Unselected Individuals Research Articles

Adenoma detection rate by colonoscopy in real-world population-based studies: a systematic review and meta-analysis.

Adenoma detection rate (ADR) is a quality indicator set at a minimum of 25% in unselected populations by the European Society of Gastrointestinal Endoscopy (ESGE). Nevertheless, a lack of pooled observational data resembling real-world practice limits support for this threshold. We aimed to perform a systematic review with meta-analysis to evaluate the pooled rates for conventional adenoma detection, polyp detection (PDR), cecal intubation, bowel preparation, and complications in population-based studies. The PubMed, Scopus, and Web of Science databases were searched until May 2023 for populational-based studies reporting overall ADR in unselected individuals. A random-effects model was used for meta-analysis. 31 studies were included, comprising 3 644 561 subjects. A high quality of procedures was noticeable, with a high cecal intubation rate and low complication rate. The overall pooled ADR, PDR, and rate of cancer detection were 26.5% (95%CI 23.3% to 29.7%), 38.3% (95%CI 32.5% to 44.1%), and 2.7% (95%CI 1.5% to 3.9%), respectively. ADR varied according to indication: screening 33.3% (95%CI 24.5% to 42.2%), surveillance 42.9% (95%CI 36.9% to 49.0%), and diagnostic 24.7% (95%CI 19.5% to 29.9%), with subgroup analysis revealing rates of 34.4% (95%CI 22.0% to 40.5%) for post-fecal occult blood test and 26.6% (95%CI 22.6% to 30.5%) for primary colonoscopy screening. Diminutive conventional adenomas yielded a pooled rate of 59.9% (95%CI 43.4% to 76.3%). The pooled rate for overall serrated lesion detection was 12.4% (95%CI 8.8% to 16.0%). Male sex and higher age were significantly associated with an ADR above the benchmark. This first meta-analysis relying on real-world observational studies supports the ESGE benchmark for ADR, while suggesting that different benchmarks might be used according to indication, sex, and age.

Daily Social Isolation Maps Onto Distinctive Features of Anhedonic Behavior: A Combined Ecological and Computational Investigation

BackgroundLoneliness and social isolation have detrimental consequences for mental health and act as vulnerability factors for the development of depressive symptoms, such as anhedonia. The mitigation strategies used to contain COVID-19, such as social distancing and lockdowns, allowed us to investigate putative associations between daily objective and perceived social isolation and anhedonic-like behavior. MethodsReward-related functioning was objectively assessed using the Probabilistic Reward Task. A total of 114 unselected healthy individuals (71% female) underwent both a laboratory and an ecological momentary assessment. Computational modeling was applied to performance on the Probabilistic Reward Task to disentangle reward sensitivity and learning rate. ResultsFindings revealed that objective, but not subjective, daily social interactions were associated with motivational behavior. Specifically, higher social isolation (less time spent with others) was associated with higher responsivity to rewarding stimuli and a reduced influence of a given reward on successive behavioral choices. ConclusionsOverall, the current results broaden our knowledge of the potential pathways that link (COVID-19–related) social isolation to altered motivational functioning.

Diabetes distress and depression are independently associated with gastrointestinal symptoms in type 2 diabetes in Bangladesh.

Gastrointestinal (GI) symptoms, common in type 2 diabetes (T2D), are typically bothersome, socially embarrassing, and impact negatively on quality of life. They may also contribute to diabetes distress (DD), but this has never been formally evaluated. We aimed to investigate the relationships between GI symptoms, DD and depressive symptoms in a large cohort of individuals with T2D in Bangladesh. 1406 unselected T2D individuals (female 58.8%; mean age 51.0 ± 12.5 years) from four diabetes clinics in Bangladesh completed validated questionnaires evaluating GI symptoms (PAGI-SYM), DD (DDS-17) and depressive symptoms (PHQ-9). 31.1% of participants reported GI symptoms (36.2% females, 23.7% males), while 51.1% had elevated DD and 37.8% depressive symptoms. GI symptoms exhibited independent relationships with both DD and depressive symptoms, and their likelihood was higher among those with DD (OR: 3.6 [2.2-5.6] and with depressive symptoms (OR: 5.9 [3.5-9.9]). GI symptoms are independently associated with both DD and depressive symptoms in people with T2D in Bangladesh.

Associations between alcohol consumption and empathy in a non-clinical sample: drinking motives as a moderator

People consume alcohol for multiple reasons. Negative motives are often associated with alcohol-related problems. These problems might be explained by negative effects of high alcohol consumption on empathy. Past studies have associated alcohol use disorder (AUD) with reduced cognitive and affective empathy. Few studies have focused on non-clinical samples and considered behavioral empathy. We examined the links between alcohol consumption and multiple aspects of empathy, and if these links were moderated by negative drinking motives. We collected online data of 520 unselected individuals. All completed the AUD Identification Test (AUDIT) and a Drinking Motives Questionnaire. Affective and cognitive empathy were assessed using the Empathy Quotient. Behavioral empathy was assessed by asking participants how likely they would help the person in each of 24 scenarios involving pain. Helping others in pain was positively predicted by affective and cognitive empathy. Higher AUDIT scores were associated with helping others less, particularly among participants who scored higher on drinking to cope with negative affect. People who drink more and do so to cope with negative affect appear to have less behavioral empathy. This supports the view that negative drinking motives contribute to AUD risk.

Penetrance and expressivity of mitochondrial variants in a large clinically unselected population.

Whole genome sequencing (WGS) from large clinically unselected cohorts provides a unique opportunity to assess the penetrance and expressivity of rare and/or known pathogenic mitochondrial variants in population. Using WGS from 179 862 clinically unselected individuals from the UK Biobank, we performed extensive single and rare variant aggregation association analyses of 15 881 mtDNA variants and 73 known pathogenic variants with 15 mitochondrial disease-relevant phenotypes. We identified 12 homoplasmic and one heteroplasmic variant (m.3243A>G) with genome-wide significant associations in our clinically unselected cohort. Heteroplasmic m.3243A>G (MAF = 0.0002, a known pathogenic variant) was associated with diabetes, deafness and heart failure and 12 homoplasmic variants increased aspartate aminotransferase levels including three low-frequency variants (MAF ~0.002 and beta~0.3 SD). Most pathogenic mitochondrial disease variants (n = 66/74) were rare in the population (<1:9000). Aggregated or single variant analysis of pathogenic variants showed low penetrance in unselected settings for the relevant phenotypes, except m.3243A>G. Multi-system disease risk and penetrance of diabetes, deafness and heart failure greatly increased with m.3243A>G level ≥ 10%. The odds ratio of these traits increased from 5.61, 12.3 and 10.1 to 25.1, 55.0 and 39.5, respectively. Diabetes risk with m.3243A>G was further influenced by type 2 diabetes genetic risk. Our study of mitochondrial variation in a large-unselected population identified novel associations and demonstrated that pathogenic mitochondrial variants have lower penetrance in clinically unselected settings. m.3243A>G was an exception at higher heteroplasmy showing a significant impact on health making it a good candidate for incidental reporting.

Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing

As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n= 95), breast cancer (n= 96), cardiomyopathy (n= 95), colorectal cancer (n= 105), or familial hypercholesterolemia (n= 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p<0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p<0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p<0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return.

Chronic hand eczema: A prevalent disease in the general population associated with reduced quality of life and poor overall health measures.

The impact of hand eczema (HE) on Health-Related Quality of Life (HRQoL) has only been sparsely studied in a general population setting, and never by use of the disease specific Quality Of Life in Hand eczema Questionnaire (QOLHEQ). To examine the HRQoL of unselected individuals with HE using the QOLHEQ. Further, to provide prevalence estimates of severe and chronic HE (CHE), and to contrast overall health related outcomes between individuals with and without HE. In this nationwide, cross-sectional study a questionnaire covering questions on HE related outcomes, and overall health was sent to a random sample of 100 000 Danish adults via a secure digital mailbox, linked to their unique civil registration numbers. Data on demographic characteristics were retrieved from the civil registration system. Individuals reporting HE, further answered the QOLHEQ and other disease specific questions. The response rate was 42.7% (n = 42 691). Total estimates of lifetime, 1-year and point prevalences of HE were 24.4%, 13.3% and 5.8%. Of individuals reporting a 1-year prevalence, 35.1% reported moderate-severe disease and 82.6% CHE. Individuals with HE were more likely to report less good or poor overall health, and sick leave (any reason), compared to those without. In the 2176 (92.5%) with current HE who completed the QOLHEQ, median QOLHEQ scores corresponded to a moderate impairment of the symptoms and treatment and prevention domains and a slight impairment overall and for the emotions and functioning domains. Factors that were strongly associated with moderate to severe HRQoL impairment included severe, chronic and occupational HE as well as female sex. HE is highly prevalent, bears a considerable burden on society and significantly affects the lives of impacted individuals. Our findings indicate a necessity for targeted prevention aimed at high-risk groups, and support and treatment for those most affected.

Germline Mutations in 12 Genes and Risk of Ovarian Cancer in Three Population-Based Cohorts.

With the widespread use of multigene panel genetic testing, population-based studies are necessary to accurately assess penetrance in unselected individuals. We evaluated the prevalence of germline pathogenic or likely pathogenic variants (mutations) in 12 cancer-predisposition genes and associations with ovarian cancer risk in three population-based prospective studies [Nurses' Health Study (NHS), NHSII, Cancer Prevention Study II]. We included women with epithelial ovarian or peritoneal cancer (n = 776) and controls who were alive and had at least one intact ovary at the time of the matched case diagnosis (n = 1,509). Germline DNA was sequenced for mutations in 12 genes. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for ovarian cancer risk by mutation status. The mutation frequency across all 12 genes was 11.2% in cases and 3.3% in controls (P < 0.0001). BRCA1 and BRCA2 were the most frequently mutated (3.5% and 3.8% of cases and 0.3% and 0.5% of controls, respectively) and were associated with increased ovarian cancer risk [OR, BRCA1 = 12.38; 95% confidence interval (CI) = 4.72-32.45; OR, BRCA2 = 9.18; 95% CI = 3.98-21.15]. Mutation frequencies for the other genes were ≤1.0% and only PALB2 was significantly associated with risk (OR = 5.79; 95% CI = 1.09-30.83). There was no difference in survival for women with a BRCA germline mutation versus no mutation. Further research is needed to better understand the role of other mutations in ovarian cancer among unselected populations. Our data support guidelines for germline genetic testing for BRCA1 and BRCA2 among women diagnosed with epithelial ovarian cancer; testing for PALB2 may be warranted.

Time for Routine Helicobacter pylori Screening in Coronary Artery Disease?

Time for Routine Helicobacter pylori Screening in Coronary Artery Disease?

Diagnostic yield of genetic screening in a diverse, community-ascertained cohort

BackgroundPopulation screening for genetic risk of adult-onset preventable conditions has been proposed as an attractive public health intervention. Screening unselected individuals can identify many individuals who will not be identified through current genetic testing guidelines.MethodsWe sought to evaluate enrollment in and diagnostic yield of population genetic screening in a resource-limited setting among a diverse population. We developed a low-cost, short-read next-generation sequencing panel of 25 genes that had 98.4% sensitivity and 99.98% specificity compared to diagnostic panels. We used email invitations to recruit a diverse cohort of patients in the University of Washington Medical Center system unselected for personal or family history of hereditary disease. Participants were sent a saliva collection kit in the mail with instructions on kit use and return. Results were returned using a secure online portal. Enrollment and diagnostic yield were assessed overall and across race and ethnicity groups.ResultsOverall, 40,857 people were invited and 2889 (7.1%) enrolled. Enrollment varied across race and ethnicity groups, with the lowest enrollment among African American individuals (3.3%) and the highest among Multiracial or Other Race individuals (13.0%). Of 2864 enrollees who received screening results, 106 actionable variants were identified in 103 individuals (3.6%). Of those who screened positive, 30.1% already knew about their results from prior genetic testing. The diagnostic yield was 74 new, actionable genetic findings (2.6%). The addition of more recently identified cancer risk genes increased the diagnostic yield of screening.ConclusionsPopulation screening can identify additional individuals that could benefit from prevention, but challenges in recruitment and sample collection will reduce actual enrollment and yield. These challenges should not be overlooked in intervention planning or in cost and benefit analysis.

Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank

Several breast cancer susceptibility genes have been discovered, but more are likely to exist. To identify additional breast cancer susceptibility genes, we used the founder population of Poland and performed whole-exome sequencing on 510 women with familial breast cancer and 308 control subjects. We identified a rare mutation in ATRIP (GenBank: NM_130384.3: c.1152_1155del [p.Gly385Ter]) in two women with breast cancer. At the validation phase, we found this variant in 42/16,085 unselected Polish breast cancer-affected individuals and in 11/9,285 control subjects (OR= 2.14, 95% CI= 1.13-4.28, p= 0.02). By analyzing the sequence data of the UK Biobank study participants (450,000 individuals), we identified ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR= 3.28, 95% CI= 1.76-6.14, p<0.001). Immunohistochemistry and functional studies showed the ATRIP c.1152_1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress. We showed that tumors of women with breast cancer who have a germline ATRIP mutation have loss of heterozygosity at the site of ATRIP mutation and genomic homologous recombination deficiency. ATRIP is a critical partner of ATR that binds to RPA coating single-stranded DNA at sites of stalled DNA replication forks. Proper activation of ATR-ATRIP elicits a DNA damage checkpoint crucial in regulating cellular responses to DNA replication stress. Based on our observations, we conclude ATRIP is a breast cancer susceptibility gene candidate linking DNA replication stress to breast cancer.

Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on liver tests at a large single adult cystic fibrosis centre

BackgroundElexacaftor/tezacaftor/ivacaftor (E/T/I) therapy has resulted in substantial improvements in health status for many with cystic fibrosis. Monitoring of liver tests is recommended due to observed rises in transaminases in trials and cases of hepatotoxicity. Comprehensive data in large populations of unselected individuals and those with established CF related liver disease (CFLD) is lacking. MethodsPatients prescribed E/T/I at a large, adult centre had liver tests monitored at least 3 monthly for 12 months. Changes in individual liver tests were analysed and abnormalities were compared in those with and without CFLD. Results255 of 267 eligible patients were included. Mild rises in median ALT, AST and bilirubin from baseline to 3 months (all p < 0.001) within normal limits were noted which were sustained. There were no differences in changes in liver tests between those with or without CFLD. There was a significant difference in alkaline phosphatase for those with raised levels at baseline versus those with normal baseline level (-18.5 vs +2.0 IU/L, p = 0.002). Clinically significant rises in ALT and AST occurred in 8 (3.1%) and 6 (2.4%) cases respectively, with derangements in 2 individuals attributed to therapy. ConclusionsE/T/I leads to a mild, likely clinically insignificant increase in ALT, AST and bilirubin after 3 months which is sustained but does not appear to increase further in the vast majority. Underlying CFLD should not be a barrier to treatment. Although there was a reduction in ALP when elevated at baseline, this was not unique to those with pre-existing CFLD.

Prospective surveillance for cholangiocarcinoma in unselected individuals with primary sclerosing cholangitis

The evidence for hepatobiliary tumour surveillance in patients with primary sclerosing cholangitis (PSC) is scarce. In this study, we aimed to prospectively evaluate cholangiocarcinoma (CCA) surveillance with yearly MRI with cholangiopancreatography (MRI/MRCP) in a nationwide cohort. In total, 512 patients with PSC from 11 Swedish hospitals were recruited. The study protocol included yearly clinical follow-ups, liver function tests and contrast-enhanced MRI/MRCP and carbohydrate antigen (CA) 19-9. Patients with severe/progressive bile duct changes on MRI/MRCP were further investigated with endoscopic retrograde cholangiopancreatography. Patients were followed for 5 years or until a diagnosis of CCA, liver transplantation (LT) and/or death. Risk factors associated with CCA were analysed with Cox regression. Eleven patients (2%) were diagnosed with CCA, and two (0.5%) with high-grade bile duct dysplasia. Severe/progressive bile duct changes on MRI/MRCP were detected in 122 patients (24%), of whom 10% had an underlying malignancy. The primary indication for LT (n= 54) was biliary dysplasia in nine patients (17%) and end-stage liver disease in 45 patients (83%), of whom three patients (7%) had unexpected malignancy in the explants. The median survival for patients with CCA was 13 months (3-22 months). Time to diagnosis of high-grade dysplasia and/or hepatobiliary malignancy was significantly associated with severe/progressive bile duct changes on MRI/MRCP (hazard ratio 10.50; 95% CI 2.49-44.31) and increased levels of CA19-9 (hazard ratio 1.00; 95% CI 1.00-1.01). In an unselected cohort of patients with PSC, yearly CA19-9 and MRI/MRCP surveillance followed by ERCP was ineffective in detecting cancer early enough to support long-term survival. Given the low occurrence of CCA, studies on individualised strategies for follow-up and improved diagnostic methods for PSC-related CCA are warranted. A prospective nationwide 5-year study was conducted to evaluate yearly cholangiocarcinoma surveillance using MRI and CA19-9 in patients with primary sclerosing cholangitis. Only 2% of the patients were diagnosed with cholangiocarcinoma during follow-up and their prognosis remained poor despite surveillance. This surveillance strategy failed to detect cancer early enough to support long-term survival. Therefore, individualised strategies and improved diagnostic methods will be required to improve the early detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.

Real-life evaluation of a rapid antigen test (DPP SARS-CoV-2 Antigen) for COVID-19 diagnosis of primary healthcare patients, in the context of the Omicron-dominant wave in Brazil

ObjectivesWe aimed to investigate the real-life performance of the rapid antigen test in the context of a primary healthcare setting, including symptomatic and asymptomatic individuals that sought diagnosis during an Omicron infection wave. MethodsWe prospectively accessed the performance of the DPP SARS-CoV-2 Antigen test in the context of an Omicron-dominant real-life setting. We evaluated 347 unselected individuals (all-comers) from a public testing centre in Brazil, performing the rapid antigen test diagnosis at point-of-care with fresh samples. The combinatory result from two distinct real-time quantitative PCR (RT-qPCR) methods was employed as a reference and 13 samples with discordant PCR results were excluded. ResultsThe assessment of the rapid test in 67 PCR-positive and 265 negative samples revealed an overall sensitivity of 80.5% (CI 95% = 69.1%–89.2%), specificity of 99.2% (CI 95% = 97.3%–99.1%) and positive/negative predictive values higher than 95%. However, we observed that the sensitivity was dependent on the viral load (sensitivity in Ct < 31 = 93.7%, CI = 82.8%–98.7%; Ct > 31 = 47.4%, CI = 24.4%–71.1%). The positive samples evaluated in the study were Omicron (BA.1/BA.1.1) by whole-genome sequencing (n = 40) and multiplex RT-qPCR (n = 17). ConclusionsAltogether, the data obtained from a real-life prospective cohort supports that the rapid antigen test sensitivity for Omicron remains high and underscores the reliability of the test for COVID-19 diagnosis in settings with high disease prevalence and limited PCR testing capability.

Abstract 9375: Role of Cardiac MRI in the Evaluation of T Wave Inversion in a Large Pre-Participation Cohort of Young Asian Males

Introduction: Abnormal T wave inversion (ATWI) in the pre-participation screening (PPS) electrocardiogram (ECG) may signify underlying myocardial disorders (e.g. cardiomyopathy, myocarditis) associated with sudden cardiac death. Current guidelines for competitive athletes recommend evaluation of ATWI with transthoracic echocardiography (TTE) and follow-on cardiac magnetic resonance imaging (CMR) if TTE is normal (i.e. echo-negative). However, data on evaluation of ATWI detected on PPS outside of competitive athletes (e.g. recreational athletes or military enlistees) is lacking. Methods: We studied the yield of ATWI evaluation in a large unselected cohort of 48115 young Asian male military enlistees who underwent PPS between 2019-2021. Individuals with ATWI meeting the International Criteria 2017 definition underwent TTE. Echo-negative individuals with persistent ATWI on repeat ECG further underwent CMR and were followed up for 12 ± 8 months. Routine demographic, anthropometric and ECG parameters were collected. Individuals with known heart disease or conduction abnormalities (e.g. RBBB) were excluded. Results: 133 (0.3%) individuals had ATWI, amongst whom TTE detected 3 (2.3%) individuals with cardiomyopathy. 105 echo-negative individuals had persistent ATWI and underwent CMR, which detected a further 5 (4.8%) cases of cardiomyopathy and 2 (1.9%) cases of prior myocarditis with residual scar. Echo-negative individuals with myocardial disorders on CMR had deeper ATWI of ≥ 2mm (p=0.047), ATWI in lateral (p=0.046) or all 3 territories (p=0.006), and concomitant ST segment depressions (p=0.030). ATWI depth of &lt; 2mm demonstrated 100% negative predictive value for myocardial disorders on TTE or CMR. Conclusions: Evaluation of ATWI in our unselected cohort of young Asian males identified myocardial disorders in 7.5%, with follow-on CMR increasing the diagnostic yield by 3-fold compared to TTE alone. Our findings confirm that CMR has utility in the evaluation of ATWI detected by PPS even in unselected individuals outside the competitive athletic setting. ATWI depth of ≥2mm was present in all individuals with myocardial disorders, and may serve as a cut-off value for further CMR evaluation in settings with resource limitations.

Head-to-head comparison of the accuracy of saliva and nasal rapid antigen SARS-CoV-2 self-testing: cross-sectional study

BackgroundThe diagnostic accuracy of unsupervised self-testing with rapid antigen diagnostic tests (Ag-RDTs) is mostly unknown. We studied the diagnostic accuracy of a self-performed SARS-CoV-2 saliva and nasal Ag-RDT in the general population.MethodsThis large cross-sectional study consecutively included unselected individuals aged ge 16 years presenting for SARS-CoV-2 testing at three public health service test sites. Participants underwent molecular test sampling and received two self-tests (the Hangzhou AllTest Biotech saliva self-test and the SD Biosensor nasal self-test by Roche Diagnostics) to perform themselves at home. Diagnostic accuracy of both self-tests was assessed with molecular testing as reference.ResultsOut of 2819 participants, 6.5% had a positive molecular test. Overall sensitivities were 46.7% (39.3–54.2%) for the saliva Ag-RDT and 68.9% (61.6–75.6%) for the nasal Ag-RDT. With a viral load cut-off (≥ 5.2 log10 SARS-CoV-2 E-gene copies/mL) as a proxy of infectiousness, these sensitivities increased to 54.9% (46.4–63.3%) and 83.9% (76.9–89.5%), respectively. For the nasal Ag-RDT, sensitivities were 78.5% (71.1–84.8%) and 22.6% (9.6–41.1%) in those symptomatic and asymptomatic at the time of sampling, which increased to 90.4% (83.8–94.9%) and 38.9% (17.3–64.3%) after applying the viral load cut-off. In those with and without prior SARS-CoV-2 infection, sensitivities were 36.8% (16.3–61.6%) and 72.7% (65.1–79.4%). Specificities were > 99% and > 99%, positive predictive values > 70% and > 90%, and negative predictive values > 95% and > 95%, for the saliva and nasal Ag-RDT, respectively, in most analyses. Most participants considered the self-performing and result interpretation (very) easy for both self-tests.ConclusionsThe Hangzhou AllTest Biotech saliva self Ag-RDT is not reliable for SARS-CoV-2 detection, overall, and in all studied subgroups. The SD Biosensor nasal self Ag-RDT had high sensitivity in individuals with symptoms and in those without prior SARS-CoV-2 infection but low sensitivity in asymptomatic individuals and those with a prior SARS-CoV-2 infection which warrants further investigation.

Allocation of food resource by experimentally evolved lines of developmental variants of Propylea dissecta: a food exploitation strategy.

The effects of selection on developmental variants have not yet been rigorously investigated on variable prey quantities. We investigated the food exploitation strategy of first (F1) and fifteenth (F15) generation slow and fast developers of Propylea dissecta (Mulsant) in the presence of scarce and abundant quantities of pea aphid, Acyrthosiphon pisum (Harris), and its effect on adult body mass and reproductive attributes. Both selected slow developers and selected fast developers were higher in number than their counter unselected generation on scarce and abundant diets, respectively. Immature survivals of selected slow developers were depressed after the selection process while it was enhanced for selected fast developers on both diet regimes. On both diets, the total developmental duration was longer for selected slow developers and shorter for selected fast developers. Fecundity and percent egg viability were greater in selected fast developers with plentiful prey supply and lower in control slow developers with inadequate prey supply. More adult body mass was found for pre-selected slow developers than selected slow developers on a scarce diet but selected fast developers enhanced their body weight than unselected individuals of fast developers on an abundant diet. The present experimental evolution findings point to the presence and persistence of developmental variations with variability in their developmental and reproductive traits on allocating scarce and abundant prey supplies.

Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts

The true prevalence and penetrance of monogenic disease variants are often not known because of clinical-referral ascertainment bias. We comprehensively assess the penetrance and prevalence of pathogenic variants in HNF1A, HNF4A, and GCK that account for >80% of monogenic diabetes. We analyzed clinical and genetic data from 1,742 clinically referred probands, 2,194 family members, clinically unselected individuals from a US health system-based cohort (n= 132,194), and a UK population-based cohort (n= 198,748). We show that one in 1,500 individuals harbor a pathogenic variant in one of these genes. The penetrance of diabetes for HNF1A and HNF4A pathogenic variants was substantially lower in the clinically unselected individuals compared to clinically referred probands and was dependent on the setting (32% in the population, 49% in the health system cohort, 86% in a family member, and 98% in probands for HNF1A). The relative risk of diabetes was similar across the clinically unselected cohorts highlighting the role of environment/other genetic factors. Surprisingly, the penetrance of pathogenic GCK variants was similar across all cohorts (89%-97%). We highlight that pathogenic variants in HNF1A, HNF4A, and GCK are not ultra-rare in the population. For HNF1A and HNF4A, we need to tailor genetic interpretation and counseling based on the setting in which a pathogenic monogenic variant was identified. GCK is an exception with near-complete penetrance in all settings. This along with the clinical implication of diagnosis makes it an excellent candidate for the American College of Medical Genetics secondary gene list.

Understanding the Patient Experience of Receiving Clinically Actionable Genetic Results from the MyCode Community Health Initiative, a Population-Based Genomic Screening Initiative.

Understanding unselected individuals’ experiences receiving genetic results through population genomic screening is critical to advancing clinical utility and improving population health. We conducted qualitative interviews with individuals who received clinically actionable genetic results via the MyCode© Genomic Screening and Counseling program. We purposively sampled cohorts to seek diversity in result-related disease risk (e.g., cancer or cardiovascular) and in personal or family history of related diseases. Transcripts were analyzed using a two-step inductive coding process of broad thematic analysis followed by in-depth coding of each theme. Four thematic domains identified across all cohorts were examined: process assessment, psychosocial response, behavioral change due to the genetic result, and family communication. Coding of 63 interviews among 60 participants revealed that participants were satisfied with the results disclosure process, initially experienced a range of positive, neutral, and negative psychological reactions to results, adjusted positively to results over time, undertook clinically indicated actions in response to results, and communicated results with relatives to whom they felt emotionally close. Our findings of generally favorable responses to receiving clinically actionable genetic results via a genomic screening program may assuage fear of patient distress in such programs and guide additional biobanks, genomic screening programs, and research studies.

Transfusional iron overload in heavily transfused patients: Real-life data from a 10-year retrospective study of 611 cases managed in a French general hospital

Epidemiological studies on transfusional iron overload (TIO) in the general population of heavily transfused patients are scarce. The aim of this work was to provide a picture on the distribution and management of this complication within the context of unselected individuals attending a general hospital. We retrospectively assessed the characteristics of 611 patients from a single institution having received at least 20 red blood cell (RBC) units over a 10-year period. About two-thirds of these individuals were males and their median age at the 20th RBC was 72years (range: 10-98). Myelodysplastic syndromes (MDS) and acute myeloid leukemia represented the most frequent underlying conditions (53%) but lymphoid malignancies and solid malignancies accounted for 13.6 and 7.3% respectively. In the vast majority of cases various comorbidities (range: 1-6 per patient) were registered including especially cardiovascular disorders. The highest cumulative RBC numbers were observed in MDS patients. Serum ferritin was assessed in 451 patients (73.8%) and ≥1000μg/L in 250 cases, ≥2000μg/L in 100 cases and ≥2500μg/L in 71 cases. Only 97 patients (15.9%) received a treatment for TIO using either a chelator (n=93) or phlebotomy (n=4). TIO is not limited to MDS or hemoglobin disorders. Its assessment and management are suboptimal in clinical practice. The ratio of patients receiving iron chelation is markedly lower than theoretically expected mainly because of comorbidities or drug intolerance.