title: Predicting mortality, duration of treatment, pulmonary embolism and required ceiling of ventilatory support for COVID-19 inpatients: A Machine-Learning Approach

abstract:
IntroductionWithin the UK, COVID-19 has contributed towards over 103,000 deaths. Multiple risk factors for COVID-19 have been identified including various demographics, co-morbidities, biochemical parameters, and physical assessment findings. However, using this vast data to improve clinical care has proven challenging.

Aimsto develop a reliable, multivariable predictive model for COVID-19 in-patient outcomes, to aid risk-stratification and earlier clinical decision-making.

MethodsAnonymized data regarding 44 independent predictor variables of 355 adults diagnosed with COVID-19, at a UK hospital, was manually extracted from electronic patient records for retrospective, case-controlled analysis. Primary outcomes included inpatient mortality, level of ventilatory support and oxygen therapy required, and duration of inpatient treatment. Secondary pulmonary embolism was the only secondary outcome. After balancing data, key variables were feature selected for each outcome using random forests. Predictive models were created using Bayesian Networks, and cross-validated.

ResultsOur multivariable models were able to predict, using feature selected risk factors, the probability of inpatient mortality (F1 score 83.7%, PPV 82%, NPV 67.9%); level of ventilatory support required (F1 score varies from 55.8% "High-flow Oxygen level" to 71.5% "ITU-Admission level"); duration of inpatient treatment (varies from 46.7% for "[≥] 2 days but < 3 days" to 69.8% "[≤] 1 day"); and risk of pulmonary embolism sequelae (F1 score 85.8%, PPV of 83.7%, and NPV of 80.9%).

ConclusionOverall, our findings demonstrate reliable, multivariable predictive models for 4 outcomes, that utilize readily available clinical information for COVID-19 adult inpatients. Further research is required to externally validate our models and demonstrate their utility as clinical decision-making tools.

HighlightsO_LIUsing COVID-19 risk-factor data to assist clinical decision making is a challenge
C_LIO_LIAnonymous data from 355 COVID-19 inpatients was collected & balanced
C_LIO_LIKey independent variables were feature selected for 4 different outcomes
C_LIO_LIAccurate, multi-variable predictive models were computed, using Bayesian Networks
C_LIO_LIFuture research should externally validate our models & demonstrate clinical utility
C_LI


title: Evaluation of rapid antibody test and chest computed tomography results of COVID-19 patients: A retrospective study

abstract:
BackgroundThe coronavirus disease 2019 (COVID-19) continues to spread around the world. Therefore, rapid, simpler, and more accurate diagnostic tests are urgently needed to diagnose the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The purpose of this study was to evaluate the SARS-CoV-2 IgM/ IgG rapid antibody test results in symptomatic patients with COVID-19 and their chest computed tomography (CT) data.

MethodsA total of 320 patients admitted to our hospital for different durations due to COVID-19 were included in the study. Serum samples were obtained within 0 to 7 days from COVID-19 patients confirmed by RT-PCR and chest CT scan. According to the SARS-CoV-2 RT-PCR results, the patients included in the study were divided into two groups: PCR positive group (n=46), and PCR negative group (n=274).

ResultsOf the 320 COVID-19 serum samples, IgM, IgG, and IgM/IgG were detected in 9.4%, 3.1%, and 17.8% within one week respectively. IgG/IgM antibodies were not detected in 69.7% of the patients. In the study, it was determined that 249 (77.8%) of 320 patients had positive chest CT scans. Four (5.6%) of 100 patients with negative chest CT scan had IgM positive and 2 (2.8%) had both IgM/ IgG positive. IgM was detected in 23 (9.2%), IgG in 1 (0.4%) and IgM/IgG in 35 (14%) of chest CT scan positive patients. The rate of CT findings in patients with antibody positivity (n=97) was found to be significantly higher than those with antibody negativity.

ConclusionsThe results of the present study show the accurate and equivalent performance of serological antibody assays and chest CT in detecting SARS-CoV-2 0 to 7 days from the onset of COVID19 symptoms. When the RT-PCR is not available, we believe that the combination of immunochromatographic test and chest CT scan can increase diagnostic sensitivity for COVID-19.

category: infectious diseases


title: The effect of special educational assistance in early childhood education and care on psycho-social difficulties in elementary school children

abstract: Three to seven percent of preschoolers have developmental problems or child psychiatric disorders. Randomized controlled trials (RCTs) indicate that interventions in early childhood education and care improve long-term outcomes of children from disadvantaged backgrounds. It is unknown if effects generalize beyond the well-structured context of RCTs and to children who may not have a disadvantaged background but have developmental problems or psychiatric disorders. We use data from the population-based Norwegian Mother, Father and Child Cohort Study, recruiting pregnant women from 1999 to 2008, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. This sub-study included 2499 children with developmental problems or psychiatric disorders at age five. We investigate the effects of special educational assistance at age five on mother-reported internalizing, externalizing, and communication problems at age eight. We analyze bias due to treatment by indication with directed acyclic graphs, adjust for treatment predictors to reduce bias, and estimate effects in different patient groups and outcome domains with a hierarchical Bayesian model. In the adjusted analysis, preschoolers with special educational assistance had on average by 0.1 (0.03-0.16) standardized mean deviation weaker psycho-social difficulties in elementary school. Mean effect sizes varied between groups and outcomes. We estimate positive effects of educational assistance during the transition from preschool to the school years. It should therefore be considered as an intervention for preschoolers with developmental or behavior problems. More research with improved measurements of treatment and outcomes is needed to identify success factors for their implementation.

category: psychiatry and clinical psychology


title: Lack of Causal Effects or Genetic Correlation between Restless Legs Syndrome and Parkinson's Disease

abstract:
BackgroundEpidemiological studies have reported association between Parkinsons disease (PD) and restless legs syndrome (RLS).

ObjectivesWe aimed to use genetic data to study whether these two disorders are causally linked or share genetic architecture.

MethodsWe performed two-sample Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) using summary statistics from recent genome-wide meta-analyses of PD and RLS.

ResultsWe found no evidence for a causal relationship between RLS (as the exposure) and PD (as the outcome, inverse variance-weighted; b=-0.003, se=0.031, p=0.916, F-statistic=217.5). Reverse MR also did not demonstrate any causal effect of PD on RLS (inverse variance-weighted; b=-0.012, se=0.023, p=0.592, F-statistic=191.7). LDSC analysis demonstrated lack of genetic correlation between RLS and PD (rg=-0.028, se=0.042, p=0.507).

ConclusionsThere was no evidence for a causal relationship or genetic correlation between RLS and PD. The associations observed in epidemiological studies could be, in part, attributed to confounding or non-genetic determinants.

category: neurology


title: Cognitive, emotional, and social functioning of preschoolers with attention deficit hyperactivity problems

abstract: Attention Deficit Hyperactivity Disorder (ADHD) is associated with deficits in a number of functional domains, which have been described both as causes and effects of ADHD. It remains unclear if deficits in different domains are equally strong in early childhood, and which deficits are specific to ADHD. Here, we describe functional domains in preschoolers and assess deficits in children with ADHD problems, by comparing them to preschoolers who have other mental health problems or who develop typically. The ADHD Study assessed 1195 ca. 3.5 years old preschoolers through a semi-structured parent interview, parent questionnaires, and with neuropsychological tests. We determined functional domains by applying factor analytic methods to a broad set of questionnaire- and test-scales. Using resulting factor scores, we employed a Bayesian hierarchical regression to estimate functional deficits in children with ADHD. We found that preschoolers functioning could be described along the seven relatively independent dimensions activity level and regulation, executive function, cognition, language, emotion regulation, introversion, and sociability. Compared to typically developing preschoolers, those with ADHD had deficits in all domains except introversion and sociability. Only deficits in activity level and regulation and executive functions were larger than 0.5 standardized mean deviations and larger than deficits of children with other mental health problems. Preschoolers with ADHD have deficits in multiple functional domains, but only impairments in activity level and regulation and executive functions are specific for ADHD and large enough to be clinically significant. Research on functioning in these domains will likely be central for understanding the development of ADHD in later the childhood, and for improving treatment and prevention approaches.


title: Association between Psychotropic Medications Functionally Inhibiting Acid Sphingomyelinase and reduced risk of Intubation or Death among Individuals with Mental Disorder and Severe COVID-19: an Observational Study

abstract: Prior preclinical and clinical evidence suggests that the acid sphingomyelinase (ASM)/ceramide system may provide a useful framework for better understanding SARS-CoV-2 infection and the repurposing of psychotropic medications with functional inhibition of acid sphingomyelinase, called FIASMA psychotropic medications, against COVID-19. We examined the potential usefulness of FIASMA psychotropic medication use among patients with mental disorder hospitalized for severe COVID-19, in an observational multicenter retrospective study conducted at AP-HP Greater Paris University hospitals. Of 545 adult patients with mental disorder hospitalized for severe COVID-19, 164 (30.1%) received a psychotropic FIASMA medication at study baseline, which was defined as the date of hospital admission for COVID-19. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received a psychotropic FIASMA medication at baseline and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, psychiatric and other medical comorbidity, and psychotropic and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). There was a significant association between FIASMA psychotropic medication use at baseline and reduced risk of intubation or death both in the crude analysis (HR=0.42; 95%CI=0.31-0.57; p<0.01) and in the primary IPW analysis (HR=0.50; 95%CI=0.37-0.67; p<0.01). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggested that this association was not specific to one FIASMA psychotropic class or medication. These results suggest the usefulness of the ASM/ceramide system framework in COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

category: public and global health


title: Low somatosensory cortex excitability in the acute stage of low back pain causes chronic pain

abstract:
BACKGROUNDDetermining the mechanistic causes of complex biopsychosocial health conditions such as low back pain (LBP) is challenging, and research is scarce. Cross-sectional studies demonstrate altered excitability and organisation of the primary somatosensory and primary motor cortex in people with acute and chronic LBP, however, no study has explored these mechanisms longitudinally or attempted to draw causal inferences.

METHODSProspective, longitudinal, cohort study including 120 people with an acute episode of LBP. Sensory evoked potential area measurements were used to assess primary and secondary somatosensory cortex excitability. Transcranial magnetic stimulation derived map volume was used to assess corticomotor excitability. Directed acyclic graphs identified variables potentially confounding the exposure-outcome relationship. The effect of acute-stage sensorimotor cortex excitability on six-month LBP outcome was estimated using multivariable regression modelling, with adjusted and unadjusted estimates reported. Sensitivity analyses were performed to explore the effect of unmeasured confounding and missing data.

RESULTSLower primary (OR = 2.08, 95% CI = 1.22 to 3.57) and secondary (OR = 2.56, 95% CI = 1.37 to 4.76) somatosensory cortex excitability in the acute stage of LBP increased the odds of developing chronic pain at six-month follow-up. This finding was robust to confounder adjustment and unmeasured confounding (E-Value = 2.24 & 2.58, respectively). Corticomotor excitability in the acute stage of LBP was associated with higher pain intensity at 6-month follow-up (B = -0.15, 95% CI: -0.28 to -0.02) but this association did not remain after confounder adjustment.

CONCLUSIONThese data provide the first evidence that low somatosensory cortex excitability in the acute stage of LBP is a cause of chronic pain. Interventions designed to increase somatosensory cortex excitability in acute LBP may be relevant to the prevention of chronic pain.

category: rehabilitation medicine and physical therapy


title: Cavernoma in septum pellucidum: descriptive analysis and review of existing literature.

abstract:
BackgroundCavernomas are rare central nervous system (CNS) lesions that constitute a distinct type of vascular malformation encountered in the brain parenchyma or ventricular system. A cavernoma can be familial or sporadic forms and exhibit a range of presentation from incidental findings to seizures, headaches, hemorrhage. Septum pellucidum cavernoma is exceedingly rare and should be studied for its unique topographical location and clinical course.

MethodWe performed a comprehensive literature search and review using multiple databases. the title/abstract and MeSH keywords used included "cavernoma," "cavernous hemangioma," "cavernous malformation," "cavernous angioma," "CM," "septum pellucidum" "SP" and "intraventricular," along with "AND" and "OR" operators. Demographic and clinical data of each patient were collected for qualitative synthesis.

ResultReported cases were diagnosed at a median age of 42 years; the most frequent symptom was headaches. The incidence of hemorrhage and hydrocephalus was 30%. Gross total resection was performed in 100% of patients and exhibit clinical improvement.

ConclusionThe unique location of the cavernoma exhibits clinical presentations seen and the surgical approach used. Gross total resection conveys the impression of optimum management strategy and leads to a magnificent outcome in most cases.


title: Statewide Impact of COVID-19 on Social Determinants of Health - A First Look: Findings from the Survey of the Health of Wisconsin

abstract: There is an urgent need to track the early and ongoing impact of the COVID-19 pandemic on population health from local to global scales. At the same time, there is an overall lack of U.S. state-specific surveillance data tracking social determinants of health (SDOH) and associations with population well-being, individual mitigation and coping strategies, family dynamics and other economic shocks of the pandemic in populations. Statewide data can offer important insights into how SDOH shape the long-term effects of COVID-19 in the population since implementation of many policies and programs varied widely early on in the pandemic. In May of 2020, the Survey of the Health of Wisconsin (SHOW) program launched a statewide online/phone survey of early and ongoing impacts of COVID-19 on health and well-being across diverse communities and families. The goal of this study is to provide descriptive data including perceived COVID-19 risks, access to and results of COVID-19 antigen testing, individual mitigation and coping strategies, family dynamics and other economic shocks of the pandemic on health and mental health in populations. Key findings include higher rates of testing and perceived past infection from COVID-19 among non-white respondents. Higher economic shifts and job changes in female vs male respondents. Families with children reported overall higher levels of stress, and stress from the pandemic. There were urban and rural differences in changes to access to care. Rural regions, which had a lower prevalence of infections early in the pandemic as compared to urban areas, also reported fewer delays or missed appointments due to COVID-19. Key findings show that SDOH are shaping impacts of health and well-being early on in the pandemic and future longitudinal follow-up will be important to shape policies and programs well into the future.

category: epidemiology


title: Gut microbiota link dietary fiber intake and short-chain fatty acid metabolism with eating behaviour

abstract:
BackgroundThe gut microbiome modulates human brain function and eating behavior through multiple factors, including short-chain fatty acid (SCFA) signaling. We aimed to explore which bacterial genera relate to eating behavior, diet and SCFA metabolites in overweight adults. In addition, we tested whether eating-related microbiota relate to treatment success in patients after Roux-en-Y gastric bypass (RYGB).

MethodsAnthropometrics, dietary fibre intake, eating behaviour, 16S-rRNA-derived microbiota and SCFA measured in feces and blood were correlated in young overweight adults (n=27 (9F), 21-36 years, BMI 25-31 kg/m2). Correlated genera were compared in RYGB (n=23 (16F), 41-70 years, BMI 25-62 kg/m2) and in control patients (n=17 (11F), 26-69 years, BMI 25-48 kg/m2).

ResultsIn young adults, 7 bacteria genera, i.e. Alistipes, Blautia, Clostridiales cluster XVIII, Gemmiger, Roseburia, Ruminococcus and Streptococcus, correlated with healthier eating behavior, while 5 genera, i.e. Clostridiales cluster IV and XIVb, Collinsella, Fusicatenibacter and Parabacteroides, correlated with unhealthier eating (all |r| > 0.4, FDR-corrected p < 0.05). Some of these genera including Parabacteroides related to fiber intake and SCFA metabolites, and to weight status and treatment response in overweight/obese patients.

ConclusionsSpecific bacterial genera, particularly Parabacteroides, were associated with weight status and eating behavior in two independent well-characterized cross-sectional samples. These exploratory findings indicate two groups of presumably beneficial and unfavourable genera that relate to eating behaviour and weight status, and indicate that dietary fiber and SCFA metabolism may modify these relationships.

category: nutrition


title: Lack of latent tuberculosis screening in HIV patients and delay in Anti-Retroviral Therapy initiation in HIV-TB co-infection: A 11-year study in an intermediate TB-burden country

abstract:
ObjectivesTuberculosis (TB) is a common infection in HIV patients. Our study aims to determine the prevalence and characteristics of HIV-TB co-infected patients in Singapore, a high-income, intermediate TB-burden country.

MethodsRetrospective data of 11-years was obtained from the National University Hospital (NUH), a quaternary care hospital and the National Centre for Infectious Diseases, the national HIV centre.

ResultsFrom December 2005 to December 2016, 48 out of 819 HIV patients and 272 out of 3,196 HIV patients who were managed in NUH and TTSH respectively, were diagnosed with TB. 89.1% (n=285) were males and 2 (0.6%) were screened for latent TB on HIV diagnosis. The median age at TB diagnosis was 47.3 years old (Interquartile range, IQR 41-57). Mean CD4 count at TB diagnosis was 125.0 {+/-} 153.9 cells/mm3. 124 (38.6%) patients had CD4 < 50 cells/mm3. 41.3% (n=132) of patients had HIV diagnosed at least 6 weeks before TB diagnosis, indicating an opportunity to initiate latent TB preventive therapy. 55.0% (n=176) had HIV and TB concomitantly diagnosed within 6 weeks whilst 2.25% (n=7) had TB diagnosed before HIV. Of those HIV-TB co-infected patients with CD4 [≤] 50 cells/mm3, 18 (14.2%) had anti-retroviral therapy (ART) started <2 weeks. TB-related mortality was 5.3% (n=17) and 3.75% (n=12) were lost to follow-up.

ConclusionThere is a lack of latent TB screening in HIV patients and a delay in initiation of ART in HIV-TB patients with low CD4 counts in our study. Clinical practices can be further improved for the benefit of outcomes in HIV-TB patients.

category: hiv aids


title: Persisting adaptive immunity to SARS-CoV-2 in Lower Austria

abstract: The prevalence and persistence of adaptive immunity responses following a SARS-CoV-2 infection provides insights into potential population immunity. Adaptive immune responses comprise of antibody-based responses as well as T cell responses mainly addressing viruses and virus-infected human cells, respectively. A comprehensive analysis of both types of adaptive immunity is essential to follow population-based SARS-CoV-2-specific immunity. In this study, we assessed SARS-CoV-2-specific immunoglobulin A (IgA) levels, SARS-CoV-2-specific immunoglobulin G (IgG) levels, and SARS-CoV-2-specific T cell activities in patients who recovered from a COVID-19 infection in spring and autumn 2020. Here we observed a robust and stable SARS-CoV-2-specific adaptive immune response in both groups with persisting IgA and IgG levels as well as stable T cell activity. Moreover, there was a positive correlation of a lasting immune response with the severity of disease. Our data give evidence for a persisting adaptive immune memory, which suggest a continuing immunity for more than six months post infection.


title: Profile of SARS-CoV-2-specific CD4 T cell response: Relationship with disease severity and impact of HIV-1 and active Mycobacterium tuberculosis co-infection

abstract: T cells are involved in control of COVID-19, but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we assessed the magnitude, function and phenotype of SARS-CoV-2-specific CD4 T cells in 95 hospitalized COVID-19 patients (38 of them being HIV-1 and/or tuberculosis (TB) co-infected) and 38 non-COVID-19 patients, using flow cytometry. We showed that SARS-CoV-2-specific CD4 T cell attributes, rather than magnitude, associates with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity and enhanced HLA-DR expression. Moreover, HIV-1 and TB co-infection skewed the SARS-CoV-2 T cell response. HIV-1 mediated CD4 T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2; and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4 T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mtb-specific CD4 T cells, with possible implications for TB disease progression. There results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.


title: A computationally efficient approach to segmentation of the aorta and coronary arteries using deep learning

abstract: A fully automatic two-dimensional Unet model is proposed to segment aorta and coronary arteries in computed tomography images. Two models are trained to segment two regions of interest, (1) the aorta and the coronary arteries or (2) the coronary arteries alone. Our method achieves 91.20% and 88.80% dice similarity coefficient accuracy on regions of interest 1 and 2 respectively. Compared with a semi-automatic segmentation method, our model performs better when segmenting the coronary arteries alone. The performance of the proposed method is comparable to existing published two-dimensional or three-dimensional deep learning models. Furthermore, the algorithmic and graphical processing unit memory efficiencies are maintained such that the model can be deployed within hospital computer networks where graphical processing units are typically not available.

category: cardiovascular medicine


title: Applicability of Neighborhood and Building Scale Wastewater-Based Genomic Epidemiology to Track the SARS-CoV-2 Pandemic and other Pathogens.

abstract:
The benefits of wastewater-based epidemiology (WBE) for tracking the viral load of SARS-CoV-2, the causative agent of COVID-19, have become apparent since the start of the pandemic. However, most sampling occurs at the wastewater treatment plant influent and therefore can only monitor SARS-CoV-2 concentration and spread within the entire catchment, which can encompass multiple municipalities. Furthermore, most WBE only quantifies the virus, and therefore miss crucial information that can be gained by sequencing SARS-CoV-2. Here we demonstrate feasibility of sampling at the neighborhood or building complex level using a mix of quantitative polymerase chain reaction (qPCR) and targeted sequencing to provide a more refined understanding of the local dynamics of SARS-CoV-2 strains. When coupled with the higher-level treatment plant samples, this creates an opportunity for health officials to monitor the spread of the virus at different spatial and temporal scales to inform policy decisions.

Here we demonstrate the feasibility of tracking SARS-CoV-2 at the neighborhood, hospital, and nursing home level with the ability to detect one COVID-19 positive out of 60 nursing home residents. The viral load obtained was correlative with the number of COVID-19 patients being treated in the hospital. Sequencing of the samples over time demonstrated that nonsynonymous mutations fluctuate in the viral population, and wastewater-based sequencing could be an efficient approach to monitor for vaccine or convalescent plasma escape mutants, as well as mutations that could reduce the efficacy of diagnostics. Furthermore, while SARS-CoV-2 was detected by untargeted RNA sequencing, qPCR and targeted whole genome amplicon sequencing were more reliable methods for tracking the pandemic. From our sequencing data, clades and shifts in mutation profiles within the community were traceable and could be used to determine if vaccine or diagnostics need to be adapted to ensure continued efficacy.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/21251939v1_ufig1.gif" ALT="Figure 1">
View larger version (20K):
org.highwire.dtl.DTLVardef@110f217org.highwire.dtl.DTLVardef@185d3f0org.highwire.dtl.DTLVardef@11d3a8corg.highwire.dtl.DTLVardef@1eef33d_HPS_FORMAT_FIGEXP  M_FIG C_FIG HighlightsO_LINeighborhood or building level wastewater analysis accurately detects SARS-CoV-2
C_LIO_LISARS-CoV-2 was detected in wastewater from one infected person out of 60 residents
C_LIO_LITotal RNAseq did not accurately detect SARS-CoV-2 in wastewater samples.
C_LIO_LITargeted whole genome sequencing of wastewater samples identified Spike mutations.
C_LI


title: The nature of individual heterogeneity shape outbreak dynamics

abstract: There is known heterogeneity between individuals in infectious disease transmission patterns. The source of this heterogeneity is thought to affect epidemiological dynamics but studies tend not to control for the overall heterogeneity in the number of secondary cases caused by an infection. To explore the role of individual variation in infection duration and transmission rate on parasite emergence and spread, while controlling for this potential bias, we simulate stochastic outbreaks with and without parasite evolution. As expected, heterogeneity in the number of secondary cases decreases the probability of outbreak emergence. Furthermore, for epidemics that do emerge, assuming more realistic infection duration distributions leads to faster outbreaks and higher epidemic peaks. When parasites require adaptive mutations to cause large epidemics, the impact of heterogeneity depends on the underlying evolutionary model. If emergence relies on within-host evolution, decreasing the infection duration variance decreases the probability of emergence. These results underline the importance of accounting for realistic distributions of infection rates to anticipate the effect of individual heterogeneity on epidemiological dynamics.


title: The source of individual heterogeneity shapes infectious disease outbreaks


title: Estimates of the COVID-19 pandemic dynamics in Ukraine based on two data sets

abstract:
BackgroundTo simulate how the number of COVID-19 cases increases versus time, various data sets for the number of new cases and different mathematical models can be used. Since there are some differences in statistical data, the results of simulations can be different. Complex mathematical models contain many unknown parameters, the values of which must be determined using a limited number of observations of the disease over time. Even long-term monitoring of the epidemic may not provide reliable estimates of its parameters due to the constant change of testing conditions, isolation of infected and quarantine. Therefore, simpler approaches are necessary. In particular, previous simulations of the COVID-19 epidemic dynamics in Ukraine were based on smoothing of the dependence of the number of cases on time and the generalized SIR (susceptible-infected-removed) model. These approaches allowed to detect the waves of pandemic and to make adequate predictions of the their duration and final sizes. In particular, eight waves of the COVID-19 pandemic in Ukraine were investigated.

ObjectiveWe will compare the results simulation of a new epidemic wave in Ukraine based on national statistics and data reported by Johns Hopkins University (JHU).

MethodsIn this study we use the smoothing method for the dependences of the number of cases on time, the generalized SIR model for the dynamics of any epidemic wave, the exact solution of the linear differential equations, and statistical approach developed before.

ResultsNinth epidemic wave in Ukraine was simulated. The optimal values of the SIR model parameters were calculated and compared with the use of two data sets. Both predictions are not very optimistic: new cases will not stop appearing until June-July 2021.

ConclusionsNew waves of COVID-19 pandemic can be detected, calculated and predicted with the use of rather simple mathematical models. The results of calculations depend on the data sets for the number of confirmed cases. The expected long duration of the pandemic forces us to be careful and in solidarity. The government and all Ukrainians must strictly adhere to quarantine measures in order to avoid fatal consequences. Probably the presented results could be useful in order to estimate the efficiency of future vaccinations.


title: Visuospatial processing impairment following mild COVID-19

abstract: Severe Acute Respiratory Syndrome Coronavirus 2 infection causes coronavirus disease 2019. COVID-19 was an unknown infection that reached pandemic proportions in 2020 and has shown to bring long-term negative consequences. Here, we used a case-control design to investigate the performance of relatively young people recovered from COVID 19 in objective neuropsychological tests. We found significant differences between groups for all measures of the ROCFT with a large difference in the copy, a moderate difference in immediate recall, and a large difference in delayed recall. No significant differences were found for the measures from all the other five neuropsychological tests used.About one quarter of COVID 19 patients were below the 10th percentile according to normative data.


title: Early Identification of SARS-CoV-2 Emergence in the DoD via Retrospective Analysis of 2019-2020 Upper Respiratory Illness Samples

abstract:
The first case of non-travel related SARS-COV-2 was detected late February 2020 in California, however the delay of diagnostic testing and initial stringent testing criteria made it difficult to identify those who could have acquired it through community spread. There was speculation by many that the virus may have been circulating at least a month earlier [1], and environmental sampling has suggested that versions of this virus were found many months before the first human samples were identified [2]. Here we performed a retrospective study from residual samples collected from a global DoD Respiratory Surveillance Program to establish a tentative timeline by which this virus was circulating in our DoD population. We performed RT-PCR for SARS-COV-2 and compared to the dates of these cases to the first cases identified in respective states and counties using the Johns Hopkins COVID tracker website. Twenty-four positive samples were identified out of approximately 7,000 tested. Although we found some early cases in certain regions, we did not see circulation before late February in samples collected both in the US and outside the USA.

SUMMARYO_ST_ABSWhat is already known about this topic?C_ST_ABSWe know that the first reported case of SARS-COV-2 was mid-January; however, there has been conjecture that the virus was found in the community before this date.

What is added by this report?Here we took samples collection from a global respiratory surveillance program and evaluated for the presence of SARS-COV-2 RNA. The first case we found in the surveillance program was approximately 30-60 days before the first case was identified on military installations via diagnostic testing, however was not earlier than the mid-January reported case in California.

What are the implications for public health practice?The implementation of new and emerging pathogen detection assays into already established surveillance programs could detect early community spread and possibly reduce spread of pathogen among vulnerable populations.


title: Obesity and COVID-19 Mortality: A Cross-Country Analysis

abstract: We highlight a robust correlation between COVID-19 mortality and obesity prevalence using available country level data on COVID-19 mortality as of August 10, 2020. Such association is robust to controlling for other potential comorbidity factors: diabetes, cardio-vascular, and respiratory diseases, further to a set of demographics, urban, and economic, and containment policies controls. We estimate that .6 log point increase in obesity prevalence, or 1 standard deviation, is associated with about an extra .9 log point per 100,000 deaths (or 50% of a standard deviation, .5{sigma}).


title: Reported COVID-19 Incidence in Wisconsin High School Athletes During Fall 2020

abstract:
IntroductionThe purpose of this study was to describe the reported incidence of COVID-19 in Wisconsin high school athletes in September 2020, and to investigate the relationship of COVID-19 incidence with sport and face mask use.

MethodsSurveys were sent to athletic directors of all Wisconsin high schools regarding sports during September 2020. The association between reported case rates in athletes in each county and the county general population were evaluated with a weighted linear model. Multivariable negative binomial regression models evaluated the associations between COVID-19 incidence and sport type and face mask use by players, adjusting for the county COVID-19 incidence for each school.

Results207 schools that had reinitiated sport reported 270 COVID-19 cases among 30,074 players, for case and incidence rates of 809 cases per 100,000 players and 32.6 cases per 100,000 player-days, respectively. The case rates for athletes in each county were positively correlated with the case rates for the countys general population ({beta} =1.14{+/-}0.20, r=0.60, p<0.001). One hundred fifteen (55%) of cases were attributed to household contact, 85 (41%) to contact outside sport or school, 5 (2.4%) to school contact, and 1 (0.5%) to sport contact. No difference was identified between team and individual sports (incidence rate ratio (IRR)=1.03 [95% CI=0.49-2.2], p=0.93) or between non-contact and contact sports (IRR=0.53 [0.23-1.3], p=0.14), although the difference between outdoor and indoor sports approached statistical significance (IRR=0.52 [0.26-1.1], p=0.07). 84% of schools required face masks while playing. For those sports with >50 participating schools, there were no significant associations between COVID-19 incidence and face mask use in cross country (IRR=0.71 [0.2-2.2], p=0.52), football (IRR=1.6 [0.6-5.1], p=0.404), boys soccer (IRR=2.3 [0.5-17], p=0.31), or girls volleyball (IRR=1.4 [0.3-6.6], p=0.64).

ConclusionsIncidence of reported COVID-19 among athletes was related to background county incidence and most cases were attributed to household and community contact. Although not statistically significant, reported COVID-19 incidence may be lower in outdoor sports. Face mask use did not have a significant benefit, which may be due to relatively low rates of COVID-19 and the small number of schools that did not report using face masks.

category: sports medicine


title: Mortality after surgery with SARS-CoV-2 infection in England: A population-wide epidemiological study

abstract:
ObjectivesTo confirm the incidence of perioperative SARS-CoV-2 infection and associated mortality after surgery.

Design and settingAnalysis of routine electronic health record data from National Health Service (NHS) hospitals in England.

MethodsWe extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between 1st January 2020 and 31st October 2020. The exposure was SARS-CoV-2 infection defined by ICD-10 codes. The primary outcome measure was 90-day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson co-morbidity index, index of multiple deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals.

ResultsWe identified 1,972,153 patients undergoing surgery of whom 11,940 (0.6%) had SARS-CoV-2. In total, 19,100 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 2,618/11,940 [21.9%] vs No SARS-CoV-2: 16,482/1,960,213 [0.8%]; OR: 5.8 [5.5 - 6.1]; p<0.001). Amongst patients undergoing elective surgery 1,030/1,374,985 (0.1%) had SARS-CoV-2 of whom 83/1,030 (8.1%) died, compared with 1,092/1,373,955 (0.1%) patients without SARS-CoV-2 (OR: 29.0 [22.5 -37.3]; p<0.001). Amongst patients undergoing emergency surgery 9,742/437,891 (2.2%) patients had SARS-CoV-2, of whom 2,466/9,742 (25.3%) died compared with 14,817/428,149 (3.5%) patients without SARS-CoV-2 (OR: 5.7 [5.4 - 6.0]; p<0.001).

ConclusionsThe low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.

Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIHigh mortality rates have been reported amongst surgical patients who develop COVID-19 but we dont know how this compares to the concurrent surgical population unaffected by COVID-19.
C_LIO_LIStrict infection prevention and control procedures have substantially reduced the capacity of surgical treatment pathways in many hospitals.
C_LIO_LIThe very large backlog in delayed and cancelled surgical procedures is a growing public health concern.
C_LI

What this study addsO_LIFewer than 1 in 100 surgical patients are affected by COVID-19 in the English National Health Service.
C_LIO_LIElective surgical patients who do develop COVID-19 are 30 times more likely to die while in hospital.
C_LIO_LIInfection prevention and control procedures in NHS surgical pathways are highly effective but cannot be safely relaxed.
C_LI

category: surgery


title: A glomerular transcriptomic landscape of APOL1 in Black patients with focal segmental glomerulosclerosis

abstract:
Apolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black people. There are no targeted therapies for this condition, in part because the molecular mechanisms underlying APOL1s pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk (HR) APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black FSGS patients with a HR vs 14 with a low-risk ("LR") APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways illuminated in these studies.

We discovered (1) increased expression of APOL1 in HR and nine other significant differentially expressed genes, including stanniocalcin (STC1), which has a role in mitochondrial and calcium-related processes, (2) differential correlations between HR and LR APOL1 and metabolism pathway genes, but similar correlations with extracellular matrix- and immune-related genes, (3) significant loss of co-expression of mitochondrial genes in HR FSGS, and (4) an NF-{kappa}B -down-regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family and immune-related genes. Overall, differences in mitochondrial gene regulation appear to underlie many differences observed between HR and LR FSGS. All data are available for secondary analysis through the "APOL1 Portal" (http://APOL1portal.org).

category: nephrology


title: Neuropsychiatric and cognitive symptoms across the Alzheimer's disease clinical spectrum: Cross-sectional and longitudinal associations

abstract:
ObjectiveTo investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of amyloid-{beta} positive individuals across the Alzheimers disease (AD) clinical spectrum.

MethodsWe included 1,524 amyloid-{beta} positive individuals from the Amsterdam Dementia Cohort with subjective cognitive decline (SCD, n=113), mild cognitive impairment (MCI, n=321), or dementia (n=1,090). We measured NPS with the neuropsychiatric inventory (NPI), examining total scores and the presence of specific NPI-items. Cognition was assessed across five cognitive domains and with the MMSE. We examined trajectories including model based trends for NPS and cognitive functioning over time. We used linear mixed models to relate baseline NPI scores to cognitive functioning at baseline (whole-sample) and longitudinal time-points (subsample n=520, Mean=1.8 [SD=0.7] years follow-up).

ResultsNPS were prevalent across all clinical AD stages (NPI total score [≥]1 81.4% in SCD, 81.2% in MCI, 88.7% in dementia). Cognitive functioning showed an uniform gradual decline; while in contrast, large intra-individual heterogeneity of NPS was observed over time across all groups. At baseline, we found associations between NPS and cognition in dementia that were most pronounced for NPI total scores and MMSE (range {beta}:-0.18-0.11, FDR-adjusted p<0.05), while there were no cross-sectional relationships in SCD and MCI ({beta}:-0.32- 0.36, FDR-adjusted p>0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage ({beta}:-0.13-0.44, FDR-adjusted p>0.05).

ConclusionNPS and cognitive symptoms are both prevalent across the AD continuum, but show a different evolution during the course of the disease.


title: The utility of homologous recombination deficiency biomarkers across cancer types

abstract:
BackgroundGenomic alterations in BRCA1/2 and genomic scar signatures are associated with homologous recombination DNA repair deficiency (HRD) and serve as therapeutic biomarkers for platinum and PARP inhibitors in breast and ovarian cancers. However, the clinical significance of these biomarkers in other homologous recombination repair-related genes or other cancer types is not fully understood.

ResultsWe analyzed the datasets of all solid cancers from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia, and found that the association between biallelic alterations in the homologous recombination pathway genes and genomic scar signatures differed greatly depending on gender and the presence of somatic TP53 mutation. Additionally, HRD cases identified by a combination of these indicators showed higher sensitivity to DNA-damaging drugs than non-HRD cases both in clinical samples and cell lines.

ConclusionOur work provides novel proof of the utility of HRD analysis for all cancer types and will improve the precision and efficacy of chemotherapy selection in clinical oncology.

category: oncology


title: openEHR is FAIR-Enabling by Design

abstract: The FAIR Principles are a set of recommendations that aim to underpin knowledge discovery and integration by making the research outcomes Findable, Accessible, Interoperable and Reusable. These guidelines encourage the accurate recording and exchange of structured data, coupled with contextual information about their creation, expressed in domain-specific standards and machine readable formats. This paper analyses the potential support to FAIRness of the openEHR e-health standard, by theoretically assessing the compliance with each of the 15 FAIR principles of a hypothetical Clinical Data Repository (CDR) developed according to the openEHR specifications. Our study highlights how the openEHR approach, thanks to its computable semantics-oriented design, is inherently FAIR-enabling and is a promising implementation strategy for creating FAIR-compliant CDRs.

category: health informatics


title: Preservation of neutralizing antibody function in COVID-19 convalescent plasma treated using a riboflavin and ultraviolet light-based pathogen reduction technology

abstract:
Background and ObjectiveConvalescent plasma (CP) has been embraced as a safe therapeutic option for coronavirus disease 2019 (COVID-19) while other treatments are developed. However, transfusion-transmitted disease is a risk, particularly in regions with high endemic prevalence of transfusion-transmissible diseases. Pathogen reduction can mitigate this risk; thus, the objective of this study was to evaluate the effect of riboflavin and ultraviolet light (R+UV) pathogen reduction technology on the functional properties of CCP.

Materials and MethodsCCP units (n = 6) from recovered COVID-19 research donors were treated with R+UV. Pre- and post-treatment samples were tested for coagulation factor and immunoglobulin retention. Antibody binding to spike protein receptor binding domain (RBD), S1, and S2 epitopes of SARS-CoV-2 was assessed by ELISA.

Neutralizing antibody (nAb) function was assessed by pseudovirus reporter viral particle neutralization (RVPN) assay and plaque reduction neutralization test (PRNT).

ResultsMean retention of coagulation factors was [≥] 70% while retention of immunoglobulins was 100%. Starting nAb titers were low, but PRNT50 titers did not differ between pre- and post-treatment samples. No statistically significant differences were detected in levels of IgG (P [≥] 0.3665) and IgM (P [≥] 0.1208) antibodies to RBD, S1, and S2 proteins before and after treatment.

ConclusionR+UV PRT effects on coagulation factors were similar to previous reports, but no significant effects were observed on immunoglobulin concentration and antibody function. SARS-CoV-2 nAb function in COVID-19 convalescent plasma is conserved following R+UV PRT treatment.

category: hematology


title: Rapid increase of SARS-CoV-2 seroprevalence during the 2020 pandemic year in the population of the city of Tirana, Albania

abstract:
IntroductionWhile the identification of anti SARS-CoV-2 antibodies has been used to measure the hidden circulation of the COVID-19 in communities, there are few publications on the dynamics of SARS-CoV-2 seroprevalence during both waves of 2020. This study provides original data about the change in proportion of individuals showing immune response to COVID-19 between beginning of July and end of December 2020.

MethodsThe study was conducted in two rounds, 27 June -3 July, and 21-28 December 2020, using two independently selected samples of individuals 20-70 years old. Study participants were randomly selected from lists of the inhabitants of the catchment communities of four primary health care centers in Tirana City. Serological testing was performed by an ELISA method which determines IgG class antibodies anti S1 protein of SARS-CoV-2 virus. The validity of the method was tested in a sample of blood donors sera of 2018.

ResultsThe proportion of individuals classified as seropositive during the first round, in early July was 7.5% (95% CI: 4.3% -10.7%). The proportion rose sharply in the second round, by late December 2020, reaching 48.2% (95% CI: 44.8% -51.7%). The same increasing pattern was observed in all studied categories. No statistical significance was found between men and women and between age categories. The prevalence of seropositive individuals was always significantly higher among those who reported symptoms and those who had done the molecular test.

ConclusionThe ratio of total infected cases over confirmed cases was estimated to be higher than 10 to 1 in Albania. The rapid increase in SARS-CoV-2 seroprevalence observed in Tirana City may have been facilitated by a number of factors, including the very low infection exposure during the period March -May 2020, and the consecutive high susceptibility in population. Despite the observed high seroprevalence, one month after the study, COVID-19 incidence continued to increase in Tirana.


title: Accessible LAMP-Enabled Rapid Test (ALERT) for detecting SARS-CoV-2

abstract:
The COVID-19 pandemic has highlighted bottlenecks in large-scale, frequent testing of populations for infections. PCR-based diagnostic tests are expensive, reliant on expensive centralized labs, can take days to deliver results, and are prone to backlogs and supply shortages. Antigen tests, that bind and detect the surface proteins of a virus, are rapid and inexpensive but suffer from high false negative rates. To address this problem, we have created an inexpensive, simple, and robust 60-minute Do-It-Yourself (DIY) workflow to detect viral RNA from nasal swabs or saliva with high sensitivity (0.1 to 2 viral particles/{micro}l) and specificity (>97% True Negative Rate) utilizing reverse transcription loop-mediated isothermal amplification (RT-LAMP).

Our workflow, ALERT (Accessible LAMP-Enabled Rapid Test), incorporates the following features: 1) Increased shelf-life and ambient temperature storage by using wax layers to isolate enzymes from reaction, 2) Improved specificity by using sequence-specific QUASR reporters, 3) Increased sensitivity through use of a magnetic wand to enable pipette-free concentration of sample RNA and cell debris removal, 4) Quality control with a nasopharyngeal-specific mRNA target, and 5) Co-detection of other respiratory viruses, such as Influenza B, by duplexing QUASR-modified RT-LAMP primer sets.

The flexible nature of the ALERT workflow allows easy, at-home and point-of-care testing for individuals and higher-throughput processing for centralized labs and hospitals. With minimal effort, SARS-CoV-2-specific primer sets can be swapped out for other targets to repurpose ALERT to detect other viruses, microorganisms or nucleic acid-based markers.


title: A Multivariate Forecasting Model for the COVID-19 Hospital Census Based on Local Infection Incidence

abstract:
COVID-19 has been one of the most serious global health crises in world history. During the pandemic, healthcare systems require accurate forecasts for key resources to guide preparation for patient surges. Fore-casting the COVID-19 hospital census is among the most important planning decisions to ensure adequate staffing, number of beds, intensive care units, and vital equipment. In the literature, only a few papers have approached this problem from a multivariate time-series approach incorporating leading indicators for the hospital census. In this paper, we propose to use a leading indicator, the local COVID-19 infection incidence, together with the COVID-19 hospital census in a multivariate framework using a Vector Error Correction model (VECM) and aim to forecast the COVID-19 hospital census for the next 7 days. The model is also applied to produce scenario-based 60-day forecasts based on different trajectories of the pandemic. With several hypothesis tests and model diagnostics, we confirm that the two time-series have a cointegration relationship, which serves as an important predictor. Other diagnostics demonstrate the goodness-of-fit of the model. Using time-series cross-validation, we can estimate the out-of-sample Mean Absolute Percentage Error (MAPE). The model has a median MAPE of 5.9%, which is lower than the 6.6% median MAPE from a univariate Autoregressive Integrated Moving Average model. In the application of scenario-based long-term forecasting, future census exhibits concave trajectories with peaks lagging 2-3 weeks later than the peak infection incidence. Our findings show that the local COVID-19 infection incidence can be successfully in-corporated into a VECM with the COVID-19 hospital census to improve upon existing forecast models, and to deliver accurate short-term forecasts and realistic scenario-based long-term trajectories to help healthcare systems leaders in their decision making.

Author summaryDuring the COVID-19 pandemic, healthcare systems need to have adequate resources to accommodate demand from COVID-19 cases. One of the most important metrics for planning is the COVID-19 hospital census. Only a few papers make use of leading indicators within multivariate time-series models for this problem. We incorporated a leading indicator, the local COVID-19 infection incidence, together with the COVID-19 hospital census in a multivariate framework called the Vector Error Correction model to make 7-day-ahead forecasts. This model is also applied to produce 60-day scenario forecasts based on different trajectories of the pandemic. We find that the two time-series have a stable long-run relationship. The model has a good fit to the data and good forecast performance in comparison with a more traditional model using the census data alone. When applied to different 60-day scenarios of the pandemic, the census forecasts show concave trajectories that peak 2-3 weeks later than the infection incidence. Our paper presents this new model for accurate short-term forecasts and realistic scenario-based long-term forecasts of the COVID-19 hospital census to help healthcare systems in their decision making. Our findings suggest using the local COVID-19 infection incidence data can improve and extend more traditional forecasting models.


title: Identifying intergenerational risk factors for ADHD symptoms using polygenic scores in the Norwegian Mother, Father and Child Cohort

abstract:
ImportanceKnowledge of the mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) symptoms can inform psychosocial interventions.

ObjectiveTo investigate whether parental genetic risk factors associate with their childrens ADHD symptoms due to genetic transmission of risk or due to parental genetic liability that influences offspring ADHD via parenting environments (genetic nurture).

Design and participantsThis study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. This prospective cohort study consisted of 5,405 mother-father-offspring trios recruited between 1999 - 2008.

ExposuresWe calculated polygenic scores for parental traits previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment and intellectual ability.

Main outcomes and measuresMothers reported on their 8-year-old childrens ADHD symptoms using the Parent/Teacher Rating Scale for Disruptive Behavior Disorders.

ResultsMaternal polygenic scores for ADHD, autism spectrum disorder (ASD), neuroticism and smoking predicted child ADHD symptoms in bivariate analyses. After jointly modelling maternal, paternal and child polygenic scores, ADHD symptoms were predicted by childrens polygenic scores for ADHD ({beta} = 0.10; 95% CI 0.07 to 0.14), smoking ({beta} = 0.07; 95% CI 0.03 to 0.10) and educational attainment ({beta} = -0.09; 95% CI -0.13 to -0.05), indicating direct genetic transmission of risk. Mothers polygenic scores for ASD ({beta} = 0.05; 95% CI 0.02 to 0.08) and neuroticism ({beta} = 0.05; 95% CI 0.01 to 0.08) predicted childrens ADHD symptoms conditional on fathers and childrens scores, implicating genetic nurture, or effects due to population stratification or assortative mating.

ConclusionsThese results suggest that associations between some parental traits and offspring ADHD symptoms likely reflect a nuanced mix of direct genetic transmission (ADHD, smoking and educational attainment) and genetic nurture (ASD and neuroticism). If confirmed, these findings support previous evidence that maternal ASD or neuroticism may be possible targets for intervention to help break the chain of the intergenerational transmission of ADHD risk.


title: Association between benzodiazepine receptor agonist use and increased mortality among patients hospitalized for COVID-19: results from an observational study

abstract:
ObjectiveTo examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalized for COVID-19.

MethodsWe conducted an observational multicenter retrospective cohort study at AP-HP Greater Paris University hospitals. The sample involved 14,381 adult patients hospitalized for COVID-19. 686 (4.8%) inpatients received a BZRA within at the time of hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (SD=25.4). The study baseline was the date of hospital admission and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for patient characteristics (such as age, sex, obesity and comorbidity) and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW).

ResultsOver a mean follow-up of 14.5 days (SD=18.1), the primary endpoint occurred in 186 patients (27.1%) who received a BZRA and in 1,134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (HR=3.20; 95% CI=2.74-3.74; p<0.01) and in the primary IPW analysis (HR=1.61; 95% CI=1.31-1.98, p<0.01), with a significant dose-dependent relationship (HR=1.55; 95% CI=1.08-2.22; p=0.02). This association remained significant in multiple sensitivity analyses.

ConclusionsBZRA use was associated with increased mortality among patients hospitalized for COVID-19 with a dose-dependent relationship, suggesting a potential benefit of decreasing dose or tapering off these medications when possible in these patients.


title: Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, ACE2. Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid August to late November, 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.


title: Central diabetes insipidus induced by temozolomide: A literature review.

abstract: Temozolomide has been the most used chemotherapeutic drug for glioblastoma and various CNS malignancies. Although myelosuppression has the most severe adverse effect, central diabetes insipidus (CDI) has been found as an infrequent side effect. CDI is characterized by decreased antidiuretic hormone secretion from posterior pituitary, thereby the inability to concentrate the urine with variable degrees of polyuria and compensatory polydipsia. Following a comprehensive literature search of several databases from 1990 to October 2020, which were limited to the English language, patient data were analyzed to demonstrate the risk factors, severity, reversibility of the disease, and overall survival. Total nine cases found who developed CDI following TMZ treatment. All patients manifest hyperosmolar symptoms like polyuria and polydipsia within 3 to 12 weeks following temozolomide initiation. Clinical and laboratory features, therapeutic response to exogenous desmopressin, and clinical course have been summarized.


title: Patient prioritisation methods to shorten waiting times for elective surgery: a systematic review of how to improve access to surgery

abstract:
BackgroundConcern about long waiting times for elective surgeries is not a recent phenomenon, but it has been heightened by the impact of the COVID-19 pandemic and its associated measures. One way to alleviate the problem might be to use prioritisation methods for patients on the waiting list and a wide range of research is available on such methods. However, significant variations and inconsistencies have been reported in prioritisation protocols from various specialties, institutions, and health systems. To bridge the evidence gap in existing literature, this comprehensive systematic review will synthesise global evidence on policy strategies with a unique insight to patient prioritisation methods to reduce waiting times for elective surgeries. This will provide evidence that might help with the tremendous burden of surgical disease that is now apparent in many countries because of operations that were delayed or cancelled due to the COVID-19 pandemic and inform policy for sustainable healthcare management systems.

MethodsWe searched PubMed, EMBASE, SCOPUS, Web of Science, and the Cochrane Library, with our most recent searches in January 2020. Articles published after 2013 on major elective surgery lists of adult patients were eligible, but cancer and cancer-related surgeries were excluded. Both randomised and non-randomised studies were eligible and the quality of studies was assessed with ROBINS-I and CASP tools. We registered the review in PROSPERO (CRD42019158455) and reported it in accordance with the PRISMA statement.

ResultsThe electronic search in five bibliographic databases yielded 7543 records (PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane) and 17 eligible articles were identified in the screening. There were four quasi-experimental studies, 11 observational studies and two systematic reviews. These demonstrated moderate to low risk of bias in their research methods. Three studies tested generic approaches using common prioritisation systems for all elective surgeries in common. The other studies assessed specific prioritisation approaches for re-ordering the waiting list for a particular surgical specialty.

ConclusionsExplicit prioritisation tools with a standardised scoring system based on clear evidence-based criteria are likely to reduce waiting times and improve equitable access to health care. Multiple attributes need to be considered in defining a fair prioritisation system to overcome limitations with local variations and discriminations. Collating evidence from a diverse body of research provides a single framework to improve the quality and efficiency of elective surgical care provision in a variety of health settings. Universal prioritisation tools with vertical and horizontal equity would help with re-ordering patients on waiting lists for elective surgery and reduce waiting times.

category: health systems and quality improvement


title: The COVID-19 Incarceration Model: a tool for corrections staff to analyze outbreaks of COVID-19

abstract: Correctional facilities are at high risk of COVID-19 outbreaks due to the inevitable close contacts in the environment. Such facilities are a high priority in the public health response to the epidemic. We developed a user-friendly Excel spreadsheet model (building on the previously developed Recidiviz model) to analyze COVID-19 outbreaks in correctional facilities and the potential impact of prevention strategies -the COVID-19 Incarceration Model. The model requires limited inputs and can be used by non-modelers. The impact of a COVID-19 outbreak and mitigation strategies is illustrated for an example prison setting.


title: Perception of yips among professional Japanese golfers: perspectives and challenges.

abstract:
BackgroundYips in golf is a complex spectrum of psychological anxiety and movement disorder that affects competitive sporting performance. Existing literature is limited to several western studies and the manifestations of this problem in Japanese golfers is currently unknown.

ObjectiveTo quantify self-reported perception and manifestation of yips among Japanese golfers from the professional golfers association (PGA).

MethodsWe analyzed 1271 (of 1356) elite golfers in a cross-sectional manner. Golfers were sensitized beforehand about yips by a movement-disorder specialist. Based on a positive history for yips, participants were categorized into yips and non-yips groups. Survey questionnaire focused on demographic information, golfing habits, anxiety and musculoskeletal problems, performance deficits during golfing, changes in training and their outcomes. Statistical procedures included multiple logistic regression and network analysis to assess factors associated with yips.

Results35% (N=450) of the respondents had experienced symptoms of yips in their career, their odds increasing proportionally to their golfing experience. Severity of musculoskeletal symptoms were higher in those with yips. Regardless, about 57% of all yips-golfers attributed their symptoms to psychological causes. Putting, approach and teeing shots, in that order, were highly susceptible to movement problems. Network analysis highlighted characteristic movement patterns i.e. slowing, forceful or freezing of movement for putting, approach and teeing respectively. Golfers self-administered strategies to relieve yips symptoms were generally inconsequential, though improvements were seen only for approach-yips.

ConclusionOur findings align firmly with prior studies on yips. Though aware of the problem, most Japanese golfers were untouched by yips. Those that were affected, perceived yips to be a psychological issue despite substantial evidence pointing to a movement-disorder. While self-administered interventions for symptom relief in such golfers is satisfactory at best, it may be imperative to sensitize golfers from a movement-disorder standpoint for early identification and management of the problem.


title: SARS-CoV-2 infection drives a glycan switch of peripheral T cells at diagnosis

abstract: COVID-19 is a highly selective disease in which SARS-CoV-2 infection can result in different clinical manifestations ranging from asymptomatic/mild to severe disease that requires hospitalization. Here, we demonstrated that SARS-CoV-2 infection results in a glycosylation reprogramming of circulating lymphocytes at diagnosis. We identified a specific glycosignature of T cells, defined upon SARS-CoV-2 infection and apparently triggered by a serological factor. This specific glycan switch of T cells is detected at diagnosis being more pronounced in asymptomatic patients. We further demonstrated that asymptomatic patients display an increased expression of a viral-sensing receptor, through the up-regulation of DC-SIGN in monocytes. We showed that higher levels of DC-SIGN in monocytes at diagnosis correlates with better COVID-19 prognosis. These new evidences pave the way to the identification of a novel glycan-based response in T cells that may confer protection against SARS-CoV-2 infection in asymptomatic patients, highlighting a novel prognostic biomarker and potential therapeutic target.


title: Factors influencing self-harm thoughts and self-harm behaviours over the first 45 weeks of the COVID-19 pandemic in the UK: a longitudinal analysis of 48,446 adults

abstract:
BackgroundThere is concern that the COVID-19 pandemic and its aftermath will result in excess suicides by increasing known risk factors such as self-harm, but evidence on how pandemic-related risk factors contribute to changes in these outcomes is lacking.

AimsTo examine how different COVID-19-related adverse experiences and adversity worries contribute to changes in self-harm thoughts and behaviours.

MethodData from 49,324 UK adults in the UCL COVID-19 Social Study were analysed (1 April 2020 to 17 May 2021). Fixed effects regressions explored associations between weekly within-person variation in five categories of adversity experiences and adversity worries with changes in self-harm thoughts and behaviours across age groups (18-29, 30-44, 45-59, and 60+ years).

Results26.1% and 7.9% respondents reported self-harm thoughts and behaviours, respectively, at least once over the study period. More adverse experiences were more strongly related to outcomes than worries. The largest specific adversity contributing to increases in both outcomes was having experienced physical or psychological abuse. Financial worries increased the likelihood of both outcomes in most age groups, whilst having had COVID-19 increased the likelihood of both outcomes in young (18-29 years) and middle-aged (45-59 years) adults.

ConclusionsFindings suggest that a significant portion of UK adults may be at increased risk for self-harm thoughts and behaviours during the pandemic. Given the likelihood that the economic and social consequences of the pandemic will accumulate, policy makers can begin adapting evidence-based suicide prevention strategies and other social policies to help mitigate its consequences.


title: Factors influencing self-harm thoughts and self-harm behaviours over the first year of the COVID-19 pandemic in the UK: a longitudinal analysis of 49,324 adults


title: SARS-CoV-2 serostatus of healthcare worker in the Austrian state Vorarlberg between June 2020 and January 2021

abstract:
BackgroundAustria, and particularly its westernmost federal state Vorarlberg, developed an extremely high COVID-19 incidence rate in November 2020. Health care workers (HCW) may be at higher risk of contracting the disease within the working environment and therefore the seroprevalence in this population is of particular interest. Here, we analyzed SARS-CoV-2-specific antibody response in Vorarlberg HCW in a prospective cohort study.

MethodsA total of 395 HCW have been tested at three different time points for the prevalence of anti-SARS-CoV-2 IgG antibodies specific for NP and RBD. Enrollment started in June 2020 (t1), two months after the end of the first wave. Re-testing took place between October to November at the beginning of the second wave (t2), and again at the end of the second wave in January 2021 (t3).

ResultsAt t1, 3% of HCW showed a strong IgG-specific responses to either NP or RBD. At t2, the rate increased to 4%, and after the second wave in January 2021, 14% had a strong response, which was assessed to be stable for up to ten months. The amount of HCW with anti-SARS-CoV-2 IgG antibodies was 38% higher than the number of infections found by RT-PCR.

ConclusionWe found low numbers of SARS-CoV-2-seropositive HCW in a hotspot setting after the first wave but a very high increase during the second massive wave. Though the seroprevalence in HCW was comparable to the general population. Our findings offer support for the routine application of serological testing in management of the ongoing COVID-19 pandemic.

Main summaryA relatively low percentage of 3% SARS-CoV-2 seropositive HCW with strong IgG-specific antibody responses was found in the Austrian federal state Vorarlberg after the first wave increasing to 14% after the second massive wave lasting until January 2021.

category: occupational and environmental health


title: Evaluation of VIDAS diagnostic assay prototypes detecting dengue virus NS1 antigen and anti-dengue virus IgM and IgG antibodies

abstract: Dengue is a tropical disease caused by the mosquito-borne dengue virus (DENV) and affecting an estimated 96 million people each year. Performant, rapid and easy-to-use assays are needed for the accurate diagnosis of acute DENV infection. This study evaluated the performance of three prototype assays developed for the VIDAS(R) automated platform to detect dengue NS1 antigen and anti-dengue IgM and IgG antibodies. Positive and negative agreement with competitor enzyme-linked immunosorbent assays (ELISA) and rapid diagnostic tests (RDT) was evaluated in 91 Lao patients (57 adults, 34 children) with acute DENV infection. The VIDAS(R) NS1 assay showed the best overall agreement (95.6%; 95% confidence interval [CI]: 89.1-98.8%) with the competitor NS1 ELISA (Focus Diagnostics). Both assays also demonstrated high sensitivity relative to DENV RNA real-time RT-PCR set as gold standard (85.7% [95% CI: 74.3-92.6%] and 83.9% [95% CI: 72.2-91.3%], respectively). Concordance of the VIDAS(R) results was overall higher with the competitor ELISA than with the RDT, suggesting a better performance of VIDAS(R) assays over RDT. The overall agreement of VIDAS(R) IgM and IgG assays with the competitor ELISA (Panbio/Abbott) was moderate (72.5%, 95% CI [62.6-80.6%] for IgM; 76.9%, 95% CI [67.3-84.4%] for IgG), highlighting differences in sensitivity and/or specificity between these assays. In all comparisons, test agreements did not differ significantly between adults and children, indicating comparable performance of the VIDAS(R) assays in both populations. Altogether, the VIDAS(R) dengue prototypes performed very well and appear to be suitable for routine detection of dengue NS1 antigen and anti-dengue IgM/IgG antibodies.

category: infectious diseases


title: Face-to-face interventions to encourage enrolment in cardiac rehabilitation; a scoping review protocol

abstract:
IntroductionCardiac rehabilitation has become an integral part of secondary treatment of cardiovascular heart disease. Despite evidence demonstrating that cardiac rehabilitation improves prognoses, reduces disease progression, and helps patients to find a new foothold in life, many patients do not enrol. Face-to-face interventions can encourage patients to enrol, however, it is unclear which strategies have been developed, how they are structured in a hospital context, and whether they target the life-world of the patients. The objective of this scoping review is to map and evaluate the nature and characteristics of studies that have reported on face-to-face interventions to encourage patients to enrol in cardiac rehabilitation.

Methods and analysisThis review will be guided by the Joanna Briggs Institute Methodology for Scoping Reviews. A search strategy developed in cooperation with a research secretary will be applied in six databases including studies published from 2000 in English, Danish, Norwegian, Swedish, and German with no restriction on publication type or study design. Studies involving adult patients with ischemic heart disease or heart failure will be included. Studies providing the intervention after enrolment in cardiac rehabilitation will be excluded. Study selection will be performed independently by two reviewers. Data will be extracted by two reviewers using predefined data charting forms. The presentation of data will be a narrative summary of the characteristics and key findings to facilitate the integration of diverse evidence, and as we deem appropriate will be supported by a diagrammatic or tabular presentation.

Ethics and disseminationThis scoping review will use data from existing publications and does not require ethical approval. Results will be reported through publication in a scientific journal and presented on relevant conferences and disseminated as part of future workshops with professionals involved in communication with patients about enrolment in cardiac rehabilitation.

ARTICLE SUMMARYO_ST_ABSStrength and Limitations of this studyC_ST_ABSO_LIThis protocol outlines a rigorous design that includes the use of an established scoping review methodology and a search strategy developed in cooperation with a research librarian
C_LIO_LIThe search strategy has no restrictions to study design, includes five different languages, and will cover six different databases
C_LIO_LIAs this review is inclusive to all study types and aims to provide an overview of the landscape of interventions to encourage enrolment in cardiac rehabilitation a quality assessment will not be performed
C_LIO_LIWhile the review will be non-discriminant towards article study types and methodologies, a limitation of the study is that books and grey literature will not be included
C_LI


title: Sequencing individual genomes with recurrent deletions reveals allelic architecture and disease loci for autosomal recessive traits

abstract: In medical genetics, discovery and characterization of disease trait contributory genes and alleles depends on genetic reasoning, study design, and patient ascertainment; we now suggest a segmental haploid genetics approach to enhance gene discovery and molecular diagnostics. We present novel genomic insights to enhance discovery in the challenging context of autosomal recessive (AR) traits and bi-allelic variation. We demonstrate computationally that new mutation mediated by nonallelic homologous recombination (NAHR), involving recurrent deletions at 30 genomic regions, likely drives recessive disease burden for over 70% of loci within these segmental deletions or at least 2% of loci genome wide. Meta-analyses of literature-reported patients implicate that NAHR-deletions are depleted from the ascertained pool of AR trait alleles. Exome reanalysis of personal genomes from subjects harboring recurrent deletions uncovered new disease-contributing variants in genes including COX10, ERCC6, PRRT2 and OTUD7A. Our data demonstrate that genomic sequencing of personal genomes with NAHR-deletions could dramatically foment allele and gene discovery, enhance clinical molecular diagnosis, and could potentially enable human haploid genetics screens as an approach to disease biology.

category: genetic and genomic medicine


title: Sequencing individual genomes with recurrent genomic disorder deletions reveals genes for autosomal recessive traits


title: Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traits


title: Demographic benchmarks for equitable coverage of the COVID-19 vaccination program among priority populations

abstract: We report the demographic distribution of non-institutionalized populations in the US who are prioritized for COVID-19 vaccination by ethnicity, age and sex and region. The composition of non-institutionalized priority populations was estimated using a nationally representative sample of 25,417 adults interviewed in the National Health Interview Survey (NHIS) in 2018. A relatively large fraction of individuals prioritized for the earliest distribution of the vaccine are women, non-Hispanic Black, and young to middle aged adults. Overall, the study provides a platform to track equity in vaccine coverage and to better tailor health communication strategies.


title: Diagnostic accuracy of RT-PCR for detection of SARS-CoV-2 compared to a composite reference standard in hospitalized patients

abstract:
BackgroundCOVID-19 caused by the novel coronavirus SARS-CoV-2 has caused the greatest public health emergency of our time. Accurate laboratory detection of the virus is critical in order to contain the spread. Although real-time polymerase chain reaction (PCR) has been the cornerstone of laboratory diagnosis, there have been conflicting reports on the diagnostic accuracy of this method.

MethodsA retrospective review was performed on all hospitalized patients tested for SARS-CoV-2 (at St. Pauls Hospital in Vancouver, BC) from March 13 - April 12, 2020. Diagnostic accuracy of initial PCR on nasopharyngeal (NP) swabs was determined against a composite reference standard which included a clinical assessment of the likelihood of COVID-19 by medical experts, initial and repeat PCR, and post-hoc serological testing.

ResultsA total of 323 patients were included in the study, 33 (10.2%) tested positive and 290 (89.8%) tested negative by initial PCR. Patients testing positive were more likely to exhibit features of cough (66.7% vs 39.3%), shortness of breath (63.6% vs 35.9%), fever (72.7% vs 27.6%), radiographic findings (83.3% vs 39.6%) and severe outcomes including ICU admission (24.2% vs 9.7%) and mortality (21.2% vs 6.2%) compared to patients testing negative. Serology was performed on 90 patients and correlation between serology and PCR was 98.9%. There were 90 patients included in the composite reference standard. Compared to the composite reference standard, initial PCR had sensitivity of 94.7% (95% CI 74.0 to 99.9%), specificity of 100% (95% CI 94.9 to 100%), positive predictive value of 100% (95% CI 81.5 to 100%) and a negative predictive value of 98.6% (95% CI 92.5 to 100%).

DiscussionOur study showed high sensitivity of PCR on NP swab specimens when compared to composite reference standard in hospitalized patients. High correlation of PCR with serological testing further increased confidence in the diagnostic reliability of properly collected NP swabs.


title: Targeting the Coronavirus Nucleocapsid Protein through GSK-3 Inhibition

abstract:
The coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome (MERS-CoV), and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication. Here we report that the SARS-CoV-2 N protein contains GSK-3 consensus sequences and that this motif is conserved in diverse coronaviruses, raising the possibility that SARS-CoV-2 may be sensitive to GSK-3 inhibitors including lithium. We conducted a retrospective analysis of lithium use in patients from three major health systems who were PCR tested for SARS-CoV-2. We found that patients taking lithium have a significantly reduced risk of COVID-19 (odds ratio = 0.51 [0.35 - 0.74], p = 0.005). We also show that the SARS-CoV-2 N protein is phosphorylated by GSK-3. Knockout of GSK3A and GSK3B demonstrates that GSK-3 is essential for N phosphorylation. Alternative GSK-3 inhibitors block N phosphorylation and impair replication in SARS-CoV-2 infected lung epithelial cells in a cell-type dependent manner. Targeting GSK-3 may therefore provide a new approach to treat COVID-19 and future coronavirus outbreaks.

SignificanceCOVID-19 is taking a major toll on personal health, healthcare systems, and the global economy. With three betacoronavirus epidemics in less than 20 years, there is an urgent need for therapies to combat new and existing coronavirus outbreaks. Our analysis of clinical data from over 300,000 patients in three major health systems demonstrates a 50% reduced risk of COVID-19 in patients taking lithium, a direct inhibitor of glycogen synthase kinase-3 (GSK-3). We further show that GSK-3 is essential for phosphorylation of the SARS-CoV-2 nucleocapsid protein and that GSK-3 inhibition blocks SARS-CoV-2 infection in human lung epithelial cells. These findings suggest an antiviral strategy for COVID-19 and new coronaviruses that may arise in the future.


title: Essential hypertension is associated with changes in gut microbial metabolic pathways: A multi-site analysis of ambulatory blood pressure

abstract: Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure (BP) is associated with gut microbiota and their metabolites remains unclear. We characterised the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory BP, faecal microbiome predicted from 16S rRNA gene sequencing, plasma and faecal metabolites called short-chain fatty acid (SCFAs), and expression of their receptors were analysed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared to hypertensives (35%, P<0.01), but there was no difference in age between the groups (59.2{+/-}7.7 versus 60.3{+/-}6.6-years-old). Based on machine-learning multivariate covariance analyses of de-noised amplicon sequence variant prevalence data, we determined that there were no significant differences in predicted gut microbiome - and {beta}-diversity metrics between normotensives versus essential, white coat or masked hypertensives. However, select taxa were specific to these groups, notably Acidaminococcus spp., Eubacterium fissicatena and Muribaculaceae were higher, while Ruminococcus and Eubacterium eligens were lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of SCFA-activated G-protein coupled re1ceptor 43 (GPR43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to BP-lowering metabolites.


title: Wearable alcohol monitors for alcohol use data collection among college students: feasibility and acceptability in a pilot study

abstract:
ObjectiveTo assess the feasibility and acceptability of using BACtrack Skyn wearable alcohol monitors in a college student population.

MethodIn September 2019, we enrolled n=5 Indiana University undergraduate students in a study to wear alcohol monitor wristbands continuously over a 5-day period. Concurrently, participants completed daily surveys querying details about their alcohol use in the previous 24 hours. We measured acceptability at endline with the Acceptability of Intervention Measure (AIM) scale (min=1, max=5). We measured feasibility with process measures: 1) amount of alcohol monitor data produced, and 2) correlation between drinking events identified by the alcohol monitors and drinking events reported by participants.

ResultParticipants reported high acceptability of the wearable alcohol monitors with a mean AIM score of 4.3 (range: 3.3 to 5.0). Feasibility of monitor use was high: A total of 589 hours of alcohol use data was collected. All participants were able to successfully use the alcohol monitors, producing a total of 24 out of 25 possible days of alcohol monitoring data. Participants reported a total of 15 drinking events during follow-up and we detected 12 drinking events with the alcohol monitors. The self-reported drinking event start times were highly correlated with the monitor detected event start time (Spearmans {rho}=0.9, p<0.0001). The self-reported number of drinks during a drinking event was correlated with the area under the curve of each drinking event peak (Pearsons r=0.7, p=0.008).

ConclusionWearable alcohol monitors are a promising data collection tool for more objective real-time measures of alcohol use in college student populations.


title: Methodological Approach for Wastewater Based Epidemiological Studies for SARS-CoV-2

abstract: Post COVID-19 outbreak, wastewater-based epidemiology (WBE) studies as surveillance system is becoming an emerging interest due to its functional advantage as tool for early warning signal and to catalyze effective disease management strategies based on the community diagnosis. A comprehensive attempt was made in this study to define a methodological approach for conducting WBE studies in the framework of identifying/selection of surveillance sites, standardizing sampling policy, designing sampling protocols to improve sensitivity, adopting safety protocol, and interpreting the data. The methodology was applied to a community and studied its epidemiological status with reference to occurrence, persistence, and variation of SARS-CoV-2 genome load in wastewater system to understand the prevalence of infection. Hourly and daily grab samples were analyzed and compared with the composite samples over a surveillance window of 7 days. Based on the SARS-CoV-2 RNA copies/L, faeces shedding, and volume of sewage generated the infected individuals and the population who are in active phase in the studied community was estimated.


title: What is the extent of COVID-19 vaccine hesitancy in Bangladesh? : A cross-sectional rapid national survey

abstract:
objectivesTo assess COVID-19 vaccine hesitancy in Bangladesh and identify population subgroups with higher odds of vaccine hesitancy.

designA nationally representative cross-sectional survey was used. Univariate analysis was employed to compute vaccine hesitancy proportions and compare them across groups and multiple logistic regression analyses were performed to compute the adjusted odds ratio.

settingBangladesh

participantsA total of 1134 participants from the general population, aged 18 years and above.

outcome measuresPrevalence and predictors of vaccine hesitancy.

results32.5% of participants showed COVID-19 vaccine hesitancy. Hesitancy was high among respondents who were males, over age 60, unemployed, from low-income families, from central Bangladesh including Dhaka, living in rented houses, tobacco users, politically affiliated, participants who did not believe in the vaccines effectiveness for Bangladeshis and those who did not have any physical illnesses in the last year. In the multilevel logistic regression models, respondents who were transgender (AOR= 3.62), married (AOR=1.49), tobacco users (AOR=1.33), those who did not get any physical illnesses in the last year (AOR=1.49), those with political affiliations with opposition parties (AOR= 1.48), those who believed COVID-19 vaccines will not be effective for Bangladeshis (AOR= 3.20), and those who were slightly concerned (AOR = 2.87) or not concerned at all (AOR = 7.45) about themselves or a family member getting infected with COVID-19 in the next one year were significantly associated with vaccine hesitancy (p < 0.05).

conclusionsGiven the high prevalence of COVID-19 vaccine hesitancy, it is important to promote evidence-based communication, mass media campaigns, and policy initiatives across Bangladesh to reduce vaccine hesitancy among the Bangladeshi population.

Strengths and Limitations of the studyO_LIThis study is the first its kind to measure COVID-19 vaccine hesitancy in Bangladesh.
C_LIO_LIIn this study, randomly selected participants were interviewed face to face, enabling a nearly true representative sample of the Bangladeshi general population.
C_LIO_LIThis study identified a wide range of sub-groups of the general population with higher odds of COVID-19 vaccine hesitancy relating to their sociodemographic characteristics in Bangladesh; thus, providing baseline evidence for the low and middle-income and low-resourced countries worldwide.
C_LIO_LITraditional media and social media influence on COVID-19 vaccine hesitancy was not measured which is a major limitation of this study.
C_LI


title: Effectiveness of Non-Pharmaceutical Interventions on Child and Staff COVID-19 Cases in US Summer Camps

abstract:
BackgroundMost camps remained closed during Summer 2020, due to concerns regarding child transmission of SARS-CoV-2 and limited information about the effectiveness of non-pharmaceutical interventions (NPIs) within child congregate settings.

MethodsWe surveyed US camps about on-site operations, camper and staff demographics, COVID-19 cases amongst campers and staff, and NPI usage as related to pre-camp quarantines, facial coverings, physical distancing, cleaning, and facility modifications. For all NPIs, save quarantines, responses were provided on a 5-point Likert scale format.

ResultsWithin 486 on-site camps, a range of NPIs were instituted, most often related to reduced camper interactions, staff face coverings, cleaning, and hand hygiene. Camper facial coverings were less common, with campers always wearing masks at [~]34% of the camps. Approximately 15% of camps reported 1+ confirmed COVID-19 case in either campers or staff, with three camps reporting a COVID outbreak. In both single and multi-NPI analyses, the risk of COVID-19 cases was lowest when campers always wore facial coverings. While less effective, constant use of staff facial coverings and targeted physical distancing measures, but not pre-camp quarantine, also reduced COVID-19 risks.

ConclusionsWe found constant facial coverings, especially for campers, and targeted physical distancing measures to reduce risks of SARS-CoV-2 transmission within summer camps. Our findings provide valuable guidance for future operations of camp and other child congregate settings with regard to efficient and effective NPI usage to mitigate SARS-CoV-2 infection.

Whats Known on This SubjectApproximately 82% of US overnight camps did not open during Summer 2020 due to concerns regarding childrens ability to transmit SARS-CoV-2. Camps that did operate during this time instituted varied non-pharmaceutical interventions (NPIs) to reduce SARS-CoV-2 transmission, with little information available on the effectiveness of these NPIs within child congregate settings. Large population-based studies are needed to improve our understanding of the extent of SARS-CoV-2 infection amongst children and their caregivers and to determine whether and to what degree child congregate programs can safely open during the pandemic.

What This Study AddsOur study, the largest survey of COVID-19 cases in child congregate settings at the national level, provides new information on the relative effectiveness of NPIs on mitigating COVID cases among children and staff within camp settings. We showed COVID-19 case rates in campers and staff to be low relative to corresponding case rates in the US and found constant camper facial coverings to be the most effective risk reduction method for SARS-CoV-2 transmission within camps. While less effective, constant use of staff facial coverings and targeted physical distancing measures, but not pre-camp quarantines, were also shown to reduce COVID-19 risks. Our findings has important implications for child congregate settings, helping to guide their successful opening and operation.