Actus Santé

Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study

Venous thromboembolism (VTE) occurs in up to one third patients with COVID-19. VTE and COVID-19 may share a common genetic architecture in etiology, which has not been comprehensively investigated. In this study, we leveraged summary-level data from the latest COVID-19 host genetics consortium and UK Biobank to study the genetic commonality between COVID-19 traits and VTE. We found a positive genetic correlation between COVID-19 hospitalization and VTE (rg = 0.2320, P-value= 0.0092). The cross-trait analysis identified shared genetic loci between VTE and COVID-19 traits, including 8 for severe COVID-19, 11 for COVID-19 hospitalization, and 7 for SARS-CoV-2 infection. We identified seven novel mapped genes (LINC00970, TSPAN15, ADAMTS13, F5, DNAJB4, SLC39A8 and OBSCN) that were enriched for expression in the lung tissue, and in coagulation and immune related pathways. Eight genetic loci were found to share causal variants between COVID-19 and VTE, which are localized in the ABO, ADAMTS13 and FUT2 gene regions. Bi-directional Mendelian randomization analysis did not suggest a causal relationship between VTE and COVID-19 traits. Our study advances the understanding of shared genetic etiology of COVID-19 and VTE at the molecular and functional levels.
Catégories: Actus Santé

Factors Associated With Regional Differences in Healthcare Quality for Patients With Acute Myocardial Infarction in Japan

Objectives: Regional medical coordination is essential for health-system reform in Japan, and the quality of healthcare at the regional level is of great interest. Regional differences in the quality of healthcare for cardiovascular diseases have been pointed out in previous research, and we aimed to clarify regional factors that influence the quality. Design: Insurance claims database study. Setting: Patients of acute care in Japan. Participants: Japanese patients included in the national Diagnosis Procedure Combination (DPC) databases who admitted to hospitals with diagnosis of acute myocardial infarction (AMI) from April 2016 to March 2019. Main outcome and measures: Using the national DPC databases, risk-adjusted mortality (RAM) in each secondary medical area (SMA) was derived as an indicator for the quality of the healthcare for patients with AMI. Factors associated with RAM were analysed using the partial least squares (PLS) regression model. Results: There is a wide variation in RAM in the SMAs; the maximum value was 0.593 and the minimum value was 1.445. The PLS regression identified two components positively correlated with RAM. The first component (Component 1) positively correlates with the proportion of the elderly within the population and negatively correlates with the number of medical facilities per area, the population density, and the intra-SMA access to centres with a high volume of emergency percutaneous coronary interventions (ePCI). The second component (Component 2) positively correlates with the number of medical facilities per area and negatively correlates with the number of physicians per person and the intra-SMA access to centres with a high volume of ePCI. Conclusion: There was wide regional variation in the quality of in-hospital AMI treatments. Results suggested the degree of rurality, the sufficiency of medical resources, the access to high-volume ePCI centres, and coordination of healthcare delivery were associated with healthcare quality for AMI patients.
Catégories: Actus Santé

The negative impact of COVID-19 on working memory revealed using a rapid online quiz

Although coronavirus disease 2019 (COVID-19) affects the respiratory system, it can also have neurological consequences leading to cognitive deficits such as memory problems. The aim of our study was to assess the impact of COVID-19 on working memory function. We developed and implemented an online anonymous survey with a working memory quiz incorporating aspects of gamification to engage participants. 5428 participants successfully completed the survey and memory quiz between 8 th December 2020 and 5 th July 2021 (68.6% non-COVID-19 and 31.4% COVID-19). Most participants (93.3%) completed the survey and memory quiz relatively rapidly (mean time of 8.84 minutes). Categorical regression was used to assess the contribution of COVID status, age, time post-COVID (number of months elapsed since having had COVID), symptoms, ongoing symptoms and gender, followed by non-parametric statistics. A principal component analysis explored the relationship between subjective ratings and objective memory scores. The objective memory scores were significantly correlated with participants own assessment of their cognitive function. The factors significantly affecting memory scores were COVID status, age, time post-COVID and ongoing symptoms. Our main finding was a significant reduction in memory scores in all COVID groups (self-reported, positive-tested and hospitalised) compared to the non-COVID group. Memory scores for all COVID groups combined were significantly reduced compared to the non-COVID group in every age category 25 years and over, but not for the youngest age category (18-24 years old). We found that memory scores gradually increased over a period of 17 months post-COVID-19. However, those with ongoing COVID-19 symptoms continued to show a reduction in memory scores. Our findings demonstrate that COVID-19 negatively impacts working memory function, but only in adults aged 25 years and over. Moreover, our results suggest that working memory deficits with COVID-19 can recover over time, although impairments may persist in those with ongoing symptoms.
Catégories: Actus Santé

Comorbidities and sociodemographic factors on COVID-19 fatalities

Introduction: Previous studies have evaluated comorbidities and sociodemographic factors individually or by type but not comprehensively. This study aims to analyze the influence of a wide variety of factors in a single study to better understand the big picture of their effects on case-fatalities. Methods: County-level comorbidities, social determinants of health such as income and race, measures of preventive healthcare, age, education level, average household size, population density, and political voting patterns were all evaluated on a national and regional basis. Analysis was performed through Generalized Additive Models and adjusted by CCVI. Results: Factors associated with reducing COVID-19 case fatality rates were mostly sociodemographic factors such as age, education and income, and preventive health measures. Obesity, minimal leisurely activity, binge drinking, and higher rates of individuals taking high blood pressure medication were associated with increased case fatality rate in a county. Political leaning influences case case-fatality rates. Regional trends showed contrasting effects where larger household size was protective in the Midwest, yet harmful in Northeast. Notably, higher rates of respiratory comorbidities such as asthma and COPD diagnosis were associated with reduced case-fatality rates in the Northeast. Increased rates of CKD within counties were often the strongest predictor of increased case-fatality rates for several regions. Conclusion: Our findings highlight the importance of considering the full context when evaluating contributing factors to case-fatality rates. The spectrum of factors identified in this study must be analyzed in the context of one another and not in isolation.
Catégories: Actus Santé

Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination

SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have documented serial Omicron infections. We characterized SARS-CoV-2 humoral responses in a healthy young person who acquired laboratory-confirmed Omicron BA.1.15 ten weeks after a third dose of BNT162b2, and BA.2 thirteen weeks later. Responses were compared to those of 124 COVID-19 naive vaccinees. One month after the second and third vaccine doses, the participant's wild-type and BA.1-specific IgG, ACE2 competition and virus neutralization activities were average for a COVID-19 naive triple-vaccinated individual. BA.1 infection boosted the participant's responses to the cohort >95th percentile, but even this strong "hybrid" immunity failed to protect against BA.2. Moreover, reinfection increased BA.1 and BA.2-specific responses only modestly. Results illustrate the risk of Omicron infection in fully vaccinated individuals and highlight the importance of personal and public health measures as vaccine-induced immune responses wane.
Catégories: Actus Santé

Population health impact, cost-effectiveness, and affordability of community-based HIV treatment and monitoring in South Africa: a health economics modelling study

Introduction: Community-based delivery and monitoring of antiretroviral therapy (ART) for HIV has the potential to increase viral suppression for individual- and population-level health benefits. However, the cost-effectiveness and budget impact are needed for public health policy. Methods and Findings: We used a mathematical model of HIV transmission in KwaZulu-Natal, South Africa, to estimate population prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 2020 to 2060 for two scenarios: 1) standard clinic-based HIV care and 2) five-yearly home testing campaigns with community ART for people not reached by clinic-based care. We parameterised model scenarios using observed community-based ART efficacy. We evaluated incremental cost-effectiveness and net health benefits using a threshold of $750/DALY averted. Sensitivity analyses varied costs of ART, hospitalisation, and testing. Uncertainty ranges (URs) were estimated across 25 best-fitting parameter sets. By 2060, community ART following home testing averted 27.9% (UR: 24.3-31.5) of incident HIV infections, 27.8% (26.8-28.8) of HIV-related deaths, and 18.7% (17.9-19.7) of DALYs compared to standard of care. Adolescent girls and young women aged 15-24 years experienced the greatest reduction in incident HIV (30.7%, 27.1-34.7). In the first five years (2020-2024), community ART required an additional $44.9 million (35.8-50.1) annually, representing 14.3% (11.4-16.0) of the current HIV budget. The cost per DALY averted was $102 (85-117) for community ART compared with standard of care. Providing six-monthly refills instead of quarterly refills further increased cost-effectiveness to $78.5 per DALY averted (62.9-92.8). Cost-effectiveness was robust to sensitivity analyses. Conclusions: In a high-prevalence setting, scale-up of decentralised ART dispensing and monitoring for people not already virally suppressed can provide large population health benefits and is cost-effective in preventing death and disability due to HIV.
Catégories: Actus Santé

The Role of HIV Partner Services in the Modern Biomedical HIV Prevention Era: A Network Modeling Study

BACKGROUND. HIV partner services can accelerate the use of antiretroviral-based HIV prevention tools (ART and PrEP), but its population impact on long-term HIV incidence reduction is challenging to quantify with traditional PS metrics of partner identified or HIV-screened. Understanding the role of partner services within the portfolio of HIV prevention interventions, including using it to efficiently deliver antiretrovirals, is needed to achieve HIV prevention targets. METHODS. We used a stochastic network model of HIV/STI transmission for men who have sex with men (MSM), calibrated to surveillance-based estimates in the Atlanta area, a jurisdiction with high HIV burden and suboptimal partner services uptake. Model scenarios varied successful delivery of partner services cascade steps (newly diagnosed "index" patient and partner identification, partner HIV screening, and linkage or reengagement of partners in PrEP or ART care) individually and jointly. RESULTS. At current levels observed in Atlanta, removal of HIV partner services had minimal impact on 10-year cumulative HIV incidence, as did improving a single partner services step while holding the others constant. These changes did not sufficiently impact overall PrEP or ART coverage to reduce HIV transmission. If all index patients and partners were identified, maximizing partner HIV screening, partner PrEP provision, partner ART linkage, and partner ART reengagement would avert 6%, 11%, 5%, and 18% of infections, respectively. Realistic improvements in partner identification and service delivery were estimated to avert 2-8% of infections, depending on the combination of improvements. CONCLUSIONS. Achieving optimal HIV prevention with partner services depends on pairing improvements in index patient and partner identification with maximal delivery of HIV screen-ing, ART, and PrEP to partners if indicated. Improving the identification steps without improvement to antiretroviral service delivery steps, or vice versa, is projected to result in negligible population HIV prevention benefit.
Catégories: Actus Santé

Levels and determinants of COVID-19 vaccine hesitancy among sub-Saharan African adolescents

COVID-19 vaccine hesitancy among adolescents poses a challenge to the global effort to control the pandemic. This multi-country survey aimed to assess the levels and determinants of COVID-19 vaccine hesitancy among adolescents in sub-Saharan Africa between July and December 2021. The survey was conducted using computer-assisted telephone interviewing among adolescents in five sub-Saharan African countries, Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania. A rural area and an urban area were included in each country (except Ghana, which only had a rural area), with approximately 300 adolescents in each area and 2803 in total. Sociodemographic characteristics and perceptions and attitudes on COVID-19 vaccines were measured. Vaccine hesitancy was defined as definitely not getting vaccinated or being undecided on whether to get vaccinated if a COVID-19 vaccine were available. Log-binomial models were used to calculate the adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for associations between potential determinants and COVID-19 vaccine hesitancy. The percentage of COVID-19 vaccine hesitancy was 15% in rural Kersa, 24% in rural Ibadan, 31% in rural Nouna, 33% in urban Ouagadougou, 37% in urban Addis Ababa, 48% in rural Kintampo, 64% in urban Lagos, 76% in urban Dar es Salaam, and 88% in rural Dodoma. Perceived low necessity, concerns about vaccine safety, and concerns about vaccine effectiveness were the leading reasons for hesitancy. Healthcare workers, parents or family members, and schoolteachers had the greatest impacts on vaccine willingness. Perceived lack of safety (aPR: 3.61; 95% CI: 3.10, 4.22) and lack of effectiveness (aPR: 3.59; 95% CI: 3.09, 4.18) were associated with greater vaccine hesitancy. The levels of COVID-19 vaccine hesitancy among adolescents are alarmingly high across the five sub-Saharan African countries, especially in Tanzania. COVID-19 vaccination campaigns among sub-Saharan African adolescents should address their concerns and misconceptions about vaccine safety and effectiveness.
Catégories: Actus Santé

Sex-Related Differences in Eicosanoids Levels in Chronic Thromboembolic Pulmonary Hypertension

A sex paradox is seen in pulmonary arterial hypertension (PAH) whereby female sex is a risk factor for development of the disease but male sex is often associated with poorer outcomes. Although data are limited regarding the potential molecular mechanisms underlying sex-specific variations in PAH including its various subtypes, there is emerging evidence regarding the potential role of sex differences in pathways governing the balance between underlying inflammatory and vasoactive mechanisms. Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension that is classically characterized as a procoagulant state and yet also involving some degree of proinflammatory activity. Therefore, we sought to determine whether eicosanoid mediators, endogenous lipid signaling molecules that have been implicated in a range of inflammatory and vasoactive responses, vary by sex in patients with CTEPH. We studied 287 patients (43.5% female) with confirmed CTEPH from a single center and assayed plasma samples using liquid chromatography-mass spectrometry to profile 500 eicosanoid analytes. We found significant sex-specific variations in eicosanoid profiles after adjusting for age and BMI, with males demonstrating a predominance of inflammatory-pathway related eicosanoids. Sex-specific variation in eicosanoid pathway related mechanisms may underlie sexual dimorphism in CTEPH outcomes.
Catégories: Actus Santé

IMPROVE-DD: Integrating Multiple Phenotype Resources Optimises Variant Evaluation in genetically determined Developmental Disorders

Diagnosing rare developmental disorders using genome-wide sequencing data commonly necessitates review of multiple plausible candidate variants, often using ontologies of categorical clinical terms. We show that Integrating Multiple Phenotype Resources Optimises Variant Evaluation in Developmental Disorders (IMPROVE-DD) by incorporating additional classes of data commonly available to clinicians and recorded in health records. In doing so, we quantify the distinct contributions of gender, growth, and development in addition to Human Phenotype Ontology (HPO) terms, and demonstrate added value from these readily-available information sources. We use likelihood ratios for nominal and quantitative data and propose a novel classifier for HPO terms in this framework. This Bayesian framework results in more robust diagnoses. Using data systematically collected in the DDD study, we considered 77 genes with pathogenic/likely pathogenic variants in >=10 probands. All genes showed at least a satisfactory prediction by ROC when testing on training data (AUC>=0.6), and HPO terms were the best individual predictor for the majority of genes, though a minority (13/77) of genes were better predicted by other phenotypic data types. Overall, classifiers based upon multiple integrated phenotypic data sources performed better than those based upon any individual source, and importantly, integrated models produced notably fewer false positives. Finally, we show that IMPROVE-DD models with good predictive performance on cross-validation can be constructed from relatively few cases. This suggests new strategies for candidate gene prioritisation, and highlights the value of systematic clinical data collection to support diagnostic programmes.
Catégories: Actus Santé

Neonatal outcomes and indirect consequences following maternal SARS-CoV-2 infection in pregnancy: A systematic review

Objectives: Identify the association between maternal SARS-CoV-2 infection in pregnancy and individual neonatal morbidities and outcomes, particularly longer-term outcomes such as neurodevelopment. Setting: Case-control and cohort studies from any location published after 1st January 2020, including pre-print articles. Participants: Neonates born to pregnant women diagnosed with a SARS-CoV-2 infection at any stage during pregnancy, including asymptomatic women. Primary and secondary outcome measures: Neonatal mortality and morbidity, including preterm birth, Caesarean delivery, small for gestational age, admission to neonatal intensive care unit, level of respiratory support required, diagnosis of culture-positive sepsis, evidence of brain injury, necrotising enterocolitis, visual or hearing impairment, neurodevelopmental outcomes, and feeding method. These outcomes were selected according to a Core Outcome Set developed between health professionals, researchers and parents. Results: The search returned 3234 papers, from which 204 were included with a total of 45,646 infants born to mothers with SARS-CoV-2 infection during pregnancy across 36 countries. We found limited evidence of an increased risk of some neonatal morbidities, including respiratory disease. There was minimal evidence from low-income settings (1 study) and for neonatal outcomes following first trimester infection (17 studies). Neonatal mortality was very rare. Preterm birth, neonatal unit admission and small for gestational age status were more common in infants born following maternal SARS-CoV-2 infection in pregnancy in most larger studies. Conclusions: There is limited data on neonatal morbidity and mortality following maternal SARS-CoV-2 infection in pregnancy, particularly from low-income countries and following early pregnancy infections. Large, representative studies addressing these outcomes are needed to better understand the consequences for babies born to women with SARS-CoV-2 in pregnancy. Trial registration: PROSPERO ID: CRD42021249818
Catégories: Actus Santé

Exploring barriers and facilitators to physical activity during the COVID-19 pandemic: a qualitative study

Objectives Quantitative data show that physical activity (PA) reduced during the COVID-19 pandemic, with differential impacts across demographic groups. Qualitative research is limited, so reasons for this have not been explored in-depth. This study aimed to understand barriers and facilitators to PA during the pandemic, focusing on groups more likely to have been affected by restrictions, and to map these onto the Capability, Opportunity, Motivation Model of Behaviour (COM-B). Design Semi-structured qualitative interview study. Methods One-to-one telephone/videocall interviews were conducted with younger (aged 18-24) and older adults (aged 70+), those with long-term physical health conditions or mental health conditions, and parents of young children, probing about their experiences of PA. Barriers and facilitators were identified using reflexive thematic analysis, and themes were mapped onto COM-B dimensions. Results 116 participants were included (18-93 years old, 61% female, 71% White British). Key themes were the importance of the outdoor environment, impact of COVID-19 restrictions, fear of contracting COVID-19, and level of engagement with home exercise. Caring responsibilities and conflicting priorities were a barrier. PA as a method of socialising, establishing new routines, and the importance of PA for protecting mental health were motivators. Most themes mapped onto the physical opportunity (environmental factors) and reflective motivation (evaluations and plans) COM-B domains. Conclusions Future interventions should increase physical opportunity and reflective motivation for PA during pandemics, to avoid further negative health outcomes following periods of lockdown. Strategies could include tailoring PA guidance depending on location and giving education on the health benefits of PA.
Catégories: Actus Santé

A DSM-5 AMPD and ICD-11 compatible measure for an early identification of personality disorders in adolescence - LoPF-Q 12-18 latent structure and short form

The LoPF-Q 12-18 (Levels of Personality Functioning Questionnaire) was designed for clinical use and to promote early detection of personality disorder (PD). It is a self-report measure with 97 items to assess personality functioning in adolescents from 12 years up. It operationalizes the dimensional concept of personality disorder (PD) severity used in the Alternative DSM-5 Model for Personality Disorders and the ICD-11. In this study, we investigated the factorial structure of the LoPF-Q 12-18. Additionally, a short version was developed to meet the need of efficient screening for PD in clinical and research applications. To investigate the factorial structure, several confirmatory factor analysis models were compared. A bifactor model with a strong general factor and four specific factors showed the best nominal fit (CFI = .91, RMSEA = .04, SRMR = .07). The short version was derived using the ant colony optimization algorithm. This procedure resulted in a 20-item version with excellent fit for a hierarchical model with four first order factors to represent the domains and a secondary higher order factor to represent personality functioning (CFI = .98, RMSEA = .05, SRMR = .04). Clinical validity (effect size d= 3.1 between PD patients and controls) and clinical utility (cutoff >= 36 providing 87.5% specificity and 80.2% sensitivity) for detecting patients with PD were high for the short version. Both, the long and short LoPF-Q 12-18 version are ready to be used for research and diagnostic purposes.
Catégories: Actus Santé

Investigating relations between the NICU speech environment and weight gain in infants born very preterm

Background: Children born very preterm (< 32 weeks gestational age), are at risk for poor growth and adverse neurodevelopmental outcomes. Poor outcomes in preterm children have been attributed to the aversive sounds and relative speech paucity of the neonatal intensive care unit (NICU). Experimental studies that directly expose preterm infants to speech sounds in the NICU find significant improvements in health factors relevant for neurodevelopment. Few studies have examined whether natural variations in the speech environment of the NICU are related to short-term health outcomes in preterm infants. Such data are important for optimizing the sound environment of the NICU. Objective: Examine relations between the NICU speech environment and rate of weight gain during hospitalization, an important determinant of physical health and neurodevelopmental outcomes for preterm infants. Methods: Participants were infants born very preterm (n = 20). The speech environment of each infant was assessed at 32-36 weeks postmenstrual age using a speech-counting device known as a Starling. Speech rates were averaged for each infant over the 4-week period. Average rates of weight gain (g/kg/day) were ascertained over the same period. Calories were derived from charted intake (kcals/kg/day). Linear regressions examined associations between weight gain and both caloric intake and speech counts. Control analyses explored whether effects remained after controlling for family visitation, time in incubator, and health acuity. Results: Infants who received more calories gained more weight, accounting for more than 30% of the variance. Importantly, speech counts accounted for nearly 29% additional variance (p < .001). These effects were not reduced when controlling for family visitation, time in incubator, or health acuity. Conclusions: Enhancing speech exposure in the NICU may be beneficial for physical growth. NICU infant care plans should consider opportunities to increase speech exposure.
Catégories: Actus Santé

Background noise in an Emergency Department: an observational study from staff and patient perspectives.

Background and importance: Noise is a contributing factor to mis-communication, poor sleep patterns and stress in healthcare. There has been little research on noise in the Emergency Department (ED). Objective(s) (1) To identify the noise levels experienced by staff and patients in different areas of an emergency department over the 24 hour cycle, (2) to examine the impact of cubicle doors on the background noise experienced by the patient, and (3) to assess the impact of monitor alarms on staff and patient noise levels. Design Observational study. Setting A large urban teaching hospital Emergency Department. Measures and analysis Using a standard protocol monitoring of staff and patient experience of noise was carried out in 3 areas of the ED (a resuscitation room, an area of patient cubicles with solid doors and and an area of patient cubicles with curtains). The overall distributions of noise levels in each area were described and circadian variation plotted. The proportion of time that background noise was above key cutoff values known to impair communication was calculated (45dB and 65dB). Non-parametric methods were used to compare: (1) a patient cubicle with curtains compared to a solid door, (2) having the door open or closed, and (3) staff and patient exposure a monitor alarm. Main results Noise was greater than 45dB for staff between 76% and 96% of the time (30% to 100% for patients). There was little difference across the 24hr cycle. A door decreased the noise experienced by patients, but only if left closed. In the resuscitation rooms monitor alarms were much louder for patients than for staff. Conclusion Noise levels likely to impair communication are present in the ED for most of the time. Staff awareness and improved design of both buildings and equipment might mitigate this negative acoustic environment.
Catégories: Actus Santé

BNT162b2 induces robust cross-variant SARS-CoV-2 immunity in children

Currently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of novel variants of concerns has highlighted the importance of high population-based vaccine rates to effectively suppress viral transmission and breakthrough infections. While initially left out from vaccine efforts, children have become one of the most affected age groups and are key targets to stop community and household spread. Antibodies are central for vaccine induced protection and emerging data points to the importance of additional Fc effector functions like opsononophagocytosis or cytotoxicity, particularly in the context of variants of concern that escape neutralizing antibodies. Here, we observed delayed induction and reduced magnitude of vaccine induced antibody titers in children 5-11 years receiving two doses of the age recommended 10 g dose of the Pfizer SARS-CoV-2 BNT162b2 vaccine compared to adolescents (12-15 years) or adults receiving the 30 g dose. Conversely, children mounted equivalent or more robust neutralization and opsonophagocytic functions at peak immunogenicity, pointing to a qualitatively more robust humoral functional response in children. Moreover, broad cross-variants of concern responses were observed across children, with enhanced IgM and parallel IgG cross-reactivity to variants of concern (VOCs) in children compared to adults. Collectively, these data argue that despite the lower magnitude of the BNT162b2 induced antibody response in children, vaccine induced immunity in children target VOCs broadly and exhibit enhanced functionality that may contribute to attenuation of disease.
Catégories: Actus Santé

Bias-adjusted predictions of county-level vaccination coverage from the COVID-19 Trends and Impact Survey

The potential for bias in non-representative, large-scale, low-cost survey data can limit their utility for population health measurement and public health decision-making. We developed a multi-step regression framework to bias-adjust vaccination coverage predictions from the large-scale US COVID-19 Trends and Impact Survey that included post-stratification to the American Community Survey and secondary normalization to an unbiased reference indicator. As a case study, we applied this framework to generate county-level predictions of long-run vaccination coverage among children ages 5 to 11 years. Our vaccination coverage predictions suggest a low ceiling on long-term national coverage (46%), detect substantial geographic heterogeneity (ranging from 11% to 91% across counties in the US), and highlight widespread disparities in the pace of scale-up in the three months following Emergency Use Authorization of COVID-19 vaccination for 5 to 11 year-olds. Generally, our analysis demonstrates an approach to leverage differing strengths of multiple sources of information to produce estimates on the time-scale and geographic-scale necessary for proactive decision-making. The utility of large-scale, low-cost survey data for improving population health measurement is amplified when these data are combined with other representative sources of data.
Catégories: Actus Santé

Predicting Age-Related Macular Degeneration Progression with Contrastive Attention and Time-Aware LSTM

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. Identifying patients at high risk of progression to late AMD, the sight-threatening stage, is critical for clinical actions, including medical interventions and timely monitoring. Recently, deep-learning-based models have been developed and achieved superior performance for late AMD prediction. However, most existing methods are limited to the color fundus photography (CFP) from the last ophthalmic visit and do not include the longitudinal CFP history and AMD progression during the previous years' visits. Patients in different AMD subphenotypes might have various speeds of progression in different stages of AMD disease. Capturing the progression information during the previous years' visits might be useful for the prediction of AMD progression. In this work, we propose a Contrastive-Attention-based Time-aware Long Short-Term Memory network (CAT-LSTM) to predict AMD progression. First, we adopt a convolutional neural network (CNN) model with a contrastive attention module (CA) to extract abnormal features from CFPs. Then we utilize a time-aware LSTM (T-LSTM) to model the patients' history and consider the AMD progression information. The combination of disease progression, genotype information, demographics, and CFP features are sent to T-LSTM. Moreover, we leverage an auto-encoder to represent temporal CFP sequences as fixed-size vectors and adopt k-means to cluster them into subphenotypes. We evaluate the proposed model based on real-world datasets, and the results show that the proposed model could achieve 0.925 on area under the receiver operating characteristic (AUROC) for 5-year late-AMD prediction and outperforms the state-of-the-art methods by more than 3%, which demonstrates the effectiveness of the proposed CAT-LSTM. After analyzing patient representation learned by an auto-encoder, we identify 3 novel subphenotypes of AMD patients with different characteristics and progression rates to late AMD, paving the way for improved personalization of AMD management.
Catégories: Actus Santé

In Utero Exposure to the Great Depression is Reflected in Late-Life Epigenetic Aging Signatures

Research on maternal-fetal epigenetic programming argues that adverse exposures to the intrauterine environment can have long-term effects on adult morbidity and mortality. However, causal research on epigenetic programming in humans at a population level is rare and is often unable to separate intrauterine effects from conditions in the postnatal period that may continue to impact child development. In this study, we used a quasi-natural experiment that leverages state-year variation in economic shocks during the Great Depression to examine the causal effect of environmental exposures in early life on late-life accelerated epigenetic aging for 832 participants in the U.S. Health and Retirement Study (HRS). HRS is the first population-representative study to collect epigenome-wide DNA methylation data that has the sample size and geographic variation necessary to exploit quasi-random variation in environments, which expands possibilities for causal research in epigenetics. Our findings suggest that exposure to changing economic conditions in the 1930s had lasting impacts on next-generation epigenetic aging signatures that were developed to predict mortality risk (GrimAge) and physiological decline (DunedinPoAm). We show that these effects are localized to the in utero period specifically as opposed to the pre-conception, postnatal, childhood, or early adolescent periods. After evaluating changes in mortality rates for Depression-era birth cohorts, we conclude that these effects likely represent lower bound estimates of the true impacts of the economic shock on long-term epigenetic aging.
Catégories: Actus Santé

Assessment of glucocorticoid-induced enhancer activity of eSNP regions using STARR-seq reveals novel molecular mechanisms in psychiatric disorders

Exposure to stressful events increases risk for psychiatric disorders. Mechanistic insight into genetic factors moderating the impact of stress can increase our understanding of disease processes. Here, we test 3662 SNPs from preselected expression quantitative trait loci in massively parallel reporter assays to identify genetic variants that modulate the activity of regulatory elements sensitive to glucocorticoids, important mediators of the stress response. Of the tested SNP sequences, 547 were located in glucocorticoid-responsive regulatory elements of which 233 showed allele-dependent activity. Transcripts regulated by these variants were enriched for those differentially expressed in psychiatric disorders in postmortem brain. Phenome-wide Mendelian randomization analysis in 4,439 phenotypes revealed potentially causal associations specifically in neuro-behavioral traits, including psychiatric disorders. Finally, functional gene scores derived from these variants were significantly associated with differences in physiological stress measures, suggesting that these may alter disease risk by moderating the individual set point of the stress response.
Catégories: Actus Santé

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