title: Assessment of Motion Bias on the Detection of Dopamine Response to Challenge

abstract:
11C-Raclopride (RAC) positron emission tomography (PET) is used to study dopamine response to pharmacological and behavioral challenges. Behavioral challenges produce smaller responses than pharmacological challenges and are more susceptible to sources of bias, including motion bias. The purpose of this study was to characterize the effect of motion bias within the context of a behavioral task challenge, examining the impact of different motion correction strategies, different task response magnitudes, and intra-versus interframe motion.

MethodsSeventy healthy young adults were administered bolus plus constant infusion 11C-Raclopride (RAC) and imaged for 90 min on a 3-Tesla simultaneous PET/magnetic resonance (MR) scanner during which a functional MRI (fMRI) reward task experiment was conducted. Kinetic analysis was performed using an extension of the multilinear reference tissue model (MRTM), which encoded the task response as a unit step function at the start of the task (t = 40 min). The quantitative impacts of different approaches to motion correction (frame-based, reconstruction-based, none) were compared using voxel maps of change in binding potential ({Delta}BPND). Motion bias was compared to task effect by simulating different levels of {Delta}BPND (0%, 5%, 10%, 20%) in conjunction with simulating high and no motion. Intraframe motion was simulated using motion estimates derived from the simultaneously acquired MR data. The relative impact of intraframe motion was evaluated by comparing maps of bias in {Delta}BPND before and after applying frame-based motion correction.

ResultsAmong the high-motion subjects, failure to perform motion correction resulted in large artifacts. Frame- and reconstruction-based approaches both corrected for motion effectively, with the former showing moderately more intense {Delta}BPND values (both positive and negative) in and around the striatum. At low task response magnitudes, simulations showed that motion bias can have a greater relative effect. At 5% {Delta}BPND, motion bias accounted for 60% of the total bias, while at 10% {Delta}BPND, it accounted for only 34%. Simulating high-temporal resolution motion, frame-based motion correction was shown to counteract the majority of the of the motion bias effect. The remaining bias attributable to intraframe motion accounted for only 8% of the total.

ConclusionMotion bias can have a corrupting effect on RAC studies of behavioral task challenges, particularly as the magnitude of the response decreases. Applying motion correction mitigates most of the bias, and specifically correcting for interframe motion provides the bulk of the benefit.

category: radiology and imaging


title: International travel in times of the COVID-19 pandemic: Evidence from German school breaks

abstract: The COVID-19 pandemic has triggered severe global restrictions on international travel with the intention of limiting the spread of SARS-CoV-2 across countries. This paper studies the effects of the partial relaxation of these travel restrictions in Europe during the summer months of 2020. It exploits the staggered start of the summer school breaks across German states as an exogenous shock to the travel opportunities of the population. While the school breaks also increased mobility within Germany, the event study regressions include disaggregated and time-varying controls for domestic mobility and local COVID-19-related restrictions. The resulting intention-to-treat effects of the relaxed travel restrictions show a significant and sizable increase of the COVID-19 incidence in German counties during the later weeks of the school breaks.

category: epidemiology


title: Advancing data science in drug development through an innovative computational framework for data sharing and statistical analysis.

abstract:
BackgroundNovartis and the University of Oxfords Big Data Institute (BDI) have established a research alliance with the aim to improve health care and drug development by making it more efficient and targeted. Using a combination of the latest statistical machine learning technology with an innovative IT platform developed to manage large volumes of anonymised data from numerous data sources and types we plan to identify novel patterns with clinical relevance which cannot be detected by humans alone to identify phenotypes and early predictors of patient disease activity and progression.

MethodThe collaboration focuses on highly complex autoimmune diseases and develops a computational framework to assemble a research-ready dataset across numerous modalities. For the Multiple Sclerosis (MS) project, the collaboration has anonymised and integrated phase II to phase IV clinical and imaging trial data from {approx}35,000 patients across all clinical phenotypes and collected in more than 2,200 centres worldwide. For the "IL-17" project, the collaboration has anonymised and integrated clinical and imaging data from over 30 phase II and III Cosentyx clinical trials including more than 15,000 patients, suffering from four autoimmune disorders (Psoriasis, Axial Spondyloarthritis, Psoriatic arthritis (PsA) and Rheumatoid arthritis (RA)).

ResultsA fundamental component of successful data analysis and the collaborative development of novel machine learning methods on these rich data sets has been the construction of a research informatics framework that can capture the data at regular intervals where images could be anonymised and integrated with the de-identified clinical data, quality controlled and compiled into a research-ready relational database which would then be available to multi-disciplinary analysts. The collaborative development from a group of software developers, data wranglers, statisticians, clinicians, and domain scientists across both organisations has been key. This framework is innovative, as it facilitates collaborative data management and makes a complicated clinical trial data set from a pharmaceutical company available to academic researchers who become associated with the project.

ConclusionsAn informatics framework has been developed to capture clinical trial data into a pipeline of anonymisation, quality control, data exploration, and subsequent integration into a database. Establishing this framework has been integral to the development of analytical tools.

category: health informatics


title: Reproduction as a Means of Evaluating Policy Models: A Case Study of a COVID-19 Simulation

abstract: This article proposes (and demonstrates the effectiveness of) a new strategy for assessing the results of epidemic models which we designate reproduction. The strategy is to build an independent model that uses (as far as possible) only the published information about the model to be assessed. In the example presented here, the independent model also follows a different modelling approach (agent-based modelling) to the model being assessed (the London School of Hygiene and Tropical Medicine compartmental model which has been influential in COVID lockdown policy). The argument runs that if the policy prescriptions of the two models match then this independently supports them (and reduces the chance that they are artefacts of assumptions, modelling approach or programming bugs). If, on the other hand, they do not match then either the model being assessed is not provided with sufficient information to be relied on or (perhaps) there is something wrong with it. In addition to justifying the approach, describing the two models and demonstrating the success of the approach, the article also discusses additional benefits of the reproduction strategy independent of whether match between policy prescriptions is actually achieved.


title: Lockdown benefit varies among countries and sub-national units: a reanalysis of the data by Bendavid et al. (2021)

abstract: Are the lockdown measures limiting the propagation of COVID-19? Recent analyses on the effectiveness of non-pharmaceutical interventions in reducing COVID-19 growth rates delivered conflicting conclusions. While Haug et al. (2020) did find strong empirical support for reductions in COVID-19 growth rates, Bendavid et al. (2021) did not. Here, I present the results of a reanalysis of the data by Bendavid et al. (2021). Instead of relying on pairwise comparisons between 10 countries with fixed-effects regression models to isolate the effect of lockdown measures, I modelled the development of the pandemic with and without lockdown measures for the entire period and all countries included in the data with one mixed-effects regression model. My results reconciled the conflicting conclusions of Haug et al. (2020) and Bendavid et al. (2021): while mandatory business closure orders did not affect COVID-19 growth rates, a general decrease in COVID-19 growth rates was attributable to the implementation of mandatory stay-at-home orders. However, the effect of mandatory stay-at-home orders varied, being weaker, even zero, in some countries and sub-national units and stronger in others, where COVID-19 growth rates only decreased due to the implementation of mandatory stay-at-home orders. The heterogeneity in the effect of mandatory stay-at-home orders on the spread of COVID-19 is challenging from a scientific and political point of view.

category: health policy


title: Absence of Glutathione S-Transferase Theta 1 Gene is Significantly Associated with Breast Cancer Susceptibility in Pakistani Population and Poor Overall Survival in Breast Cancer Patients: A Case-Control and Case Series Analysis

abstract:
PurposeDeletion of Glutathione S-Transferase Theta 1 (GSTT1) encoding gene is implicated in breast cancer susceptibility, clinical outcomes, and survival. Contradictory results have been reported in different studies. The present investigation evaluated GSTT1-absent genotype for its contribution to breast cancer risk in Pakistani population and specific clinical outcomes in breast tumours.

MethodsA prospective study comprising case-control analysis and case series analysis components was designed. Peripheral blood samples were collected from enrolled participants. After DNA extraction, GSTT1 genotyping was carried out by a multiplex PCR with {beta}-globin as an amplification control. Association evaluation of GSTT1 genotypes with breast cancer risk, specific tumour characteristics, and survival was the primary endpoint.

ResultsA total of 264 participants were enrolled in the molecular investigation (3 institutions). The study included 121 primary breast cancer patients as cases and 143 age-matched female subject, with no history of any cancer, as controls. A significant genetic association between GSTT1-absent genotype and breast cancer susceptibility (p-value: 0.003; OR: 2.13; 95% CI: 1.08-4.29) is reported. The case-series analysis showed lack of association of GSTT1 genotypes with tumour stage (p-value: 0.12), grade (p-value: 0.32), and size (p-value: 0.07). The survival analysis revealed that GSTT1-absent genotype cases had a statistically significant shorter overall survival (OS) than those with GSTT1-present genotype cases (mean OS: 23 months vs 33 months). The HR (95% CI) for OS in patients carrying GSTT1-absent genotype was 8.13 (2.91-22.96) when compared with GSTT1-present genotype.

ConclusionsThe present study is the first report of an independent, population-oriented significant genetic association between GSTT1-absent genotype and breast cancer susceptibility as well as OS in breast cancer cases. Upon further validation, GSTT1 variation may serve as a marker for devising better and population-specific strategies for screening and treatment in breast cancer management.

category: genetic and genomic medicine


title: A Scoping Review of Community Based Geriatric Health Assessment and Screening Tools used in South Asia Region

abstract:
BackgroundHome-based comprehensive assessment and integrated care of the older people could be a key to relieve the pressure on the already overburdened health system. This review summarises evidence on validated community-based geriatric health assessment tools in South Asia.

MethodsGuided by Arksey and OMalleys five-stage scoping review framework, a total of 46 studies were included in the scoping review after searching from electronic databases and reference lists using predefined eligibility criteria. Data were extracted on main characteristics of included studies, identified instruments and their psychometric properties of the tools. This review was reported in accordance with PRISMA-ScR guidelines.

ResultsAmong the 46 included studies, 10 reported on instruments for medical assessment, 12 on tools for psychological conditions, 13 on tools for functional issues, 2 on social wellbeing, and 9 on tools with multiple domains of health. Most studies included participants from both gender and different social classes. Majority used measurements that were both self-reported or measured by the investigator. whereas only two instruments were designed to be used by clinicians. In the existing geriatric health assessment tools, environmental domain was neglected completely, and not a single tool considered in this review covered all 5 domains which influence regular life of elderly.

ConclusionThere are no validated tools available that can be used for comprehensive geriatric assessment in South Asia. There is a need to develop and validate culturally sensitive tools that can be used for assessing all the geriatric health domains.

category: geriatric medicine


title: An MRI-based Deep Learning Model to Predict Parkinson Disease Stages

abstract: Parkinsons disease (PD) is amongst the relatively prevalent neurodegenerative disorders with its course of progression classified as prodromal, stage1, 2, 3 and sever conditions. With all the shortcomings in clinical setting, it is often challenging to identify the stage of PD severity and predict its progression course. Therefore, there appear to be an ever-growing need need to use supervised and unsupervised artificial intelligence and machine learning methods on clinical and paraclinical datasets to accurately diagnose PD, identify its stage and predict its course. In todays neuro-medicine practices, MRI-related data are regarded beneficial in detecting various pathologies in the brain. In addition, the field has recently witnessed a growing application of deep learning methods in image processing often with outstanding results. Here, we applied Convolutional Neural Networks (CNN) to propose a model helping to distinguish different stages of PD. The results showed that our current MRI-based CNN model may potentially be employed as a suitable method for the distinction of PD stages at a high accuracy rate (0.94).


title: Learning Decision Thresholds for Risk-Stratification Models from Aggregate Clinician Behavior

abstract: Using a risk-stratification model to guide clinical practice often requires the choice of a cutoff - called the decision threshold - on the models output to trigger a subsequent action such as an electronic alert. Choosing this cutoff is not always straightforward. We propose a flexible approach that leverages the collective information in treatment decisions made in real life to learn reference decision thresholds from physician practice. Using the example of prescribing a statin for primary prevention of cardiovascular disease based on 10-year risk calculated by the 2013 Pooled Cohort Equations, we demonstrate the feasibility of using real world data to learn the implicit decision threshold that reflects existing physician behavior. Learning a decision threshold in this manner allows for evaluation of a proposed operating point against the threshold reflective of the community standard of care. Furthermore, this approach can be used to monitor and audit model-guided clinical decision-making following model deployment.


title: Chronic Kidney Disease in Ecuador: An Epidemiological and Health System Analysis of an Emerging Public Health Crisis

abstract:
BackgroundThe absence of a chronic kidney disease (CKD) registry in Ecuador makes it difficult to assess the burden of disease, but there is an anticipated increase in the incidence of end-stage kidney disease along with increasing diabetes, hypertension and population age. From 2008, augmented funding for renal replacement treatment expanded dialysis clinics and patient coverage.

MethodsWe conducted 73 in-depth interviews with healthcare providers in eight provinces. Findings were analyzed using qualitative methods and triangulated with quantitative data on patients with CKD diagnoses from six national-level databases between 2015 and 2018. We also reviewed grey and scientific literature on CKD and health systems in Ecuador.

ResultsDatasets show a total of 17 484 dialysis patients in 2018, or 567 patients per million population (pmp), with an annual cost exceeding 11% of Ecuadors public health budget. Each year, there were 139--162 pmp new dialysis patients, while doctors report waiting lists. The number of patients on peritoneal dialysis was stable; those on hemodialysis increased over time. Only 13 of 24 provinces have dialysis services, and nephrologists are in major cities, which limits access, delays medical attention, and adds a travel burden on patients. Prevention and screening programs are scarce, while hospitalization is an important reality of CKD patients.

ConclusionCKD is an emerging public health crisis that has increased dramatically over the last decade in Ecuador and is expected to continue, making coverage for all patients impossible and the current structure, unsustainable. A patient registry would permit to estimate the demand and progression of patients with consideration for comorbidities, requirements and costs, and mortality, and identify where to focus prevention efforts. Health policy should clearly state CKD definitions and required patient data, including cause, disease stage and follow-up statistics. Organized monitoring of patients would benefit from improvements in patient referral.

category: health systems and quality improvement


title: Antigen production and development of an indirect ELISA based on the nucleocapsid protein to detect human SARS-CoV-2 seroconversion

abstract: Serological assays are important tools to identify previous exposure to SARS-CoV-2, helping to track COVID-19 cases and determine the level of humoral response to SARS-CoV-2 infections and/or immunization to future vaccines. Here the SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to homogeneity and high yield using a single chromatography step. The purified SARS-CoV-2 nucleocapsid protein was used to develop an indirect enzyme-linked immunosorbent assay for the identification of human SARS-CoV-2 seroconverts. The assay sensitivity and specificity were determined analyzing sera from 140 PCR-confirmed COVID-19 cases and 210 pre-pandemic controls. The assay operated with 90% sensitivity and 98% specificity; identical accuracies were obtained in head-to-head comparison with a commercial ELISA kit. Antigen coated plates were stable for up to 3 months at 4{degrees}C). The ELISA method described is ready to mass production and will be an additional toll to track COVID-19 cases.

category: infectious diseases


title: Healthcare personnel knowledge, motivations, concerns and intentions regarding COVID-19 vaccines: a cross-sectional survey

abstract:
BackgroundHealthcare personnel (HCP) are prioritized for earliest SARS-CoV-2 vaccine administration, yet relatively few data exist on HCPs knowledge, motivations, concerns, and intentions regarding COVID-19 vaccines.

MethodsWe conducted a cross-sectional survey Nov.16-Dec.8, 2020 among HCP enrolled in a cohort study at three Northern California medical centers serving diverse roles including COVID-19 patient care. Eligible HCP were adult (age[≥]18) on-site employees of the University of California, San Francisco, San Francisco General Hospital, and Stanford Healthcare. A one-time electronically-administered survey was sent to cohort HCP on November 16, 2020 and responses analyzed.

ResultsOverall, among 2,448 HCP invited, 2,135 completed the COVID-19 vaccine survey (87.2% response rate). HCPs had mean age 41 years, were 73% female, and had diverse jobs including COVID-19 patient contact. Enthusiasm for vaccination was overall strong, and more HCP (1,453, 69%) said they would definitely/likely receive vaccine if formally FDA-approved versus if approved via emergency use authorization only (785, 35%). While 541 (25%) respondents wanted to be among the earliest to receive vaccine, more desired vaccination after the first round (777, 36%) or >2 months after vaccinations began (389, 18%). Top factors increasing motivation for vaccination included perceiving risk from COVID-19 to self (1,382, 65%) or to family/friends (1355, 63%). Top concerns were vaccine side effects, cited by 596 (28%), and concerns about political involvement in FDAs approval process (249, 12%).

ConclusionsHCP were enthusiastic about COVID-19 vaccination for individual protection and protecting others, but harbored concerns about vaccine side effects. Our data may inform emerging vaccine education campaigns.

Key PointsAmong 2,135 healthcare personnel surveyed, we found enthusiasm for COVID-19 vaccination both for individual benefit and protecting others. However, healthcare personnel rated their knowledge of COVID-19 vaccines as only moderate and harbored concerns about vaccine side effects. Education raising awareness of vaccine efficacy and side effects may help maximize vaccine uptake.


title: The U-shaped association of serum iron level with COVID-19 severity: Is iron a potential therapeutic target?

abstract: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.


title: The U-shaped association of serum iron level with COVID-19 severity


title: Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial

abstract:
BackgroundIn the search for active drugs against COVID-19, the indications of many have been redirected. Ivermectin and Hydroxychloroquine are drugs that inhibit viral replication in vitro and that have been used in several medical centers.

ObjectivesThis clinical trial analyzes the efficacy of Ivermectin and Hydroxychloroquine in patients with moderate COVID-19 and in need of hospitalization.

MethodsThis a controlled, clinical, randomized, double-blind trial that included patients with COVID-19-induced pneumonia and hospitalization criteria, but no severe respiratory failure. Patients were randomized to one of three groups: Group1-hydroxychloroquine, 400 mg every 12 hours on the first day and subsequently, 200 mg every 12 hours for 4 days, Group 2-ivermectin, 12 mg or 18 mg, according to patient weight and, Group 3-placebo. At inclusion, blood samples for arterial blood gases and biochemical markers associated with a poor prognosis were obtained. The primary outcome was established as the duration of hospitalization until discharge due to patient improvement, the total duration of hospitalization, and the safety outcomes were either respiratory deterioration or death.

ResultsDuring the month of August, the admission of patients requiring hospitalization mostly encompassed cases with severe respiratory failure, so we ended the recruitment process and analyzed the data that was available at the time. One hundred and six (106) patients with an average age of 53 yrs. ({+/-}16.9) were included, with a greater proportion of males (n=66, 62.2 %). Seventy-two percent (72%) (n= 76) had an associated comorbidity. Ninety percent (90 %) of patients were discharged due to improvement (n=96). The average duration of hospitalization was 6 days (IQR, 3 - 10). No difference in hospitalization duration was found between the treatment groups (Group1: 7 vs Group 2: 6 vs Group 3: 5, p=0.43) nor in respiratory deterioration or death (Group 1: 18 % vs Group 2: 22.2 % vs Group 3: 24.3 %, p =0.83).

ConclusionsIn non-critical hospitalized patients with COVID-19 pneumonia, neither ivermectin nor hydroxychloroquine decreases the number of in-hospital days, respiratory deterioration, or deaths.

ClinicalTrials identifier NCT04391127


title: In search for the SARS-CoV-2 protection correlate: A head-to-head comparison of two quantitative S1 assays in a group of pre-characterized oligo-/asymptomatic patients

abstract:
BackgroundQuantitative serological assays detecting response to SARS-CoV-2 infection are urgently needed to quantify immunity. This study analyzed the performance and correlation of two independent quantitative anti-S1 assays in oligo-/asymptomatic individuals from a previously characterized population-based cohort.

MethodsA total of 362 samples included 108 from individuals who had viral RNA detected in pharyngeal swabs, 111 negative controls and 143 samples with positive serology but not confirmed by RT-PCR. Blood plasma was tested with quantitative assays Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (IgG) (EI-S1-IgG-quant) and Roche Elecsys(R) Anti-SARS-CoV-2 CoV-2 S (Ro-RBD-Ig-quant), which were compared with each other and with confirmatory tests, including wild-type virus micro-neutralization (NT) and GenScript(R)cPass. Results were analyzed using square roots R of coefficients of determination for association among continuous variables and non-parametric tests for paired comparisons.

ResultsQuantitative anti-S1 serology correlated well with each other (96%/97% for true-positives and true-negatives, respectively). Antibody titers decreased over time (from <30 days to >240 days after initial positive RT-PCR). Agreement with GenScript-cPass was 96%/99% for true-positives and true-negatives, respectively, for Ro-RBD-Ig-quant and 93%/97% for EI-S1-IgG-quant. Ro-RBD-Ig-quant allowed a distinct separation between positive and negative values, and less non-specific reactivity compared with EI-S1-IgG-quant. Raw values (with 95% CI) [≥]28.7 U/mL (22.6-36.4) for Ro-RBD-Ig-quant and [≥]49.8 U/mL (43.4-57.1) for EI-S1-IgG-quant predicted virus neutralization >1:5 in 95% of cases.

ConclusionsBoth quantitative anti-S1 assays, Ro-RBD-Ig-quant and EI-S1-IgG-quant, may replace direct neutralization assays in quantitative measurement of immune protection against SARS-CoV-2 in certain circumstances in the future.

Key pointsTwo quantitative anti-S1 assays showed similar performance and a high level of agreement with direct virus neutralization and surrogate neutralization tests, arguing for their utility in quantifying immune protection against SARS-CoV-2.


title: Role of Heterogeneous Transmission in the Decline of COVID-19 Cases During Winter of 2020/2021 in Massachusetts

abstract:
ImportanceHeterogeneity in transmission of COVID-19 is a significant multiscale phenomenon. However, the role of this heterogeneity in shaping the overall dynamics of disease transmission is not well understood.

ObjectiveTo investigate the role of heterogeneous transmission among different towns in Massachusetts in shaping the dynamics of COVID-19 transmission, especially the recent decline during winter of 2020/2021.

Design, Setting, ParticipantsAnalysis of COVID-19 data collected and archived by the Massachusetts Department of Public Health.

ExposuresThe entire population of the state of Massachusetts is exposed to the virus responsible for COVID-19, to varying degrees. This study quantifies this variation.

Main outcome measuresWeekly observations, by town, on confirmed COVID-19 cases in Massachusetts, during the period (April 15th, 2020 to February 9th 2021).

ResultsThe relative decline in COVID-19 cases, during January 12th, 2021 to February 9th, 2021, in the group of towns with higher total accumulated cases in the period before January 12th, 2021 is significantly larger than the corresponding relative decline in the group of towns with lower accumulated cases during the same period.

Conclusions and RelevanceHeterogeneous nature of transmission is playing a significant role in shaping the rapid recent decline (January 12th to February 9th, 2021) in reported cases in Massachusetts, and probably around the country. These findings are relevant to how we estimate the threshold defining "herd" immunity, suggesting that we should account for effects due to heterogeneity.

Key PointsO_ST_ABSQuestionC_ST_ABSDoes heterogeneity in disease transmission play a role in shaping the overall dynamics of COVID-19 in Massachusetts, including the recent decline in cases during the 2020/2021 winter.

FindingsBased on analysis of data on cases in Massachusetts, the consistent and widespread decline of COVID-19 spread during winter of 2020/2021 (January 12th, 2021 to February 9th, 2021) appears to be shaped to a significant degree by the heterogeneous nature of transmission at the scale of different towns. Towns with a history of high (low) transmission rates during 2020 are experiencing a faster (slower) relative decline.

MeaningWe suggest that heterogeneity in transmission of COVID-19 may impact the dynamics of disease transmission including the emergence of "herd" immunity, in line with some recent theoretical studies. This finding deserves some attention from other research groups investigating "herd" immunity, and from federal and state public health authorities concerned with the future evolution of the pandemic.


title: The Association of Opioid Use Disorder and COVID-19 in Shahroud, Iran

abstract:
BackgroundCOVID-19 quickly spread to the world, causing a pandemic. While some studies have found no link between Opioid Use Disorder (OUD) and COVID-19, the role of the opioid on COVID-19 is challenging. The present study aimed to determine the relationship between OUD and COVID-19.

MethodsThis was a prospective cohort study. We used data from the third phase of the Shahroud eye cohort study on 4394 participants which started in September 2019 and ended before the COVID-19 epidemic in Shahroud in February 2020. The participants were followed for 10.5 months till November 2020. COVID-19 was detected by RT-PCR on swap samples from the oropharynx and nasopharynx. The incidence of COVID-19 compared in OUD and Non-OUD participants, and relative risk was calculated in Log Binomial Regression model.

ResultsAmong the 4394 participants with a mean age of 61.1 years, 120 people had OUD. The incidence of COVID-19 in participants with OUD and Non-OUD were 3.3% and 4.5%, respectively. The relative risk of OUD for COVID-19 was 0.75 (95% Confidence intervals: 0.28 - 1.98; P= 0.555).

ConclusionsOpioid use disorder was not associated with COVID-19. The claim that people with OUD are less likely to develop COVID-19 is not supported by this data.

category: addiction medicine


title: Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory programming and continual clearance of apoptotic cells

abstract: COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV2-infected apoptotic cells exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that lung monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppress macrophage anti-inflammation and efficient tissue repair programs and provide mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.

category: allergy and immunology


title: Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells


title: Machine learning algorithm to predict delirium from emergency department data

abstract:
IntroductionDelirium is a cerebral dysfunction seen commonly in the acute care setting. Delirium is associated with increased mortality and morbidity and is frequently missed in the emergency department (ED) by clinical gestalt alone. Identifying those at risk of delirium may help prioritize screening and interventions.

ObjectiveOur objective was to identify clinically valuable predictive models for prevalent delirium within the first 24 hours of hospitalization based on the available data by assessing the performance of logistic regression and a variety of machine learning models.

MethodsThis was a retrospective cohort study to develop and validate a predictive risk model to detect delirium using patient data obtained around an ED encounter. Data from electronic health records for patients hospitalized from the ED between January 1, 2014, and December 31, 2019, were extracted. Eligible patients were aged 65 or older, admitted to an inpatient unit from the emergency department, and had at least one DOSS assessment or CAM-ICU recorded while hospitalized. The outcome measure of this study was delirium within one day of hospitalization determined by a positive DOSS or CAM assessment. We developed the model with and without the Barthel index for activity of daily living, since this was measured after hospital admission.

ResultsThe area under the ROC curves for delirium ranged from .69 to .77 without the Barthel index. Random forest and gradient-boosted machine showed the highest AUC of .77. At the 90% sensitivity threshold, gradient-boosted machine, random forest, and logistic regression achieved a specificity of 35%. After the Barthel index was included, random forest, gradient-boosted machine, and logistic regression models demonstrated the best predictive ability with respective AUCs of .85 to .86.

ConclusionThis study demonstrated the use of machine learning algorithms to identify the combination of variables that are predictive of delirium within 24 hours of hospitalization from the ED.

category: emergency medicine


title: Human mobility data from the BBC Pandemic project

abstract: We present human mobility data for the United Kingdom collected from the "BBC Pandemic", a public science project linked to the BBC Four television documentary of the same name. Mobile phone GPS trajectories submitted by users and collected over a 24 hour period were aggregated to construct anonymised origin-destination flux matrices at the local administrative district (LAD). We use these data to explore how mobility patterns change with age and employment status - unique stratifications that are not available from other publicly and privately held mobility data sets. We validate the consistency of the aggregated BBC mobility data set against census workflow data and illustrate how the systematic differences in mobility rates with age affect the risk and pattern of transmission between regions with 18-30 year olds contributing the greatest risk of transmission to adjacent regions, but older 60-100 years playing the most important role in more remote low-density locations.


title: Impact of the COVID-19 pandemic on mental health among Greek adults: a cross-sectional survey.

abstract:
ObjectivesThe coronavirus disease 2019 (COVID-19) pandemic and mitigation measures based on social distancing are expected to have serious adverse effects on mental health. This cross-sectional study aimed to examine self-reported changes in the mental health status of Greek adults.

Study designThe current study is a primary research conducted on Greek adults during the first wave of the epidemic (March to April 2020).

MethodsA total of 527 individuals participated in an online survey using a validated questionnaire (State-Trait Anxiety Inventory-STAI and DASS-21).

ResultsThe respondents had a moderate mental health status based on the following scores: STAI-S, 45.8; STAI-T, 40.7; depression, 4.6; anxiety, 3.1; and stress, 6.1. Women, younger respondents, those from lower income households, and those living in smaller apartments experienced increased depression, anxiety, and stress. Additionally, infection control practices during the COVID-19 pandemic such as the use of masks, gloves, and antiseptic can drastically decrease the prevalence of mental health illnesses.

ConclusionsThese findings can be used by the Greek State to reduce the effects of COVID-19 on the mental health of the population and protect socially vulnerable groups.


title: IQ moderation of cognitive decline supports cognitive reserve and not brain maintenance

abstract:
Age-related cognitive changes can be influenced by both brain maintenance (BM), which refers to the relative absence over time of changes in neural resources or neuropathologic changes, and cognitive reserve (CR), which encompasses brain processes that allow for better-than-expected behavioral performance given the degree of life-course related brain changes. This study evaluated the effects of age, BM, and CR on longitudinal changes over two visits, 5 years apart, in four reference cognitive abilities that capture most of age-related variability. Participants included 254 healthy adults aged 20-80 years at recruitment. Potential BM was estimated using whole brain cortical thickness and white matter mean diffusivity at both visits. Education and IQ (estimated with AMNART) were tested as moderating factors for cognitive changes in the four reference abilities. Consistent with BM, after accounting for age, sex, and baseline performance, individual differences in the preservation of mean diffusivity were associated with relative preservation in the four abilities; differential preservation of cortical thickness was associated with preservation of reasoning, processing speed, and memory. Consistent with CR, after accounting for structural brain changes, higher IQ, but not education, was associated with reduced 5-year decline in reasoning. A similar marginal association was seen for memory but not for processing speed. These results demonstrate that both CR and BM can moderate cognitive changes in healthy aging and that the two mechanisms can make differential contributions to preserved cognition.

SignificanceThe theoretical constructs of brain maintenance (BM) and cognitive reserve (CR) are postulated to account for individual differences in age-related cognitive decline. To further understand BM and CR mechanisms, this study used a lifespan sample to examine 5-year changes in four cognitive abilities that comprehensively capture cognitive aging. Education has been the most used life exposure when studying CR, but recent studies suggest that education does not moderate age-related changes in brain and cognition in healthy aging so IQ was also considered. The results demonstrated that BM and CR can both exert unique influences on the same cognitive ability and that the two mechanisms differentially moderate change in the four reference abilities.


title: Differential effects of brain maintenance and cognitive reserve on age-related cognitive decline


title: Does pre-notification increase questionnaire response rates: a nested randomised control trial.

abstract:
BackgroundStudy results can be badly affected by non-response. One way to potentially reduce non-response is by sending potential study participants advance communication. During the update of a systematic review examining the effect of pre-notification on response rates, a number of study authors needed to be contacted for further information.

ObjectivesTo conduct an RCT to investigate the effect of pre-notification, nested within the request for further information for a systematic review.

MethodsStudy authors included in the systematic review, whose studies were at unclear risk of bias, and who were contactable, were randomly sent or not set a pre-notification email prior to being sent the request for further information email.

ResultsAt the end of follow up, 14/33 (42.4%) authors in the pre-notification condition had returned responses to the questionnaire, and 18/42 (42.9%). There was not evidence of a difference between these groups.

ConclusionsThis studys results do not support the hypothesis that pre-notification does increase response from participants.


title: Follow-up study in the ski-resort Ischgl: Antibody and T cell responses to SARS-CoV-2 persisted for up to 8 months after infection and transmission of virus was low even during the second infection wave in Austria

abstract:
BackgroundIn early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a cross-sectional study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April. To answer the question of how long immunity persists and what effect this high-level immunity had on virus transmission, we performed a follow-up study in early November, 2020.

MethodsOf the 1259 adults that participated in the baseline study, 801 could be included in the follow-up. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 infections in Ischgl was compared to the incidence in similar municipalities in Tyrol throughout 2020.

FindingsFor the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9 - 54.9) to 45.4% (95% CI 42.0 - 49.0). Median antibody concentrations dropped considerably but antibody avidity increased. T cell responses were analysed in 93 cases, including all 4 formerly seropositive cases that had lost antibodies in all assays, three of which still had detectable T cell memory. In addition, the incidence in the second COVID-19 wave that hit Austria in November 2020, was significantly lower in Ischgl than in comparable municipalities in Tyrol or the rest of Austria.

InterpretationThis study has important implications as it shows that although antibodies to SARS-CoV-2 declined, T and B cell memory can be detected for up to 8 months. Complemented by infection prevention measures a level of around 40-45% immunity in Ischgl significantly reduced local virus transmission during the second wave in Austria in November 2020.

FundingFunding was provided by the government of Tyrol and the FWF Austrian Science Fund.


title: Long-term air pollution and other risk factors associated with COVID-19 at the census-tract-level in Colorado

abstract: An effective response to the COVID-19 pandemic requires identification of the factors that affect the severity and mortality of the disease. Previous nationwide studies have reported links between long-term PM2.5 concentrations and COVID-19 infection and mortality rates. In order to translate these results to the state level, we use Bayesian hierarchical models to explore potential links between long-term PM2.5 concentrations and census tract-level rates of COVID-19 outcomes (infections, hospitalizations, and deaths) in Colorado. We explicitly consider how the uncertainty in PM2.5 estimates affect our results by comparing four different PM2.5 surfaces from academic and governmental organizations. After controlling for 20 census tract level covariates including race/ethnicity, socioeconomic status, social distancing, age demographics, comorbidity rates, meteorology, and testing rate, we find that our results depend heavily on the choice of PM2.5 surface. Using PM2.5 estimates from the United States EPA, we find that a 1 {micro}g/m3 increase in long term PM2.5 is associated with a statistically significant 25% increase in the relative risk of hospitalizations and a 35% increase in mortality. Results for all other surfaces and outcomes were not statistically significant. At the same time, we find a clear association between communities of color and COVID-19 outcomes at the Colorado census-tract level that is minimally affected by the choice of PM2.5 surface. A per-interquartile range (IQR) increase in the percent of non-African American people of color was associated with a 31%, 44%, and 59% increase in the relative risk of infection, hospitalization, and mortality respectively, while a per-IQR increase in the proportion of non-Hispanic African Americans was associated with a 4% and 7% increase in the relative risk of infections and hospitalizations. These results have strong implications for the implementation of an equitable public health response during the crisis and suggest targeted areas for additional air monitoring in Colorado.


title: Clinical profile and factors associated with COVID-19 in Cameroon: a prospective cohort study

abstract:
ObjectivesThis study explores the clinical profiles and factors associated with COVID-19 in Cameroon.

Research design and methodsIn this prospective cohort study, we followed patients admitted for suspicion of COVID-19 at Djoungolo Hospital between 01st April and 31st July 2020. Patients were categorised by age groups and disease severity: mild (symptomatic without clinical signs of pneumonia pneumonia), moderate (with clinical signs of pneumonia without respiratory distress) and severe cases (clinical signs of pneumonia and respiratory distress not requiring invasive ventilation). Demographic information and clinical features were summarised. Multivariable analysis was performed to predict risk.

ResultsA total of 323 patients were admitted during the study period; 262 were confirmed cases of COVID-19 by Polymerase Chain Reaction (PCR). Among the confirmed cases, the male group aged 40 to 49 years (13.9%) was predominant. Disease severity ranged from mild (77%; N=204) to moderate (15%; N=40) to severe (7%; N=18); the case fatality rate was 1% (N=4). Dysgusia (46%; N=111) and hyposmia/anosmia (39%; N=89) were common features of COVID-19. Nearly one-third of patients had comorbidities (29%; N=53), of which hypertension was the most common (20%; N=48). Participation in a mass gathering (OR=5.47; P=0.03) was a risk factor for COVID-19. Age groups 60 to 69 (OR=7.41; P=0.0001), 50 to 59 (OR=4.09; P=0.03), 40 to 49 (OR=4.54; P=0.01), male gender (OR=2.53; P=0.04), diabetes (OR= 4.05; P= 0.01), HIV infection (OR=5.57; P=0.03), lung disease (OR= 6.29; P=0.01), dyspnoea (OR=3.70; P=0.008) and fatigue (OR=3.35; P=0.02) significantly predicted COVID-19 severity.

ConclusionUnlike many high-income settings, most COVID-19 cases in this study were benign with low fatality. Such findings may guide public health decision-making.


title: Cohort profile: 10K - a large-scale prospective longitudinal study in Israel

abstract: The 10K is a large-scale prospective longitudinal cohort and biobank that was established in Israel. The primary aims of the study include development of prediction models for disease onset and progression and identification of novel molecular markers with a diagnostic, prognostic and therapeutic value. The recruitment was initiated in 2018 and is expected to complete in 2021. Between 28/01/2019 and 13/12/2020, 4,629 from the expected 10,000 participants were recruited (46%). Follow-up visits are scheduled every year for a total of 25 years. The cohort includes individuals between the age of 40 and 70 years old. Predefined medical conditions were determined as exclusions. Information collected at baseline includes medical history, lifestyle and nutritional habits, vital signs, anthropometrics, blood tests results, Electrocardiography (ECG), Ankle-brachial pressure index (ABI), liver US and Dual-energy X-ray absorptiometry (DXA) tests. Molecular profiling includes transcriptome, proteome, gut and oral microbiome, metabolome and immune system profiling. Continuous measurements include glucose levels using a continuous glucose monitoring (CGM) device for 2 weeks and sleep monitoring by a home sleep apnea test (HSAT) device for 3 nights. Blood and stool samples are collected and stored at -80 {degrees}C in a storage facility for future research. Linkage is being established with national disease registries.


title: Occupational exposures and mitigation strategies among homeless shelter workers at risk of COVID-19

abstract:
ObjectiveTo describe the work environment and COVID-19 mitigation measures for homeless shelter workers and assess occupational risk factors for COVID-19 infection

MethodsBetween June 9-August 10, 2020, we conducted a self-administered survey among homeless shelter workers in Washington, Massachusetts, Utah, Maryland, and Georgia. We calculated frequencies for work environment, personal protective equipment use, and SARS-CoV-2 testing history. We used generalized linear models to produce unadjusted prevalence ratios (PR) to assess risk factors for SARS-CoV-2 infection.

ResultsOf the 106 respondents, 43.4% reported frequent close contact with clients; 75% were worried about work-related SARS-CoV-2 infections; 15% reported testing positive. Close contact with clients was associated with testing positive for SARS-CoV-2 (PR 3.97, 95%CI 1.06, 14.93).

ConclusionsHomeless shelter workers may be at higher risk of being infected with SARS-CoV-2 during the course of their work. Protecting these critical essential workers by implementing mitigation measures and prioritizing for COVID-19 vaccination, is imperative during the pandemic.

category: public and global health


title: Controlling the first wave of the COVID-19 pandemic in Malawi: results from a panel study

abstract: Many African countries have experienced a first wave of the COVID-19 pandemic between June and August of 2020. According to case counts reported daily by epidemiological surveillance systems, infection rates remained low in most countries. This defied early models of the potential impact of COVID-19 on the continent, that projected large outbreaks and massive strain on health systems. Theories proposed to explain the apparently limited spread of the novel coronavirus in most African countries have emphasized 1) early actions by health authorities (e.g., border closures) and 2) biological or environmental determinants of the transmissibility of SARS-CoV-2 (e.g., warm weather, cross-immunity). In this paper, we explored additional factors that might contribute to the low recorded burden of COVID-19 in Malawi, a low-income country in Southeastern Africa. To do so, we used 4 rounds of panel data collected among a sample of adults during the first 6 months of the pandemic in the country. Our analyses of survey data on SARS-CoV-2 testing and COVID-related symptoms indicate that the size of the outbreak that occurred in June-August 2020 might be larger than recorded by surveillance systems that rely on RT-PCR testing. Our data also document the widespread adoption of physical distancing and mask use in response to the outbreak, whereas most measured patterns of social contacts remained stable during the course of the panel study. These findings will help better project, and respond to, future waves of the pandemic in Malawi and similar settings.


title: Health-related quality of life of adult COVID-19 patients following one-month illness experience since diagnosis: findings of a cross-sectional study in Bangladesh

abstract:
BackgroundThe pandemic coronavirus disease 2019 (COVID-19) stances an incredible impact on the quality of life of the patients. The disease not only denigrates the physical health of the patients but also affects their mental health. This cross-sectional study aimed to assess the health-related quality of life (HRQOL) of patients.

MethodsThe study was conducted at the National Institute of Preventive and Social Medicine (NIPSOM), Dhaka, Bangladesh during the period from June to November 2020. The study enrolled 1204 adult (>18 years) COVID-19 patients diagnosed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay and completed the one-month duration of illness. The patients were interviewed with the CDC HRQOL-14 questionnaire to assess their HRQOL. Data were collected by telephone-interview and reviewing medical records using a semi-structured questionnaire and checklist respectively. Informed consent was obtained from each patient before data collection.

ResultsThe majority of the COVID-19 patients were males (72.3%), urban residents (50.2%), and diverse service holders (49.6%). More than one-third (35.5%) of patients had comorbidity including hypertension (55.6%), diabetes mellitus (55.6%), ischaemic heart disease (16.4%), chronic lung (12.4%), kidney (2.8%), and liver (4.2%) diseases. The mean{+/-}SD duration of physical illness was 9.83({+/-}7.09) days, and it was 7.97({+/-}8.12) days for mental illness. During the one-month disease course, the general health condition was excellent/very good/good in 70.1% of the patients while it was fair/poor in 29.8% of the patients. Older age, sex, and marital status were significantly associated with at least one dimension of HRQOL. Patients having symptoms of COVID-19 and comorbidity had significantly poorer HRQOL.

ConclusionCOVID-19 pretenses a significant impact on the HRQOL of the patients including physical and mental illness during the clinical course. Our findings suggest more pragmatic preventive, promotive, and curative measures considering illness experiences of the COVID-19 patients to restore their quality of life.

HighlightsSince COVID-19 was identified first in china in 2019, it has been transmitted globally and caused a significant impact on human health. A few studies have been carried out on HRQOL of COVID-19 patients and struggled with an accurate estimation of the severity of their physical and mental illness. Most of the studies recognized the poor quality of life of COVID-19 patients after the one-month disease course. Our study provides new insights on the HRQOL of the COVID-19 patients using the CDC HRQOL-14 questionnaire. We measured the HRQOL following one-month illness experience of the patients using three modules: the healthy days core; the activity limitations; and the healthy days symptoms. The study adds information regarding general health conditions including both the physical and mental health of COVID-19 patients. The study also complements information regarding the activity limitations of the patients. The study findings could contribute to designing an efficient clinical algorithm to alleviate the illness sufferings of the COVID-19 patients using a more pragmatic approach. The study conserves decisive policy implications to concoct effective interventions for improving the HRQOL of COVID-19 patients in the country and elsewhere in other countries world-wide.


title: Rehabilitation clinicians' perspectives of reactive balance training.

abstract:
PurposeReactive balance training (RBT) aims to improve reactive balance control. However, because RBT involves clients losing balance, clinicians may view that it is unsafe or not feasible for some clients. We aimed to explore how clinicians are specifically implementing RBT to treat balance and mobility issues.

Materials and methodsPhysiotherapists and kinesiologists across Canada who reported that they include RBT in their practices were invited to complete telephone interviews about their experience with RBT. Interviews were transcribed verbatim, and analysed using a deductive thematic analysis.

ResultsTen participants completed telephone interviews, which lasted between 30-60 minutes. Participants were primarily working in a hospital setting (inpatient rehabilitation (n=3); outpatient rehabilitation (n=2), and were treating those with neurological disorders (n=5). Four main themes were identified: 1) there is variability in RBT approaches; 2) knowledge can be a barrier and facilitator to RBT; 3) reactive balance control is viewed as an advanced skill; and 4) RBT experience builds confidence.

ConclusionsOur findings suggest a need for resources to make clinical implementation of RBT more feasible.

category: rehabilitation medicine and physical therapy


title: Aetiologies of chronic cough diagnosed using a pathophysiologic diagnostic procedure and their treatment outcomes

abstract:
BackgroundWe previously elucidated the fundamental pathophysiological features of various aetiologies of chronic cough, such as cough variant asthma, atopic cough, and sinobronchial syndrome. We also established a pathophysiological diagnostic procedure for aetiology identification. In this study, we aimed to disclose the aetiologies of chronic cough using the pathophysiological diagnostic procedure and to determine the outcomes of treatment administered on the basis of aetiology.

Patients and MethodsWe retrospectively reviewed the medical records of patients with chronic cough who visited our cough specialty clinic from September 2013 to August 2018 and analyzed the pathophysiological diagnostic procedure-based aetiologies and corresponding treatments. The pathophysiological diagnostic procedure included the capsaicin cough test, methacholine cough test, bronchial reversibility test, bronchial responsiveness test, chest and sinus CT, and sputum examinations.

ResultsInitially, 303 patients were selected, and 300 patients underwent the diagnostic procedure. Aetiologies of chronic cough were diagnosed in 297 patients (99.0%). In the other three patients (1.0%), all results of the diagnostic procedure were within normal limits; their aetiologies were evaluated using the therapeutic diagnostic procedure. Tweleve patients discontinued follow-up before completing treatment. Of the 291 remaining patients, cough resolved completely in 283 patients. The median time required for the complete resolution of cough was 5.0 weeks (95% CI 4.3[~]5.7 weeks).

ConclusionsThe pathophysiological diagnostic procedure can lead to rapid and objective diagnosis of causes of chronic cough, which leads to superior treatment results compared to therapeutic diagnostic procedure.

Trial registration numberUMIN ID: UMIN000018679

Key MessagesOur pathophysiological diagnostic procedure can lead to rapid and objective diagnosis of the aetiology of chronic cough, leading to superior treatment results compared to those of therapeutic diagnostic procedures.

category: respiratory medicine


title: Tissue Stress from Laparoscopic Grasper Use and Bowel Injury in Humans: Establishing Intraoperative Force Boundaries

abstract:
BackgroundInappropriate force in laparoscopic surgery can lead to inadvertent tissue injury. It is currently unknown however at what magnitude of compressive stress trauma occurs in gastrointestinal tissues.

MethodsThis study included 10 small bowel and 10 colon samples. Each was compressed with pressures ranging from 100 kPa to 600 kPa by a novel device to induce compressive "grasps" to simulate those of a laparoscopic grasper. Experimentation was performed ex-vivo, in-vitro. Grasp conditions of 0 to 600 kPa for a duration of 10 seconds were utilized. Two pathologists who were blinded to all study conditions, performed a histological analysis of the tissues. Patients were eligible if their surgery procured healthy tissue margins for experimentation (a convenience sample). 26 patient samples were procured; six samples were unusable. 10 colon and 10 small bowel samples were tested for a total of 120 experimental cases. No patients withdrew their consent. Two metrics of damage were quantified: an intestinal layer thickness calculation where the serosa layer was measured in the area of compression and compared to a local control and a histological scoring scale for tissue trauma.

ResultsSmall bowel (10), M:F was 7:3, average age was 54.3 years. Colon (10), M:F was 1:1, average age was 65.2 years. All 20 patients experienced a significant difference (p<0.05) in serosal thickness post-compression at both 500 and 600 kPa for both tissue types. A logistic regression analysis with a sensitivity of 100% and a specificity of 84.6% on a test set of data predicts a safety threshold of 329-330 kPa.

ConclusionA threshold was discovered that corresponded to both significant serosal thickness change and a positive histological trauma score rating. This "force limit" could be used in novel sensorized laparoscopic tools to avoid intraoperative tissue injury.

category: surgery


title: Transmission of SARS-CoV-2 Considering Shared Chairs in Outpatient Dialysis: A Real-World Case-Control Study

abstract:
BackgroundSARS-CoV-2 is primarily transmitted through aerosolized droplets; however, the virus can remain transiently viable on surfaces.

ObjectiveWe examined transmission within hemodialysis facilities, with a specific focus on the possibility of indirect patient-to-patient transmission through shared dialysis chairs.

DesignWe used real-world data from hemodialysis patients treated between February 1st and June 8th, 2020 to perform a case-control study matching each SARS-CoV-2 positive patient (case) to a non-SARS-CoV-2 patient (control) in the same dialysis shift and traced back 14 days to capture possible exposure from chairs sat in by SARS-CoV-2 patients. Cases and controls were matched on age, sex, race, facility, shift date, and treatment count.

Setting2,600 hemodialysis facilities in the United States.

PatientsAdult (age [≥]18 years) hemodialysis patients.

MeasurementsConditional logistic regression models tested whether chair exposure after a positive patient conferred a higher risk of SARS-CoV-2 infection to the immediate subsequent patient.

ResultsAmong 170,234 hemodialysis patients, 4,782 (2.8%) tested positive for SARS-CoV-2 (mean age 64 years, 44% female). Most facilities (68.5%) had 0 to 1 positive SARS-CoV-2 patient. We matched 2,379 SARS-CoV-2 positive cases to 2,379 non-SARS-CoV-2 controls; 1.30% (95%CI 0.90%, 1.87%) of cases and 1.39% (95%CI 0.97%, 1.97%) of controls were exposed to a chair previously sat in by a shedding SARS-CoV-2 patient. Transmission risk among cases was not significantly different from controls (OR=0.94; 95%CI 0.57 to 1.54; p=0.80). Results remained consistent in adjusted and sensitivity analyses.

LimitationAnalysis used real-world data that could contain errors and only considered vertical transmission associated with shared use of dialysis chairs by symptomatic patients.

ConclusionsThe risk of indirect patient-to-patient transmission of SARS-CoV-2 infection from dialysis chairs appears to be low.

Primary Funding SourceFresenius Medical Care North America; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK130067)

category: nephrology


title: Does Subthalamic Deep Brain Stimulation Impact Asymmetry and Dyscoordination of Gait in Parkinson's Disease?

abstract:
BackgroundSubthalamic deep brain stimulation is an effective treatment for selected Parkinsons disease patients. Axial deficits including postural stability and gait characteristics are often altered after surgery, but quantitative gait-related therapeutic effects are poorly described.

ObjectiveThe goal of this study was to systematically investigate modifications in asymmetry and dyscoordination of gait six-months post-operatively in patients with Parkinsons disease, and compare the outcomes with preoperative baseline and to asymptomatic controls.

MethodsThirty-two patients with Parkinsons disease (19 with postural instability and gait disorder type, 13 with tremor-dominant disease) and 51 asymptomatic controls participated. Parkinson patients were tested prior to the surgery in both OFF and ON medication states, and six months post-operatively in the ON stimulation condition. Clinical outcome parameters and medication were compared to preoperative conditions. Asymmetry ratios, phase coordination index, and walking speed were assessed.

ResultsPatients clinical outcomes as assessed by standard clinical parameters at six-months improved significantly, and levodopa-equivalent daily dosages were significantly decreased. STN-DBS increased step time asymmetry (hedges g effect sizes [confidence intervals] between pre- and post-surgery: 0.27 [-0.13,0.73]) and phase coordination index (0.29 [-0.08,0.67]). These effects were higher in the Postural Instability and Gait Disorder subgroup than the Tremor Dominant (step time asymmetry: 0.38 [-0.06,0.90] vs. 0.09 [-0.83,1.0] and phase coordination index: 0.39 [-0.04,0.84] vs. 0.13 [-0.76,0.96]).

ConclusionThis study provides objective evidence of how subthalamic deep brain stimulation increases asymmetry and dyscoordination of gait in patients with Parkinsons disease, and suggests motor subtypes-associated differences in the treatment response.

category: neurology


title: Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy

abstract: Cognitive impairment is a common comorbidity of epilepsy, and adversely impacts people with both frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). While the underlying neural substrates in TLE have been extensively investigated, functional imaging studies in FLE are scarce. In this study, we profiled cognitive dysfunction in FLE, and directly compared FLE and TLE patients to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE, and 52 controls), using neuropsychological tests and four functional MRI tasks probing the neural correlates of expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-epileptic drug load. We devised a multiscale approach to map the landscape of brain activation and deactivation during cognition, and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects (i) across intrinsic functional systems, and (ii) along the principal functional connectivity gradient, which encodes a continuous transition from lower-level sensory to higher-order transmodal brain areas. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, and reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. Functional abnormalities in FLE were modulated by disease load. Patterns of dysfunction in FLE were broadly similar to those in TLE, but some traits were syndrome-specific: altered default-mode deactivation was more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands was more marked in TLE. Our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies, and sheds light on system behavior that may be amenable to future remediation strategies.


title: Cytokine status of patients with atherosclerotic injury of carotid arteries

abstract:
The research was aimed at studying interleukin-6 (IL-6), interleukin-10 (IL-10) and C-reactive protein (CRP) levels in serum of 61 patients suffering from atherosclerotic injury of carotid arteries. The results received by the immunoferment method were compared with ultrasound features of atherosclerotic plaques and morphological peculiarities of their biopsies which were obtained during carotid endarterectomy.

An increased concentration of cytokines under analysis and CRP in serum of patients with atherosclerotic injury of carotid arteries was detected. It was found out that high levels of IL-6 and CRP are associated with progressing atherosclerosis of carotid arteries and its cerebral complications. The research revealed that detection of cytokines and CRP in serum can be used as an additional method to diagnose unstable character of atherosclerotic plaques.


title: Assessment of presentation patterns of repetitive behaviors in Autism: a cross-sectional video-recording study. Preliminary report.

abstract: Twenty expert caregivers wearing a body cam recorded 1868 videoclips in 67 autistic subjects along a 3 months close follow-up. A team consisting of a senior child neuro-psychiatrist and a senior psychologist selected 780 of them as expressing repetitive behaviors (RB) and made an empirical classification according to components, complexity, body parts and sensory channels involved, with the aim to understand better the pattern complexity and correlate with autism severity. The RB spectrum for each subject ranged from 1 to 33 different patterns (average= 11.6; S.D.= 6.82). Forty subjects expressed prevalent simple pattern and 27 prevalent complex patterns. No significant differences are found between the two groups according to ADOS score severity. This study represents a first attempt to systematically document expression patterns of RB with a data driven approach. This may provide a better understanding of the pathophysiology, diagnosis, and treatment of RB.


title: Subtle oromotor signs in early Parkinsons disease before clinical manifestations of dysphagia

abstract:
BackgroundSwallowing is complex phenomena comprising oral (preparatory and pre-swallow positioning), oropharyngeal, pharyngeal and esophageal phases. The timing of these phases is controlled by brain stem pattern generators including reflex for oropharyngeal propulsion and transit. Dysphagia in Parkinsons disease (PD) commonly observed at late stages with aspiration, pneumonia and hospitalization.

ObjectiveCan subtle oromotor signs (if any) be observed for planning early interventions in PD

MethodsThe present study investigated oromotor function in fourteen early PD (onset [≤]2years; H&Y score [≤]2.5) with dynamic MRI using saline (water) bolus and compared with seven age-matched healthy controls.

ResultsAll the patients with PD were non-symptomatic for dysphagia by self-reporting, and on clinical assessment (Part-II MDS-UPDRS, Swallowing disturbance questionnaire, SDQ and Clinical assessment of dysphagia in neurodegeneration, CADN). Qualitatively MR images visualized, differences in PD compared to healthy controls for tongue-wave, velar-closure or release, bolus placement, oropharyngeal reflex-initiation, transit-time, epiglottic-closure-coordination and post-swallow oral or pharyngeal residue. Descriptive analysis showed higher variability of velar-closure, oropharyngeal- and pharygoesophageal-transit time in patient with PD. Group analysis (two-sample) show significant difference for velar-closure.

ConclusionMultiple lingual-waves, reverse-tongue thrust, with delayed velar control attributed to incoordinated muscular rhythm. Variable oropharyngeal transit time (0.64 to 2.25 msec) in PD ascribed to brainstem degenerative changes. Findings imply that subtle observable early oromotor signs as pre-clinical manifestation when evaluated with non-invasive, non-contrast dynamic MRI support early intervention, to prevent late-stage aspiration episodes and consequent hospitalizations.


title: Impact of early life nutrition on gut health in children: A prospective clinical study

abstract:
IntroductionThe first 1000 days of life could contribute to individual susceptibility to the later development of chronic non-communicable diseases. Nutrition in early life appears to be an important determinant factor for a sustainable childs health. In this study, we propose to investigate the impact of exclusive breastfeeding on gut health in children.

Methods and analysisA prospective cohort of newborns (n=350) will be recruited at birth and followed up to 4 years of age. The main objective is to evaluate the link between exclusive breastfeeding for at least 3 months and the gut health of the child at 4 years. The primary endpoint of assessment of gut health will be based on the non-invasive measurement of fecal secretory immunoglobulin A (sIgA) as a sensitive biomarker of the intestinal ecosystem. The presence of gastrointestinal disorders will be defined according to the clinical criteria of ROME IV. Information on parents nutritional habits and life style, breastfeeding duration and childs complementary feeding will be collected along the follow-up. Cord blood cells and plasma at birth will be purified for further analysis. The meconium and stools collected at birth, 6 months, 2 years and 4 years of age will allow sIgA analysis.

Ethics and disseminationThis clinical study has obtained the approval from the national ethical committee. We plan to publish the results of the study in peer-review journals and by means of national and international conference.

Trial registration numberNCT04195425

Strengths and limitations of the study- This is a prospective and longitudinal mother/child cohort with minimal constraints (3 visits over 4 years) and minimal risk (no intervention and minimally invasive procedures).
- The study will collect a great deal of longitudinal information on children during the first years of life, their parents and their environment via questionnaires and biological samples (cord blood, meconium, stools).
- This study will obtain precise data on breastfeeding practices and their short- and medium-term effects on the health of the child, in particular and in an innovative way on gut health through stool samples for immunological analysis, and by using the ROME IV paediatric questionnaire.
- Weaknesses could be relied to confounding factors at the selection process and during the follow-up.
- Due to the non-interventional study design we will be able to study association but no causal relationship.
- The nutritional survey during the study is primarily based on reports from parents and is retrospective which could contribute to inaccuracies due to long delay between each visit.

category: nutrition


title: Association between Intimate Partner Violence and Nutritional Status of Children: A Systematic Review and Mata-Analysis

abstract:
IntroductionIntimate Partner Violence (IPV) against women is a universal problem and an important social determinant of health. Studies indicate a relationship between maternal exposure to IPV and negative pregnancy and child health outcomes. The present review is aimed at doing a comprehensive review to assess the evidence for the association of IPV with the nutritional status of children.

MethodologyData on the association between IPV and nutritional outcomes were extracted from 24 studies. Separate sub-group analyses were conducted for studies measuring IPV and different nutritional measures (Stunting, Underweight, and Wasting). A random-effect model was used for analysing the effect-size and the pooled effect for each subgroup.

FindingsThe pooled estimates of  any violence [OR=1.16 (1.08-1.25)],  physical violence [OR=1.12 (1.07-1.18)] and  sexual violence [OR=1.21 (1.03-1.43)] indicated significant relationship with nutritional status of children. The relationship was found significant for stunting and underweight, but not for wasting. Values of I2 indicated a high level of heterogeneity across the studies on stunting and underweight.

ConclusionThe present review contributes to a better understanding of the nutritional outcomes for children exposed to maternal IPV. It emphasises the need to intervene for improving the well-being of these individuals as children and, subsequently, as adults.


title: SARS-CoV-2 disinfection in aqueous solution by UV222 from a krypton chlorine excilamp

abstract:
There is an urgent need for evidence-based development and implementation of engineering controls to reduce transmission of SARS-CoV-2, the etiological agent of COVID-19. Ultraviolet (UV) light can inactivate coronaviruses, but the practicality of UV light as an engineering control in public spaces is limited by the hazardous nature of conventional UV lamps, which are Mercury (Hg)-based and emit a peak wavelength (254 nm) that penetrates human skin and is carcinogenic. Recent advances in the development and production of Krypton Chlorine (KrCl) excimer lamps hold promise in this regard, as these emit a shorter peak wavelength (222 nm) and are recently being produced to filter out emission above 240 nm. However, the disinfection kinetics of KrCl UV excimer lamps against SARS-CoV-2 are unknown. Here we provide the first dose response report for SARS-CoV-2 exposed to a commercial filtered KrCl excimer light source emitting primarily 222 nm UV light (UV222), using multiple assays of SARS-CoV-2 viability. Plaque infectivity assays demonstrate the pseudo-first order rate constant of SARS-CoV-2 reduction of infectivity to host cells to be 0.64 cm2/mJ (R2 = 0.95), which equates to a D90 (dose for 1 log10 or 90% inactivation) of 1.6 mJ/cm2. Through RT-qPCR assays targeting the nucleocapsid (N) gene with a short (<100 bp) and long ([~]1000 bp) amplicon in samples immediately after UV222 exposure, the reduction of ability to amplify indicated an approximately 10% contribution of N gene damage to disinfection kinetics. Through ELISA assay targeting the N protein in samples immediately after UV222 exposure, we found no dose response of the ability to damage the N protein. In both qPCR assays and the ELISA assay of viral outgrowth supernatants collected 3 days after incubation of untreated and UV222 treated SARS-CoV-2, molecular damage rate constants were similar, but lower than disinfection rate constants. These data provide quantitative evidence for UV222 doses required to disinfect SARS-CoV-2 in aqueous solution that can be used to develop further understanding of disinfection in air, and to inform decisions about implementing UV222 for preventing transmission of COVID19.

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category: occupational and environmental health


title: Microbiota long-term dynamics and prediction of acute graft-versus-host-disease in pediatric allogeneic stem cell transplantation

abstract:
BackgroundPatients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we performed integrated host-microbiota analyses of the gut, oral, and nasal microbiotas in 29 children undergoing allo-HSCT.

ResultsThe bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1-3 months after allo-HSCT. The microbial community composition traversed three phases over one year. Distinct taxa discriminated the microbiota temporally at all three body sides, including Enterococcus spp., Lactobacillus spp., and Blautia spp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared to healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT, in particular from Parabacteroides distasonis, Lachnospiraceae NK4A136 sp. and Lactobacillus sp. abundances in the gut. The reconstitution of CD4+ T cells, TH17 and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota.

ConclusionsThis study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Surveillance of the microbiota at different body sites in HSCT may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that both, host factors and the microbiota, could provide actionable information to guiding precision medicine.

category: oncology


title: Prevalence of cancer susceptibility variants in patients with multiple Lynch syndrome related cancers

abstract:
BackgroundAlong with early onset cancers, multiple primary cancers (MPCs) are likely resulting from increased genetic susceptibility; however, the associated predisposition genes or prevalence of the pathogenic variants genes in MPC patients are often unknown.

MethodsWe screened 71 patients with MPC of the stomach, colorectal, and endometrium, sequencing 65 cancer predisposition genes. A subset of 19 patients with early onset MPC of stomach and colorectum were further evaluated for at DNA repair and cancer related genes using both normal (germline) and tumor (somatic) whole exome sequencing.

ResultsAmong 71 patients with MPCs, variants predicted to be pathogenic were observed in 15 (21.1%) patients and affected Lynch Syndrome (LS) genes: MLH1 (n=10), MSH6 (n=2), PMS2 (n=2), and MSH2 (n=1). All carriers had tumors with high microsatellite instability and 13 of them (86.7%) were early-onset, consistent with LS. In 19 patients with early-onset MPCs, loss of function (LoF) variants in RECQL5, including a rare East-Asian specific variant, were more prevalent in non-LS MPC than in matched sporadic cancer patients (OR=31.6, p=0.001). Additional evaluation of bi-allelic alterations in the tumor correctly identified LS genes in LS patients and candidates genes in non-LS patients including high-confidence LoF variants in 2 patients, FANCG (c.307+1G>C) and CASP8 (p.R221Sfs*17) both accompanied by somatic loss of heterozygosity in a gastric and a colorectal tumor, respectively.

ConclusionsThe results suggest that genetic screening should be considered for synchronous cancers and metachronous MPCs of the LS tumor spectrum, particularly in early-onset patients. Susceptibility variants in non-LS genes for MPC patients may exist, but evidence for their role is more elusive than for LS patients.


title: Impact of exposures to persistent endocrine disrupting compounds on the sperm methylome in regions associated with neurodevelopmental disorders

abstract:
BackgroundAlthough autism spectrum disorder (ASD) is among the most heritable of neurodevelopmental disorders, the rapidly rising prevalence of ASD suggests that environmental factors may interact with genetic risk for ASD. Environmental factors may impact both gene expression and phenotypes in ASD through epigenetic modifications that, in turn, could lead to intergenerational effects influencing risk for ASDs. Endocrine disrupting compounds (EDCs), such as the long-lived organochlorines, are of particular interest with respect to risk for autism because of their ability to interfere with sex hormones that have been implicated in the regulation of RORA, a dysregulated gene in ASD that is a master regulator of many other ASD risk genes.

ObjectivesThe specific aims of this study are to: 1) investigate whether high versus low exposures to the persistent organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) are associated with differentially methylated regions (DMRs) in sperm from a Faroese cohort whose natural diet of pilot whale meat and blubber exposes them to higher than average levels of organic pollutants; 2) determine if genes associated with DDE DMRs are enriched for ASD risk genes; 3) identify pathways and functions over-represented among genes associated with DMRs.

MethodsWhole genome bisulfite sequencing (WGBS) was used to identify genome-wide DMRs in sperm from individuals divided by high and low exposure levels. Gene ontology and pathway analyses were used to determine enrichment in functional relationships to ASD.

ResultsGenes in DMRs not only could discriminate between high and low exposures to DDE, but also were enriched in autism risk genes. Gene ontology and pathway analyses of these genes show significant enrichment for neurodevelopmental processes frequently impacted by ASD.

ConclusionResults of this study show that elevated exposure to certain organochlorines is associated with genome-wide DNA methylation patterns in sperm affecting genes involved in neurological functions and developmental disorders, including ASD.


title: Optical genome mapping as a next-generation cytogenomic tool for detection of structural and copy number variations for prenatal genomic analyses

abstract: Global medical associations (ACOG, ISUOG, ACMG) recommend diagnostic prenatal testing for the detection and prevention of genetic disorders. Historically, cytogenetic methods such as karyotype analysis, fluorescent in situ hybridization (FISH), and chromosomal microarray (CMA) are utilized worldwide to diagnose common syndromes. However, the limitations of each of these methods, either performed in tandem or simultaneously, demonstrates the need of a revolutionary technology that can alleviate the need of multiple technologies. Optical genome mapping (OGM) is a novel technology that fills this void by being able to detect all classes of structural variations (SVs), including copy number variations (CNVs). OGM is being adopted by laboratories as a next-generation cytogenomic tool for both postnatal constitutional genetic disorders and hematological malignancies. This commentary highlights the potential of OGM to become a standard of care in prenatal genetic testing by its ability to identify large balanced and unbalanced SVs (currently the strength of karyotyping and metaphase FISH), CNVs (by CMA), repeat contraction disorders (by Southern blotting) and multiple repeat expansion disorders (by PCR based methods or Southern blotting). Also, next-generation sequencing (NGS) methods are excellent at detecting sequence variants but are unable to accurately detect the repeat regions of the genome which limits the ability to detect all classes of SVs. Notably, multiple molecular methods are used to identify repeat expansion and contraction disorders in routine clinical laboratories around the world. With non-invasive prenatal screening test (NIPT) as the standard of care screening assay for all global pregnancies, we anticipate OGM as a high-resolution cytogenomic diagnostic tool employed following a positive NIPT screen or for high-risk pregnancies with an abnormal ultrasound. Accurate detection of all types of genetic disorders by OGM, such as liveborn aneuploidies, sex chromosome anomalies, microdeletion/microduplication syndromes, repeat expansion/contraction disorders is key to reducing the global burden of genetic disorders.


title: The Association of Opening K-12 Schools and Colleges with the Spread of COVID-19 in the United States: County-Level Panel Data Analysis

abstract: AO_SCPLOWBSTRACTC_SCPLOWThis paper empirically examines how the opening of K-12 schools and colleges is associated with the spread of COVID-19 using county-level panel data in the United States. Using data on foot traffic and K-12 school opening plans, we analyze how an increase in visits to schools and opening schools with different teaching methods (in-person, hybrid, and remote) is related to the 2-weeks forward growth rate of confirmed COVID-19 cases. Our debiased panel data regression analysis with a set of county dummies, interactions of state and week dummies, and other controls shows that an increase in visits to both K-12 schools and colleges is associated with a subsequent increase in case growth rates. The estimates indicate that fully opening K-12 schools with in-person learning is associated with a 5 (SE = 2) percentage points increase in the growth rate of cases. We also find that the positive association of K-12 school visits or in-person school openings with case growth is stronger for counties that do not require staff to wear masks at schools. These results have a causal interpretation in a structural model with unobserved county and time confounders. Sensitivity analysis shows that the baseline results are robust to timing assumptions and alternative specifications.

category: health economics


title: The Association of Opening K-12 Schools with the Spread of COVID-19 in the United States: County-Level Panel Data Analysis


title: Regulatory-approved deep learning/machine learning-based medical devices in Japan as of 2020: A systematic review

abstract: Machine learning (ML) and deep learning (DL) are changing the world and reshaping the medical field. Thus, we conducted a systematic review to determine the status of regulatory-approved ML/DL-based medical devices in Japan, a leading stakeholder in international regulatory harmonization. Information about the medical devices were obtained from the Japan Association for the Advancement of Medical Equipment search service. The usage of ML/DL methodology in the medical devices was confirmed using public announcements or by contacting the marketing authorization holders via e-mail when the public announcements were insufficient for confirmation. Among the 114,150 medical devices found, 11 were regulatory-approved ML/DL-based Software as a Medical Device (SaMD), with 6 products (54.5%) related to radiology and 5 products (45.5%) related to gastroenterology. The domestic ML/DL-based SaMD were mostly related to health check-ups, which are common in Japan. Our review provides a global overview that can foster international competitiveness and further tailored advancements.

category: health informatics


title: Phased implementation of COVID-19 vaccination: rapid assessment of policy adoption, reach and effectiveness to protect the most vulnerable in the US

abstract:
ObjectivesThe US and rest of the world have suffered from the COVID-19 pandemic for over a year. The high transmissibility and severity of this virus have provoked governments to adopt a variety of mitigation strategies. Some of these previous measures, such as social distancing and mask mandates, were effective in reducing the case growth rate yet became economically and administratively difficult to enforce as the pandemic continued. In late December 2020, COVID-19 vaccines were first approved in the US and states began a phased implementation of COVID-19 vaccination. However, there is limited quantitative evidence regarding the effectiveness of the phased COVID-19 vaccination. This study aims to provide a rapid assessment of the adoption, reach, and effectiveness of the phased implementation of COVID-19 vaccination.

MethodsWe utilize an event-study analysis to evaluate the effect of vaccination on the state-level, daily COVID-19 case growth rate.

ResultsThrough this analysis, we assert that vaccination is effective in reducing the spread of COVID-19 shortly after the first shots were given. Specifically, the case growth rate declined by 0.124, 0.347, 0.345, 0.464, 0.490, and 0.756 percentage points corresponding to the 1-5, 6-10, 11-15, 16-20, 21-25, and 26 or more day periods after the initial shots.

ConclusionsThe findings could be insightful for policymakers as they work to optimize vaccine distribution in later phases, and also for the public as the COVID-19 related health risk is a contentious issue.

category: health policy


title: Analysis of key factors of a SARS-CoV-2 vaccination program: A mathematical modeling approach

abstract: The administration of vaccines against the coronavirus disease 2019 (COVID-19) just started in early December of 2020. Currently, there are only a few approved vaccines, each with different efficacies and mechanisms of action. Moreover, vaccination programs in different regions may vary due to differences in implementation, for instance, simply the availability of the vaccine. In this article, we study the impact of the pace of vaccination and the intrinsic efficacy of the vaccine on prevalence, hospitalizations, and deaths related to the SARS-CoV-2 virus. Then we study different potential future scenarios regarding the burden of the COVID-19 pandemic in the near future. We construct a compartmental mathematical model and use computational methodologies to study these different scenarios. Thus, we are able identify some key factors to reach the aims of the vaccination programs. We use some metrics related to the outcomes of the COVID-19 pandemic in order to assess the impact of the efficacy of the vaccine and the pace of the vaccine inoculation. We found that both factors have a high impact on the outcomes. However, the rate of vaccine administration has a higher impact in reducing the burden of the COVID-19 pandemic. This result shows that health institutions need to focus in increasing the vaccine inoculation pace and create awareness in the population about the importance of COVID-19 vaccines.


title: Analyzing Socioeconomic Factors and Health Disparity of COVID-19 Spatiotemporal Spread Patterns at Neighborhood Levels in San Diego County

abstract: This study analyzed spatiotemporal spread patterns of COVID-19 confirmed cases at the zip code level in the County of San Diego and compared them to neighborhood social and economic factors. We used correlation analysis, regression models, and geographic weighted regression to identify important factors and spatial patterns. We broke down the temporal confirmed case patterns into four stages from 1 April 2020 to 31 December 2020. The COVID-19 outbreak hotspots in San Diego County are South Bay, El Cajon, Escondido, and rural areas. The spatial patterns among different stages may represent fundamental health disparity issues in neighborhoods. We also identified important variables with strong positive or negative correlations in these categories: ethnic groups, languages, economics, and education. The highest association variables were Pop5andOlderSpanish (Spanish-speaking) in Stage 4 (0.79) and Pop25OlderLess9grade (Less than 9th grade education) in Stage 4 (0.79). We also observed a clear pattern that regions with more well-educated people have negative associations with COVID-19. Additionally, our OLS regression models suggested that more affluent populations have a negative relationship with COVID-19 cases. Therefore, the COVID-19 outbreak is not only a medical disease but a social inequality and health disparity problem.

category: health systems and quality improvement


title: Synthesizing evidence regarding community-based volunteer facilitated programs supporting integrated care transitions from hospital to home: A scoping review protocol

abstract:
BackgroundGiven the risks inherent in care transitions, it is imperative that patients discharged from hospital to home receive the integrated care services necessary to ensure that the transition is successful. Despite efforts by the health care sector to develop health system solutions to improve transitions, problems persist. Research on transitional support has predominantly focused on services delivered by health care professionals; the evidence for services provided by lay navigators or volunteers in supporting people transitioning from hospital to home has not been synthesized to guide practice, policy or future research.

AimThis is a protocol for a scoping review that will examine the role and contributions of voluntary sector personnel and services to support transitions from hospital to home.

MethodsUsing the well-established scoping review methodology outlined by Arksey and OMalley, a six-stage study is outlined (1) identifying the research question, (2) identifying relevant studies, (3) selecting studies, (4) charting the data, (5) collating, summarizing and reporting the results, and (6) providing consultation. The search strategy, designed by an information scientist, is applied to ten databases reflecting empirical and grey literature sources. A two-stage screening process will be used to determine eligibility of articles. To be included in the review, articles must report on a community-based program that engages volunteers in the provisions of services that support adults transitioning from hospital to home. All articles will be independently assessed for eligibility, and data from eligible articles will be abstracted and charted using a standardized form. Extracted data will be analyzed using narrative and descriptive analyses. Research ethics approval is not required for this scoping review.

DiscussionThis scoping review will map the available literature focused on the contributions of voluntary sector personnel and services to support transitions from hospital to home.