title: Association of machine learning-derived measures of body fat distribution in >40,000 individuals with cardiometabolic diseases

abstract:
BackgroundObesity is defined based on body-mass index (BMI), a proxy for overall adiposity. However, for any given BMI, individuals vary substantially in fat distribution. The clinical implications of this variability are not fully understood.

MethodsWe studied MRI imaging data of 40,032 UK Biobank participants. Using previously quantified visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volume in up to 9,041 to train convolutional neural networks, we quantified these depots in the remainder of the participants. We derived new metrics for each adipose depot - fully independent of BMI - by quantifying deviation from values predicted by BMI (e.g. VAT adjusted for BMI, VATadjBMI) and determined associations with cardiometabolic diseases.

ResultsMachine learning models based on two-dimensional projection images enabled near-perfect estimation of VAT, ASAT, and GFAT, with r2 in a holdout testing dataset >0.97 for each. Using the newly derived measures of local adiposity - residualized based on BMI - we note marked heterogeneity in associations with cardiometabolic diseases. Taking presence of type 2 diabetes as an example, VATadjBMI was associated with significantly increased risk (odds ratio per standard deviation increase (OR/SD) 1.49; 95%CI: 1.43-1.55), while ASATadjBMI was largely neutral (OR/SD 1.08; 95%CI: 1.03-1.14) and GFATadjBMI conferred protection (OR/SD 0.75; 95%CI: 0.71-0.79). Similar patterns were observed for coronary artery disease.

ConclusionsFor any given BMI, measures of local adiposity have variable and divergent associations with cardiometabolic diseases.

category: endocrinology


title: Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling

abstract:
Checkpoint inhibitor therapy of cancer has led to markedly improved survival of a subset of patients in multiple solid malignant tumor types, yet the factors driving these clinical responses or lack thereof are not known. Here we present a translational mathematical model dependent on three key parameters for describing efficacy of checkpoint inhibitors in human cancer: tumor growth rate (), tumor immune infiltration ({Lambda}), and immunotherapy-mediated amplification of anti-tumor response ({micro}). The model was validated by fitting it to a compiled clinical tumor response dataset (n = 189 patients) obtained from published anti-PD-1 and anti-PD-L1 clinical trials, and then validated on an additional validation cohort (n = 64 patients) obtained from our in-house clinical trials. The derived parameters{Lambda} and {micro} were both significantly different between responding versus non-responding patients. Of note, our model appropriately classified response in 81.4% of patients by using only tumor volume measurements and within two months of treatment initiation in a retrospective analysis. The model reliably predicted clinical response to the PD-1/PD-L1 class of checkpoint inhibitors across multiple solid malignant tumor types. Comparison of model parameters to immunohistochemical measurement of PD-L1 and CD8+ T cells confirmed robust relationships between model parameters and their underlying biology, demonstrating reliable methods to inform model parameters directly from biopsy samples, which are conveniently obtainable as early as the start of treatment. Together, these results suggest that the model parameters may serve as early and robust biomarkers of the efficacy of checkpoint inhibitor therapy on an individualized per-patient basis.

SIGNIFICANCECheckpoint inhibitors have revolutionized cancer immunotherapy, but only a subset of patients with solid tumors responds clinically. The ability to predict tumor responses a priori or soon after starting therapy would allow for personalized and timely adaptive clinical applications of checkpoint inhibitor- based immunotherapy in patients. By applying a mechanistic mathematical model, we show that checkpoint inhibitor therapeutic effectiveness is accurately predictable in most patients within two months after treatment initiation. Our method may be implemented directly into clinical practice, as it relies on standard-of-care imaging and pathology. If successful in prospective studies, this model will improve selection of cancer patients for checkpoint inhibitor therapy, and perhaps for other forms of humoral- or cell-based immunotherapy.

category: oncology


title: Association of Obesity with COVID-19 Severity and Mortality: A Systemic Review and Meta-Regression

abstract:
ObjectiveTo estimate the association of obesity with severity (defined as use of invasive mechanical ventilation or intensive care unit admission) and all-cause mortality in coronavirus disease 2019 (COVID-19) patients.

Patients and MethodsA systematic search was conducted from inception of COVID-19 pandemic through January 31st, 2021 for full-length articles focusing on the association of increased BMI/ Obesity and outcome in COVID-19 patients with help of various databases including Medline (PubMed), Embase, Science Web, and Cochrane Central Controlled Trials Registry. Preprint servers such as BioRxiv, MedRxiv, ChemRxiv, and SSRN were also scanned. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used for study selection and data extraction. The severity in hospitalized COVID-19 patients, such as requirement of invasive mechanical ventilation and intensive care unit admission with high BMI/ Obesity was the chief outcome. While all-cause mortality in COVID-19 hospitalized patients with high BMI/ Obesity was the secondary outcome.

ResultsA total of 576,784 patients from 100 studies were included in this meta-analysis. Being obese was associated with increased risk of severe disease (RR=1.46, 95% CI 1.34-1.60, p<0.001, I2 = 92 %). Similarly, high mortality was observed in obese patients with COVID-19 disease (RR=1.12, 95% CI 1.06-1.19, p<0.001, I2 = 88%). In a multivariate meta-regression on severity outcome, the covariate of female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2= 50% of the between-study heterogeneity for severity. Similarly, for mortality outcome, covariate of female gender, proportion of pulmonary disease, diabetes, hypertension, and cardiovascular diseases were significant, these covariates collectively explained R2=53% of the between-study variability for mortality.

ConclusionsOur findings suggest that obesity is significantly associated with increased severity and higher mortality among COVID-19 patients. Therefore, the inclusion of obesity or its surrogate body mass index in prognostic scores and streamlining the management strategy and treatment guidelines to account for the impact of obesity in patient care management is recommended.


title: A Direct Capture Method for Purification and Detection of Viral Nucleic Acid Enables Epidemiological Surveillance of SARS-CoV-2

abstract: Studies have demonstrated that SARS-CoV-2 RNA can be detected in the feces of infected individuals. This finding spurred investigation into using wastewater-based epidemiology (WBE) to monitor SARS-CoV-2 RNA and track the appearance and spread of COVID-19 in communities. SARS-CoV-2 is present at low levels in wastewater, making sample concentration a prerequisite for sensitive detection and utility in WBE. Whereas common methods for isolating viral genetic material are biased toward intact virus isolation, it is likely that a relatively low percentage of the total SARS-CoV-2 RNA genome in wastewater is contained within intact virions. Therefore, we hypothesized that a direct unbiased total nucleic acid extraction method could overcome the cumbersome protocols, variability and low recovery rates associated with the former methods. This led to development of a simple, rapid, and modular alternative to existing purification methods. In an initial concentration step, chaotropic agents are added to raw sewage allowing binding of nucleic acid from free nucleoprotein complexes, partially intact, and intact virions to a silica matrix. The eluted nucleic acid is then purified using manual or semi-automated methods. RT-qPCR enzyme mixes were formulated that demonstrate substantial inhibitor resistance. In addition, multiplexed probe-based RT-qPCR assays detecting the N1, N2 (nucleocapsid) and E (envelope) gene fragments of SARS-CoV-2 were developed. The RT-qPCR assays also contain primers and probes to detect Pepper Mild Mottle Virus (PMMoV), a fecal indicator RNA virus present in wastewater, and an exogenous control RNA to measure effects of RT-qPCR inhibitors. Using this workflow, we monitored wastewater samples from three wastewater treatment plants (WWTP) in Dane County, Wisconsin. We also successfully sequenced a subset of samples to ensure compatibility with a SARS-CoV-2 amplicon panel and demonstrated the potential for SARS-CoV-2 variant detection. Data obtained here underscore the potential for wastewater surveillance of SARS-CoV-2 and other infectious agents in communities.

category: epidemiology


title: Can we use machine learning to discover risk factors? Testing the proof of principle using data on >11,000 predictors and mortality in the UK Biobank

abstract:
BackgroundWe present a simple and fast hypothesis-free machine learning pipeline for risk factor discovery that accounts for non-linearity and interaction in large biomedical databases with minimal variable pre-processing.

MethodsMortality models were built using gradient boosting decision trees (GBDT) and important predictors were identified using SHAP values. Cox models controlled for false discovery rate were used for interpretability and further validation. The pipeline was tested using information from 502,506 UK Biobank participants, aged 37-73 years at recruitment and followed over seven years for mortality registrations.

ResultsFrom the 11,639 predictors included in GBDT, 193 potential risk factors had SHAP values 0.05 or greater and were selected for further modelling. Of the total variable importance summed up, 60% was directly health related, and baseline characteristics, sociodemographics, and lifestyle factors each contributed about 10%.

Cox models adjusted for baseline characteristics, showed evidence for an association with mortality for 166 out of the 193 predictors. These included mostly well-known risk factors (e,g, age, sex, ethnicity, education, material deprivation, smoking, physical activity, self-rated health, BMI, and many disease outcomes), and the pipeline was able to detect associations in the presence of interactions and non-linear relationships. For 19 predictors we saw evidence for an association in the unadjusted but not adjusted analyses, suggesting bias by confounding..

ConclusionOur GBDT-SHAP pipeline was able to identify relevant predictors  hidden within thousands of variables, providing a fast and pragmatic solution for the first stage of hypothesis free risk factor identification.

O_TEXTBOXWhat was known before this study?Existing studies have used ML for variable selection in general settings, however, we are not aware of studies integrating epidemiological approaches with ML for risk factor discovery in deeply phenotyped large scale population cohorts. We present a simple and fast method for risk factor discovery using GBDT-SHAP pipeline, followed by subsequent standard epidemiological analyses. We test this pipeline using mortality prediction in the UK Biobank as an example.

What this study adds?Machine learning pipeline integrated with traditional epidemiological practices as described in our study can be used a simple and fast method for discovering potential risk factors in extensively phenotyped high dimensional biomedical databases. GBDT-SHAP pipeline was able to detect associations with factors presenting with interactions with other explanatory variables and non-linear relationships with the outcome with minimal variable pre-processing. However, ML does not replace the requirement for content knowledge and more refined modelling to ensure lack of confounding and accurate interpretation.

C_TEXTBOX


title: A Targeted Geospatial Approach to COVID-19 Vaccine Delivery: Findings from the Johns Hopkins Hospital Emergency Department

abstract: While COVID-19 vaccines have been shown to significantly decrease morbidity and mortality, there is still much debate about optimal strategies of vaccine rollout. We tested identity-unlinked stored remnant blood specimens of patients at least 18 years presenting to the Johns Hopkins Hospital emergency department (ED) between May to November 2020 for IgG to SARS-CoV-2. Data on SARS-CoV-2 RT PCR were available for patients who were tested due to suspected infection. SARS-CoV-2 infections was defined as either a positive IgG and/or RT-PCR. SARS-CoV-2 infection clustering by zipcode was analyzed by spatial analysis using the Bernoulli model (SaTScan software, Version 9.7). Median age of the 7,461 unique patients visiting the ED was 47 years and 50.8% were female; overall, 740 (9.9%) unique patients had evidence of SARS-CoV-2 infection. Prevalence of infection in ED patients by ZIP code ranged from 4.1% to 22.3%. The observed number of cases in ZIP code C was nearly double the expected (observed/expected ratio = 1.99; 95% CI: 1.62, 2.42). These data suggest a targeted geospatial approach to COVID vaccination should be considered to maximize vaccine rollout efficiency and include high-risk populations that may otherwise be subjected to delays, or missed.


title: Social and racial/ethnic differences in parental willingness to vaccinate children against COVID-19 in Montreal, Canada

abstract:
BackgroundThe success of current and prospective COVID-19 vaccine campaigns for children and adolescents will in part depend on the willingness of parents to accept vaccination. This study examined social determinants of parental COVID-19 vaccine acceptance and uptake for children and adolescents.

MethodsWe used cross-sectional data from an ongoing COVID-19 cohort study in Montreal, Canada and included all parents of 2 to 18-year-olds who completed an online questionnaire between May 18 and June 26, 2021 (n=809). We calculated child age-adjusted prevalence estimates of vaccine acceptance by parental education, race/ethnicity, birthplace, household income, and neighbourhood, and used multinomial logistic regression to estimate adjusted prevalence differences (aPD) and ratios (aPR). Social determinants of vaccine uptake were estimated for the vaccine-eligible sample of 12 to 18 year-olds (n=306).

ResultsIntention to vaccinate children against COVID-19 was high, with only 12.4% of parents unlikely to have their child vaccinated. Parents with younger children were less likely to accept vaccination, as were those from lower-income households, racialized groups, and those born outside Canada. The percent of parents whose child was vaccinated or very likely to be vaccinated was 18.4 percentage points lower among those with annual household incomes <$100,000 vs. [≥]$150,000 (95% CI: 10.1 to 26.7). Racialized parents reported greater unwillingness to vaccinate compared to White parents (aPD=10.3; 95% CI: 1.5, 19.1). Vaccine-eligible adolescents from the most deprived neighbourhood were half as likely to be vaccinated compared to those from the least deprived neighbourhood (aPR = 0.48; 95% CI: 0.18 to 0.77).

InterpretationThis study identified marked social inequalities in COVID-19 vaccine acceptance and uptake for children and adolescents. Efforts are needed to reach disadvantaged and marginalized populations with tailored strategies that promote informed decision making and facilitate access to vaccination.


title: Social inequalities in COVID-19 vaccine acceptance and uptake for children and adolescents in Montreal, Canada: a cross-sectional study


title: Effect of using personal protective equipment during the COVID-19 pandemic on the quality indicators of screening colonoscopies.

abstract:
BackgroundCoronavirus Disease 2019 (COVID-19) has affected many facets of the practice of medicine including screening colonoscopies.

AimsOur study looks to observe if there has been an effect on the quality of colonoscopies, as indicated by quality measures such as cecal intubation rate (CIR), cecal intubation time (CIT), scope withdrawal time (SWT) and adenoma detection rate (ADR) with the adoption of standard COVID-19 precautions.

MethodsWe conducted a retrospective chart review to analyze the effects of the COVID-19 pandemic on screening colonoscopies. The study utilized data on CIR, CIT, SWT and ADR from outpatient, non-emergent procedures conducted at 3 endoscopy suites of St Lukes University Health Network. All inpatient and emergent procedures were excluded.

ResultsOur study demonstrated that the total number of screening colonoscopies was decreased between 2019 to 2020 (318 in 2019 vs 157 in 2020, p= 0.005). CIT (320{+/-}105 seconds in 2019 vs 392{+/-}107 seconds in 2020, p=0.001) and SWT (706{+/-}232 seconds in 2019 vs 830{+/-}241 seconds in 2020, p=0.001) were increased while CIR (98.2% in 2019 vs 96.6% in 2020, p=0.04) was decreased between 2019 and 2020 likely due to PPE introduction. ADR was similar between the two groups (38.23 (12.50-66.66) in 2019 vs 38.18(16.66-66.00) in 2020, p=0.8).

ConclusionOur study showed that quality indices for screening colonoscopies like CIR, CIT, and SWT were negatively impacted during the COVID-19 time period. ADR, however, were similar. Thus, the efficiency of the procedures was affected by the use of PPE but it did not affect the colonoscopys clinical benefit.

category: gastroenterology


title: Protocol for a bibliometric analysis and mapping review of parental anxiety and postpartum depression across the perinatal period

abstract:
IntroductionThroughout the perinatal period from pregnancy to the first year postpartum, both men and women experience significant physical, psychological, and social changes which may increase their risk of a mental illness, including anxiety and depression. There has been significant growth in the frequency literature around anxiety and depression across the perinatal period over the past decades with significant variation in definition, measurement outcomes, and populations. To focus future research and identify gaps, it is important to explore current patterns and trends in the current literature.

ObjectiveThe objective of this bibliometric analysis is to analyze the characteristics and trends in published research on anxiety and depression across the perinatal period from January 1, 1920 to end of 2020.

Inclusion criteriaAll published literature in Web of Science on perinatal anxiety and depression from January 1, 1920 to December 31, 2020.

MethodsWeb of Science will be used to analyze bibliometric information through their built-in analysis feature and citation report that generates a list of leading publications, publication years, document types, authors, source titles, countries/regions, organizations, and research areas. VOSViewer will be utilized to analyze and visualize the networks of linkages between the identified reports, including bibliometric networks, including co-authorship, co-occurrence, and co-citation, as well as co-occurrence between keywords.

ConclusionThe findings from this study will provide useful information to guide future work on perinatal anxiety and depression. This bibliometric review will provide an overview of the work to date in perinatal mental health, identify key contributions to the field, and identify knowledge gaps and future directions.

category: psychiatry and clinical psychology


title: Bibliometric analysis of parental anxiety and postpartum depression across the perinatal period from 1920-2020: A protocol


title: Psychosis-like experiences and cognition in young adults: an observational and Mendelian randomisation study

abstract:
BackgroundPsychosis-like experiences (PLEs) are common and associated with mental health problems and poorer cognitive function. There is limited longitudinal research examining associations between cognition and PLEs in early adulthood.

AimsWe investigated the association of PLEs with different domains of cognitive function, using cross-sectional and longitudinal observational, and Mendelian randomisation (MR) analyses.

MethodParticipants from the Avon Longitudinal Study of Parents and Children (ALSPAC) completed tasks of working memory at age 18 and 24, and tasks of response inhibition and facial emotion recognition at age 24. Semi-structured interviews at age 18 and 24 established presence of PLEs (none vs. suspected/definite). Cross-sectional and prospective regression analysis tested associations between PLEs and cognition (N=3,087 imputed sample). MR examined causal pathways between schizophrenia liability and cognition.

ResultsThe fully adjusted models indicated that PLEs were associated with poorer working memory performance (cross-sectional analyses: b=-0.18, 95% CI -0.27 to -0.08, p<0.001; prospective analyses: b=-0.18, 95% CI -0.31 to -0.06, p<0.01). A similar pattern of results was found for PLEs and response inhibition (cross-sectional analyses: b=7.29, 95% CI 0.96 to 13.62, p=0.02; prospective analyses: b=10.29, 95% CI 1.78 to 18.97, p=0.02). We did not find evidence to suggest an association between PLEs and facial emotion recognition. MR analyses were underpowered and did not support observational results.

ConclusionsIn young adults, PLEs are associated with poorer concurrent and future working memory and response inhibition. Better powered genetically informed studies are needed to determine if these associations are causal.


title: Transdiagnostic digital phenotyping of psychopathology in a help-seeking population (PhenoNetz) - a study protocol for an experience sampling study

abstract: Prevention in psychiatry provides a promising way to address the burden by mental illness. However, established approaches focus on specific diagnoses and do not address the heterogeneity and manifold potential outcomes of help-seeking populations that present at early recognition services. Conceptualizing psychopathology manifested in help-seeking populations from a network perspective of interacting symptoms allows transdiagnostic investigations beyond binary disease categories. Furthermore, modern technologies such as smartphones facilitate the application of Experience Sampling Methods (ESM). A combination of ESM with network analyses provides valid insights beyond established assessment instruments. We will examine n = 75 individuals (age 18-40 years) of the help-seeking population of the Cologne early recognition centre (FETZ). For a maximally naturalistic sample, only minimal exclusion criteria will be applied. We will collect data for 14 days utilizing a mobile application to assess ten transdiagnostic symptoms, i.e., depressive, anxious and psychotic symptoms as well as distress level. With these data, we will generate average group-level symptom networks and personalized symptom networks using a two-step multilevel vector autoregressive model. Additionally, we will explore associations between symptom networks and sociodemographic, risk and resilience factors, as well as psychosocial functioning. Our study will provide insights about feasibility and utility of ESM in a help-seeking population. Providing a first explorative phenotyping of the transdiagnostic help-seeking population, this study will contribute to innovation of early recognition in psychiatry. Results will help to pave the way for prevention and targeted early intervention in a broader patient group and thus, enable greater intended effects in alleviating the burden of psychiatric disorders.


title: Transdiagnostic phenotyping of psychopathology in a help-seeking population (PhenoNetz): a study protocol for an experience sampling study


title: Yet another lockdown? A large-scale study on people's unwillingness to be confined during the first 5 months of the COVID-19 pandemic in Spain

abstract: Population confinements have been one of the most widely adopted non-pharmaceutical interventions (NPIs) implemented by governments across the globe to help contain the spread of the SARS-CoV-2 virus. While confinement measures have been proven to be effective to reduce the number of infections, they entail significant economic and social costs. Thus, different policy makers and social groups have exhibited varying levels of acceptance of this type of measures. In this context, understanding the factors that determine the willingness of individuals to be confined during a pandemic is of paramount importance, particularly, to policy and decision-makers. In this paper, we study the factors that influence the unwillingness to be confined during the COVID-19 pandemic by means of a large-scale, online population survey deployed in Spain. We apply both quantitative (logistic regression) and qualitative (automatic pattern discovery) methods and consider socio-demographic, economic and psychological factors, together with the 14-day cumulative incidence per 100,000 inhabitants. Our analysis of 109,515 answers to the survey covers data spanning over a 5-month time period to shed light on the impact of the passage of time. We find evidence of pandemic fatigue as the percentage of those who report an unwillingness to be in confinement increases over time; we identify significant gender differences, with women being generally less likely than men to be able to sustain long-term confinement of at least 6 months; we uncover that the psychological impact was the most important factor to determine the willingness to be in confinement at the beginning of the pandemic, to be replaced by the economic impact as the most important variable towards the end of our period of study. Our results highlight the need to design gender and age specific public policies, to implement psychological and economic support programs and to address the evident pandemic fatigue as the success of potential future confinements will depend on the populations willingness to comply with them.

category: public and global health


title: An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS

abstract:
AimsTau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations human cerebrospinal fluid (CSF) without antibody-based enrichment strategies.

ResultsWe demonstrate that the fit-for-purpose validated method in Alzheimers Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF.

ConclusionOur Tau LC-MS/MS method is a translational bioanalytical tool for assaying target engagement and pharmacodynamics for anti-tau antibody drug development campaigns.

category: neurology


title: On Gaps of Clinical Diagnosis of Dementia Subtypes: A Study of Alzheimer's Disease and Lewy Body Disease

abstract:
BACKGROUNDAlzheimers disease (AD) and Lewy body disease (LBD) are the two most common neurodegenerative dementias, and can occur in combination (AD+LBD). Due to overlapping biomarkers and symptoms, especially at early stages, clinical differentiation of these subtypes could be difficult. Yet it is unclear how the magnitude of diagnostic uncertainty varies across the dementia spectrum and demographic variables. We aimed to compare clinical diagnosis and post-mortem autopsy-confirmed pathological results to assess the clinical subtype diagnosis quality across these various factors.

METHODSWe studied data from the National Alzheimers Coordinating Center. Selection criteria included an autopsy-based neuropathological assessment for AD and/or LBD, and initial visit with Clinical Dementia Rating CDR(R) Dementia Staging Instrument (CDR) of 0, 0.5, or 1.0 corresponding to normal, mild cognitive impairment, or mild dementia, respectively. Longitudinally, we analyzed first visits at each subsequent CDR stage, and focused on the clinical diagnosis for AD and/or LBD in these visits. This analysis included positive predictive values (PPV), specificity and sensitivity and false negative rates of the clinical diagnosis, as well as disparities in these metrics by sex, race/ethnicity, age and education. If autopsy-confirmed AD, LBD, or AD+LBD was missed, the alternative clinical diagnosis was analyzed.

FINDINGSRecords of 1887 qualified participants from September 1, 2005 to August 20, 2019 were included in the study. Clinical diagnosis of AD+LBD had poor sensitivity from 2.7% (95% CI: 1.2%, 4.8%) at CDR 0.5 to 4.7% (2.1%, 7.8%) at CDR 3.0. Over 60% of participants with autopsy-confirmed AD+LBD were diagnosed clinically as AD. Clinical diagnosis of AD had low sensitivities at early dementia stage (56.8% (95% CI: 52.4%, 61.1%)) and low specificities at all stages. Among participants diagnosed as AD in the clinic, over 33% had concurrent LBD neuropathology at autopsy. Clinical diagnosis of LBD had poor PPVs from mild cognitive impairment (22% (95% CI: 12%, 33%)) to severe dementia (20% (95% CI: 9%, 33%)). Among participants diagnosed as LBD in the clinic, 32% to 54% revealed AD pathology during autopsy. When the three subtypes were missed by clinicians, "No cognitive impairment", "Undecided" and "primary progressive aphasia or behavioral variant frontotemporal dementia" were the leading primary etiologic clinical diagnosis. With increasing dementia stages, the difference in clinical diagnosis accuracy significantly increased between White and Black/African-American participants, and diagnosis quality significantly improved for males but not for females.

INTERPRETATIONOur findings demonstrate that clinical diagnosis of AD, LBD and AD+LBD are inaccurate and harbor significant disparities based on race and sex. These findings have important implications for clinical management, anticipatory guidance, trial enrollment, and applicability of potential disease modifying therapies for AD. They also promote research into better biomarker-based assessment of LBD pathology.


title: Superiority of serum NFL in predicting Multiple Sclerosis severity

abstract:
ObjectiveSerum neurofilament light chain (sNFL) is becoming an important biomarker of neuroaxonal injury. While sNFL correlates with cerebrospinal fluid NFL (cNFL), 40-60% of variance remains unexplained. Assuming that for diseases of the central nervous system (CNS), such as multiple sclerosis (MS), the cNFL better reflects CNS injury, our goal was to develop and validate adjustment of sNFL for relevant confounders, to strengthen cNFL-sNFL correlations.

MethodsWe used 1,378 matched cNFL-sNFL pairs divided into training and validation cohort with matching data on 11 confounders, neuroexam, and magnetic resonance imaging (MRI). The effect of confounders on cNFL-sNFL relationship was tested using multiple linear regression (MLR) model. Propensity score matching was used to identify effect of spinal cord damage on sNFL levels.

ResultsIn the training cohort (n=898) we correlated 11 confounders with the residuals from cNFL-sNFL linear regression. Four non-overlapping confounders explaining highest proportion of variance (12%: age, 8.7%: blood urea nitrogen, 3%: alkaline phosphatase, and 3.9%: weight) were used in MLR model. The model strengthened the cNFL-sNFL correlation from R2 = 0.52 to 0.64 in the independent validation cohort and strengthened correlation of adjusted sNFL with number of contrast-enhancing lesions (from R2 0.11 to 0.18). However, only sNFL, but not cNFL correlated with MS severity outcomes. Using propensity score matching, we demonstrated that subjects with proportionally higher sNFL to cNFL levels have significantly higher clinical and radiological evidence of spinal cord injury.

InterpretationSuperiority of sNFL likely resides in the release of NFL from axons of lower motor or dorsal ganglia neurons directly to blood.


title: Prodromal Progressive Supranuclear Palsy: insights from the UK Biobank

abstract:
BackgroundProdromal Parkinsons Disease is well described but prodromal Progressive Supranuclear Palsy (PSP) is much less understood. The diagnosis of PSP is typically delayed by an average of three years after symptom onset. Understanding the changes that occur in the prodromal and pre-diagnostic period will aid earlier diagnosis, clarify the natural history, and aid the design of early disease-modifying therapy trials.

ObjectivesTo determine motor and cognitive markers of prodromal PSP, with Parkinsons disease as a comparator condition, in a large prospective cohort.

MethodsBaseline UK Biobank data from 502,504 individuals were collected between 2006 and 2010. Subsequent PSP and Parkinsons disease cases were identified from primary and secondary care electronic health records diagnostic coding data and death registry, with 5,404 matched controls.

Results176 PSP cases (time to diagnosis 7.8{+/-}2.8 years) and 2,526 Parkinsons disease cases (time to diagnosis 7.8{+/-}2.9 years) were identified. At baseline, those later diagnosed with PSP had slower reaction times, weaker hand grip, lower fluid intelligence, poorer prospective memory, worse self-rated health score and lower digit recall than controls. They had higher mortality than both Parkinsons disease and control groups.

ConclusionsMotor slowing, cognitive dysfunction, and postural instability are clinical diagnostic features of PSP and are typically symptomatic three years before diagnosis. However, objective markers of these features are evident over seven years before diagnosis. This suggests a long prodromal course in PSP with subtle changes in motor and cognitive function.


title: DETECTION OF ITALIAN NURSES' THOUGHTS ON SEXUAL HEALTH AND THEIR KNOWLEDGE ON THE HIV-TRANSMISSION: A WEB SURVEY.

abstract:
INTRODUCTIONDespite the prevention of sexually transmitted infections included HIV and promotion of sexual health are fundamental parts of human health, the education system in Italy does not seem to provide healthcare professionals with specific knowledge requested by the most recent discoveries on HIV transmission.

METHODSA web survey was randomly administered to Italian nurses to collect their thoughts about the academic education they received and analyse their knowledge on one of the newest discoveries related to HIV transmission.

RESULTSMore than half of the participants never received any specific academic training on sexual health and sexually transmitted infections, and more than three-quarters of the respondents did not know that a gay couple where only one of the partners is HIV positive will not have to use condoms forever and for every sexual intercourse.

CONCLUSIONSThe survey suggests that training on sexual health and sexually transmitted infections of Italian nurses need to be reinforced and it also highlights the need of updating nurses on the <undetectable equals untransmittable> campaign.

KEY POINTKnowledge related to sexual health and HIV needs to be expanded in Italian nurses.

category: nursing


title: Midwives attitudes toward participation of pregnant women in a preventive vaccine hypothetical clinical trial

abstract:
IntroductionPregnant women are frequently excluded from clinical trials. Yet, inclusion of pregnant women is of interest in vaccinology including during health crisis. Promotion of clinical trials by midwives may facilitate the decision making of pregnant women. Attitudes of midwives about participation in a vaccine clinical trial have been little explored.

MethodsWe conducted an anonymous survey from the 11th of September to the 11th of November 2020. Primary endpoint was the willingness to encourage pregnant women to participate in a hypothetical respiratory syncytial virus (RSV) vaccine clinical trial.

ResultsAmong 398 midwives who answered the questionnaire, 113 (28.3 %) were likely to encourage pregnant women to participate in the vaccine clinical trial, this proportion ranged from 25 % in senior midwives to 34.5 % among the students. After adjustment on age, parenthood, previous vaccine hesitancy attitudes, and the 5 components of the 5C model, the only predictor of the promotion of the clinical trial was the training score with an adjusted odds ratio of 1.09 (1.01-1.18, p=0.027) for a one-point increase. Vaccine hesitancy and psychological antecedents of vaccinations were not associated with a lower promotion of pregnant women trial participation among midwives.

ConclusionFew respondents were likely to encourage pregnant women to participate in a vaccine clinical trial. Midwives who considered having a good training about vaccines were more prone to encourage pregnant women to participate in a RSV vaccine clinical trial.

Problem or IssueRecruitment of pregnant women in vaccine clinical trial is challenging

What is Already KnownPregnant women are more prone to accept participation in a clinical trial if the proposal is made by a midwife.

What this Paper AddsEvaluation of attitudes and their determinants of midwives about vaccine clinical trial participation of pregnant women.

category: obstetrics and gynecology


title: Evaluation the angle of posterosuperior horn of normal fetal Sylvian fissure and its morphological changes by trans-cerebellar section

abstract:
ObjectiveOn the basis of retrospectively analysis the trans-cerebellar section showing the Sylvian fissure of normal fetus is better than trans-thalamic section in middle and late trimester, we prospectively studied the morphological changes of the Sylvian fissure of normal fetus on the trans-cerebellar section in order to provide valuable information for the diagnosis of fetal cerebral cortical dysplasia.

MethodsA prospective cross-sectional study was conducted on 845 normal fetuses at 21 to 32 weeks of gestation from January 2019 to September 2020. The angle of the posterosuperior horn of the Sylvian fissure was measured. Based on the angle, the morphology of the Sylvian fissure was divided into four shapes included [Formula] shape (Angle >90{degrees}), [Pcy] shape (Angle {approx}90{degrees}), {pi} shape (Angle <90{degrees}) and  shape (Angle {approx}0{degrees}).

ResultsThe angle of the posterosuperior horn of the Sylvian fissure was negatively correlated with gestational age which correlation coefficient was 0.966 (P < 0.001). Taking gestational age as the independent variable and the angle of posterosuperior horn of the Sylvian fissure as the dependent variable, it showed that there was a linear relationship between the gestational age and the angle of posterosuperior horn of the Sylvian fissure. We got a simple correlation formula that the angle of posterosuperior horn of the Sylvian fissure ({degrees}) =140-13x(gestational weeks-21). It was found that the morphological changes of the Sylvian fissure were related to the gestational age. The morphology of the Sylvian fissure was [Formula]-shaped at 21 to 24 weeks of gestation, [Pcy]-shaped at 25 to 26 weeks of gestation, {pi}-shaped at 26 to 30 weeks of gestation, and the Sylvian fissure was almost closed and appeared  shape after 31 to 32 weeks of gestation.

ConclusionThis study preliminarily elucidates that the morphological changes of the posterosuperior horn of the Sylvian fissure of normal fetuses at 21 to 32 weeks of gestation through the trans-cerebellar section, which could provide valuable information for the evaluation of the normal development of the Sylvian fissure and the prenatal diagnosis of cerebral cortical hypoplasia of fetuses.


title: COVID-19 Compromises In The Medical Practice And The Consequential Effect On Endometriosis Patients

abstract:
Background and purposeIn response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, self-isolation practices aimed to curb the spread of COVID-19 have severely complicated the medical management of patients suffering from endometriosis and their physical and mental well- being. Endometriosis, the main cause for chronic pelvic pain (CPP), is a highly prevalent disease characterized by the presence of endometrial tissue in locations outside the uterine cavity that affects up to 10% of women in their reproductive age. This study aimed to explore the effects of the global COVID-19 pandemic on patients suffering from endometriosis across multiple countries, and to investigate the different approaches to the medical management of these patients based on their self-reported experiences.

MethodsA cross-sectional survey, partially based on validated quality of life questionnaires for endometriosis patients, was initially created in English, which was then reviewed by experts. Through the process of assessing face and content validity, the questionnaire was then translated to fifteen different languages following the WHO recommendations for medical translation. After evaluation, the questionnaire was converted into a web form and distributed across different platforms. An analysis of 2964 responses of participants from 59 countries suffering from self-reported endometriosis was then conducted.

ResultsThe data shows an association between COVID-19 imposed compromises with the reported worsening of the mental state of the participants, as well as with the aggravation of their symptoms. For the 1174 participants who had their medical appointments cancelled, 43.7% (n=513) reported that their symptoms had been aggravated, and 49.3% (n=579) reported that their mental state had worsened. In comparison, of the 1180 participants who kept their appointments, only 29.4% (n=347) stated that their symptoms had been aggravated, and 27.5% (n=325) stated their mental health had worsened. 610 participants did not have medical appointments scheduled, and these participants follow a similar pattern as the participants who kept their appointments, with 29.0% (n=177) reporting aggravation of symptoms and 28.2% (n=172) reporting that their mental state had worsened.

ConclusionsThese findings suggest that COVID-19 pandemic has had a clinically significant negative effect on the mental and physical well-being of participants suffering from endometriosis based on their self-reported experiences. Thus, they show the importance of further assessment and reevaluation of the current and future management of this condition in medical practices worldwide.


title: The Association Between Threatened Miscarriage And Development Of Gestational Hypertension/Pre-Eclampsia

abstract:
IntroductionGestational hypertension (GH)/Pre-eclampsia (PEC) is an important cause of direct maternal deaths in Sri Lanka. GH/PEC and threatened miscarriage (TM) share common pathophysiological mechanisms. This study was conducted to determine the association between TM and development of GH/PEC.

MethodologyA case control study was conducted at Castle Street Hospital for Women, Sri Lanka from April 2015 to October 2015. Cases consisted of patients with GH/PEC and compared with age and parity matched controls. A systematic random sampling method was used. Similar number of cases and controls were compared while each group consisted of 245 subjects. Data was obtained from medical records. Its also important to note that mothers aged 20-35 years were included and medical disorders other than GH/PEC was excluded.

ResultsThere were 245 subjects in each group of the study. Among the cases, 56% had GH and the rest had PEC. There were 25 patients with TM in the study population and 64% of them subsequently developed GH or PEC. There is also a significant risk of developing PEC in a patient who had a history of threatened miscarriage (OR 3.31, 95% CI 1.35-8.11). Moreover the patients who had a history of TM tend to develop GH or PEC early, within 20-32 weeks of gestation (OR 11.49, 95% CI 3.88-33.99). As we identified, 62% of patients who had TM developed GH/PEC early (from 20 to 32 weeks) but among the cases who had no history of TM, only 12% developed GH/PEC between 20 to 32 weeks of gestation (O.R. 20.7 (5.66 to 91.96). There is a significant risk of developing severe GH/PEC in the group of patients who had a history of TM (OR 8.59, 95% CI 2.87-25.66). Eighty one percent (81%) of the cases, who had a history of TM, developed severe and moderate GH/PEC rather than mild. But the majority (63%) of the cases, who had no history of TM, developed mild GH/PEC (O.R. 7.6 (2.00 to 42.55).

ConclusionsShared pathophysiological mechanisms of GH/PEC and TM may explain the observed association between these obstetric complications. Early onset, severe GH/PEC in cases with TM suggests temporality and a biological gradient which favors causality.


title: Evaluation of the depth and width of normal fetal Sylvian fissure by trans-cerebellar section

abstract:
ObjectiveOn the basis of retrospectively analysis the trans-cerebellar section showing the Sylvian fissure of normal fetus is better than trans-thalamic section in middle and late trimester, we prospectively established the normal reference range of developmental parameters related to the Sylvian fissure of normal fetus in the trans-cerebellar section in order to provide valuable information for the diagnosis of fetal cerebral cortical dysplasia.

MethodsA prospective cross-sectional study was conducted on 845 normal fetuses at 21 to 32 weeks of gestation from January 2019 to September 2020. The depth and width of the Sylvian fissure was measured respectively, and regression analysis was performed according to different gestational age groups.

ResultsThe depth of Sylvian fissure was positively correlated with gestational weeks, and the width of Sylvian fissure was negatively correlated with gestational weeks, with correlation coefficients 0.751 and 0.825 respectively (all P < 0.001).Taking gestational weeks as the independent variable, and the depth and width of Sylvian fissure of fetus as the dependent variables, linear regression analysis showed that there was a linear relationship between the independent variables and the dependent variables. The obtained equation was simplified to a formula: Fetal Sylvian fissure depth (mm)=7+0.6x (gestational weeks-21), Sylvian fissure width (mm)=8-0.6x (gestational weeks-21).

ConclusionThe reference range of the depth and width of Sylvian fissure of normal fetus at 21 to 32 weeks of pregnancy through the trans-cerebellar section was established, which could provide valuable information for the evaluation of the normal development of the lateral fissure of fetus and the prenatal diagnosis of fetal cortical hypoplasia.


title: ARTIFICIAL INTELLIGENCE ACCURATELY DETECTS TRAUMATIC THORACOLUMBAR FRACTURES ON SAGITTAL RADIOGRAPHS

abstract:
Background contextTraumatic thoracolumbar (TL) fractures are frequently encountered in emergency rooms. Sagittal and anteroposterior radiographs are the first step in the trauma routine imaging. Up to 30% of TL fractures are missed in this imaging modality, thus requiring a CT and/or MRI to confirm the diagnosis. A delay in treatment leads to increased morbidity, mortality, exposure to ionizing radiation and financial burden. Fracture detection with Machine Learning models has achieved expert level performance in previous studies. Reliably detecting vertebral fractures in simple radiographic projections would have a significant clinical and financial impact.

PurposeTo develop a deep learning model that detects traumatic fractures on sagittal radiographs of the TL spine.

Study design/settingRetrospective Cohort study.

MethodsWe collected sagittal radiographs, CT and MRI scans of the TL spine of 362 patients exhibiting traumatic vertebral fractures. Cases were excluded when CT and/or MRI where not available. The reference standard was set by an expert group of three spine surgeons who conjointly annotated the sagittal radiographs of 171 cases. CT and/or MRI were reviewed to confirm the presence and type of the fracture in all cases. 302 cropped vertebral images were labelled  fracture and 328  no fracture. After augmentation, this dataset was then used to train, validate, and test deep learning classifiers based on ResNet18 and VGG16 architectures. To ensure that the models prediction was based on the correct identification of the fracture zone, an Activation Map analysis was conducted.

ResultsVertebras T12 to L2 were the most frequently involved, accounting for 48% of the fractures. A4, A3 and A1 were the most frequent AO Spine fracture types. Accuracies of 88% and 84% were obtained with ResNet18 and VGG16 respectively. The sensitivity was 89% with both architectures but ResNet18 showed a higher specificity (88%) compared to VGG16 (79%). The fracture zone was precisely identified in 81% of the heatmaps.

ConclusionsOur AI model can accurately identify anomalies suggestive of vertebral fractures in sagittal radiographs by precisely identifying the fracture zone within the vertebral body.

Clinical significanceClinical implementation of a diagnosis aid tool specifically trained for TL fracture identification is anticipated to reduce the rate of missed vertebral fractures in emergency rooms.

category: orthopedics


title: Hearing aids reduce daily-life fatigue and increase social activity: a longitudinal study

abstract: People with hearing loss experience fatigue, and it is unknown whether this is alleviated by treatment with hearing aids. The objective of this study was to address this issue, and to investigate the possible concomitant effect of hearing-aid fitting on activity levels. An intervention group (n=53) who were due to be fitted with their first ever hearing aid(s) and a control group (n=53) who had hearing loss but no change in hearing aid status completed a battery of self-report outcome measures four times: once before fitting, and at two weeks, three months and six months post fitting. Self-report outcome measures at each assessment captured fatigue, listening effort, hearing handicap, auditory lifestyle, social participation restrictions and work, social and physical activity levels. Hearing-aid fitting led to a significant reduction in listening-related fatigue, but not general fatigue, in the intervention group compared to the control group. Additionally, social activity level increased and social participation restriction decreased significantly after hearing aid fitting in the intervention group compared to the control group. No significant interaction was found between working status and change in listening-related fatigue score. This study is the first to make longitudinal measurement of fatigue before and after first-ever hearing aid fitting and to identify an increase in social activity level after hearing aid fitting. These findings have important implications for future research and the clinical practice of hearing aid fitting.

category: otolaryngology


title: Genetic variant in SPDL1 reveals novel mechanism linking pulmonary fibrosis risk and cancer protection

abstract:
Idiopathic Pulmonary Fibrosis (IPF) is a rare disease with poor prognosis. By contrast, cancer is common in any elderly population and a leading killer, but is now often curable. Of note, whereas IPF is driven by cellular senescence, cancer is characterized by uncontrolled cell division.

Using data available from two large biobank-based studies (Finnish FinnGen study and UK biobank), we conducted a comprehensive analysis of the shared genetic background of IPF and cancer. In a population sample of 218,792 Finns with complete longitudinal health histories, we estimated the effect of individual genetic variants to the lifetime risk of IPF and cancer. We extend the analysis from IPF-GWAS to pan-cancer meta-analysis over FinnGen and UK Biobank and finally to the identification of genetic drivers of somatic chromosomal alterations.

We detected six loci (SPDL1, MAD1L1, MAP2K1, RTEL1-STMN3, TERC-ACTRT3, OBFC1) associated with both IPF and cancer, all closely related to cellular division. However, each individual signal is found with opposite effects over the two diseases, termed as antagonistic pleiotropy. Several of these loci (TERC-ACTRT3, RTEL1-STMN3, OBFC1) are among the strongest inherited factors for constitutive telomere length variation and consistently indicate that shorter telomere length would increase the risk for IPF but protect from malignancy. However, a Finnish enriched SPDL1 missense variant and a common MAD1L1 intronic variant had no effect on telomere length but were shown to protect individuals from accumulation of somatic mutations.

The decreased risk of cancer in SPDL1 and MAD1L1 variant carriers might result from a lower number of chromosomal alterations accumulated over time, conversely leading to fibrosis in the lung due to cellular senescence-induced inflammation. We hypothesize that the SPDL1 missense variant functions as gain-of-function mutation, leading to cellular senescence, a barrier to cancer and a driver of fibrosis in IPF. If translated to therapy, these findings might not only be able to offer relief to individuals with IPF, but also to protect from onset of cancer.

category: genetic and genomic medicine


title: Multivariate Modeling of Direct and Proxy GWAS Indicates Substantial Common Variant Heritability of Alzheimer's Disease

abstract: Genome-wide association studies (GWAS) of proxy-phenotypes using family history of disease (GWAX) substantially boost power for genetic discovery when combined with direct case-control GWAS, most prominently in the context of Alzheimers Disease (AD). However, despite twin study heritability estimates of approximately 60%, recent SNP-based estimates of common variant heritability of AD from meta-analyzed GWAS-GWAX data have been particularly low (2.5%), calling into question the prospects of continued progress in AD genetics. We demonstrate that commonly used approaches for combining GWAX and GWAS data produce dramatic underestimates of heritability, and we introduce a multivariate method for estimating individual SNP effects and recovering unbiased estimates of SNP heritability when combining GWAS and GWAX summary data. We estimate the SNP heritability of Clinical AD diagnoses excluding the APOE region at [~]6-10%, with the corresponding estimate for biological AD (based on prevalence rate estimates from recently published molecular imaging data) as high as [~]20%. Common variant risk for AD appears to represent a very strong effect of APOE superimposed upon a relatively diffuse polygenic signal that is distributed across the genome.


title: INDIA'S PRAGMATIC VACCINATION STRATEGY AGAINST COVID-19: A MATHEMATICAL MODELLING BASED ANALYSIS

abstract:
ObjectivesTo investigate the impact of targeted vaccination strategies on morbidity and mortality due to COVID-19, as well as on the incidence of SARS-CoV-2, in India.

DesignMathematical modelling.

SettingsIndian epidemic of COVID-19 and vulnerable population.

Data sourcesCountry specific and age-segregated pattern of social contact, case fatality rate and demographic data obtained from peer-reviewed literature and public domain.

ModelAn age-structured dynamical model describing SARS-CoV-2 transmission in India incorporating uncertainty in natural history parameters was constructed.

InterventionsComparison of different vaccine strategies by targeting priority groups such as key workers including health care professionals, individuals with comorbidities (24 - 60 year), and all above 60.

Main outcome measuresIncidence reduction and averted deaths in different scenarios, assuming that the current restrictions are fully lifted as vaccination is implemented.

ResultsThe priority groups together account for about 18% of Indias population. An infection preventing vaccine with 60% efficacy covering all these groups would reduce peak symptomatic incidence by 20.6% (95% uncertainty intervals (CrI) 16.7 - 25.4), and cumulative mortality by 29.7% (95% CrI 25.8-33.8). A similar vaccine with ability to prevent symptoms (but not infection) will reduce peak incidence of symptomatic cases by 10.4% (95% CrI 8.4 - 13.0), and cumulative mortality by 32.9% (95% CrI 28.6 - 37.3). In the event of insufficient vaccine supply to cover all priority groups, model projections suggest that after keyworkers, vaccine strategy should prioritise all who are > 60, and subsequently individuals with comorbidities. In settings with weakest transmission, such as sparsely-populated rural areas, those with comorbidities should be prioritised after keyworkers.

ConclusionsAn appropriately targeted vaccination strategy would witness substantial mitigation of impact of COVID-19 in a country like India with wide heterogenity.  Smart vaccination, based on public health considerations, rather than mass vaccination, appears prudent.

O_TEXTBOXStrengths and limitation of this study

O_LIThe model in this study is informed by age-dependent risk factors for SARS-CoV-2 infection among contacts, and is stratified by co-morbidities (diabetes and/or hypertension), and vaccination status.
C_LIO_LIData on mortality and large-scale contact tracing from within India, and the recent national sero-survey results were used, which constituted a major strength of this investigation.
C_LIO_LIDistinguishing between  infection and  symptomatic disease   preventing vaccines, the model was simulated under a range of scenarios for the basic reproduction number (R0).
C_LIO_LIShould they have been available, real life country-specific data on excess risks of deaths due to comorbidities would have added strength to the presented model.
C_LIO_LIKey priority group-specific data on social mixing and potential associated transmission was not available, and remained as a limitation.
C_LI

C_TEXTBOX

category: health policy


title: Adaptation of the Person-Centered Maternity Care scale for people of color in the United States

abstract:
IntroductionMistreatment by healthcare providers disproportionately affects people of color in the United States (US). The goal of this study is to adapt the global Person-Centered Maternity Care (PCMC) scale to the experiences of people of color in the US using a community-engaged approach.

MethodsWe conducted expert reviews to improve content validity and cognitive interviews with potential respondents were conducted to assess relevance, comprehension, and comprehensiveness. Surveys of 297 postpartum people, 82% of whom identified as Black, were used for psychometric analysis in which we assessed construct and criterion validity and reliability. The University of California, San Francisco, California Preterm Birth Initiatives Community Advisory Board (CAB), which consists of community members, community-based health workers, and social service providers in Northern California, provided input during all stages of the project.

ResultsThrough an iterative process of factor analysis, discussions with the CAB, and a prioritization survey, we eliminated items that performed poorly in psychometric analysis, yielding a 35-item PCMC-US scale with sub-scales for "dignity and respect," "communication and autonomy," and "responsive and supportive care." The Cronbachs alpha for the full scale is 0.95 and for the sub-scales is 0.87. Standardized summative scores range from 0 to 100, with higher scores indicating higher PCMC. Correlations with related measures indicated high criterion validity.

ConclusionsThe 35-item PCMC-US scale and its sub-scales have high validity and reliability in a sample of predominantly Black women. This scale provides a tool to support efforts to reduce the disparities in birth outcomes among people of color.

category: health systems and quality improvement


title: Comparing the effectiveness of secondary distribution of HIV self-testing to testing card referral in promoting HIV testing among men who have sex with men in China: A quasi-experimental study

abstract:
BackgroundSocial network-based HIV self-testing (HIVST) is useful to promote HIV testing. Secondary distribution is one social network-based method whereby individuals (indexes) access multiple HIVST kits and distribute them to their social networks (alters). This quasi-experimental study compared the effectiveness and cost of two social network-based HIV testing strategies (HIVST secondary distribution and HIV testing card referral) in promoting HIV testing among Chinese men who have sex with men (MSM).

MethodsMSM aged 18 years or older were recruited in Guangzhou, Guangdong Province. From May to September 2019, indexes recruited during that period could distribute HIVST kits to people within their social network. Indexes recruited from October 2019 to January 2020 could refer HIV testing cards to people within their social network for free facility-based tests. Participants could access 1-5 HIVST kits or testing referral cards for distribution. Alters were encouraged to upload a picture of their test results and complete an online survey. Indexes and alters received an incentive to report test results.

ResultsTwo hundred thirty-nine potential participants were assessed for eligibility and 208/245 (84.9%) were eligible. Among those who completed baseline assessment, 154/208 (74.0%) completed one month of follow-up. Overall,106 indexes were recruited in the HIVST arm and 102 in the testing card arm. The two arms had similar socio-demographic characteristics. At the one-month follow-up, 92 indexes in the HIVST arm self-reported having distributed self-test kits to 179 unique alters, and 62 in the testing card arm self-reported having distributed testing referral cards to 26 unique alters. Additionally, 69/92 (75%) in the HIVST arm distributed any test to friends or sexual partners compared to 18/62 (29%) in the testing card arm, with a risk difference of 46% (95% CI 31%, 61%). Indexes in the HIVST arm distributed an average of 1.95 (SD=1.90) tests, compared to 0.42 (SD=0.78) in the testing card arm, with a risk difference of 1.53 (95% CI 1.09, 1.96). Subgroup analysis suggested that indexes in the HIVST arm who self-identified as gay (p = 0.007) or were previously tested for HIV (p = 0.02) were more likely to distribute. The HIVST arm had a higher total cost and higher testing coverage compared to the testing card referral arm. The ICER per alter tested was $52.78.

ConclusionsSecondary distribution of HIVST engaged more MSM to distribute tests to their social network and reached more MSM for test. MSM who self-identify as gay or who have previously tested for HIV were more effective in distributing tests. Future testing approaches should include HIVST kits in voluntary counselling and testing settings and incorporate digital strategies for secondary distribution.

category: hiv aids


title: PREVALENCE THRESHOLDS THAT SHOULD BE APPLIED IN SCHISTOSOMIASIS MASS DRUG ADMINISTRATION PRGROGRAMMES: SYSTEMATIC REVIEW AND META-ANALYSIS

abstract:
BackgroundThe WHO-recommended prevalence thresholds for deciding schistosomiasis mass drug administration (MDA) are based on anecdotal evidence and may mislead. This study systematically synthesized evidence to generate a single optimal  global prevalence threshold that should guide schistosomiasis MDA programmes worldwide.

MethodsWe searched several databases from 1978 to 31st October 2021 without language restriction. Two reviewers selected studies, extracted data, and assessed risk of bias using relevant risk of bias tools, and resolved disagreements through discussion. The review followed best practices protocols and guidelines. Data were analysed and presented as prevalence reduction (PR) and relative risk (RR) for dichotomous outcomes or mean difference for continuous outcomes, each presented with their 95% confidence intervals (CI). Meta-regression of observations on prevalence rates and intensity of infection were performed to assess the effect of repeat MDA over time. Sensitivity analysis was performed to test the robustness of the results to the risk of bias components. The overall level of evidence was graded using GRADE.

FindingsOf the 1,232 studies retrieved, 38 met our inclusion criteria and 34 were included in the meta-analysis. No direct relation was observed between prevalence and intensity of infection. Praziquantel reduced prevalence of S. mansoni in school age children (SAC) at 12 months (RR 0.56, 95% CI 0.46 to 0.69; 14 studies, n=86,073); 24 months (RR 0.46; 95% CI 0.32 to 0.66; 14 studies; n=83,721); 36 months (RR 0.44, 95% CI 0.33 to 0.58; 7 studies, n=70,933) and 48 months (RR 0.25, 95% CI 0.11 to 0.59; 5 studies; n=27,483). Similarly for S. haematobium, there were reductions in prevalence in school age children (SAC) at 12 months (RR 0.38, 95% CI 0.28 to 0.52; 8 studies, n=37,868); at 24 months (RR 0.30; 95% CI 0.30[boxh]0.52; 7 studies; n=37,107); and 36 months (RR 0.39, 95% CI 0.21 to 0.71; 5 studies, n=28,146). There was no significant reduction in prevalence at 48 months (2 studies, n=10,954). Further analyses were performed from a series of prevalence thresholds created from the data at 5%, 10%, 15%, 20%, 30% and [≥]40% and the results showed differences in the effect of MDA when each threshold was applied in the regression model. For annual MDA involving SAC, school-based treatment (SBT) appeared to perform better than community-wide treatment (CWT) in terms of prevalence reduction; but this could be subject to the frequency of treatment and retreatment applied in SAC compared to CWT. Using the optimal prevalence threshold of 10%, the model suggested it will take over 10 years to bring the prevalence of schistosomiasis to 1% for S. haematobium and up to 15 years for S. mansoni with repeated annual MDA.

InterpretationThis systematic review and meta-analysis provides evidence that 10% prevalence is the optimum that should be used as the  standard global threshold for implementing MDA in endemic countries.

FundingThis work was commissioned and supported by the World Health Organization, Geneva, Switzerland as part of evidence-based schistosomiasis guideline development.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSCurrently, the prevalence thresholds used in implementing mass drug administration within the preventive chemotherapy strategy for schistosomiasis control are based on anecdotal evidence and unreliable. We identified relevant studies regardless of language or publication status (published, unpublished, in press, and ongoing). We searched PubMed, CINAHL and LILACS from 1978 to 31st October 2021 without language restriction. We also searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2021), mRCT, Hinari, the WHO Library Database, Africa Journals Online and Google Scholar. Experts in the field of schistosomiasis were contacted, preprint repositories were searched and the reference lists of articles were reviewed for additional or unpublished data. This study was commissioned by the WHO to provide systematically synthesized evidence to inform on a single global prevalence threshold that should be applied by endemic countries when deciding MDA campaigns for the prevention and control of schistosomiasis.

Added value of this studyThis is the first systematic review and meta-analysis commissioned by the WHO to determine a single prevalence threshold that should be employed by endemic countries for the implementation of global schistosomiasis mass drug administration. This study pooled data involving thousands of participants across thousands of villages from all endemic settings, making it unique in terms of statistical power and generalizability of the main findings and conclusions. The study used PICOS (P-population, I-intervention, C-comparator, O-outcomes and S-study) to formulate an appropriate review question, clear objectives, stringent inclusion and exclusion criteria as well as rigorous quality assessment and data synthesis, following strictly best practices for preparing and reporting systematic reviews. The search has been very comprehensive including all relevant electronic databases and non-electronic sources, done in close collaboration with experienced information specialist. The review process ensured meticulous attention to details, making the necessary effort to minimize bias, carrying out aspects of the review independently by the reviewers and addressing disagreements through discussions between the reviewers. Given the geographical variations, and differences in the levels of baseline endemicities, diagnostic criteria, age groups treated and follow-up times across studies, this necessitated robust sub-group analyses to detect any sub-group effects. We ran meta-regression analyses to identify any potentially useful trends, and tested the robustness of effect estimates from sensitivity analyses. We have assembled world-class experts from diverse backgrounds and geographical locations, including epidemiologists, evidence synthesis specialists, economists, allied health professionals, statisticians, biomedical scientists, clinicians and non-medical experts to produce this innovative, demand-driven, policy- and context-relevant systematic review and meta-analysis that will help guide policy and practice in the global control of schistosomiasis.

Implications of all the available evidenceOur review provides evidence that 10% baseline prevalence is the minimum optimal threshold that should be used to decide the implementation of MDA programmes in schistosomiasis endemic countries. Praziquantel is effective in reducing the prevalence of schistosomiasis at 12 months, but incremental benefit of repeated annual treatment appears to be minimal after 12 months. Effectiveness depends on several factors, which are difficult to disentangle, however, the rate at which prevalence decreases does not appear to be influenced by baseline intensity of infection and treatment approach (whether whole community or school-based). From exploratory analysis, intensity of infection appears to be more stable than prevalence for assessing outcome of MDA. Therefore, further research is needed to determine an optimal intensity threshold and compare it with prevalence threshold. In terms of policy, the difficulty in achieving elimination with mass drug administration alone means that integration of non-pharmacological interventions such access to clean water, improved sanitation, hygiene education (WASH) and snail control to complement MDA if elimination is to be achieved.

This systematic review was registered in PROSPERO CRD422020221548.

category: infectious diseases


title: PREVALENCE THRESHOLD THAT SHOULD BE APPLIED IN SCHISTOSOMIASIS MASS DRUG ADMINISTRATION PRGROGRAMMES: SYSTEMATIC REVIEW AND META-ANALYSIS


title: PREVALENCE THRESHOLD THAT SHOULD BE APPLIED WHEN DECIDING SCHISTOSOMIASIS MASS DRUG ADMINISTRATION: SYSTEMATIC REVIEW AND META-ANALYSIS


title: Optimal Prevalence Threshold To Guide The Implementation Of Mass Drug Administration In Countries Endemic For Schistosomiasis: Comprehensive Synthesis Of Evidence For Developing The Tool


title: Concurrent circulation of dengue serotype 1, 2 and 3 among acute febrile patients in Cameroon

abstract: Acute febrile patients presenting at hospitals in Douala, Cameroon between July and December 2020, were screened for dengue infections using RT-PCR on fragments of the 5 and 3 UTR genomic regions. In total, 12.8% (41/320) of cases examined were positive for dengue. Dengue virus 3 (DENV-3) was the most common serotype found (68.3%), followed by DENV-2 (19.5%) and DENV-1 (4.9%). Co-infections of DENV-3 and DENV-2 were found in 3 cases. Jaundice and headache were the most frequent clinical signs associated with infection and 176 cases (55%) were co-infections with malaria. Phylogenetic analysis of the envelope gene identified DENV-1 as belonging to genotype V, DENV-2 to genotype II and DENV-3 to genotype III. The simultaneous occurrence of three serotypes in Douala reveals dengue as a serious public health threat for Cameroon and highlights the need for further epidemiological studies in the major cities of this region.


title: Estimated Spike Evolution and Impact of Emerging SARS-CoV-2 Variants

abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been mutating and thus variants emerged. This suggests that SARS-CoV-2 could mutate at an unsteady pace. Supportive evidence comes from the accelerated evolution which was revealed by tracking mutation rates of the genomic location of Spike protein. This process is sponsored by a small portion of the virus population but not the largest viral clades. Moreover, it generally took one to six months for current variants that caused peaks of COVID-19 cases and deaths to survive selection pressure. Based on this statistic result and the above speedy Spike evolution, another upcoming peak would come around July 2021 and disastrously attack Africa, Asia, Europe, and North America. This is the prediction generated by a mathematical model on evolutionary spread. The reliability of this model and future trends out of it comes from the comprehensive consideration of factors mainly including mutation rate, selection course, and spreading speed. Notably, if the prophecy is true, then the new wave will be the first determined by accelerated Spike evolution.


title: Rapid detection of neutralizing antibodies to SARS-CoV-2 variants in post-vaccination sera

abstract: The uncontrolled spread of the COVID-19 pandemic has led to the emergence of different SARS-CoV-2 variants across the globe. The ongoing global vaccination strategy to curtail the COVID-19 juggernaut, is threatened by the rapidly spreading Variants of Concern (VOC) and other regional mutants, which are less responsive to neutralization by infection or vaccine derived antibodies. We have previously developed the hiVNT system which detects SARS-CoV-2 neutralizing antibodies in sera in less than three hours. In this study, we modify the hiVNT for rapid qualitative screening of neutralizing antibodies (nAb) to multiple variants of concern (VOC) of SARS-CoV-2, and assess the neutralizing efficacy of the BNT162b2 mRNA vaccine on seven epidemiologically relevant SARS-CoV-2 variants. Here we show that the BNT162b2 mRNA vaccine can activate humoral immunity against the major SARS-CoV-2 mutants that are currently in circulation. Albeit a small sample size, we observed that one dose of vaccine was sufficient to elicit a protective humoral response in previously infected people. Using a panel of seven SARS-CoV-2 variants and a single prototype virus, our modified hiVNT would be useful for large-scale community wide testing to detect protective immunity that may confer vaccine/immune passport in the ongoing COVID-19 pandemic.


title: A new SARS-CoV-2 variant poorly detected by RT-PCR on nasopharyngeal samples, with high lethality

abstract:
BackgroundIn early January 2021, an outbreak of nosocomial cases of COVID-19 emerged in Western France, with RT-PCR tests repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole genome sequencing (WGS) revealed a new variant, currently defining a novel SARS-CoV-2 lineage: B.1.616. In March, WHO classified this variant as  under investigation (VUI). We analyzed the characteristics and outcomes of COVID-19 cases related to this new variant.

MethodsClinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled patients with at least one of the following: i) positive SARS-CoV-2 RT-PCR on a respiratory sample; ii) seroconversion with anti-SARS-CoV-2 IgG/IgM; iii) suggestive symptoms and typical features of COVID-19 on chest CT scan. Cases were categorized as either: i) B.1.616; ii) variant of concern (VOC); iii) unknown.

FindingsFrom January 1st to March 24th, 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n=34), VOC (n=32), and unknown (n=48). B.1.616-related cases were older than VOC-related cases (81 years [73-88], vs 73 years [67-82], P<0.05) and their first RT-PCR tests were less often positive (5/34, 15% vs 31/32, 97%, P<0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.2 [1.3- 13.5], P=0.018), and increased lethality (logrank test P=0.01): 28-day mortality 15/34 (44%) with B.1.616, vs. 5/32 (16%) for VOC, P=0.036.

InterpretationWe report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, poorly detected by RT-PCR on nasopharyngeal samples, with high lethality.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAmong the numerous SARS-CoV-2 variants described worldwide, only 3 are currently classified as Variant of Concern (VOC) by the WHO, since they are associated with either an increased risk in transmissibility, severity, or significant reduction in neutralization by antibodies: B.1.1.7, B.1.351 and P.1 (Pango lineage nomenclature). With the ongoing circulation of SARS-CoV-2 in many places worldwide, the emergence of new variants may reduce the efficacy of vaccines and jeopardize our prospects to control the pandemic. In early January 2021, an outbreak of cases highly suggestive of COVID-19 despite negative RT-PCR tests on repeated nasopharyngeal (NP) samples was reported in Western France, leading to several nosocomial clusters. Whole-genome sequencing (WGS) from lower respiratory tract samples identified a new lineage of SARS-CoV-2 virus, classified as B1.616. Consequently, the French public health agency (Sante publique France) and the WHO classified B.1.616 as  variant under investigation (VUI).

Added value of this studyOur observational study, conducted from January 1st to March 24th 2021 in the B.1.616 identified area, provides the first clinical and virological description of B.1.616-associated COVID-19. The 34 cases had clinical, biological and radiological findings in line with classical features of COVID-19, while RT-PCR tests on nasopharyngeal (NP) samples failed to detect SARS-CoV-2 in most patients. Indeed, this gold-standard test was positive in only 15% of the first tests in B.1.616-related COVID-19 patients. Of note, the diagnostic performance of RT-PCR tests was satisfactory on lower respiratory tract samples, suggesting that failure to detect B.1.616 on NP samples would be due to a viral load below the limit of detection in the upper respiratory tract, rather than to genomic mismatches between routine RT-PCR targets and this variant. In our cohort, B.1.616 was independently associated with worse clinical outcome, with high 28-day mortality (44%).

Implications of all the available evidenceDiagnosis of B.1.616-related COVID-19 cases should not rely on RT-PCR tests on NP samples. In the epidemic area, strict infection control measures must be maintained as long as COVID-19 diagnosis is not ruled out, in order to limit nosocomial clusters and case fatality. Further studies are needed to confirm and investigate the association between genomic characteristics of B.1.616, and i) poor detection by RT-PCR tests on NP samples; ii) prognosis.


title: Making the invisible visible: New perspectives on the intersection of human-environment interactions of clinical teams in intensive care

abstract: Understanding human behaviour is essential to the adoption practices for new technologies that promote safer care. This requires capturing the detail of clinical workflows to inform the design of new interactions including those with touchless technologies that decipher human-speech, gesture and motion and allow for interactions that are free of contact. Many environments in hospitals are sub-optimally designed, with a poor layout of work surfaces, cumber-some equipment that requires space and effort to manoeuvre, designs that require healthcare staff to reach awkwardly and medical devices that require extensive touch. This suggests there is a need to better understand how they can be designed. Here, we employ a new approach by installing a single 360{degrees} camera into a clinical environment to analyse touch patterns and human-environment interactions across a clinical team to recommend design considerations for new technologies with potential to reduce avoidable touch.

category: intensive care and critical care medicine


title: Ankle and Toe Brachial Index Extraction from Clinical Reports For Peripheral Artery Disease Identification: Unlocking Clinical Data through Novel Methods

abstract:
ImportanceDespite its high prevalence and poor outcomes, research on peripheral artery disease (PAD) remains limited due to the poor accuracy of billing codes for identifying PAD in health systems.

ObjectiveDesign a natural language processing (NLP) system that can extract ankle brachial index (ABI) and toe brachial index (TBI) values and evaluate the performance of extracted ABI/TBI values to identify patients with PAD in the Veterans Health Administration (VHA).

Design, Setting, ParticipantsFrom a corpus of 392,244 ABI test reports at 94 VHA facilities during 2015-2017, we selected a random sample of 800 documents for NLP development. Using machine learning, we designed the NLP system to extract ABI and TBI values and laterality (right or left).

Performance was optimized through sequential iterations of 10-fold cross validation and error analysis on 3 sets of 200 documents each, and tested on a final, independent set of 200 documents.

Performance of NLP-extracted ABI and TBI values to identify PAD in a random sample of Veterans undergoing ABI testing was compared to structured chart review.

ExposureABI [≤]0.9, or TBI [≤]0.7 in either right or left limb was used to define PAD at the patient-level

Main OutcomePrecision (or positive predictive value), recall (or sensitivity), F-1 measure (overall measure of accuracy, defined as harmonic mean of precision and recall)

ResultsThe NLP system had an overall precision of 0.85, recall of 0.93 and F1-measure of 0.89 to correctly identify ABI/TBI values and laterality. The F-1 measure was similar for both ABI and TBI (0.88 to 0.91). Recall was higher for ABI (0.95 to 0.97) while precision was higher for TBI (0.94 to 0.95). Among 261 patients with ABI testing (49% with PAD), the NLP system achieved a positive predictive value of 92.3%, sensitivity of 83.1% and specificity of 93.1% to identify PAD when compared to a structured chart review.

ConclusionWe have successfully developed and validated an NLP system to extract ABI and TBI values which can be used to accurately identify PAD within the VHA. Our findings have broad implications for PAD research and quality improvement efforts in large health systems.

category: cardiovascular medicine


title: Subgroups of young type 2 diabetes in India reveal insulin deficiency as a major driver

abstract:
Aim/HypothesisFive subgroups were described in European diabetes patients using a data driven machine learning approach on commonly measured variables. We aimed to test the applicability of this phenotyping in Indian young-onset type 2 diabetes patients.

MethodsWe applied the European derived centroids to the Indian type 2 diabetes patients diagnosed before 45 years of age from the WellGen (n = 1612) cohort. We also applied de novo k-means clustering to the WellGen cohort to validate the subgroups. We then compared clinical and metabolic-endocrine characteristics and the complication rates between the subgroups. We also compared characteristics of the WellGen subgroups with those of two young European cohorts ANDIS (n= 962) and DIREVA (n=420). Subgroups were also assessed in two other Indian cohorts, Ahmedabad (n = 187) and PHENOEINDY-2 (n = 205).

ResultsBoth Indian and European young type 2 diabetes patients were predominantly classified into severely insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severely insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to figures in Europeans (Swedish: 26% vs 68%, Finnish: 24% vs 71% respectively). A higher proportion of SIDD compared to MOD was also seen in Ahmedabad (57% vs 33%) and in PHENOEINDY-2 (67% vs 23%). Both in Indians and Europeans, the SIDD subgroup was characterized by insulin deficiency and hyperglycemia, MOD by obesity, SIRD by severe insulin resistance and MARD by mild metabolic-endocrine disturbances. In WellGen, nephropathy and retinopathy were more prevalent in SIDD compared to MOD while the latter had higher prevalence of neuropathy.

Conclusions /InterpretationOur data identified insulin deficiency as the major driver of type 2 diabetes in young Indians, unlike in young European patients in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in young Indian type 2 diabetes, and suggest a need to review management strategies.

category: endocrinology


title: Community-level face mask usage in Boston, MA

abstract:
What is already known about this topic?Community-level face mask use is encouraged as an important preventive measure against COVID-19 transmission, and evidence suggests that jurisdictions which implement face mask mandates see a subsequent decline in COVID incidence.

What is added by this report?In the Greater Boston area when a face mask mandate is in effect, 95% of people observed were wearing some type of face covering. Most of which were wearing fabric/cloth coverings (51%) or single use surgical masks (40%). Of those wearing a face covering, 85% were appropriately fitted. Indoor locations have higher adherence of appropriately worn face masks, compared to outdoor locations.

What are the implications for public health practice?Adherence with face mask mandates was very high, but many individuals wore fabric face masks with unknown filtration efficacy. In addition, it was common for individuals to mis-wear, adjust, or remove their masks. Public health policies requiring mask use should include messaging about appropriate type and best practices for use.

category: epidemiology


title: Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients

abstract: Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of import and transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein by mass-spectrometry analysis. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. We provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.


title: Seroprevalence of SARS-CoV-2 antibodies in social housing areas in Denmark

abstract:
BackgroundCOVID-19 is suggested to be more prevalent among ethnic minorities and individuals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas.

MethodsAs part of "Testing Denmark", a nationwide sero-epidemiological surveillance survey, we conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas in Denmark. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning previous testing (viral throat- and nasopharyngeal swab or antibody test), test results for COVID-19, demographics, household characteristics, employment, risk factors for SARS-CoV-2 infection and history of symptoms associated with COVID-19. Data on seroprevalence from Danish blood donors in same period using a total Ig ELISA assay were used as a proxy for the general Danish population.

FindingsOf the 13,279 included participants, 2,296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78-3.16, p>0.001). Seropositivity was higher among males than females (RR 1.1, 95% CI 1.05-1.22%, p=0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00-1.06, p=0.031). Close contact with COVID-19-infected individuals was associated with a higher risk of infection, especially among members of the same households (OR 5.0, 95% CI 4.1-6.2 p<0,001). Adjusted for age, gender and region living at least 4 people in a household significantly increased the OR of seropositivity (OR 1.3, 95% CI 1.1-1.6, p=0.02) as did living in a multi-generational household (OR 1.3 per generation, 95% CI 1.1-1.5, p=0.007). Only 1.6% of participants reported not following any of the national COVID-19 recommendations. Anosmia (RR 3.2 95% CI 2.8-3.7, p<0.001) and ageusia (RR 3.3, 95% CI 2.9-3.8, p<0.001) were strongest associated with seropositivity.

InterpretationDanish citizens living in SH areas of low socioeconomic status had a three times higher SARS-CoV-2 seroprevalence compared to the general Danish population. The seroprevalence was significantly higher in males and increased with age. Living in multiple generations or more than four persons in a household was an independent risk factor for being seropositive. Results of this study can be used for future consideration of the need for preventive measures in the populations living in SH areas.


title: Medication use and physical assaults in the psychiatric emergency room

abstract:
ObjectiveTo evaluate the relationship between medications used to treat acute agitation (antipsychotics, mood stabilizers and benzodiazepines) and subsequent assault incidence in the psychiatric emergency room.

MethodsMedication orders and assault incident reports were obtained from electronic health records for 17,052 visits to an urban psychiatric emergency room from 2014-2019. Assault risk was modeled longitudinally using Poisson mixed-effect regression.

ResultsAssaults were reported during 0.5% of visits. Intramuscular medications (IMs) were administered in 23.3% of visits overall, and predominately administered within the first 4-hours of a visit. IM administration was correlated with assault (IRR=24.2 [5.33, 110.0]), often because IM medication was administered immediately subsequent to reported assaults. Interacted with time, IMs were not significantly associated with reduction in future assaults (IRR=0.700 [0.467, 1.04]). Neither benzodiazepines nor mood stabilizers were associated with subsequent changes to the risk of reported assault. By contrast, antipsychotic medications were associated with decreased assault risk across time (IRR=0.583 [0.360, 0.942]).

ConclusionsIM order rates are high relative to overall assault incident risk. Of the three major categories of medications administered commonly in the psychiatric emergency setting, only antipsychotic medications were associated with measurable decreases in subsequent assault risk. Careful weighing of the risks and benefits of medications is encouraged; antipsychotic medication can have a significant side effect burden, and other medications (IMs, benzodiazepines, mood stabilizers) were not associated with subsequent reduction in assault risk in this analysis.


title: Virtual Recruitment is Here to Stay: 2020 ID Fellowship Program and Matched Applicant Recruitment Experiences

abstract:
BackgroundGraduate Medical Education training programs transitioned to all-virtual recruitment in 2020. Few data have been published regarding the consequences of this transition. We desired to understand (1) infectious diseases (ID) fellowship programs recruitment efforts and the effect of virtual recruitment on application and interview numbers, and (2) the number of programs to which matched applicants applied and interviewed, and their perspectives on virtual recruitment.

MethodsIn 2020-21 we surveyed all United States ID fellowship program directors (PDs) and matched applicants. Descriptive data analysis was performed on quantitative survey items. Free-text responses were analyzed through a quantitative content analysis approach.

ResultsPD response rate was 68/158 (43%); applicant response rate was at least 23% (85/365). PDs reported a 27% increase in mean number of applications received and a 45% increase in mean number of applicants interviewed. Applicants especially valued online program structure information, PD program overview videos, fellow testimonials, didactic and curriculum content, and current fellow profiles. Most applicants preferred interviews lasting no more than 40 minutes and interview days lasting no more than 5 hours. Nearly all (60/64, 94%) PDs adequately learned about candidates; most (48/64, 75%) felt unable to showcase their program as well as when in-person. Most PDs (54/64, 84%) and applicants (56/73, 77%) want at least an option for virtual recruitment moving forward.

ConclusionsVirtual recruitment enabled programs to accommodate more applicants and highlighted applicants preferences for programs augmented online presences and time-limited interview days. Most programs and applicants want the option for virtual interviews.

Main PointsVirtual recruitment enables programs to accommodate more applicants. Applicants value programs augmented online presences and favor time-limited interview days. Most programs and applicants prefer in-person interviews and want at least an option for virtual interviews.

category: medical education


title: Differences in progression by surgical specialty: a national cohort study

abstract:
The aim of surgical training across the ten surgical specialties is to produce competent day one consultants. Progression through training is assessed by the Annual Review of Competency Progression (ARCP).

ObjectiveThis study aimed to examine variation in ARCP outcomes within surgical training and identify differences between specialties.

DesignA national cohort study using data from United Kingdom Medical Education Database (UKMED) was performed. ARCP outcome was the primary outcome measure. Multi-level ordinal regression analyses were performed, with ARCP outcomes nested within trainees.

ParticipantsHigher surgical trainees (ST3-ST8) from 9 UK surgical specialties were included (vascular surgery was excluded due to insufficient data). All surgical trainees across the UK with an ARCP outcome between 2010 to 2017 were included.

ResultsEight thousand two hundred and twenty trainees with an ARCP outcome awarded between 2010 and 2017 were included, comprising 31,788 ARCP outcomes. There was substantial variation in the proportion of non-standard outcomes recorded across specialties with general surgery trainees having the highest proportion of non-standard outcomes (22.5%) and urology trainees the fewest 12.4%. After adjustment, general surgery trainees were 1.3 times more likely to receive a non-standard ARCP outcome compared to trainees in T&O (OR 1.33 95%CI 1.21-1.45). Urology trainees were 36% less likely to receive a non-standard outcome compared to T&O trainees (OR 0.64 95%CI 0.54-0.75). Female trainees and older age were associated with non-standard outcomes (OR 1.11 95%CI 1.02-1.22; OR 1.04 95%CI 1.03-1.05).

ConclusionThere is wide variation in the training outcome assessments across surgical specialties. General surgery has higher rates of non-standard outcomes compared to other surgical specialities. Across all specialities, female sex and older age were associated with non-standard outcomes.

Article summaryO_ST_ABSStrengths and limitationsC_ST_ABSO_LIThis is the first study investigating factors affecting ARCP outcome across all surgical specialities.
C_LIO_LIThe major strength of the study is the large sample size comprising all higher surgical trainees between 2010 and 2017.
C_LIO_LIUnlike previous studies this study uses data from reliable sources and is not dependent on survey data.
C_LIO_LILimitations include the inability to investigate the causes behind our findings due to the nature of the analysis.
C_LI


title: The impact of COVID-19 pandemic on the provision of ambulatory care for patients with chronic neurological diseases in Japan: evaluation of an administrative claims database

abstract:
BackgroundThe COVID-19 pandemic has affected not only the emergency medical system, but also patients regular ambulatory care. The number of patients visiting outpatient internal medicine clinics decreased during March-April 2020 compared to 2019. Moreover, the ban on telephone re-examination for outpatient clinics in lieu of ambulatory care for chronic diseases has been lifted since March 2020. In this context, we investigate the impact of the COVID-19 pandemic on ambulatory care at Japanese outpatient clinics for patients with chronic neurological diseases during the first half of 2020.

MethodsWe collected data from the administrative claims database by DeSC Healthcare. Serial changes in the frequency of subsequent outpatient visits to clinics or hospitals (excluding large hospitals with beds >200) for chronic ambulatory care of epilepsy, migraine, Parkinsons disease (PD), and Alzheimers disease were measured. We also evaluated the utilization rate of telephone re-examination at outpatient clinics.

ResultsSince April 2020, the monthly count of outpatient clinic visits for epilepsy or PD decreased slightly but significantly. The use of telephone re-examination was facility-dependent, and it was used in less than 5% of all outpatient clinic visits for the examined neurological diseases in May 2020. The utilization rate of telephone re-examination was not associated with age or the neurological diseases of interest.

ConclusionThe impact of the COVID-19 pandemic on ambulatory care for several chronic neurological diseases may have been relatively limited, in terms of the frequency or type of outpatient visit, during the first half of 2020 in Japan.