as grade 1 and 2 endometrioid carcinoma, and the latter had pulmonary metastases and pelvic recurrences. Six TTF-1+ cases retained their original serous (3) and endometrioid (3) diagnoses; 1 was reclassified as dedifferentiated. All had negative or low ER. KRAS mutations were identified in 4 TTF-1+ non-mesonephric-like cases, including 1 serous and 1 grade 3 endometrioid with p53 abnormalities, 1 mismatch repair-deficient endometrioid with a complex molecular profile, and 1 endometrioid with mucinous differentiation. These findings suggest that TTF-1 and ER are good first-line screens for mesonephric-like carcinoma, but caution that a TTF-1+/ER- immunoprofile is not specific, even in the setting of KRAS mutations. A final diagnosis of mesonephric-like carcinoma requires integration of morphologic and immunohistochemical features, with molecular support when relevant.

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies.

The aim of this study was to determine the predictive value of expanded noninvasive prenatal testing (NIPT-plus) for fetal chromosome abnormalities in the second trimester (12-26 weeks). We conducted a retrospective cohort study of 39,580 pregnancies with NIPT-plus. Screening positive cases were diagnosed with karyotyping and single-nucleotide polymorphism array analysis (SNP array)/copy number variation sequencing (CNV-seq) with follow-up. The positive predictive values (PPVs) of trisomy 21, 18, and 13 (T21, T18, and T13), sex chromosome aneuploidies (SCAs), and microdeletion and microduplication syndromes (MMS) by NIPT-plus were recorded. We assessed the predictive value of NIPT-plus based on maternal age and conventional indications. Of 39,580 pregnancies with NIPT-plus, 511 (1.3%) had prenatal screening positive results of fetal chromosome abnormality, of which 87.7% (448/511) had invasive prenatal diagnosis. NIPT-plus performed better in predicting fetal SCAs and chromosome aneuploidies for pregnancies with advanced maternal age (AMA) than young maternal age (YMA). Besides, the PPVs of T21, T13, and chromosome aneuploidies showed an upward trend when comparison was based on maternal age in 5-year subintervals. The termination rates of 45,X, 47,XXX, 47,XXY, and 47,XYY were 100% (11/11), 20.0% (3/15), 91.7% (22/24), and 7.1% (1/14) with postnatal follow-up. Last but not least, the PPV for MMS is 41.7% (30/72), which may have a positive correlation between the size of CNVs. Pregnant women with screen-positive results for common trisomies (T13, T18, and T21) were more willing to conduct invasive prenatal diagnosis compared to those with positive results for SCAs or MMS. However, the current study demonstrated SCAs and MMS had the lowest PPV. This highlights the importance of confirmatory prenatal diagnosis in those patients and the potential impact on genetic counseling and informative decision-making.

Lynch Syndrome Screening of Women with Endometrial Cancer: Feasibility and Outcomes in a Community Program.

Universal screening of endometrial cancer for underlying Lynch syndrome (LS) using DNA mismatch repair immunohistochemistry (MMR IHC) has been recommended. The objective of this study was to assess the feasibility and outcomes of using office endometrial samplings in a community LS screening program. A community laboratory adopted Cancer Care Ontario's LS screening recommendations. All new endometrial cancers in women aged <70 years were screened for LS using MMR IHC and MLH1 promoter methylation testing cascade for MLH1/PMS2-deficient cases. This retrospective validation study analyzes the first year's results. Of 693 new endometrial cancers, 467 (67.4%) were eligible for LS screening. Both MMR IHC and MLH1 promoter methylation testing were conclusive in >98% of cases. MMR deficiency (MMRd), which includes LS screen-positive cases, was identified in 25.9% of patients (121/467). LS screen-positive tumours comprised 5.9% (27/467) of all cases. Endometrial samplings from community practice are suitable for pre-operative LS screening. This testing can identify MMRd endometrial cancers with significant prognostic implications. Approximately 1 in 20 Ontario women <70 years of age with endometrial cancer screen positive for LS. Pre-operative and/or operative assessment for co-existent colonic neoplasms needs to be considered in this high-risk group. In addition, these women should be referred to genetic counselling.

Evaluation of Mood Changes AmongPeripartum Women at PKDAS Institute of Medical Science, Vaniyamkulam, Palakkad: A Prospective, Observational, Longitudinal Study

Background: The perinatal period is well established as an increased risk for development of serious mood disorders. Maternal mental health in developing countries gets less than its due attention. The present study was undertaken to evaluate mood changes in Peripartum period in our population and to identify demographic, obstetric, social and psychosocial risk factors associated with Peripartum depression using established scales.Material &amp; Methods:A prospective, observational, longitudinal study conducted in PK das institute of medical science, vaniyamkulam, with 387 perinatal women for 12 months (February 2018– January 2019). Various scales EPDS (Edinburgh Postnatal Depression Scale), CMSS (Couple Marital Satisfaction Scale, IMS (Index of Marital Satisfaction), LES (Life Event Scale) were studied in Peripartum Period.Results:Among a total of 387 participants about half 189 (48.8%) were in 19-25 years of Age. Almost 30% and 40% had dissatisfied married life as per the CMS and IMS scales respectively. Just above 42% were screen positive for depression antenatally with EPDS &amp; 39% (n = 151) in the immediate postpartum period. From these 151 screen positive cases in immediate postpartum period, 138 participants were followed up at 4-6 weeks (13 were lost to follow up) and up to 115 of 138 (83.3%) were screen positive for depression (N= 387, 29.7%), which was statistically significant (p&lt;0.001). With EPDS during antenatal period there was no statistically significant relationship of depression with Education (p = 0.195), Occupation (p = 0.651) and pregnancy planned or unplanned (p = 0.223), whereas, Joint family, participants with dissatisfied marital relationship had increased risk of depression as evidenced by IMS and CMSS (p &lt; 0.001). Participants with a previous male gender baby had less risk of developing depression (p&lt; 0.001) &amp; participants with previous 2 female children had increased risk of depression (p&lt; 0.001).Conclusions:This study highlights importance of screening for maternal mental health problems during Peripartum period. Depression in immediate postpartum period is good predictor for increased risk of depression at 4-6 weeks postpartum.

Gender differences in positive screen for depression and diagnosis among older adults in Chile

BackgroundDifferent factors are associated with late life depression and diagnosis, including gender. It has also been reported that depression among older people is underdiagnosed. As a result, the mental health needs of this group are insufficiently met. The aim of this study was to explore gender differences in the factors associated with positive screens for depression and self-reported diagnosis among older adults in Chile.MethodsData from 3786 older adults who participated in the Social Protection Survey in 2016 were analysed. PHQ-9 was used to identify screen-positive cases. Self-reported diagnosis of depression was used to determine the proportion of people with a screen-positive result who had received a diagnosis of depression. Logistic regression models were used to determine sociodemographic and health factors associated with depression and underdiagnosis in older men and women.ResultsThe prevalence of a screen-positive result was 20.91% (5.83% major depressive disorder) among men, and 36.38% (12.43% major depressive disorder) among women. 18.77% of men and 34.11% of women with a positive depression screening had received a diagnosis. More educated men were more likely to receive a diagnosis. Older age was associated with a lower probability of diagnosis among older women.ConclusionsOur results suggest that depressive disorders are undiagnosed in a high proportion of older adults in Chile. Gender is a relevant factor in the underdiagnosis of depression in this group. Further research is needed to understand the factors involved in these gaps, to improve detection and provide timely support and treatment.

Need for Uniform Definitions in Newborn Screening for SCID: The Next Challenge for Screeners and Immunologists.

During the ISNS meeting “Newborn Screening for SCID ‘State of the Art’” on 26 and 27 January 2021, the topic of case definitions and related issues were discussed. There is currently a lack of uniform definitions and therefore a lack of uniform registration of screen-positive cases. This severely hampers the comparison of outcomes of different screening programs and the exchange of experiences gained by the different countries performing SCID screening, which is essential to improve screening programs. In this letter, I outline the current situation and indicate the need for uniform definitions and classification, which in my view needs to be a joined effort of screeners and immunologists.

Feasibility of digital atrial fibrillation screening in an elderly population : The Ulm heart rhythm weeks.

Atrial fibrillation (AF) screening in risk populations has the potential to prevent strokes. The authors tested the feasibility of adigital program with initial photoplethysmographic (PPG) self-screening and cardiologist-attended electrocardiographic (ECG) confirmation of screen-positive cases. Inhabitants of the city of Ulm aged ≥ 65years were invited to participate. After digital consent, participants were given access to asmartphone application for 14days of self-screening (two recordings per day recommended). Screen-positive participants without known AF were invited to present to acardiologist for AF confirmation with a14-day ECG event recorder. PPG recordings were first analyzed by algorithm using acombination of linear and non-linear methods. The quality of pathological (classified by algorithm) PPG and all ECG recordings were checked by atelecare service. Primary outcomes included adherence to the screening protocol defined as the proportion of participants performing at least 14PPG recordings (or until documentation of absolute arrhythmia) and the proportion of pathological PPG and all ECG recordings rejected by the telecare center. A total of 215participants registered. Of these, 204 (95%) performed at least one recording and 169 (79%) reached the performance target of two sufficient measurements per day; 75PPG recordings were automatically classified as pathological by algorithm; 14(19%) were rejected by the telecare service due to poor quality. Of the 12participants with asuspected first diagnosis of AF, five visited acardiologist as part of the study. Of 1090 ECG recordings obtained, 390 (36%) were qualified as non-diagnostic. AF was confirmed in three cases. Adigital AF screening program with initial self-screening and referral of screen-positive cases to acardiologist-attended ECG-confirmation service is feasible with meaningful results in an elderly risk population. However, the availability of the target population of persons > 65years of age for such adigital screening program appears to be limited despite extensive public relations activities.

Newborn Screening for Severe Combined Immunodeficiency: Do Preterm Infants Require Special Consideration?

The Wisconsin Newborn Screening (NBS) Program began screening for severe combined immunodeficiency (SCID) in 2008, using real-time PCR to quantitate T-cell receptor excision circles (TRECs) in DNA isolated from dried blood NBS specimens. Prompted by the observation that there were disproportionately more screening-positive cases in premature infants, we performed a study to assess whether there is a difference in TRECs between full-term and preterm newborns. Based on de-identified SCID data from 1 January to 30 June 2008, we evaluated the TRECs from 2510 preterm newborns (gestational age, 23–36 weeks) whose specimens were collected ≤72 h after birth. The TRECs from 5020 full-term newborns were included as controls. The relationship between TRECs and gestational age in weeks was estimated using linear regression analysis. The estimated increase in TRECs for every additional week of gestation is 9.60%. The 95% confidence interval is 8.95% to 10.25% (p ≤ 0.0001). Our data suggest that TRECs increase at a steady rate as gestational age increases. These results provide rationale for Wisconsin’s existing premature infant screening procedure of recommending repeat NBS following an SCID screening positive in a premature infant instead of the flow cytometry confirmatory testing for SCID screening positives in full-term infants.

Socio-demographic Characteristics of Newly Reported HIV Cases in Iraq (1986-2019)

Background: HIV/AIDS is considered as one of the most important public health concern faced by manydeveloped and developing countries.Objective: To study the basic socio-demographic characteristics of the newly reported HIV Iraqi casesduring the period extending from 1986 to 2019.Subjects and Methods: This is across sectional study conducted using data from newly reported HIVIraqi cases from March 2018 to March 2020. These data were available from the patient’s records at theIraqi National HIV/AIDS Program Centre. Annual registration statistics covering the period from 1986 to2019 were reviewed. The diagnosis was done through identification of anti-HIV antibodies using primarilyELISA as screening test and positive cases were confirmed by Western blot assay. The obtained data werecategorized according to the socio-demographic variables and were analyzed statistically.Results: A total number of newly reported HIV Iraqi cases covering the period from 1986 to 2019 was 892cases. The majority of the cases were males (83%), from 21-39 years old (60.3%), alive (65.7%), and single(53.4%). Most of them were from low educational level (45.1%), low socio-economic status (48.3%), andliving in urban areas (75.6%) from Central origin (63.2%).Conclusions: Identification of these findings may provide important directions for targeting certain sociodemographiccharacteristics of the HIV infections to provide specific support for accessing healthcareservices and evaluating the effectiveness of prevention and control measures.

The application of expanded noninvasive prenatal screening for genome-wide chromosomal abnormalities and genetic counseling

Objective To evaluate the clinical application of expanded noninvasive prenatal screening (eNIPS) for genome-wide large copy number variation (CNV), i.e. chromosomal deletion/duplication >5 Mb, and aneuploidy; also to provide practical information for counseling eNIPS positive cases. Method We recruited 34,620 women with singleton pregnancy for genome-wide cell-free plasma DNA sequencing. Screening positive cases were verified by karyotyping and/or SNP array. Result A total of 461 (1.33%) positive cases were identified through our cfDNA screening including 209 cases of common trisomies (0.60%), 124 cases of sex chromosomal abnormalities (SCA) (0.36%), 71 cases of other autosomal anueploidies (OAA) (0.21%), and 57 CNVs larger than 5 Mb (0.16%). The predictive positive values (PPV) were 70.06% in general for common trisomies with as high as 91.67% for Trisomy21 (T21), 40.22% in general for SCAs with as high as 100% for Jacob Syndrome (XYY). The PPV for OAAs was 5.45%, and T7/T8/T16/T22 were the most frequent OAAs (n = 15, 9, 9, 8, respectively). The PPV for CNVs larger than 5 Mb was 51.22% (n = 57) with the CNV mostly detected on Chr5/Chr4/Chr2/Chr7 (n = 10, 8, 5, 5, respectively). Conclusion The expanded NIPS had shown promising PPVs for CNVs (large than 5 Mb), SCAs and common trisomies, yet this method required higher efficacy in screening for OAAs. The post-test genetic counseling for expanded NIPS should be tailored to the types of positive cases and also address the origin of abnormal signals (fetal vs. maternal).

Performance of a pre-administration infection screening questionnaire in patients with rheumatoid arthritis administered biological disease-modifying antirheumatic drugs.

Pre-administration screening of active infections is imperative for the safe use of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). However, a standardized screening method is lacking. We therefore implemented a novel systematic screening method with a simple predetermined questionnaire on infections and assessed its effectiveness. We retrospectively reviewed medical records of individuals for whom intravenous bDMARDs were administered for RA from January 2016 to April 2019. We evaluated the performance of the new screening method based on physicians' assessments. In addition, a survey was administered to nurses, regarding their assessment of the usefulness of this new screening. The incidence of infections was also assessed. A total of 1636 cases underwent this new screening. The new screening method showed high sensitivity (0.97) and specificity (0.89) with a negative predictive value of 99.9%, as determined based on the physician's decision. Administration of bDMARDs was postponed in 37 (2.5%) patients, and there was only one case in which the screening failed to note an active infection. The nurses' survey demonstrated high agreement (87.5%) about the usefulness of this screening on the grounds of clarity, simplicity, ease, and time-saving effects. There was no significant increase in infections after implementation of this method. Systematic screening with a predetermined simple questionnaire is effective as an infection screening method, with a high negative predictive value. This approach contributes to high satisfaction of nurses and a time-efficient practice by focusing on screen-positive cases without increasing infections.

Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies

BackgroundThis paper describes the clinical practice and performance of cell-free DNA sequencing-based non-invasive prenatal testing (NIPT) as a screening method for fetal trisomy 21, 18, and 13 (T21, T18, and T13) and sex chromosome aneuploidies (SCA) in a general Italian pregnancy population.MethodsThe AMES-accredited laboratory offers NIPT in maternal blood as a screening test for fetal T21, T18, T13 and SCA. Samples were sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay.ResultsA retrospective analysis was performed on 36,456 consecutive maternal blood samples, including 35,650 singleton pregnancies, 800 twin pregnancies, and 6 triplet pregnancies. Samples were tested between April 2017 and September 2019. The cohort included 46% elevated-risk and 54% low-risk patients. A result indicative of a classic trisomy was found in 356 (1%) of singleton or twin samples: 254 T21, 69 T18, and 33 T13. In addition, 145 results (0.4%) were indicative of a SCA. Of the combined 501 screen-positive cases, 484 had confirmatory diagnostic testing. NIPT results were confirmed in 99.2% (247/249) of T21 cases, 91.2% (62/68) of T18 cases, 84.4% (27/32) of T13 cases, and 86.7% (117/135) of SCA cases. In the 35,955 cases reported as unaffected by a classic trisomy or SCA, no false negative cases were reported. Assuming that false negative results would be reported, the sensitivity of NIPT was 100.00% for T21 (95% Cl 98.47–100.0), T18 (95% Cl 94.17–100.0), and T13 (95% Cl 87.54–100.0). The specificities were 99.99% (95% Cl 99.98–100.0), 99.98% (95% Cl 99.96–100.0), 99.99% (95% Cl 99.97–100.0), and 99.95% (95% Cl 99.92–99.97) for T21, T18, T13, and SCA, respectively.ConclusionThis retrospective analysis of a large cohort of consecutive patients who had whole-genome sequencing-based NIPT for classic trisomies and SCA shows excellent detection rates and low false positive rates.

SMART Mental Health Project: process evaluation to understand the barriers and facilitators for implementation of multifaceted intervention in rural India

BackgroundGlobally, mental health problems are a growing public health concern. Resources and services for mental disorders are disproportionately low compared to disease burden. In order to bridge treatment gaps, The Systematic Medical Appraisal, Referral and Treatment (SMART) Mental Health Project was implemented across 12 villages in West Godavari district of the southern Indian state of Andhra Pradesh. This paper reports findings from a process evaluation of feasibility and acceptability of the intervention that focused on a mental health services delivery model to screen, diagnose and manage common mental disorders (CMDs).MethodsA mixed methods evaluation was undertaken using quantitative service usage analytics, and qualitative data from in-depth interviews and focus group discussions were conducted with stakeholders including primary care physicians, community health workers, field staff and community members. Barriers to and facilitators of intervention implementation were identified. Andersen’s Behavioral Model for Health Services Use was the conceptual framework used to guide the process evaluation and interpretation of data.ResultsIn all, 41 Accredited Social Health Activists (ASHAs) and 6 primary health centre (PHC) doctors were trained in mental health symptoms and its management. ASHAs followed up 98.7% of screen positive cases, and 81.2% of these were clinically diagnosed and treated by the PHC doctors. The key facilitators of implementation were adequate training and supervision of field staff, ASHAs and doctors, use of electronic decision support, incorporation of a door-to-door campaign and use of culturally tailored dramas/videos to raise awareness about CMDs, and organising health camps at the village level facilitating delivery of intervention activities. Barriers to implementation included travel distance to receive care, limited knowledge about mental health, high level of stigma related to mental health issues, and poor mobile network signals and connectivity in the villages. Lack of familiarity with and access to mobile phones, especially among women, to accessing health related messages as part of the intervention.ConclusionsThe evaluation not only provides a context to the interventionsdelivered, but also allowed an understanding of possible factors that need tobe addressed to make the programme scalable and of benefit to policy makers.

Efficacy of targeted screening and proactive management for placenta accreta spectrum disorder in routine clinical settings.

There is a dearth of evidence on targeted screening for placenta accreta spectrum disorder (PASD) in routine clinical practice with proactive management of screen-positive cases [1]. We prospectively reviewed our experience to shed some light on this issue. In Princess Margaret Hospital, China, all pregnancies with cesarean scar had an ultrasound for placental location and a clinical risk factor-based assessment for PASD.

Congenital hypothyroidism in Indian preterm babies - screening, prevalence, and aetiology.

Paucity of data on hypothyroidism in Indian preterms. Aim of the study: To describe the prevalence, aetiology, and experience with screening for primary hypothyroidism in preterm babies. A prospective observational study conducted for 3 years in atertiary care unit, where all babies born<37weeks screened by heel prick for Thyroid Stimulating Hormone (TSH) were included. All screen positive cases (TSH≥6µIU/ml) underwent venous testing immediately; venous TSH ≥ 20 or Free T4<0.9 ng/dl was considered as confirmed positive. All babies underwent venous testing at term. Etiological testing was performed where feasible. Confirmed cases were initiated on thyroxine therapy and followed up. 1167 preterm babies presented during the study period. 1147 (98%) underwent TSH screening and 17 (1.4%) were screen positive; 15 babies underwent confirmatory venous test. Of these 15 babies, 2 were confirmed and started on therapy. The remaining 13 babies underwent retest venous sample at term, and 8 of these were confirmed cases. Of the screen-negative babies, 94% underwent repeat venous testing at term/ prior to discharge. Five were confirmed to have congenital hypothyroidism. Thus, the prevalence of congenital hypothyroidism was 1 in 77 preterm babies. No correlation was observed between screening TSH and venous TSH (p>0.05). Aetiological evaluation in 8 babies revealed secondary to maternal antibody in 4 cases (50%) and permanent thyroid defects in 4 cases (50%). We observed ahigh prevalence (1 in 77), need for repeat venous testing, irrespective of initial screening, and significant permanent congenital hypothyroidism (50%) in our series.