title: Rates of serious clinical outcomes in survivors of hospitalisation with COVID-19: a descriptive cohort study within the OpenSAFELY platform

abstract:
BackgroundPatients with COVID-19 are thought to be at higher risk of cardiometabolic and pulmonary complications, but quantification of that risk is limited. We aimed to describe the overall burden of these complications in survivors of severe COVID-19.

MethodsWorking on behalf of NHS England, we used linked primary care records, death certificate and hospital data from the OpenSAFELY platform. We constructed three cohorts: patients discharged following hospitalisation with COVID-19, patients discharged following hospitalisation with pneumonia in 2019, and a frequency-matched cohort from the general population in 2019. We studied eight cardiometabolic and pulmonary outcomes. Absolute rates were measured in each cohort and Cox regression models were fitted to estimate age/sex adjusted hazard ratios comparing outcome rates between discharged COVID-19 patients and the two comparator cohorts.

ResultsAmongst the population of 31,716 patients discharged following hospitalisation with COVID-19, rates for majority of outcomes peaked in the first month post-discharge, then declined over the following four months. Patients in the COVID-19 population had markedly increased risk of all outcomes compared to matched controls from the 2019 general population, especially for pulmonary embolism (HR 12.86; 95% CI: 11.23 - 14.74). Outcome rates were more similar when comparing patients discharged with COVID-19 to those discharged with pneumonia in 2019, although COVID-19 patients had increased risk of type 2 diabetes (HR 1.23; 95% CI: 1.05 - 1.44).

InterpretationCardiometabolic and pulmonary adverse outcomes are markedly raised following hospitalisation for COVID-19 compared to the general population. However, the excess risks were more comparable to those seen following hospitalisation with pneumonia. Identifying patients at particularly high risk of outcomes would inform targeted preventive measures.

FundingWellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, UK Research and Innovation, Health and Safety Executive.


title: Using Non-Pharmaceutical Interventions and High Isolation of Asymptomatic Carriers to Contain the Spread of SARS-CoV-2 in Nursing Homes

abstract:
ObjectiveUsing a pandemic influenza model modified for COVID-19, this study investigated the degree of control over pre-symptomatic transmission that common non-pharmaceutical interventions (NPIs) would require to reduce the spread in long-term care facilities.

MethodsWe created a stochastic compartmental SEIR model with Poisson-distributed transition states that compared the effect of R0, common NPIs, and isolation rates of pre-symptomatic carriers primarily on attack rate, peak cases, and timing in a 200-resident nursing home. Model sensitivity was assessed with 1st order Sobol indices.

ResultsThe most rigorous NPIs decreased the peak number of infections by 4.3 and delayed the peak by 9.7 days in the absence of pre-symptomatic controls. Reductions in attack rate were not likely, even with rigorous application of all defined NPIs, unless pre-symptomatic carriers were identified and isolated at rates exceeding 76%. Attack rate was most sensitive to the pre-symptomatic isolation rate (Sobol index > 0.7) and secondarily to R0.

ConclusionsCommon NPIs delayed and reduced epidemic peaks. Reducing attack rates ultimately required efficient isolation of pre-symptomatic cases, including rapid antigen tests on a nearly daily basis. This must be accounted for in testing and contact tracing plans for group living settings.

category: epidemiology


title: Development of quantitative frailty and mortality prediction models on older patients as a palliative care needs assessment tool

abstract:
BackgroundPalliative care (PC) has demonstrated benefits for life-limiting illnesses. Cancer patients have mainly accessed these services, but there is growing consensus about the importance of promoting access for patients with non-malignant disease. Bad survival prognosis and patients frailty are usual dimensions to decide PC inclusion.

ObjectivesThe main aim of this work is to design and evaluate three quantitative models based on machine learning approaches to predict frailty and mortality on older patients in the context of supporting PC decision making: one-year mortality, survival regression and one-year frailty classification.

MethodsThe dataset used in this study is composed of 39,310 hospital admissions for 19,753 older patients (age >= 65) from January 1st, 2011 to December 30th, 2018. All prediction models were based on Gradient Boosting Machines. From the initial pool of variables at hospital admission, 20 were selected by a recursive feature elimination algorithm based on the random forests GINI importance criterion. Besides, we run an independent grid search to find the best hyperparameters in each model. The evaluation was performed by 10-fold cross-validation and area under the receiver operating characteristic curve and mean absolute error were reported. The Cox proportional-hazards model was used to compare our proposed approach with classical survival methods.

ResultsThe one-year mortality model achieved an AUC ROC of 0.87 {+/-} 0.01; the mortality regression model achieved an MAE of 329.97 {+/-} 5.24 days. The one-year frailty classification reported an AUC ROC of 0.9 {+/-} 0.01. The Spearmans correlation between the admission frailty index and the survival time was -0.1, while the point-biserial correlation between one-year frailty index and survival time was -0.16.

ConclusionsOne-year mortality model performance is at a state-of-the-art level. Frailty Index used in this study behaves coherently with other works in the literature. One-year frailty classifier demonstrated that frailty status within the year could be predicted accurately. To our knowledge, this is the first study predicting one-year frailty status based on a frailty index. We found mortality and frailty as two weakly correlated and complementary PC needs assessment criteria. Predictive models are available online at http://demoiapc.upv.es.

category: palliative medicine


title: Complementary frailty and mortality prediction models on older patients as a tool for assessing palliative care needs


title: Tracking the mental health of home-carers during the first COVID-19 national lockdown: evidence from a nationally representative UK survey

abstract:
BackgroundUnpaid carers who look after another member of their household (home-carers) have poorer mental health than the general population. The first COVID-19 national lockdown led to an increasing reliance on home-carers and we investigate the short and longer-term impact of lockdown on their mental health.

MethodsData from 9,737 adult participants (aged 16+) from the UK Household Longitudinal Study (Understanding Society) were used to explore changes in 12-item General Health Questionnaire (GHQ-12) score between (a) pre-pandemic (2019) and early lockdown (April 2020) and (b) early and later (July 2020) lockdown.

ResultsGHQ-12 scores among home-carers were higher pre-lockdown and increased more than for non-carers from 2019 to April 2020 with further increases for home-carers compared with non-carers between April and July. Compared with respondents caring for a spouse/partner, those caring for a child under 18 had a particularly marked increase in GHQ-12 score between 2019 and April, as did those caring for someone with learning difficulties. Home-carers of children under 18 improved from April to July while those caring for adult children saw a marked worsening of their mental health. Home-carers with greater care burden saw larger increases in GHQ-12 score from 2019 to April and from April to July, and increases through both periods were greater for home-carers who had formal help prior to lockdown but then lost it.

ConclusionsThe mental health of home-carers deteriorated more during lockdown than non-carers. Policies that reinstate support for them and their care-recipients will benefit the health of both vulnerable groups.

What is already known on this topicO_LICarers have poorer mental health than the general population.
C_LIO_LIAmong carers who live with the care recipient (home-carers), some subgroups have poorer mental health than others: female versus male; those who provide more hours of care and have been caring for longer; spousal carers compared with those caring for children (including adult), parents, or other relationships; those caring for individuals whose impairment results in behavioural disturbances, than those who care for individuals with physical or long-term health conditions.
C_LI

What this study addsO_LIIn a large representative UK survey, the decline in mental health during lockdown was greater among home-carers than for the general population, and stayed poorer through to July, even as the general populations mental health recovered slightly.
C_LIO_LICompared with respondents who were caring for a spouse/partner, those caring for a child under 18 had a particularly marked increase in GHQ-12 score between 2019 and April while those caring for an adult child experienced a substantial decline in their mental health between the beginning and end of the first lockdown (April to July).
C_LIO_LIThe increase in GHQ-12 in April from 2019 was highest among those caring for someone with a learning disability and lowest for those caring for someone with a problem related to old age.
C_LIO_LIHome-carers who had a greater care burden, in terms of hours of care provided, or lost formal support during lockdown, had poorer mental health.
C_LI

category: public and global health


title: An external validation of the QCovid risk prediction algorithm for risk of mortality from COVID-19 in adults: national validation cohort study in England

abstract:
BackgroundTo externally validate a risk prediction algorithm (QCovid) to estimate mortality outcomes from COVID-19 in adults in England.

MethodsPopulation-based cohort study using the ONS Public Health Linked Data Asset, a cohort based on the 2011 Census linked to Hospital Episode Statistics, the General Practice Extraction Service Data for pandemic planning and research, radiotherapy and systemic chemotherapy records. The primary outcome was time to COVID-19 death, defined as confirmed or suspected COVID-19 death as per death certification. Two time periods were used: (a) 24th January to 30th April 2020; and (b) 1st May to 28th July 2020. We evaluated the performance of the QCovid algorithms using measures of discrimination and calibration for each validation time period.

FindingsThe study comprises 34,897,648 adults aged 19-100 years resident in England. There were 26,985 COVID-19 deaths during the first time-period and 13,177 during the second. The algorithms had good calibration in the validation cohort in both time periods with close correspondence of observed and predicted risks. They explained 77.1% (95% CI: 76.9% to 77.4%) of the variation in time to death in men in the first time-period (R2); the D statistic was 3.76 (95% CI: 3.73 to 3.79); Harrells C was 0.935 (0.933 to 0.937). Similar results were obtained for women, and in the second time-period. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths in the first time period was 65.9% for men and 71.7% for women. People in the top 20% of predicted risks of death accounted for 90.8% of all COVID-19 deaths for men and 93.0% for women.

InterpretationThe QCovid population-based risk algorithm performed well, showing very high levels of discrimination for COVID-19 deaths in men and women for both time periods. It has the potential to be dynamically updated as the pandemic evolves and therefore, has potential use in guiding national policy.

FundingNational Institute of Health Research

RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSPublic policy measures and clinical risk assessment relevant to COVID-19 need to be aided by rigorously developed and validated risk prediction models. A recent living systematic review of published risk prediction models for COVID-19 found most models are subject to a high risk of bias with optimistic reported performance, raising concern that these models may be unreliable when applied in practice. A population-based risk prediction model, QCovid risk prediction algorithm, has recently been developed to identify adults at high risk of serious COVID-19 outcomes, which overcome many of the limitations of previous tools.

Added value of this studyCommissioned by the Chief Medical Officer for England, we validated the novel clinical risk prediction model (QCovid) to identify risks of short-term severe outcomes due to COVID-19. We used national linked datasets from general practice, death registry and hospital episode data for a population-representative sample of over 34 million adults. The risk models have excellent discrimination in men and women (Harrells C statistic>0.9) and are well calibrated. QCovid represents a new, evidence-based opportunity for population risk-stratification.

Implications of all the available evidenceQCovid has the potential to support public health policy, from enabling shared decision making between clinicians and patients in relation to health and work risks, to targeted recruitment for clinical trials, and prioritisation of vaccination, for example.


title: Using an Ecological and Biological Framing for an Anti-racist Covid-19 Approach

abstract: In the United States and the United Kingdom COVID-19 has disproportionately affected Black, Indigenous and People of Colour (BIPOC) and Black, Asian and Minority Ethnic (BAME) people respectively. Multiple studies identify environmental factors such as overcrowded housing and poor workplace conditions as contributing factors for the disproportionate COVID-19 rates amongst BAME and BIPOC communities. This paper will show that to fully understand the phenomenon, both an ecological and biological approach is needed. An ecological approach highlights how a persons habitat and the experiences within it mediate their susceptibility to disease. Moreover, to understand how this mediation works, this paper will use allostatic load as a biological pathway to link a person to their habitat and the poor health outcomes that contributed to COVID-19 susceptibility. In introducing this new approach, the paper will serve as an anti-racist framework for understanding how COVID-19 affected BAME and BIPOC communities. It is anti-racist by centring poor health outcomes on the habitats people are forced to live in due to structural racism rather than the physiology of a persons race or ethnicity. This is important in order to avoid similar crises in the future and to improve the health of marginalised communities.


title: Impact of gastric resection and enteric anastomotic configuration on delayed gastric emptying after pancreaticoduodenectomy: a network meta-analysis of randomized trials

abstract:
IntroductionDelayed gastric emptying (DGE) is frequent after pancreaticoduodenectomy (PD). Several randomised controlled trials (RCTs) have explored operative strategies to minimise DGE, however, the optimal combination of gastric resection approach, anastomotic route, and configuration, role of Braun enteroenterostomy remains unclear.

MethodsMEDLINE, Embase, and CENTRAL databases were systematically searched for RCTs comparing gastric resection (Classic Whipple, pylorus-resecting, and pylorus-preserving), anastomotic route (antecolic vs retrocolic) and configuration (Billroth II vs Roux-en-Y), and enteroenterostomy (Braun vs no Braun). A random-effects, Bayesian network meta-analysis with non-informative priors was conducted to determine the optimal combination of approaches to PD for minimising DGE.

ResultsTwenty-four RCTs, including 2526 patients and 14 approaches were included. There was some heterogeneity, although inconsistency was low. The overall incidence of DGE was 25.6% (n = 647). Pylorus-resecting, antecolic, Billroth II with Braun enteroenterostomy was associated with the lowest rates of DGE and ranked the best in 35% of comparisons. Classic Whipple, retrocolic, Billroth II with Braun ranked the worst for DGE in 32% of comparisons. Pairwise meta-analysis of retrocolic vs antecolic route of gastro-jejunostomy found increased risk of DGE with the retrocolic route (OR 2.1, 95% CrI; 0.92 - 4.7). Pairwise meta-analysis of Braun enteroenterostomy found a trend towards lower DGE rates with Braun compared to no Braun (OR 1.9, 95% CrI; 0.92 - 3.9). Having a Braun enteroenterostomy ranked the best in 96% of comparisons.

ConclusionBased on existing RCT evidence, a pylorus-resecting, antecolic, Billroth II with Braun enteroenterostomy may be associated with the lowest rates of DGE.

category: surgery


title: Protocol for a realist review of the influence of cultural factors on understanding the role of feedback in developing clinical competencies of health professional students in Asia.

abstract:
IntroductionClinical education has moved to a "competency-based" model with an emphasis on workplace-based learning and assessment which, in turn, depends on feedback to be effective. Further, the understanding of feedback has changed from information about a performance directed to the learner performing the task, to a dialogue, which enables the learner to act and develop.

In health professional education, feedback is a complex interaction between trainee, supervisor, and the healthcare system. Most published research on feedback in health professional education originates in Europe and North America. Our interest is on the impact of Culture on this process, particularly in the context of Asian cultures.

The (scientific) realist approach of Pawson and Tilley provides a means to examine complex interventions in social situations, and thus is an appropriate lens to use for this study. This is a protocol for a realist synthesis which asks how, why and in what circumstances do Asian Cultures influence health professional trainees to seek, respond to and use feedback given in the clinical environment, if at all.

Methods and analysisAn initial search was performed to help define the scope of the review question and develop our initial program theory. The formal electronic search was carried out in February 2020 and included: CINAHL, ERIC, MEDLINE, and PsycInfo, and repeated in October 2020.

Retrieved articles were imported into Covidence for screening and data extraction, after which components of the Context - Mechanisms - Outcomes configurations will be sought to refine the initial program theory.

Ethics and DisseminationAs this study is a literature review, ethics approval is not required.

The findings will be documented in line with the RAMESES publications standards for Realist syntheses,[41] and we plan to disseminate the findings by means of a peer-reviewed journal article and conference presentation(s).

Strengths and limitations of this studyO_LIThe synthesis aims to identify the how and why Asian Cultures may influence feedback seeking and provision to health professional trainees, if at all.
C_LIO_LITo our knowledge, there are few studies of feedback seeking and provision to health professional trainees in Asia.
C_LIO_LIA Realist approach has the potential to help explain the complex nature of Cultures impact on feedback.
C_LIO_LIOnly studies published in the English language will be included, so transferability of our findings to non-English speaking environments may be lacking.
C_LIO_LIIn addition to formal literature database searches, we will need to conduct citation mining to locate other relevant resources.
C_LI

category: medical education


title: Culture and understanding the role of feedback for health professions students: Realist synthesis protocol.


title: Bidirectional Associations between Short or Long Sleep Duration and Cognitive Function: the China Health and Retirement Longitudinal Study

abstract:
IMPORTANCEThe bidirectional association between sleep duration and cognitive function has not been conclusively demonstrated.

OBJECTIVETo investigate the longitudinal association between sleep duration and cognitive function among middle-aged and elderly Chinese participants.

Design, SETTING, AND PARTICIPANTSA national representative and prospective longitudinal study in China. 7984 participants aged 45 years and above were assessed at baseline between June 2011 and March 2012 (wave 1) and 2013 (wave 2), 2015 (wave 3) and 2018 (wave4).

MAIN OUCOMES AND MEASURESSelf-reported nighttime sleep duration was evaluated by interview. Cognitive function was evaluated via assessments of global cognition, which reflected the ability of episodic memory, visuospatial construction, calculation, orientation and attention.

ResultsRegarding the 7984 participants in wave 4, the mean (SD) age was 64.7 (8.4), 3862 (48.4) were male, and 6453 (80.7) lived in rural area. There were 14981, 11768 (78.6%), 10192 (68.0%), 7984 (53.3%) participants in the four waves of the study, respectively. Latent growth models showed both sleep duration and global cognition worsen over time. Cross-lagged models indicated that long or short sleep duration in the previous wave was associated lower global cognition in the next wave (standardized {beta}=-0.066; 95%CI: -0.073, -0.059; P<0.001; Wave 1 to 2), and lower global cognition in the previous wave was associated with long or short sleep duration in the next wave (standardized {beta}=-0.106; 95%CI: -0.116, -0.096; P<0.001; Wave 1 to 2). Global cognition was probably the major driver in this reciprocal associations.

CONCLUSIONS AND REVELANCEThere were bidirectional associations between long or short sleep duration and cognitive function. Lower cognitive function had a stronger association with worse cognitive function than the reverse. A moderate sleep duration is always recommended. Moreover, attention should be paid on the declined cognition and cognitive therapy among older adults with short or long sleep duration.

category: neurology


title: Existence of SARS-CoV-2 RNA on ambient particulate matter samples: A nationwide study in Turkey

abstract:
Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus and has been affecting the world since the end of 2019. Turkey is severely affected with the first case being reported on March 11th 2020. Ambient particulate matter (PM) samples in various size ranges were collected from 13 sites including urban and urban background locations and hospital gardens in 10 cities across Turkey between the 13th of May and the 14th of June, 2020 to investigate a possible presence of SARS-CoV-2 RNA on ambient PM. A total of 155 daily samples (TSP, n=80; PM2.5, n=33; PM2.5-10, n=23; PM10, n=19; and 6 size segregated, n=48) were collected using various samplers in each city. The N1 gene and RdRP gene expressions were analyzed for the presence of SARS-CoV-2 as suggested by the Centers for Disease Control and Prevention (CDC). According to RT-PCR and 3D-RT-PCR analysis, dual RdRP and N1 gene positivity were detected in 20 (9.8 %) of the samples. The highest percentage of virus detection on PM samples was from hospital gardens in Tekirda[g], Zonguldak, and [I]stanbul--especially in PM2.5 mode. Samples collected from two urban sites were also positive. Findings of this study have suggested that SARS-CoV-2 may be transported by ambient particles especially at sites close to the infection hot-spots. However, whether this has an impact on the spread of the virus infection remains to be determined.

Significance StatementAlthough there are several studies reporting the existence of SARS-CoV-2 in indoor aerosols is established, it remains unclear whether the virus is transported by ambient atmospheric particles. The presence of the SARS-CoV-2 RNA in ambient particles collected from characteristic sites within various size ranges was investigated, and positive results were found in urban sites especially around Turkish hospitals. In this context, this study offers a new discussion on the transmission of the virus via ambient particles.

category: occupational and environmental health


title: Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus

abstract: Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has played a vital role in SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.

category: health systems and quality improvement


title: Analytical and clinical evaluation of antibody tests for SARS-CoV-2 serosurveillance studies used in Finland in 2020

abstract:
BackgroundSensitive and highly specific antibody tests are critical for detection of SARS-CoV-2 antibodies especially in populations where seroprevalence is low.

AimTo set up, optimize and evaluate the analytical and clinical performance of a new in-house microsphere immunoassay for measurement of IgG antibodies to SARS-CoV-2 nucleoprotein for assessment of population seroprevalence in Finland.

MethodsWe set up a new in-house microsphere immunoassay (FMIA) with SARS-CoV-2 nucleoprotein and optimized its analytical performance. For evaluation of clinical performance, we tested sera collected in a well-characterized cohort of PCR positive-confirmed SARS-CoV-2 patients (n=89) with mostly mild symptoms, and before the COVID-19 pandemic (n=402), for nucleoprotein specific IgG concentrations by FMIA and a commercial chemiluminescent immunoassay and for neutralizing antibodies by the microneutralization test.

ResultsThe analytical performance of FMIA was established in terms of sensitivity, linearity and precision. FMIA discriminated between COVID-19 patient and control samples with high specificity (100%) and sensitivity (100%). We generated FMIA seropositivity cut-offs, 0.46 and 1.71 U/ml, for low- and high-seroprevalence settings, respectively. In addition, we obtained high level of agreement between FMIA results and results by the microneutralization test.

ConclusionThe fluorescent microsphere immunoassay showed excellent analytical and clinical performance and is well suited for serosurveillance studies of SARS-CoV-2. However, to optimize analytical sensitivity and clinical specificity of the assay, different seropositivity thresholds depending on the intended use of the assay and the target population, may be needed.

category: infectious diseases


title: SARS-CoV-2 seroprevalence among healthcare workers in general hospitals and clinics in Japan

abstract: Coronavirus disease 2019 (COVID-19) has become a serious public health problem worldwide. However, little is known about the prevalence of COVID-19 among healthcare workers in Japan. We aimed to examine the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies among 2,160 healthcare workers in general hospitals and clinics in Japan. The prevalence of SARS-CoV-2 immunoglobulin G was 1.2% in August and October 2020, which is relatively higher than that in the general population in Japan. Because of the higher risk of COVID-19 infection, healthcare workers should be the top priority for further social support and vaccination against SARS-CoV-2.


title: Prediction of In-hospital Mortality among Adults with COVID-19 Infection

abstract:
Prediction of mortality from COVID-19 infection might help triage patients to hospitalization and intensive care. To estimate the risk of inpatient mortality, we analyzed the data of 13,190 adult patients in the New York City Health + Hospitals system admitted for COVID-19 infection from March 1 to June 30, 2020. They had a mean age 58 years, 40% were Latinx, 29% Black, 9% White and 22% of other races/ethnicities and 2,875 died. We used Machine learning (Gradient Boosted Decision Trees; XGBoost) to select predictors of inpatient mortality from demographics, vital signs and lab tests results from initial encounters. XGBoost identified O2 saturation, systolic and diastolic blood pressure, pulse rate, respiratory rate, age, and BUN with an Area Under the Receiver Operating Characteristics Curve = 94%. We applied CART to find cut-points in these variables, logistic regression to calculate odds-ratios for those categories, and assigned points to the categories to develop a score. A score = 0 indicates a 0.8% (95% confidence interval, 0.5 - 1.0%) risk of dying and [≥] 12 points indicates a 98% (97-99%) risk, and other scores have intermediate risks. We translated the models into an online calculator for the probability of mortality with 95% confidence intervals (as pictured):

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View larger version (31K):
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title: An Online Risk Calculator for Rapid Prediction of In-hospital Mortality from COVID-19 Infection


title: Comparison of Carotid Intima Media Thickness between Women with History of Preeclampsia and Normal Pregnancy: A Meta-Analysis of Systematic Review

abstract:
BackgroundWomen with a history of preeclampsia are twice as likely to experience long term cardiovascular disease (CVD) compared to women with unaffected pregnancy. The pathophysiology of preeclampsia is not well understood, however there is general agreement that, similar to cardiovascular disease, endothelial dysfunction plays a crucial role. On a clinical level, preeclampsia and atherosclerotic cardiovascular disease share common risk factors. Carotid intima media thickness (CIMT) is ultrasound-based imaging, non-invasive, simple and reproducible method of subclinical atherosclerosis evaluation. Nowadays, there were studies concerning of CIMT among preeclamptic women, although the results were different.

ObjectiveTo prove that CIMT among women with histories of preeclampsia was greater compared to normal pregnancy.

MethodsWe conducted a meta-analysis of studies that reported CIMT, in women who had preeclampsia and had normal pregnancy. Studies were identified through three databases: PubMed, Google Scholar dan SAGE Journals with publication year of 2010- 2020. Heterogeneity was assessed using the I2 statistic. Standardized mean difference was used as measured of effect size.

ResultsNine eligible studies were included in the meta-analysis. This meta-analysis consisted of 439 women with preeclampsia histories and 526 women with normal pregnancy histories. Women who had preeclampsia had significantly higher CIMT compared to those with normal pregnancy with standardized mean difference -0.38 and 95% confidence interval (CI) -0.68 to -0.07 (p=0.02).

ConclusionCIMT was greater among women with histories of preeclampsia compared to normal pregnancy.

Prospero registration numberID 228825.

category: cardiovascular medicine


title: Do Not Attempt Resuscitation (DNAR) status in people with suspected COVID-19: Secondary analysis of the PRIEST observational cohort study

abstract:
BackgroundCardiac arrest is common in people admitted with suspected COVID-19 and has a poor prognosis. Do Not Attempt Resuscitation (DNAR) orders can reduce the risk of futile resuscitation attempts but have raised ethical concerns.

ObjectivesWe aimed to describe the characteristics and outcomes of adults admitted to hospital with suspected COVID-19 according to their DNAR status and identify factors associated with an early DNAR decision.

MethodsWe undertook a secondary analysis of 13977 adults admitted to hospital with suspected COVID-19 and included in the Pandemic Respiratory Infection Emergency System Triage (PRIEST) study. We recorded presenting characteristics and outcomes (death or organ support) up to 30 days. We categorised patients as early DNAR (occurring before or on the day of admission) or late/no DNAR (no DNAR or occurring after the day of admission). We undertook descriptive analysis comparing these groups and multivariable analysis to identify independent predictors of early DNAR.

ResultsWe excluded 1249 with missing DNAR data, and identified 3929/12748 (31%) with an early DNAR decision. They had higher mortality (40.7% v 13.1%) and lower use of any organ support (11.6% v 15.7%), but received a range of organ support interventions, with some being used at rates comparable to those with late or no DNAR (e.g. non-invasive ventilation 4.4% v 3.5%). On multivariable analysis, older age (p<0.001), active malignancy (p<0.001), chronic lung disease (p<0.001), limited performance status (p<0.001), and abnormal physiological variables were associated with increased recording of early DNAR. Asian ethnicity was associated with reduced recording of early DNAR (p=0.001).

ConclusionsEarly DNAR decisions were associated with recognised predictors of adverse outcome, and were inversely associated with Asian ethnicity. Most people with an early DNAR decision survived to 30 days and many received potentially life-saving interventions.

RegistrationISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533

category: emergency medicine


title: Prevalent comorbidities among young and underprivileged: Death portrait of COVID-19 among 235 555 hospitalized patients in Brazil

abstract:
BackgroundCOVID-19 has been alarmingly spreading worldwide, with Brazil ranking third in total number of cases and second in deaths. Being a continental country, which comprises many ethnic groups and an engrained social inequality, the pandemic evidenced this heterogeneous discrepancy. We aimed to estimate the impact of associated risk factors, isolated or combined, on COVID-19 severeness, detecting specific epidemiological profiles for multiple age ranges in hospitalized Brazilians.

MethodsIn this large retrospective cohort study, we used open-access data from the Ministry of Health of Brazil with COVID-19 confirmed hospitalized patients annotated in SRAG system between February and August 2020, a total of 235555 entries. The association of COVID-19 death with socio-demographic and clinical characteristics was analysed and presented as odds ratios adjusted by confounding co-variables. We also presented marginal mean aOR values for high-order interactions either by or not another fixed level or condition. We kept all other variables in the multivariate logistic models in their mean values or equal proportions.

FindingsYounger individuals with one or more comorbidities had an adjusted odds ratio up to four-fold compared to those without it, in the same age interval. Younger diabetic patients either self-declared as brown ethnicity (aOR 5{middle dot}58, 95% CI 4{middle dot}97-6{middle dot}25; p<0{middle dot}0001) or with some other associated comorbidities, mainly chronic hematologic disease (21{middle dot}09, 13{middle dot}64-32{middle dot}6; p<0{middle dot}0001) and obesity (aOR 21{middle dot}7, 95% CI not calculated; p<0{middle dot}0001), resulted in outstanding death risk. Age over 60, particularly over 90 (28{middle dot}91, 24{middle dot}5-34{middle dot}11; p<0.001), usage of invasive ventilatory support (16{middle dot}23, 14{middle dot}05-18{middle dot}75; p<0{middle dot}001), admission to intensive care units (3{middle dot}14, 2{middle dot}82-3{middle dot}48; p<0{middle dot}001), multiple respiratory symptoms (3{middle dot}24, 2{middle dot}79-3{middle dot}75; p<0{middle dot}0001), black ethnicity (1{middle dot}78, 1{middle dot}52-2{middle dot}07; p<0{middle dot}05), and diagnosis previous to hospitalization (1{middle dot}32, 1{middle dot}19-1{middle dot}47; p<0{middle dot}05) were associated with higher death odds. As protective factors, with roughly one third less death risk, we found hospitalization duration of (4, 7] days and illness onset to hospitalization over 6 days.

InterpretationWe found evidence for increased COVID-19 risk in two distinct groups: younger patients with prevalent comorbidities, especially in brown ethnicity, and patients with black ethnicity. We speculate that the pro-inflammatory synergism of COVID-19 and comorbidities, promoting an overproduction of cytokines, is partially the cause of higher mortality in this young group. Brazilian black and brown are underprivileged populations, with structural social inequality, limited healthcare access and, thus, remarkable disease vulnerability. Our study supplies essential data to patient stratification upon admission, optimizing hospital management, and to guide public policy determinations, including group prioritization for COVID-19 vaccination in Brazil.

FundingNone.

O_TEXTBOXResearch in context

Evidence before this studyCOVID-19 is still very active, having spread to over two hundred countries and caused more than one million deaths worldwide. Its current situation requires large-scale studies to assess the impact of preexisting comorbidities, symptoms, and socioeconomic issues regarding mortality rate, especially where lack of control is evident. We searched PubMed, Google Scholar, medRxiv, and bioRxiv on Dec 12, 2020, for studies published in English or Brazilian Portuguese, estimating the impact of several risk factors in COVID-19 prognosis. We used the search terms "Brazil" or "risk factors" or "ethnicity" or "cohort" or "diabetes mellitus" or "mortality" or "symptoms" or "comorbidities", and related synonyms, combined with "SARS-CoV-2" or "COVID-19". Many pre-existing conditions have shown to directly impact patient prognosis, out of which cancer, chronic kidney disease, chronic obstructive pulmonary disease, cardiovascular disease, obesity, and diabetes, among others, are well established in SARS-CoV-2 infection severeness. Some studies reported an increased death risk for non-white Brazilians, but no large scale cohort analyzing the impact of one or more associated risk factors in younger Brazilians patients were found.

Added value of this studyWe found that the impact of having one or two or more risk factors on mortality are progressively higher in ages (60, 80], (40, 60], (20, 40], and (0, 20], compared with people of the same age interval without comorbidities. We also found that young brown individuals with diabetes, as well as black ethnicity on its own, are population subgroups at remarkably higher risk for severe COVID-19 in Brazil. Furthermore, advanced age, usage of ventilatory support, admission to intensive care units, multiple respiratory symptoms, and diagnosis previous to hospitalization were associated with higher death odds. As protective factors, we found hospitalization duration of (4, 7] days and illness onset to hospitalization over 6 days.

Implications of all the available evidenceWe identified multiple epidemiological profiles associated with death risk in different age ranges in Brazilian COVID-19 hospitalized patients. These findings unveil that a large part of Brazilian working-age population is at a higher risk for SARS-CoV-2 death, a neglected situation that is further exacerbating inequalities, leading to a striking sociodemographic and economic impact. We hope that our analysis aids patient risk stratification, hospital management optimization, and public policy determination, including prioritization for COVID-19 vaccination in Brazil.

C_TEXTBOX


title: Mental health and wellbeing amongst people with informal caring responsibilities across different time points during the COVID-19 pandemic: A population-based propensity score matching analysis

abstract:
AimsDue to a prolonged period of national and regional lockdown measures during the coronavirus (COVID-19) pandemic, there has been an increase reliance on informal care and a consequent increase in care intensity for informal carers. In light of this, the current study compared the experiences of carers and non-carers on various mental health and wellbeing measures across 5 key time points during the pandemic.

MethodsData analysed were from the UCL COVID -19 Social Study. Our study focused on 5 time points in England: (i) the first national lockdown (March-April 2020; N=12,053); (ii) the beginning of lockdown rules easing (May 2020; N=24,374); (iii) further easing (July 2020; N=21,395); (iv) new COVID-19 restrictions (September 2020; N=4,792); and (v) the three-tier system restrictions (October 2020; N=4,526). We considered 5 mental health and wellbeing measures-depression, anxiety, loneliness, life satisfaction and sense of worthwhile. Propensity score matching were applied for the analyses.

ResultsWe found that informal carers experienced higher levels of depressive symptoms and anxiety than non-carers across all time points. During the first national lockdown, carers also experienced a higher sense of life being worthwhile. No association was found between informal caring responsibilities and levels of loneliness and life satisfaction.

ConclusionGiven that carers are an essential national health care support, especially during a pandemic, it is crucial to integrate carers needs into healthcare planning and delivery. These results highlight there is a pressing need to provide adequate and targeted mental health support for carers during and following this pandemic.


title: High-throughput sequencing of SARS-CoV-2 in wastewater provides insights into circulating variants

abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged from a zoonotic spill-over event and has led to a global pandemic. The public health response has been predominantly informed by surveillance of symptomatic individuals and contact tracing, with quarantine, and other preventive measures have then been applied to mitigate further spread. Non-traditional methods of surveillance such as genomic epidemiology and wastewater-based epidemiology (WBE) have also been leveraged during this pandemic. Genomic epidemiology uses high-throughput sequencing of SARS-CoV-2 genomes to inform local and international transmission events, as well as the diversity of circulating variants. WBE uses wastewater to analyse community spread, as it is known that SARS-CoV-2 is shed through bodily excretions. Since both symptomatic and asymptomatic individuals contribute to wastewater inputs, we hypothesized that the resultant pooled sample of population-wide excreta can provide a more comprehensive picture of SARS-CoV-2 genomic diversity circulating in a community than clinical testing and sequencing alone. In this study, we analysed 91 wastewater samples from 11 states in the USA, where the majority of samples represent Maricopa County, Arizona (USA). With the objective of assessing the viral diversity at a population scale, we undertook a single-nucleotide variant (SNV) analysis on data from 52 samples with >90% SARS-CoV-2 genome coverage of sequence reads, and compared these SNVs with those detected in genomes sequenced from clinical patients. We identified 7973 SNVs, of which 5680 were "novel" SNVs that had not yet been identified in the global clinical-derived data as of 17th June 2020 (the day after our last wastewater sampling date). However, between 17th of June 2020 and 20th November 2020, almost half of the SNVs have since been detected in clinical-derived data. Using the combination of SNVs present in each sample, we identified the more probable lineages present in that sample and compared them to lineages observed in North America prior to our sampling dates. The wastewater-derived SARS-CoV-2 sequence data indicates there were more lineages circulating across the sampled communities than represented in the clinical-derived data. Principal coordinate analyses identified patterns in population structure based on genetic variation within the sequenced samples, with clear trends associated with increased diversity likely due to a higher number of infected individuals relative to the sampling dates. We demonstrate that genetic correlation analysis combined with SNVs analysis using wastewater sampling can provide a comprehensive snapshot of the SARS-CoV-2 genetic population structure circulating within a community, which might not be observed if relying solely on clinical cases.


title: Assessing the drivers of syphilis among men who have sex with men in Switzerland reveals a key impact of testing frequency: A modelling study

abstract:
BackgroundOver the last decade, syphilis diagnoses among men-who-have-sex-with-men (MSM) have strongly increased in Europe. Understanding the drivers of the ongoing epidemic may aid to curb transmissions.

Methods and FindingsWe set up an epidemiological model to assess the drivers of syphilis in MSM in Switzerland between 2006 and 2017. We stratified the model by syphilis stage, HIV-diagnosis, and behavioral factors to account for syphilis infectiousness and risk for transmission. In the main model, we used  reported non-steady partners (nsP) as the main proxy for sexual risk. We parameterized the model using data from the Swiss HIV Cohort Study, Swiss Voluntary Counselling and Testing center, cross-sectional surveys among the Swiss MSM population, and published syphilis notifications from the Federal Office of Public Health.

The main model reproduced the increase in syphilis diagnoses from 168 cases in 2006 to 418 cases in 2017. It estimated that between 2006 and 2017, MSM with HIV diagnosis had 45.9 times the median syphilis incidence of MSM without HIV diagnosis. Defining risk as condomless anal intercourse with nsP decreased model accuracy (sum of squared weighted residuals, 378.8 vs 148.3). Counterfactual scenarios suggested that increasing screening of MSM without HIV diagnosis and with nsP from once every two-years to twice per year may reduce syphilis incidence (at most 12.8% reduction by 2017). Whereas, increasing screening among MSM with HIV diagnosis and with nsP from once per year to twice per year may substantially reduce syphilis incidence over time (at least 63.5% reduction by 2017).

ConclusionsThe model suggests that reporting nsP regardless of condom use is suitable for risk stratification when modelling syphilis transmission. More frequent screening of MSM with HIV diagnosis, particularly those with nsP may aid to curb syphilis transmission.


title: SARS-CoV-2 Airborne Surveillance Using Non-Powered Cold Traps

abstract:
BackgroundCOVID-19 pandemic is a worldwide challenge requiring efficient containment strategies. High-throughput SARS-CoV-2 testing and legal restrictions are not effective in order to get the current outbreak under control. Emerging SARS-CoV-2 variants with a higher transmissibility require efficient strategies for early detection and surveillance.

MethodsSARS-CoV-2 RNA levels were determined by quantitative RT-PCR in aerosols collected by non-powered cold traps. SARS-CoV-2 spreading kinetics and indoor hotspots could be identified in isolation units and at public places within a high-endemic area. These included an outpatient endoscopy facility, a concert hall, and a shopping mall.

ResultsIndoor COVID-19 hotspots were found in non-ventilated areas and in zones that are predisposed to a buoyancy (chimney) effect. SARS-CoV-2 RNA in those aerosols reached concentrations of 105 copies/mL. Extensive outdoor air ventilation reliably eliminates SARS-CoV-2 aerosol contamination.

ConclusionsThe method presented herein could predict SARS-CoV-2 indoor hotspots and may help to characterize SARS-CoV-2 spreading kinetics. Moreover, it can be used for the surveillance of emerging SARS-CoV-2 variants. Due to low costs and easy handling, the procedure might enable efficient algorithms for COVID-19 prevention and screening.


title: REPEATABILITY OF A CALIBRATED DIGITAL SPECTROPHOTOMETER FOR DENTAL SHADE EVALUATION IN CURRENT, FORMER AND NEVER SMOKERS STUDY PROTOCOL

abstract:
Despite the negative impact of cigarette smoking on oral health and teeth appearance, there is no data available on dental shade changes in smokers who quit smoking. Dental discoloration caused by smoking may be permanent, with minimal restoration after stopping smoking. If this is valid, former smokers can show dental shade values equivalent to those of current smokers.

The aim of this study is to compare the dental shade assessment by digital spectrophotometry (VITA Easyshade V) in current, former and never smokers and to verify the short (7 days) and long-term (30 days) repeatability of these measurements.

Confirmation of good reproducibility of VITA Easyshade V with clear objective discrimination of dental shade measurements among current, former, and never smokers will improve the power of this measurement giving more confidence in clinical research findings of dental shades in these populations.

It is also anticipated that results from the study will expand the application of this measurements to include medical and regulatory research applied to combustion-free tobacco products (e.g. e-cigarettes, heated tobacco products, oral tobacco/nicotine products, etc.), smoking cessation medications, and to consumer care product for oral hygiene and dental aesthetics.

category: dentistry and oral medicine


title: High density lipoprotein cholesterol and risk of subsequent COVID-19 hospitalisation: the UK Biobank study

abstract:
ObjectiveThere is growing evidence of, and biological plausibility for, elevated levels of high-density lipoprotein cholesterol (HDL-C), being related to lower rates of severe infection. Accordingly, we tested whether pre-pandemic HDL-C within the normal range is associated with subsequent COVID-19 hospitalisations and death.

ApproachWe analysed data on 317,306 participants from UK Biobank, a prospective cohort study, baseline data for which were collected between 2006 and 2010. Follow-up for COVID-19 was via hospitalisation records and a national mortality registry.

ResultsAfter controlling for a series of confounding factors which included health behaviours, inflammatory markers, and socio-economic status, higher levels of HDL-C were related to a lower risk of later hospitalisation for COVID-19. The effect was linear (p-value for trend 0.001) such that a 0.2 mmol/L increase in HDL-C was associated with a corresponding 9% reduction in risk (odds ratio; 95% confidence interval: 0.91; 0.86, 0.96). A very similar pattern of association was apparent when COVID-19 mortality was the outcome of interest (odds ratio per 0.2 mmol/l increase in HDL-C: 0.90; 0.81, 1.00); again, a stepwise effect was evident (p-value for trend 0.03).

ConclusionsThese novel results for HDL-C and COVID-19 events warrant testing in other studies.


title: Adjustment for energy intake in nutritional research: a causal inference perspective

abstract:
BackgroundFour models are commonly used to adjust for energy intake when estimating the causal effect of a dietary component on an outcome; (1) the  standard model adjusts for total energy intake, (2) the  energy partition model adjusts for remaining energy intake, (3) the  nutrient density model rescales the exposure as a proportion of total energy, and (4) the  residual model indirectly adjusts for total energy by using a residual. It remains underappreciated that each approach evaluates a different estimand and only partially accounts for proxy confounding by common dietary causes.

ObjectiveTo clarify the implied causal estimand and interpretation of each model and evaluate their performance in reducing dietary confounding.

DesignSemi-parametric directed acyclic graphs and Monte Carlo simulations were used to identify the estimands and interpretations implied by each model and explore their performance in the absence or presence of dietary confounding.

ResultsThe  standard model and the mathematically identical  residual model estimate the average relative causal effect (i.e., a  substitution effect) but provide biased estimates even in the absence of confounding. The  energy partition model estimates the total causal effect but only provides unbiased estimates in the absence of confounding or when all other nutrients have equal effects on the outcome. The  nutrient density model has an obscure interpretation but attempts to estimate the average relative causal effect rescaled as a proportion of total energy intake. Accurate estimates of both the total and average relative causal effects may instead be estimated by simultaneously adjusting for all dietary components, an approach we term the  all-components model.

ConclusionLack of awareness of the estimand differences and accuracy of the four modelling approaches may explain some of the apparent heterogeneity among existing nutritional studies and raise serious questions regarding the validity of meta-analyses where different estimands have been inappropriately pooled.


title: Natural Progression of Routine Laboratory Markers following Spinal Trauma: A Longitudinal, Multi-Cohort Study

abstract:
ObjectiveTo track and quantify the natural course of hematological markers over the first year following spinal cord injury.

MethodsData on hematological markers, demographics, and injury characteristics were extracted from medical records of a clinical trial (Sygen) and an ongoing observational cohort study (Murnau Study). The primary outcomes were concentration/levels/amount of commonly collected hematological markers at multiple time-points. Two-way ANOVA and mixed-effects regression techniques were used to account for the longitudinal data and adjust for potential confounders. Trajectories of hematological markers contained in both data sources were compared using the slope of progression.

ResultsAt baseline ([≤] 2 weeks post-injury), most hematological markers were at pathological levels, but returned to normal values over the course of six to twelve months post-injury. The baseline levels and longitudinal trajectories were dependent on injury severity. More complete injuries were associated with more pathological values (e.g. hematocrit, ANOVA test; Chisq = 77.10, df = 3, adjusted p-value<0.001, and Chisq = 94.67, df = 3, adjusted p-value<0.001, in the Sygen and Murnau studies, respectively). Comparing the two databases revealed some differences in the hematological markers, which are likely attributable to differences in study design, sample size, and standard of care.

ConclusionsDue to trauma-induced physiological perturbations, hematological markers undergo marked changes over the course of recovery, from initial pathological levels that normalize within a year. The findings from this study are important as they provide a benchmark for clinical decision making and prospective clinical trials. All results can be interactively explored on the Haemosurveillance website (https://jutzelec.shinyapps.io/Haemosurveillance/).

Code availabilityhttps://github.com/jutzca/Systemic-effects-of-Spinal-Cord-Injury


title: Contact patterns before and during the UK's Autumn 2020 COVID-19 lockdown among university students and staff

abstract:
IntroductionUK universities re-opened in September 2020, despite the on-going coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November. COVID-19 can spread rapidly in university-settings, and students adherence to social distancing measures is critical for controlling transmission.

MethodsWe measured university staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020-03/07/2020), relaxed guidance period (04/07/2020-13/09/2020), "rule-of-six" period (14/09/2020-04/11/2020), and the second lockdown (05/11/2020-25/11/2020).

Results722 staff (4199 responses) (mean household size: 2.6) and 738 students (1906 responses) (mean household size: 4.5) were included in the study. Contact number decreased with age. Staff in single-person households reported fewer contacts than individuals in 2-and 3-person households, and individuals in 4-and 5-person households reported more contacts.

For staff, daily contacts were higher in the relaxed guidance and "rule-of-six" periods (means: 3.2 and 3.5, respectively; medians: 3) than the post-first lockdown and second lockdown periods (means: 4.5 and 5.4, respectively; medians: 2). Few students responded until 05/10/2020, after which the median student contacts was 2 and the mean was 5.7, until the second lockdown when it dropped to 3.1.

DiscussionUniversity staff and students responded to national guidance by altering their social contacts. The response in staff and students was similar, suggesting that students are able to adhere to social distancing guidance while at university.


title: University students and staff able to maintain low daily contact numbers during various COVID-19 guideline periods


title: Integrating Operant and Cognitive Behavioral Economics to Inform Infectious Disease Response: Prevention, Testing, and Vaccination in the COVID-19 Pandemic

abstract: The role of human behavior to thwart transmission of infectious diseases like COVID-19 is evident. Yet, many areas of psychological and behavioral science are limited in the ability to mobilize to address exponential spread or provide easily translatable findings for policymakers. Here we describe how integrating methods from operant and cognitive approaches to behavioral economics can provide robust policy relevant data. Adapting well validated methods from behavioral economic discounting and demand frameworks, we evaluate in four crowdsourced samples (total N = 1,366) behavioral mechanisms underlying engagement in preventive health behaviors. We find that people are more likely to social distance when specified activities are framed as high risk, that describing delay until testing (rather than delay until results) increases testing likelihood, and that framing vaccine safety in a positive valence improves vaccine acceptance. These findings collectively emphasize the flexibility of methods from diverse areas of behavioral science for informing public health crisis management.


title: Impact of COVID-19 Pandemic on Inpatient Rehabilitation and the Original Infection Control Measures for Rehabilitation Team

abstract:
ObjectiveThis study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on inpatient rehabilitation, and to determine the effectiveness of the original infection control measures implemented for the rehabilitation team.

MethodsIn this single-center, retrospective, observational study, we calculated multiple rehabilitation indices of patients discharged from our rehabilitation ward between February 28 and May 25, 2020 when Hokkaido was initially affected by COVID-19, and compared them with those calculated during the same period in 2019. Fishers exact test and the Mann-Whitney U test were used for statistical analysis. We also verified the impact of implementing the original infection control measures for the rehabilitation team on preventing nosocomial infections.

ResultsA total of 93 patients (47 of 2020 group, 46 of 2019 group) were included. The median age was 87 and 88 years, respectively, with no differences in age, sex, and main disease between the groups. Training time per day in the ward in 2020 was significantly lower than that in 2019 (p = 0.013). No significant differences were found in the qualitative evaluation indices of Functional Independence Measure (FIM) score at admission, FIM gain, length of ward stay, FIM efficiency, and rate of discharge to home. None of the patients or staff members had confirmed COVID-19 during the study period.

ConclusionsEarly COVID-19 pandemic in Hokkaido affected the quantitative index for inpatient rehabilitation but not the qualitative indices. No symptomatic nosocomial COVID-19 infections were observed with our infection control measures.

category: rehabilitation medicine and physical therapy


title: Serum proteome analysis of systemic JIA and related pulmonary alveolar proteinosis identifies distinct inflammatory programs

abstract:
ObjectivesRecent observations in systemic Juvenile Idiopathic Arthritis (sJIA) suggest an increasing incidence of high-mortality interstitial lung disease, characterized by a variant of pulmonary alveolar proteinosis (PAP). Co-occurrence of macrophage activation syndrome (MAS) and PAP in sJIA suggested a shared pathology, but sJIA-PAP patients also commonly experience features of drug reaction such as atypical rashes and eosinophilia. We sought to investigate immunopathology and identify biomarkers in sJIA, MAS, and sJIA-PAP.

MethodsWe used SOMAscan to measure >1300 analytes in sera from healthy controls and patients with sJIA, MAS, sJIA-PAP and other related diseases. We verified selected findings by ELISA and lung immunostaining. Because the proteome of a sample may reflect multiple states (sJIA, MAS, sJIA-PAP), we used regression modeling to identify subsets of altered proteins associated with each state. We tested key findings in a validation cohort.

ResultsProteome alterations in active sJIA and MAS overlapped substantially, including known sJIA biomarkers like SAA and S100A9, and novel elevations of heat shock proteins and glycolytic enzymes. IL-18 was elevated in all sJIA groups, particularly MAS and sJIA-PAP. We also identified an MAS-independent sJIA-PAP signature notable for elevated ICAM5, MMP7, and allergic/eosinophilic chemokines, which were all previously associated with lung damage. Immunohistochemistry localized ICAM5 and MMP7 in sJIA-PAP lung. ICAM5s ability to distinguish sJIA-PAP from sJIA/MAS was independently validated.

ConclusionsSerum proteins support an sJIA-to-MAS continuum, help distinguish sJIA, sJIA/MAS, and sJIA-PAP, and suggest etiologic hypotheses. Select biomarkers, such as ICAM5, could aid in early detection and management of sJIA-PAP.

category: rheumatology


title: Serum proteome analysis of systemic JIA and related pulmonary alveolar proteinosis identifies distinct inflammatory programs and biomarkers


title: Early Detection of Alzheimer's Disease with Low-Cost Neuropsychological Tests: A Novel Predict-Diagnose Approach using Recurrent Neural Networks

abstract: Alzheimers Disease (AD) is the most expensive and currently incurable disease that affects a large number of the elderly globally. One in five Medicare dollars is spent on AD-related tests and treatments. Accurate AD diagnosis is critical but often involves invasive and expensive tests that include brain scans and spinal taps. Recommending these tests for only patients who are likely to develop the disease will save families of cognitively normal individuals and hospitals from unnecessary expenditures. Moreover, many of the subjects chosen for clinical trials for AD therapies never develop any cognitive impairment and prove not to be ideal candidates for those trials. It is thereby critical to find inexpensive ways to first identify individuals who are likely to develop cognitive impairment and focus attention on them for in-depth testing, diagnosing, and clinical trial participation. Research shows that AD is a slowly progressing disease. This slow progression allows for early detection and treatment, but more importantly, gives the opportunity to predict the likelihood of disease development from early indications of memory lapses. Neuropsychological tests have been shown to be effective in identifying cognitive impairment. Relying exclusively on a set of longitudinal neuropsychological test data available from the ADNI database, this paper has developed Recurrent Neural Networks (RNN) to diagnose the current and predict the future cognitive states of individuals. The RNNs use sequence prediction techniques to predict test scores for two to four years in the future. The predicted scores and predictions of cognitive states based on them showed a high level of accuracy for a group of test subjects, when compared with their known future cognitive assessments conducted by ADNI. This shows that a battery of neuropsychological tests can be used to track the cognitive states of people above a certain age and identify those who are likely to develop cognitive impairment in the future. This ability to triage individuals into those who are likely to remain normal and those who will develop cognitive impairment in the future, advances the quest to find appropriate candidates for invasive tests like spinal taps for disease identification, and the ability to identify suitable candidates for clinical trials.


title: Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co-infection events by two different lineages in Rio Grande do Sul, Brazil

abstract:
Emergence of novel SARS-CoV-2 lineages are under the spotlight of the media, scientific community and governments. Recent reports of novel variants in the United Kingdom, South Africa and Brazil (B.1.1.28-E484K) have raised intense interest because of a possible higher transmission rate or resistance to the novel vaccines. Nevertheless, the spread of B.1.1.28 (E484K) and other variants in Brazil is still unknown. In this work, we investigated the population structure and genomic complexity of SARS-CoV-2 in Rio Grande do Sul, the southernmost state in Brazil. Most samples sequenced belonged to the B.1.1.28 (E484K) lineage, demonstrating its widespread dispersion. We were the first to identify two independent events of co-infection caused by the occurrence of B.1.1.28 (E484K) with either B.1.1.248 or B.1.91 lineages. Also, clustering analysis revealed the occurrence of a novel cluster of samples circulating in the state (named VUI-NP13L) characterized by 12 lineage-defining mutations. In light of the evidence for E484K dispersion, co-infection and emergence of VUI-NP13L in Rio Grande do Sul, we reaffirm the importance of establishing strict and effective social distancing measures to counter the spread of potentially more hazardous SARS-CoV-2 strains.

HighlightsO_LIThe novel variant B.1.1.28 (E484K) previously described in Rio de Janeiro is currently spread across the southernmost state of Brazil;
C_LIO_LIThe novel variant VUI-NP13L was also identified by causing a local outbreak in Rio Grande do Sul;
C_LIO_LIB.1.1.28 (E484K) is able to establish successful coinfection events co-occurring simultaneously with different lineages of SARS-CoV-2.
C_LI

category: genetic and genomic medicine


title: Weighted burden analysis in 200 000 exome-sequenced UK Biobank subjects characterises effects of rare genetic variants on BMI

abstract:
IntroductionA number of genes have been identified in which rare variants can cause obesity. Here we analyse a sample of exome sequenced subjects from UK Biobank using BMI as a phenotype.

MethodsThere were 199,807 exome sequenced subjects for whom BMI was recorded. Weighted burden analysis of rare, functional variants was carried out, incorporating population principal components and sex as covariates. For selected genes, additional analyses were carried out to clarify the contribution of different categories of variant. Statistical significance was summarised as the signed log 10 of the p value (SLP), given a positive sign if the weighted burden score was positively correlated with BMI.

ResultsTwo genes were exome-wide significant, MC4R (SLP = 15.79) and PCSK1 (SLP = 6.61). In MC4R, disruptive variants were associated with an increase in BMI of 2.72 units and probably damaging nonsynonymous variants with an increase of 2.02 units. In PCSK1, disruptive variants were associated with a BMI increase of 2.29 and protein-altering variants with an increase of 0.34. Results for other genes were not formally significant after correction for multiple testing, although SIRT1, ZBED6 and NPC2 were noted to be of potential interest.

ConclusionBecause the UK Biobank consists of a self-selected sample of relatively healthy volunteers, the effect sizes noted may be underestimates. The results demonstrate the effects of very rare variants on BMI and suggest that other genes and variants will be definitively implicated when the sequence data for additional subjects becomes available.

This research has been conducted using the UK Biobank Resource.


title: Consultagene: Pre- and Post-Pandemic Experience with a Web-based Platform and Remote Delivery of Genetic Services

abstract:
Changes in genetics and genomics sequencing in recent years have created increased demand for genetics professionals, including clinical geneticists and genetic counselors. A significant workforce shortage of these professionals has become widely recognized. This shortage is driven by several factors, including the increased role of genetics in healthcare due to precision medicine initiatives and demand outside of medical practices in clinical and direct-to-consumer genetic testing companies that require genetics professionals for education and counseling.

We developed the Consultagene virtual platform for delivery of genetic care, counseling, and education to address some of these issues that have become global challenges in the field of clinical genetics and to bridge existing gaps at the point of care. The platform provides access to specific content based upon the referral indication including educational videos and resource links, allows document sharing, health and history information gathering and appointment scheduling with persistent access to the materials via secure data infrastructure. Having the platform coupled with access to our tele- and video consultation service allows clients convenient on-demand access to genetic education and services as needed.

This report describes the Consultagene platform development and use prior to and during the COVID-19 pandemic, some of the identified strengths and weaknesses of such a platform, and the current applications in the new environment where telemedicine practice has rapidly expanded.

Topic SummaryConsultagene is the first academic virtual platform to integrate a comprehensive range of genetics services including genetics education, genetics consultation, and genetic counseling. Consultagene addresses the increasing demands and unmet, evolving needs for genetic services due to widely available genomic sequencing and the platform seamlessly adapted to the pandemic-induced adjustments to clinical practice.


title: Weekly SARS-CoV-2 sentinel in primary schools, kindergartens and nurseries, June to November 2020, Germany

abstract: A 12-week sentinel programme monitored SARS-CoV-2 in primary schools, kindergartens and nurseries. Out of 3169 oropharyngeal swabs, only two tested positive on rRT-PCR while general incidence rates were surging. Thus, children attending respective institutions are not significantly contributing to the pandemic spread when appropriate infection control measures are in place.


title: Evaluation of six commercial SARS-CoV-2 Enzyme-Linked Immunosorbent assays for clinical testing and serosurveillance.

abstract:
BackgroundSerological testing for SARS-CoV-2 complements nucleic acid tests for patient diagnosis and enables monitoring of population susceptibility to inform the COVID-19 pandemic response. As we move into the era of vaccines, the detection of neutralising antibody will become increasingly important. Many serological tests have been developed under emergency use authorization, but their reliability remains unclear.

MethodsWe evaluated the performance of six commercially-available Enzyme-linked Immunosorbent Assays (ELISAs), including a surrogate virus neutralization test, for detection of SARS-CoV-2 immunoglobulins (IgA, IgM, IgG), total or neutralising antibodies and a subset of results were compared to microneutralisation.

ResultsFor sera collected > 14 days post-symptom onset the Wantai total Ab performed best with highest sensitivity 100% (95% confidence interval: 94.6-100) followed by 93.1% for Euroimmun NCP-IgG,93.1% for GenScript Surrogate Virus Neutralization Test, 90.3% for Euroimmun S1-IgG, 88.9% for Euroimmun S1-IgA and 83.3% for Wantai IgM. Specificity for the best performing assay was 99.5% and for the lowest 97.1%.

ConclusionWantai ELISA, detecting total immunoglobulins against SARS-CoV-2 receptor binding domain, had the best performance. Antibody target, timing and longevity of the immune response, and the objectives of testing should be considered in test choice. ELISAs should be used within a confirmatory testing algorithm to ensure reliable results. ELISAs provide high quality results, with flexibility for test numbers without the need for manufacturer specific analyzers.


title: SARS-CoV-2 recruits a haem metabolite to evade antibody immunity

abstract: The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of haem metabolism, with nanomolar affinity. Using cryo-electron microscopy and X-ray crystallography we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune sera and inhibited a subset of neutralizing antibodies. Access to the tetrapyrrole-sensitive epitope is gated by a flexible loop on the distal face of the NTD. Accompanied by profound conformational changes in the NTD, antibody binding requires relocation of the gating loop, which folds into the cleft vacated by the metabolite. Our results indicate that the virus co-opts the haem metabolite for the evasion of humoral immunity via allosteric shielding of a sensitive epitope and demonstrate the remarkable structural plasticity of the NTD.


title: Genomic insights into early SARS-CoV-2 strains isolated in Reunion Island

abstract:
The relative isolation of many island communities provides some protection from the COVID-19 pandemic, as imported cases can be limited and traced effectively. Until recently, this was true for the population of the French overseas department, Reunion Island, where only limited numbers of autochthonous cases were observed prior to August 2020. Since the report of the first case of COVID-19, contact tracing has been carried out for each new case identified in Reunion Island to identify transmission and clusters. To contribute to the public health response and understand the diffusion of SARS-Cov-2 strains in Reunion Island, we established in-house genome sequencing capability in Reunion using Oxford nanopore technology (MinION) as an inexpensive option for genomic typing of SARS-CoV-2 lineages on the island, and cross-validated typing results between viral isolation methods and different sequencing technologies. The results of our work during the early phase of the epidemics are presented herein.

Article Summary LineThe COVID-19 pandemic has had an unprecedented impact on the global community. Here we provide epidemiological and genomic details of the early stages of the pandemic on Reunion Island.


title: The usefulness of a quantitative olfactory test for the detection of COVID-19.

abstract:
BackgroundDuring the COVID-19 pandemic, olfactory dysfunction (anosmia or hyposmia) has been reported by many patients and recognized as a prevalent and early symptom of infection. This finding has been associated with viral-induced olfactory neuron dysfunction rather than the nasal congestion typically found in cold- or flu-like states. In literature, the prevalence of anosmia varies from 15% to 85%, and the studies, in general, were based on the subjective evaluation of patients self-reports of loss of smell (yes or no question). In the present study, we quantitatively evaluated olfactory dysfunction and the prevalence of fever in symptomatic patients suspected of having COVID-19 using a scratch-and-sniff olfactory test and infrared temperature testing with RT-PCR as the gold-standard comparator method to diagnose COVID-19 infection.

MethodsOutpatients had their forehead temperature checked with an infrared non-contact thermometer (temperature guns). After that, they received two olfactory smell identification test (SIT) cards (u-Smell-it; CT, USA) that each had 5 scent windows and were asked to scratch with a pencil and sniff each of the 10 small circles containing the microencapsulated fragrances and mark the best option on a response card. Nasopharyngeal swabs were then collected for Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) to determine if the patients were positive or negative for COVID-19 infection. We considered the number of  hits (correct answers) [≤] 5 as positive for loss of smell (LOS) in the olfactory test; [≥] 6 hits was considered negative for LOS (i.e. normal olfactory function). All data were analyzed using Excel and Matlab software.

ResultsIn the present study, 165 patients were eligible for the olfactory test and nasopharyngeal swab collection RT-PCR. Five patients were excluded because of inconclusive PCR results (n=2) and missing data (n=3). A total of 160 patients completed all the protocols. The RT-PCR positivity rate for COVID-19 was 27.5% (n=44), and PCR+ patients scored significantly worse in the olfactory test (5.5{+/-}3.5) compared to RT-PCR-patients (8.2{+/-}1.8, p<0.001). 0/44 PCR+ patients presented with a fever ([≥]37.8{degrees}C). In contrast an olfactory SIT had a specificity of 94.8% (95% CI, 89.1 - 98.1), sensitivity of 47.7% (95% CI, 32.7 - 63.3), accuracy of 0.82 (95% CI, 0.75 - 0.87), positive predictive value of 77.8% (95% CI, 59.6 - 88.8), negative predictive value of 82.7% (85% CI, 78.7 - 86.7), and odds ratio of 16.7.

ConclusionOur results suggest that temperature checking failed to detect COVID-19 infection, while an olfactory test may be useful to help identify COVID-19 infection in symptomatic patients.


title: Comparison study of commercial COVID-19 RT-PCR kits propose an approach to evaluate their performances

abstract: With the increasing number of COVID-19 cases in Indonesia, scalable and high-throughput diagnostic testing is essential nationwide. Currently, RT-PCR has been the preferred method of viral detection and many manufacturers offer commercial kits for routine clinical diagnostics. In response to the incoming of various kits, there is a need to assess their performance and compatibility of use in clinical laboratories. Kit characteristics impact the testing workflow of these laboratories and some factors can render a kit to perform sub-optimally, leading to false results that are misleading for public safety. Here, we evaluated six commercial kits that are predominantly distributed to appointed testing facilities across Indonesia. Their performance was assessed based on their ease of use, availability, robustness and accuracy for scalable testing in a manual set-up. Our findings demonstrated that all six kits are suitable for use in routine diagnostics, but their considerations for use may vary according to different use-cases. To better guide considerations in procurement of kits, our study provided a systematic approach for laboratories to assess the performance of new incoming kits.


title: Model-driven mitigation measures for reopening schools during the COVID-19 pandemic

abstract: Reopening schools is an urgent priority as the COVID-19 pandemic drags on. To explore the risks associated with returning to in-person learning and the value of mitigation measures, we developed stochastic, network-based models of SARS-CoV-2 transmission in primary and secondary schools. We find that a number of mitigation measures, alone or in concert, may reduce risk to acceptable levels. Student cohorting, in which students are divided into two separate populations that attend in-person classes on alternating schedules, can reduce both the likelihood and the size of outbreaks. Proactive testing of teachers and staff can help catch introductions early, before they spread widely through the school. In secondary schools, where the students are more susceptible to infection and have different patterns of social interaction, control is more difficult. Especially in these settings, planners should also consider testing students once or twice weekly. Vaccinating teachers and staff protects these individuals and may have a protective effect on students as well. Other mitigations, including mask-wearing, social distancing, and increased ventilation, remain a crucial component of any reopening plan.


title: A 3D CNN Classification Model for Accurate Diagnosis of Coronavirus Disease 2019 using Computed Tomography Images

abstract: The coronavirus disease (COVID-19) has been spreading rapidly around the world. As of August 25, 2020, 23.719 million people have been infected in many countries. The cumulative death toll exceeds 812,000. Early detection of COVID-19 is essential to provide patients with appropriate medical care and protect uninfected people. Leveraging a large computed tomography (CT) database from 1,112 patients provided by China Consortium of Chest CT Image Investigation (CC-CCII), we investigated multiple solutions in detecting COVID-19 and distinguished it from other common pneumonia (CP) and normal controls. We also compared the performance of different models for complete and segmented CT slices. In particular, we studied the effects of CT-superimposition depths into volumes on the performance of our models. The results show that the optimal model can identify the COVID-19 slices with 99.76% accuracy (99.96% recall, 99.35% precision and 99.65% F1-score). The overall performance for three-way classification obtained 99.24% accuracy and the area under the receiver operating characteristic curve (AUROC) of 0.9986. To the best of our knowledge, our method achieves the highest accuracy and recall with the largest public available COVID-19 CT dataset. Our model can help radiologists and physicians perform rapid diagnosis, especially when the healthcare system is overloaded.


title: Data Driven High Resolution Modeling and Spatial Analyses of the COVID-19 Pandemic in Germany

abstract: The SARS-CoV-2 virus has spread around the world with over 90 million infections to date, and currently many countries are fighting the second wave of infections. With neither sufficient vaccination capacity nor effective medication, non-pharmaceutical interventions (NPIs) remain the measure of choice. However, NPIs place a great burden on society, the mental health of individuals, and economics. Therefore the cost/benefit ratio must be carefully balanced and a target-oriented small-scale implementation of these NPIs could help achieve this balance. To this end, we introduce a modified SEIR-class compartment model and parametrize it locally for all 412 districts of Germany. The NPIs are modeled at district level by time varying contact rates. This high spatial resolution makes it possible to apply geostatistical methods to analyse the spatial patterns of the pandemic in Germany and to compare the results of different spatial resolutions. We find that the modified SEIR model can successfully be fitted to the COVID-19 cases in German districts, states, and also nationwide. We propose the correlation length as a further measure, besides the weekly incidence rates, to describe the current situation of the epidemic.


title: Prediction of Celiac Disease Severity and Associated Endocrine Morbidities through Deep Learning-based Image Analytics.

abstract:
ObjectiveDevelop a deep learning-based methodology using the foundations of systems pathology to generate highly accurate predictive tools for complex gastrointestinal diseases, using celiac disease (CD) as a prototype.

DesignTo predict the severity of CD, defined by Marsh-Oberhuber classification, we used deep learning to develop a model based on histopathologic features.

ResultsThe study was based on a pediatric cohort of 124 patients identified with different classes of CD severity. The model predicted CD with an overall 88.7% accuracy with the highest for Marsh IIIc (91.0%; 95% sensitivity; 91% specificity). The model identified EECs as a defining feature of children with Marsh IIIc CD and endocrinopathies which was confirmed using immunohistochemistry.

ConclusionThis deep learning image analysis platform has broad applications in disease treatment, management, and prognostication and paves the way for precision medicine.

SummaryO_ST_ABSWhat is already known about this subject?C_ST_ABS- Deep Learning has the potential to generate predictive models for complex gastrointestinal diseases.

What are the new findings?- Our deep learning-based model used the foundations of systems pathology to generate a highly accurate predictive tool for complex gastrointestinal diseases, using a celiac disease (CD) pediatric cohort as a prototype.
- The model predicated CD severity with high accuracy and identified enteroendocrine cells as a defining feature of children with severe CD and endocrinopathies.

How might it impact on clinical practice in the foreseeable future?- Assessment of histopathological markers at the time of diagnosis that can predict risk of severity or complications can have broad applications in disease treatment, management, and prognostication and pave the way for precision medicine.

category: gastroenterology


title: Management of conductive deafness from Otitis Media with Effusion (known as glue ear) in children using bone conduction headsets when grommet operations were unavailable during COVID-19.

abstract:
BackgroundOtitis Media with Effusion (OME) causing hearing impairments affects [~]1 in 10 children starting school in UK/ Europe. 80% have at least one episode with most having conductive hearing loss. Studies showed children with OME hear better with bone conducting headsets. During COVID-19 we investigated whether children with deafness secondary OME, without access to audiology or grommet surgery, could be aided with bone conduction kits and the HearGlueEar app.

MethodsStarting July 2020, during COVID-19, children aged 3-11 years with OME and on a grommet waiting list were invited to a single arm, prospective study. They received the kit, instructions and HearGlueEar app by post. By 3 weeks parents were asked to charge and pair the devices, attend a remote consultation and complete an OMQ-14 questionnaire. Remote follow-up lasted 3 months. Outcomes: ability to use the equipment, complete the questionnaire about childs hearing and behaviour before and with the equipment, declining grommet surgery or where deafness resolved, and give opinion about the intervention.

Findings26 children enrolled. Families used the kit at home and school. Most found remote consultations positive and convenient. OMQ-14 responses were 90% positive. Comments were: "Other people have said, wow his speech is clearer.", "It is making a real difference at home.", "He said over and over again, "I can hear everybody, wow, wow, wow.", "It is no exaggeration to say this has made an astronomical improvement to his quality of life". One child reported "I can hear my best friend again". "She is getting on really well with the headphones - pairing them with the iPad at home is simply brilliant." Three families continued with the headset to avoid grommets.

InterpretationPosting a bone conduction kit, HearGlueEar app and remote consultation is effective support for children with deafness secondary to OME.

FundingNone

category: pediatrics


title: Reduction of brooding and more general depressive symptoms after fMRI neurofeedback targeting a melancholic functional-connectivity biomarker

abstract: Depressive disorders contribute heavily to global disease burden; This is possibly because patients are usually treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. On the contrary, treatment that directly influences the neural circuit relevant to an individual patients subset of symptoms might more precisely and thus effectively aid in the alleviation of their specific symptoms. We tested this hypothesis, using fMRI functional connectivity neurofeedback to target a neural biomarker that objectively relates to a specific subset (melancholic) of depressive symptoms and that is generalizable across independent cohorts of patients. The targeted biomarker was the functional connectivity between the left dorsolateral prefrontal cortex and left precuneus, which has been shown in a data-driven manner to be less anticorrelated in patients with melancholic depression than in healthy controls. We found that the more a participant normalized this biomarker, the more related (brooding and more general depressive), but not unrelated (trait anxiety), symptoms were reduced. Thus, one-to-one correspondence between a normalized neural network and decreased depressive symptoms was demonstrated. These results were found in two experiments that took place several years apart by different experimenters, indicating their reproducibility. Indicative of their potential clinical utility, effects remained one-two months later.

category: psychiatry and clinical psychology


title: Psychiatric, Emotional, and Brain Volumetric Footprints of Childhood Conduct in Healthy Young Adults

abstract:
BackgroundConduct Disorder (CD) is defined as aggressive, antisocial, and rule-breaking behavior during childhood, and a major risk factor for developing an antisocial personality disorder. However, nearly half the patients develop into seemingly normal status. We aimed to identify psychiatric, emotional, and brain volumetric and functional footprints of childhood CD in healthy young adults with a prior history of CD.

Methods40 subjects with a prior history of CD (CC) and 1166 control subjects (HC) were identified from the Human Connectome Project. Their psychiatric, emotional, impulsivity, and personality traits were extracted. An emotion task fMRI activation of amygdala and hippocampus, as well as whole-brain and hippocampal/amygdalar segmentation volumetry were analyzed. We then statistically assessed the between-group differences and associations between the assessments and the hippocampal or amygdala nuclei measurements.

ResultsAfter correcting for multiple comparisons, we found higher anger aggression, antisocial personality problems, aggressive and rule-breaking behaviors, anxiety, attention-deficit/hyperactivity, intrusive, externalizing, neuroticism, and lower agreeableness in the CC group. The neuroimaging analysis also revealed larger subregions of the left hippocampus in CC group. Significant group x assessment association was found for aggression and left hippocampal presubiculum and basal nuclei of left amygdala.

DiscussionHealthy young adults with a prior history of CD still exhibit some forms of antisocial-like behavior, without evidence of emotional recognition disturbances, and with larger left hippocampal subregions. These larger hippocampal and amygdala volumes may play a protective role in CC subjects.


title: Childhood Conduct History is Linked to Amygdalohippocampal Changes in Healthy Adults: A Neuroimaging Behavioral Study


title: Rule of thumb in human intelligence for assessing the COVID-19 outbreak in Japan

abstract:
BackgroundThe COVID-19 outbreak in Japan exhibited its third peak at the end of 2020. Mathematical modelling and developed AI cannot explain several peaks in a single year.

ObjectThis study was conducted to evaluate a rule of thumb for prediction from past wave experiences.

MethodWe rescaled the number of newly infected patients as 100% at the peak and checked similarities among waves. Then we extrapolated the courses of the third and later waves.

ResultsResults show some similarity around the second and the third waves. Based on this similarity, we expected the bottom of the third wave will show 2131 newly positive patients including asymptomatic patients at around the end of February, 2021.

Discussion and ConclusionWe can infer the course of the third wave from similarity with the second wave. Mathematical modelling has been unable to do it, even when AI was used for prediction. Performance of the rule of thumb used with human intelligence might be superior to that of AI under these circumstances.


title: Adherence to the CONSORT statement and risk of bias assessment in Randomized Controlled Trials in rehabilitation journals: a protocol for a meta-research study

abstract:
ObjectiveThe aim of this study will be to assess the adherence to the reporting quality standards set forth in the CONSORT Statement checklist of a random sample of randomized controlled trials (RCTs) published in rehabilitation journals, and to assess the association between this adherence and the risk of bias of these RCTs.

Methods and AnalysisA cross-sectional analysis is planned on a random sample of 200 RCTs published between 2011and 2020 in the 68 journals indexed under "rehabilitation" category in InCites Journal Citation Report.

Randomization will be stratified by publication date and journal ranking (quartile range; Q1-2 and Q3-4) to include an equal number of studies from 2011 to 2015 (Q1-Q2=50 and Q3-Q4=50) and from 2016 to 2020 (Q1-Q2=50 and Q3-Q4=50). RCT with parallel group design will be included. Observational or cohort studies, interim analyses, economic analyses of RCTs, RCT protocols, quasi-experimental design post-trial follow-up studies, subgroup and secondary analyses of previously reported RCTs, RCT with cross-over design, pilot feasibility RCTs, n-of-1 trials, cluster trials, editorials, letters and news reports will be excluded. The primary analysis will address the completeness of the reporting for each study and the relationship between CONSORT adherence and risk of bias. This will be a descriptive analysis through descriptive statistics and graphical representation.

Ethics and DisseminationSeveral studies have shown the positive influence of reporting guidelines on the completeness of research reporting but no one investigated the use and the appropriateness of reporting guidelines in physical therapy research. Therefore, this study will add relevant knowledge that may contribute to improve further the reporting of rehabilitation research. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.


title: Adherence to the PRISMA statement and risk of bias assessment in Systematic Reviews in rehabilitation journals: a protocol for a meta-research study

abstract:
ObjectiveThe aim of this study will be to assess the adherence to the reporting quality standards set forth in the PRISMA Statement checklist of a random sample of systematic reviews (SRs) published in rehabilitation journals, and to assess the association between this adherence and the risk of bias of these SRs.

Methods and AnalysisA cross-sectional analysis is planned on a random sample of 200 SRs published between 2011and 2020 in the 68 journals indexed under "rehabilitation" category in InCites Journal Citation Report.

Randomization will be stratified by publication date and journal ranking (quartile range; Q1-2 and Q3-4) to include an equal number of studies from 2011 to 2015 (Q1-Q2=50 and Q3-Q4=50) and from 2016 to 2020 (Q1-Q2=50 and Q3-Q4=50). SRs (with or without meta-analysis) published between 2011 and 2020 as full-text scientific articles in the 68 rehabilitation journals will be included. Narrative reviews, mixed-methods reviews, meta-ethnography reviews, umbrella reviews, scoping reviews, editorials, letters and news reports will be excluded. The primary analysis will address the completeness of the reporting for each study and the relationship between PRISMA adherence and risk of bias. This will be a descriptive analysis through descriptive statistics and graphical representation.

Ethics and DisseminationSeveral studies have shown the positive influence of reporting guidelines on the completeness of research reporting but no one investigated the use and the appropriateness of reporting guidelines in physical therapy research. Therefore, this study will add relevant knowledge that may contribute to improve further the reporting of rehabilitation research. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.


title: Willingness to volunteer of medical students during the COVID-19 pandemic: Assessment at a tertiary care hospital in India

abstract:
Background and ObjectivesThe involvement of medical students in strategies to control COVID-19 might be considered to cope with the shortage of healthcare workers. This study aims at assessing the level of knowledge about COVID-19, willingness to volunteer, potential areas of involvement and reasons for deterrence towards volunteering among medical students.

MethodsA cross-sectional study was conducted among undergraduate medical students of a tertiary care teaching hospital in New Delhi. A web-based questionnaire was used to elicit demographic information, knowledge of COVID-19, willingness to volunteer and reasons for deterrence for working during COVID-19 pandemic and self-declared knowledge in six domains.

ResultsA total of 292 students participated in the study with a mean age of 19.9{+/-}3.1 years. The mean (S.D.) knowledge score of COVID-19 was 6.9 (1.1) (maximum score 10). Knowledge score was significantly different among preclinical (6.5), paraclinical (7.18), and clinical groups (7.03). Almost three fourth (75.3%) participants were willing to volunteer in COVID-19 pandemic, though 67.8% had not received any training in emergency medicine or public health crisis management. Willingness to work was maximum in areas of social work and indirect patient care (62.3% each). Lack of personal protective equipment was cited as a highly deterrent factor for volunteering (62.7%) followed by fear of transmitting the infection to family (45.9%), fear of causing harm to the patient (34.2%), and absence of treatment (22.2%).

Interpretation & conclusionsMajority of the students were willing to volunteer even though they had not received adequate training. Students may serve as an auxiliary force during the pandemic, especially in the non-clinical setting.