title: Deficient hand washing facilities in public toilets in the time of the COVID-19 pandemic: A survey in one high-income country

abstract:
AimsTo identify the extent of the provision of water and soap for hand washing in public toilets at the time of the COVID-19 pandemic. To also make comparisons with a pre-pandemic survey that included a sample of the same facilities.

MethodsWe collected data from 400 toilets that were open to the public; all those in three contiguous city council territories (228) and a further convenience sample of 172 around the rest of New Zealand. Comparisons were made with the data on the same facilities included in a 2012/2013 survey.

ResultsFor all the toilets in this survey, 2.5% had no water for hand washing and 14.8% had no soap. There was COVID-19 related health messaging signage in 19.5% of toilets, with posters of the COVID-19 QR code used to facilitate contact tracing in 12.3%, and generic hand washing signage in 1.8%. The hand washing water had "no touch" activation at 28.0% of toilets and at 18.5% for toilet bowl flushing. Toilet bowl lids were not present at 32.8%, and 2.3% of toilets had damage which would impair their functionality (eg, broken toilet seats). For the 128 sites that had also been examined in the previous survey, this new survey found significantly increased provision of soap (risk ratio = 1.47; 95%CI: 1.25 to 1.72), but no increased provision of water.

ConclusionsDespite the serious threat of the COVID-19 pandemic, the majority of hand washing facilities in public toilets sampled required tap touching, and did not have health messaging. Nevertheless there has been some modest improvements in soap (but not water) provision since the previous survey eight years before.


title: Head-to-head comparison of direct-input RT-PCR and RT-LAMP against RTqPCR on extracted RNA for rapid SARS-CoV-2 diagnostics

abstract: Viral pandemics, such as Covid-19, pose serious threats to human societies. To control the spread of highly contagious viruses such as SARS-CoV-2, effective test-trace-isolate strategies require population-wide, systematic testing. Currently, RT-qPCR on extracted RNA is the only broadly accepted test for SARS-CoV-2 diagnostics, which bears the risk of supply chain bottlenecks, often exaggerated by dependencies on proprietary reagents. Here, we directly compare the performance of gold standard diagnostic RT-qPCR on extracted RNA to direct input RT-PCR, RT-LAMP and bead-LAMP on 384 primary patient samples collected from individuals with suspected Covid-19 infection. With a simple five minute crude sample inactivation step and one hour of total reaction time, we achieve assay sensitivities of 98% (direct RT-PCR), 93% (bead-LAMP) and 82% (RT-LAMP) for clinically relevant samples (diagnostic RT-qPCR Ct <35) and a specificity of >98%. For direct RT-PCR, our data further demonstrate a perfect agreement between real-time and end-point measurements, which allow a simple binary classification similar to the powerful visual readout of colorimetric LAMP assays. Our study provides highly sensitive and specific, easy to implement, rapid and cost-effective alternatives to diagnostic RT-qPCR tests.

category: infectious diseases


title: The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera

abstract: The current COVID-19 (coronavirus disease 19) pandemic, caused by SARS-CoV-2, disproportionally affects the elderly and people with comorbidities like obesity and associated type 2 diabetes mellitus. Small animal models are crucial for the successful development and validation of antiviral vaccines, therapies and to study the role that comorbidities have on the outcome of viral infections. The initially available SARS-CoV-2 isolates require adaptation in order to use the mouse angiotensin converting enzyme 2 (mACE-2) entry receptor and to productively infect the cells of the murine respiratory tract. We have "mouse-adapted" SARS-CoV-2 by serial passaging a clinical virus isolate in the lungs of mice. We then used low doses of this virus in mouse models for advanced age, diabetes and obesity. Similar to SARS-CoV-2 infection in humans, the outcome of infection with mouse-adapted SARS-CoV-2 resulted in enhanced morbidity in aged and diabetic obese mice. Mutations associated with mouse adaptation occurred in the S, M, N and ORF8 genes. Interestingly, one mutation in the receptor binding domain of the S protein results in the change of an asparagine to tyrosine residue at position 501 (N501Y). This mutation is also present in the newly emerging SARS-CoV-2 variant viruses reported in the U.K. (20B/501Y.V1, B1.1.7 lineage) that is epidemiologically associated with high human to human transmission. We show that human convalescent and post vaccination sera can neutralize the newly emerging N501Y virus variant with similar efficiency as that of the reference USA-WA1/2020 virus, suggesting that current SARS-CoV-2 vaccines will protect against the 20B/501Y.V1 strain.


title: Excessive matrix metalloproteinase-1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID-19

abstract: COVID-19 starts as a respiratory disease that can progress to pneumonia, severe acute respiratory syndrome (SARS), and multi-organ failure. Growing evidence suggests that COVID-19 is a systemic illness that primarily injures the vascular endothelium, yet the underlying mechanisms remain unknown. SARS-CoV-2 infection is believed to trigger a cytokine storm that plays a critical role in the pathogenesis of endothelialitis and vascular injury, eventually leading to respiratory and multi-organ failure in COVID-19 patients. We used a multiplex immunoassay to systematically profile and compare 65 inflammatory cytokines/chemokines/growth factors in plasma samples from 24 hospitalized (severe/critical) COVID-19 patients, 14 mild/moderate cases, and 13 healthy controls (HCs). Patients with severe/critical and mild/moderate COVID-19 had significantly higher plasma levels of 20 analytes than HCs. Surprisingly, only one cytokine (MIF) was among these altered analytes, while the rest were chemokines and growth factors. In addition, only MMP-1 and VEGF-A were significantly elevated in hospitalized COVID-19 patients when compared to mild/moderate cases. Given that excessive MMP-1 plays a central role in tissue destruction in a wide variety of vascular diseases and that elevated VEGF-A, an EC activation marker, increases vascular permeability, we further studied MMP-1 enzymatic activity and other EC activation markers such as soluble forms of CD146, ICAM-1, and VCAM-1. We found that plasma MMP-1 enzymatic activity and plasma levels of MMP-1 and EC activation markers were highly dysregulated in COVID-19 patients. Some dysregulations were associated with patients age or gender, but not with race. Our results demonstrate that COVID-19 patients have distinct inflammatory profiles that are distinguished from the cytokine storms in other human diseases. Excessive MMP-1 and hyperactivation of ECs occur in COVID-19 patients and are associated with the severity of COVID-19.


title: Overcrowding and Exposure to Secondhand Smoke Increase Risk for COVID-19 Infection Among Latinx Families in Greater San Francisco Bay Area

abstract:
BackgroundThe novel coronavirus (COVID-19) has disproportionately impacted the Latinx community in the United States. Environmental risk factors, including community level pollution burden and exposure to smoking and secondhand smoke, have not been evaluated in relation to risk for infection with COVID-19.

MethodsWe evaluated self-reported infection rates of COVID-19 in three, preexisting, longitudinal, Latinx family cohorts in the San Francisco Bay Area from May through September 2020 (N=383 households, 1,875 people). All households were previously recruited during pregnancy and postpartum at Zuckerberg San Francisco General Hospital (ZSFG) and UCSF Benioff before the pandemic. For the COVID-19 sub-study, participants responded to a 15-minute telephonic interview where we assessed food consumption patterns, housing and employment status, and history of COVID-19 infection based on community and hospital-based testing. We also evaluated secondhand smoke exposure based on previously collected self-reported data. Environmental pollution exposure was determined from census tract residence using Californias EnviroScreen 2.0 data. Non-parametric tests and multiple logistic regression were used to assess possible associations and independent predictors of COVID-19 infection.

ResultsIn the combined Latinx, Eating and Diabetes Cohort (LEAD) and Hispanic, Eating and Nutrition (HEN) cohorts there was a 7.6% household infection rate (14/183) with a lower rate of 3.5% (7/200) in the Telomeres at Birth (TAB) cohort. Larger household size increased risk for infection (OR, 1.43 (95%CI 1.10-1.87)) in the combined LEAD/HEN cohorts and increasing number of children trended towards significance in the TAB cohort (OR 1.82, 95% CI 0.98-3.37). Any exposure to secondhand smoke in the household also trended towards increasing risk after adjusting for household size and other exposures (OR 3.20, 95%CI 0.80-12.73) and (OR 4.37, 95% CI 0.80-23.70). We did not find any associations between neighborhood pollution level based on census track location and risk of infection. Furthermore, we found weak evidence between dietary exposure and risk of COVID-19 infection after adjusting for possible confounders.

ConclusionCrowding as indicated by household size increases risk for COVID-19 infection in Latinx families. Exposure to secondhand smoke may also increase risk for COVID-19 through increased coughing, respiratory impairment and increased travel of virus on smoke particles. Public policy and health interventions need to ensure that multiunit residential complexes prevent any exposure to secondhand smoke.


title: A Label-Free SARS-CoV-2 Surrogate Virus Neutralization Test and a Longitudinal Study of Antibody Characteristics in COVID-19 Patients

abstract: Background. The laboratory-based methods to measure the SARS-CoV-2 humoral response include virus neutralization tests (VNTs) to determine antibody neutralization potency. For ease of use and universal applicability, surrogate virus neutralization tests (sVNTs) based on antibody-mediated blockage of molecular interactions have been proposed. Methods. A surrogate virus neutralization test established on a label-free immunoassay platform (LF-sVNT). The LF-sVNT analyzes the binding ability of RBD to ACE2 after neutralizing RBD with antibodies in serum. Results. The LF-sVNT neutralizing antibody titers (IC50) were determined from serum samples (n=246) from COVID-19 patients (n=113), as well as the IgG concentrations and the IgG avidity indices. Although there is variability in the kinetics of the IgG concentrations and neutralizing antibody titers between individuals, there is an initial rise, plateau and then in some cases a gradual decline at later timepoints after 40 days post-symptom onset. The IgG avidity indices, in the same cases, plateau after the initial rise and did not show a decline. Conclusions. The LF-sVNT can be a valuable tool in clinical laboratories for the assessment of the presence of neutralizing antibodies to COVID-19. This study is the first to provide longitudinal neutralizing antibody titers beyond 200 days post-symptom onset. Despite the decline of IgG concentration and neutralizing antibody titer, IgG avidity index increases, reaches a plateau and then remains constant up to 8 months post-infection. The decline of antibody neutralization potency can be attributed to the reduction in antibody quantity rather than the deterioration of antibody avidity, a measure of antibody quality.


title: A SARS-CoV-2 Label-Free Surrogate Virus Neutralization Test and a Longitudinal Study of Antibody Characteristics in COVID-19 Patients


title: Characterization of influenza vaccination recommendation across spatial scales in the United States

abstract: The US public health system is organized in 3 levels: national, state-level, and county-level. Public health messaging both within and across these scales may not always be consistent, and for transmissible public health threats where cases in one spatial location may impact other areas, this lack of consistency could create problems. Here, we collected and analyzed data on influenza vaccination recommendations across public health administration levels. We assess spatial heterogeneity at the county level, and analyze consistency in recommendations across spatial scales. We also compare information accessibility with influenza vaccine affordability and availability to identify factors that may be most related to vaccine uptake. We find that influenza vaccine recommendations are highly variable in both their priority group specificity and in their ease of access, and there is poor agreement across spatial scales. This lack of consistency results in a lack of clear relationship between vaccination information and vaccine uptake. This work highlights the need for greater consistency in specific, easily accessed public health information from trusted sources.

category: epidemiology


title: Modeling the population effects of epitope specific escape mutations in SARS-CoV-2 to guide vaccination strategies

abstract:
Escape mutations (EM) to SARS-Cov-2 have been detected and are spreading. Vaccines may need adjustment to respond to these or future mutations. We designed a population level model integrating both waning immunity and EM. We also designed a set of criteria for elaborating and fitting this model to cross-neutralization and other data in a manner that minimizes vaccine decision errors. We formulated four model variations. These define criteria for which prior infections provide immunity that can be escaped. They also specify different sequences where one EM follows another. At all reasonable parameter values, these model variations led to patterns where: 1) EM were rare in the first epidemic, 2) rebound epidemics after the first epidemic were accelerated more by increasing drifting than by increasing waning (with some exceptions), 3) the long term endemic level of infection was determined mostly by waning rates with small effects of the drifting parameter, 4) EM caused loss of vaccine effectiveness and under some conditions, vaccines induced EM that caused higher levels of infection with vaccines than without them. The differences and similarities across the four models suggest paths for developing models specifying the epitopes where EM act. This model is a base on which to construct epitope specific evolutionary models using new high-throughput assay data from population samples to guide vaccine decisions.

HighlightsO_LIThis model is the first to integrate both antigenic drifting from escape mutations and immunity waning in continuous time.
C_LIO_LITiny amounts of only waning or only escape mutation drifting have small or no effects. Together, they have large effects.
C_LIO_LIThere are no or few escape mutations during the first epidemic peak and no effect of drifting parameters on the size of that wave.
C_LIO_LIAfter the first epidemic peak, escape mutations accumulate rapidly. They increase with increases in waning rates and with increases in the drifting rate. Escape mutations then amplify other escape mutations since these raise the frequency of reinfections.
C_LIO_LIEscape mutations can completely negate the effects of vaccines and even lead to more infections with vaccination than without, especially at very low waning rates.
C_LIO_LIThe model generates population level cross-neutralization patterns that enable the model to be fitted to population level serological data.
C_LIO_LIThe model can be modified to use laboratory data that determine the epitope specific effects of mutations on ACE2 attachment strength or escape from antibody effects.
C_LIO_LIThe model, although currently unable to predict the effects of escape mutations in the real world, opens up a path that can guide model incorporation of molecularly studied escape mutations and improve predictive value. We describe that path.
C_LIO_LIModel analysis indicates that vaccine trials and serological surveys are needed now to detect the effects of epitope specific escape mutations that could cause the loss of vaccine efficacy.
C_LI


title: Alcohol consumption in the general population is associated with structural changes in multiple organ systems: A population-based study in UK Biobank

abstract: Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample. We assessed global effects of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta and liver of UK-Biobank participants who reported drinking alcohol. We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (-1.7x10-3{+/-}0.76x10-3 per doubling of alcohol consumption, P=3.0x10-14). Alcohol consumption also was associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption. Our results imply that there is not a "safe threshold" below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.


title: Heart Rate Variability in Patients with Cirrhosis: A Systematic Review and Meta-analysis

abstract:
BackgroundCirrhosis is associated with abnormal autonomic function and regulation of cardiac rhythm. Measurement of heart rate variability (HRV) provides an accurate and non-invasive measurement of autonomic function as well as liver disease severity currently calculated using the MELD, UKELD, or ChildPugh scores. This review assesses the methods employed for the measurement of HRV, and evaluates the alteration of HRV indices in cirrhosis, as well as their value in prognosis.

MethodWe undertook a systematic review using Medline, Embase and Pubmed databases in July 2020. Data were extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias of included studies was assessed by a modified version of the Newcastle Ottawa Scale. The studies descriptive were analysed and the standardized mean differences of HRV indices were pooled.

ResultsOf the 247 studies generated from our search, 14 studies were included. One of the 14 studies was excluded from meta-analysis because it reported only median of HRV indices. The studies included have a low risk of bias, and include 583 patients with cirrhosis and 349 healthy controls. The HRV time and frequency domains were significantly lower in cirrhotic patients. Between-studies heterogeneity was high in most of the pooled studies (P<0.05). Further, HRV indices predict survival independent of the severity of liver disease as assessed by MELD.

ConclusionHRV is decreased in patients with cirrhosis compared with healthy matched controls. HRV correlated with severity of liver disease and independently predicted survival. There was considerable variation in the methods used for HRV analysis, and this impedes interpretation and clinical applicability. Based on the data analysed, SDNN (standard deviation of inter-beat intervals) and cSDNN (i.e. SDNN corrected for basal heart rate) are the most suitable indices for prognosis in patients with cirrhosis.

category: gastroenterology


title: Novel deep learning algorithm predicts the status of molecular pathways and key mutations in colorectal cancer from routine histology images

abstract:
BackgroundDetermining molecular pathways involved in the development of colorectal cancer (CRC) and knowing the status of key mutations are crucial for deciding optimal target therapy. The goal of this study is to explore machine learning to predict the status of the three main CRC molecular pathways - microsatellite instability (MSI), chromosomal instability (CIN), CpG island methylator phenotype (CIMP) - and to detect BRAF and TP53 mutations as well as to predict hypermutated (HM) CRC tumors from whole-slide images (WSIs) of colorectal cancer (CRC) slides stained with Hematoxylin and Eosin (H&E).

MethodsWe propose a novel iterative draw-and-rank sampling (IDaRS) algorithm to select representative sub-images or tiles from a WSI given a single WSI-level label, without needing any detailed annotations at the cell or region levels. IDaRS is used to train a deep convolutional network for predicting key molecular parameters in CRC (in particular, prediction of HM tumors and the status of three main CRC molecular pathways - MSI, CIN, CIMP - as well as the detection of two key mutations, BRAF and TP53) from digitized images of routine H&E stained tissue slides of CRC patients (n=497 for TCGA cohort and n=47 cases for the Pathology AI Platform or PAIP cohort). Visual fields most predictive of each pathway and HM tumors identified by IDaRS are analyzed for verification of known histological features for the first time to reveal novel histological features. This is achieved by systematic, data-driven analysis of the cellular composition of strongly predictive tiles.

FindingsIDaRS yields high prediction accuracy for prediction of the three main CRC genetic pathways and key mutations by deep learning based analysis of the WSIs of H&E stained slides. It achieves the state-of-the-art AUROC values of 0.90, 0.83, and 0.81 for prediction of the status of MSI, CIN, and HM tumors for the TCGA cohort, which is significantly higher than any other currently published methods on that cohort. We also report prediction of status of CIMP pathway (CIMP-High and CIMP-Low) from H&E slides, with an AUROC of 0.79. We analyzed key discriminative histological features associated with HM tumors and each molecular pathway in a data-driven manner, via an automated quantitative analysis of the cellular composition of tiles strongly predictive of the corresponding molecular status. A key feature of the proposed method is that it enables a systematic and data-driven analysis of the cellular composition of image tiles strongly predictive of the various molecular parameters. We found that relatively high proportion of tumor infiltrating lymphocytes and necrosis are found to be strongly associated with HM and MSI, and moderately associated with CIMP-H and genome-stable (GS) cases, whereas relatively high proportions of neoplastic epithelial type 2 (NEP2), mesenchymal and neoplastic epithelial type 1 (NEP1) cells are found to be associated with CIN cases.

InterpretationAutomated prediction of genetic pathways and key mutations from image analysis of simple H&E stained sections with a high accuracy can provide time and cost-effective decision support. This work shows that a deep learning algorithm can mine both visually recognizable as well as sub-visual histological patterns associated with molecular pathways and key mutations in CRC in a data-driven manner.

FundingThis study was funded by the UK Medical Research Council (award MR/P015476/1).

category: pathology


title: Spatio-temporal analysis between the incidence of COVID-19 and human development in Mato Grosso do Sul, Brazil.

abstract:
ObjetiveTo analyze the spatial distribution of the Covid-19 incidence and its correlation with the municipal human development index (IDHM) in the state of Mato Grosso do Sul (MS), Brazil.

MethodsThis is an ecological, exploratory and analytical study whose units of analysis were the 79 municipalities that make up the state of MS. Covid-19 incidence coefficients, death numbers, lethality rate, mortality rate and Human Development Index for municipalities (IDHM) in the period from March 2020 to December 31, 2020 were used. spatial correlations between the variables mentioned above.

ResultsThe incidence of Covid-19 has spatial dependence with moderate positive correlation and formation of clusters located in the Metropolitan Region of Campo Grande (RMCG) and municipalities in the region.

ConclusionThe uneven mapping of Covid-19 and its relationship with IDHM in the Ministry of Health can contribute to actions to address the regional pandemic.

category: public and global health


title: Using numerical modelling and simulation to assess the ethical burden in clinical trials and how it relates to the proportion of responders in a trial sample

abstract: In order to propose a more precise definition and explore how to reduce ethical losses in randomized controlled clinical trials (RCTs), we set out to identify trial participants who do not contribute to demonstrating that the treatment in the experimental arm is superior to that in the control arm. RCTs emerged mid-last century as the gold standard for assessing efficacy, becoming the cornerstone of the value of new therapies, yet their ethical grounds are a matter of debate. We introduce the concept of unnecessary participants in RCTs, the sum of non-informative participants and non-responders. The non-informative participants are considered not informative with respect to the efficacy measured in the trial in contrast to responders who carry all the information required to conclude on the treatments efficacy. The non-responders present the event whether or not they are treated with the experimental treatment. The unnecessary participants carry the burden of having to participate in a clinical trial without benefiting from it, which might include experiencing side effects. Thus, these unnecessary participants carry the ethical loss that is inherent to the RCT methodology. On the contrary, responders to the experimental treatment bear its entire efficacy in the RCT. Starting from the proportions observed in a real placebo-controlled trial from the literature, we carried out simulations of RCTs progressively increasing the proportion of responders up to 100%. We show that the number of unnecessary participants decreases steadily until the RCTs ethical loss reaches a minimum. In parallel, the trial sample size decreases (presumably its cost as well), although the trials statistical power increases as shown by the increase of the chi-square comparing the event rates between the two arms. Thus, we expect that increasing the proportion of responders in RCTs would contribute to making them more ethically acceptable, with less false negative outcomes.

category: medical ethics


title: A Whole-Brain Functional Connectivity Model of Alzheimers Disease Pathology

abstract:
Early detection of Alzheimers disease (AD) is a necessity as prognosis is poor upon symptom onset. Although previous work diagnosing AD from protein-based biomarkers has been encouraging, cerebrospinal (CSF) biomarker measurement of AD proteins requires invasive lumbar puncture, whereas assessment of direct accumulation requires radioactive substance exposure in positron emission tomography (PET) imaging. Functional magnetic resonance imaging (fMRI)-based neuromarkers, offers an alternative, especially those built by capitalizing on variance distributed across the entire human connectome. In this study, we employed connectome-based predictive modeling (CPM) to build a model of functional connections that would predict CSF p-tau/A{beta}42 (PATH-fc model) in individuals diagnosed with Mild Cognitive Impairment (MCI) and AD dementia. fMRI, CSF-based biomarker data, and longitudinal data from neuropsychological testing from the Alzheimers Disease NeuroImaging Initiative (ADNI) were utilized to build the PATH-fc model. Our results provide support for successful in-sample fit of the PATH-fc model in predicting AD pathology in MCI and AD dementia individuals. The PATH-fc model, distributed across all ten canonical networks, additionally predicted cognitive decline on composite measures of global cognition and executive functioning. Our highly distributed pathology-based model of functional connectivity disruptions had a striking overlap with the spatial affinities of amyloid and tau pathology, and included the default mode network as the hub of such network-based disruptions in AD. Future work validating this model in other external datasets, and to midlife adults and older adults with no known diagnosis, will critically extend this neuromarker development work using fMRI.

Significance StatementAlzheimers disease (AD) is clinical-pathological syndrome with multi-domain amnestic symptoms considered the hallmark feature of the disease. However, accumulating evidence from autopsy studies evince support for the onset of pathophysiological processes well before the onset of symptoms. Although CSF- and PET-based biomarkers provide indirect and direct estimates of AD pathology, both methodologies are invasive. In here, we implemented a supervised machine learning algorithm - connectome-based predictive modeling - on fMRI data and found support for a whole-brain model of functional connectivity to predict AD pathology and decline in cognitive functioning over a two-year period. Our study provides support for AD pathology dependent functional connectivity disturbances in large-scale functional networks to influence the trajectory of key cognitive domains in MCI and AD patients.

category: neurology


title: Changes in healthcare workers' knowledge, attitudes, practices, and stress during the COVID-19 pandemic

abstract:
IntroductionCoronavirus disease 2019 (COVID-19) has caused an unprecedented health crisis around the world, not least because of its heterogeneous clinical presentation and course. The new information on the pandemic emerging daily has made it challenging for healthcare workers (HCWs) to stay current with the latest knowledge, which could influence their attitudes and practices during patient care.

MethodsThis study is a follow-up evaluation of changes in HCWs knowledge, attitudes, and practices as well as anxiety levels regarding COVID-19 since the beginning of the pandemic. Data were collected through an anonymous, predesigned, self-administered questionnaire that was sent online to HCWs in Saudi Arabia.

ResultsThe questionnaire was sent to 1500 HCWs, with a 63.8% response rate (N=957). The majority of respondents were female (83%), and the most common age group was 31-40 years (52.2%). Nurses constituted 86.3% of the respondents. HCWs reported higher anxiety during the COVID-19 pandemic which increased from 4.91{+/-}2.84 to 8.6{+/-}2.27 on an 11-point Likert scale compared to other viral outbreaks. HCWs believed that their own preparedness as well as that of their hospitals intensive care unit (ICU) or emergency room (ER) was higher during the COVID-19 pandemic than during the Middle East respiratory syndrome coronavirus pandemic (2012-2015). About 58% of HCWs attended one or more simulations concerning the management of COVID-19 patients in their ICU/ER, and nearly all had undergone N95 mask fit testing. The mean score of HCWs knowledge of COVID-19 was 9.89/12. For most respondents (94.6%), the perception of being at increased risk of infection was the main cause of anxiety related to COVID-19; the mean score of anxiety over COVID-19 increased from 4.91{+/-}2.84 before to 8.6{+/-}2.27 during the pandemic in Saudi Arabia.

ConclusionsHCWs anxiety levels regarding COVID-19 have increased since a pandemic was declared. It is vital that healthcare facilities provide more emotional and psychological support for all HCWs.


title: SARS-CoV-2 B.1.1.7 lineage-related perceptions and travel worry among healthcare workers

abstract:
BackgroundHealthcare workers (HCWs) travel-related anxiety needs to be assessed in light of the emergence of SARS-CoV-2 mutations.

MethodsAn online, cross-sectional questionnaire among HCWs between December 21, 2020 to January 7, 2021. The outcome variables were HCWs knowledge and awareness of the SARS-CoV-2 B.1.1.7 lineage, and its associated travel worry and Generalized Anxiety Disorder (GAD-7) score.

ResultsA total of 1,058 HCWs completed the survey; 66.5% were female, 59.0% were nurses. 9.0% indicated they had been previously diagnosed with COVID-19. Regarding the B.1.1.7 lineage, almost all (97.3%) were aware of its emergence, 73.8% were aware that it is more infectious, 78.0% thought it causes more severe disease, and only 50.0% knew that current COVID-19 vaccines are effective in preventing it. Despite this, 66.7% of HCWs were not registered to receive the vaccine. HCWs most common source of information about the new variant was social media platforms (67%), and this subgroup was significantly more worried about traveling. Nurses were more worried than physicians (P=0.001).

ConclusionsMost HCWs were aware of the emergence of SARS-CoV-2 B.1.1.7 variant and expressed substantial travel worries. Increased worry levels were found among HCWs who used social media as their main source of information, those with lower levels of COVID-19 vaccine uptake, and those with higher GAD-7 scores. The utilization of official social media platforms could improve accurate information dissemination among HCWs regarding the pandemics evolving mutations. Targeted vaccine campaigns are warranted to assure HCWs about the efficacy of COVID-19 vaccines toward SARS-CoV-2 variants.


title: SARS-CoV-2 B.1.1.7 lineage-related perceptions, COVID-19 vaccine acceptance and travel worry among healthcare workers


title: Hyperinflammatory conditions, gender differences and mortality in Indian COVID-19 patients

abstract:
PurposeEvidence suggests that COVID-19 induces hyperinflammatory conditions and causes relatively more deaths in males than females. The purpose of this study was to analyze gender differences associated with various hyperinflammatory conditions (HIC) and mortality in the Indian COVID-19 patients

MethodsThis study was conducted at the Eras Lucknow Medical College and Hospital (ELMCH), ERA University, which is located in the northern part of India. Starting from July 4, 2020 till December 3, 2020 a total of 2997 patients were treated at ELMCH. We randomly collected blood samples from 150 severe COVID-19 patients (required oxygen) between August 10 and September 15, 2020 for analyzing the following HIC and associated laboratory markers: hyperferritinaemia (serum ferritin), hematological dysfunctions (lymphocytopenia and neutrophil to lymphocyte ratio), cytokinaemia (C-reactive protein), coagulopathy (D-dimer), liver inflammation (aspartate aminotransferase), renal inflammation (blood urea and creatinine), and hyperglycemia (random blood glucose). The threshold values/cut off limits of these laboratory markers used for analyzing the risk of mortality in male and female COVID-19 patients were set according to the scale validated recently by Webb et al, (2020).

ResultsIn the above cohort of consecutively admitted COVID-19 patients, analysis of various HIC revealed hyperferritinaemia (odd ratio: 2.9, 95% CI 1.4-6.0), hematological dysfunctions (odd ratio: 2.10, 95% CI 1.0-4.2), hepatic inflammation (odd ratio: 2.0, 95% CI 0.52-7.40), and coagulopathy (odd ratio: 1.5, 95% CI 1.50, 95% CI 0.50-4.60) were more prevalent and sever in male COVID-19 patients. Approximately 86% male to 64% female COVID-19 patients developed lymphocytopenia. Regarding mortality, while hyperferritinaemia (odd ratio: 1.70, 95% CI 0.37-7.43) and cytokinaemia (odd ratio: 1.60, 95% CI 0.37 -7.30) were strongly associated with mortality in male COVID-19 patients, coagulopathy (odd ratio: 3.30, 95% CI 0.31-35), and hematological dysfunctions (odd ratio: 1.70, 95% CI 0.27-10) were more commonly associated with mortality in female COVID-19 patients. Nearly 80% male and female COVID-19 patients, who died had developed [≥]2 criteria of HIS criteria. Chronic renal disease was associated with more deaths in female than male COVID-19 patients (odd ratio: 2.0, 95% CI 0.54 - 7.4). While the mortality proportion was slightly higher in male (6.3%) than female (4.5%) COVID-19 patients, survival curves of the two genders were not different (hazard ratio: 1.02, 95% CI 0.71-1.40, P = 0. 953).

ConclusionDistinct HIC were associated with the severity, and mortality in male and female COVID-19 patients. Coagulopathy and renal injury were detrimental, specifically, for female COVID-19 patients. The overall mortality proportion was around 5.3%. The above results suggest that gender differences associated with COVID-19 severity and mortality arise due to differences in various HIC. These results may help in developing personalized or gender based treatments for COVID-19 patients.


title: Impact of immediate and preferential relaxation of social and travel restrictions for vaccinated people on the spreading dynamics of COVID-19 : a model-based analysis

abstract:
BackgroundFour COVID-19 vaccine candidates developed by Pfizer, Moderna, University of Oxford/ Astra Zeneca (also Oxford/ Serum Institute of India) and ICMR/ Bharat Biotech have been granted emergency use authorization in the democratic world following established clinical trial procedures in their respective countries. Vaccination of the general public is expected to begin in several weeks. We consider the question of whether people who have received the vaccine can be selectively and immediately cleared to return to normal activities, including hassle-free travel.

MethodsWe use a delay differential equation model developed previously by our group to calculate the effects of vaccinee "immunity passports" on the spreading trajectories of the disease. We consider default virus strains as well as high-transmissibility variants such as B1.1.7 in our analysis.

ResultsWe find that with high vaccine efficacy of 80 percent or greater, vaccinees may be immediately cleared for normal life with no significant increase in case counts. Free travel of such vaccinees between two regions should not jeopardize the infection control performance of either. At current vaccine administration rates, it may be eight months or more before COVID-19 transmission is significantly reduced or eliminated. With lower vaccine efficacy of approximately 60 percent however, social as well as travel restrictions for vaccinees may need to remain in place until transmission of the disease is eliminated.

ConclusionsDesigning high-efficacy vaccines with easily scalable manufacturing and distribution capacity should remain on the priority list in academic as well as industrial circles. Performance of all vaccines should continue to be monitored in real time during vaccination drive with a view to analysing socio-demographic determinants if any of efficacy, and optimizing distribution accordingly. A speedy and efficacious vaccination drive will provide the smoothest path out of the pandemic with the least additional caseloads, death toll and socioeconomic cost.


title: External Validations of Cardiovascular Clinical Prediction Models: A Large-scale Review of the Literature

abstract:
BackgroundThere are many clinical prediction models (CPMs) available to inform treatment decisions for patients with cardiovascular disease. However, the extent to which they have been externally tested and how well they generally perform has not been broadly evaluated.

MethodsA SCOPUS citation search was run on March 22, 2017 to identify external validations of cardiovascular CPMs in the Tufts PACE CPM Registry. We assessed the extent of external validation, performance heterogeneity across databases, and explored factors associated with model performance, including a global assessment of the clinical relatedness between the derivation and validation data.

Results2030 external validations of 1382 CPMs were identified. 807 (58%) of the CPMs in the Registry have never been externally validated. On average there were 1.5 validations per CPM (range 0-94). The median external validation AUC was 0.73 (25th -75th percentile [IQR] 0.66, 0.79), representing a median percent decrease in discrimination of -11.1% (IQR -32.4%, +2.7%) compared to performance on derivation data. 81% (n = 1333) of validations reporting AUC showed discrimination below that reported in the derivation dataset. 53% (n = 983) of the validations report some measure of CPM calibration. For CPMs evaluated more than once, there was typically a large range of performance. Of 1702 validations classified by relatedness, the percent change in discrimination was -3.7% (IQR -13.2, 3.1) for  closely related validations (n=123), -9.0 (IQR -27.6, 3.9) for  related validations (n=862) and -17.2% (IQR -42.3, 0) for  distantly related validations (n=717) (p<0.001).

ConclusionMany published cardiovascular CPMs have never been externally validated and for those that have, apparent performance during development is often overly optimistic. A single external validation appears insufficient to broadly understand the performance heterogeneity across different settings.

category: cardiovascular medicine


title: Association between COVID-19 Outcomes and Mask Mandates, Adherence, and Attitudes

abstract: We extend previous studies on the impact of masks on COVID-19 outcomes by investigating an unprecedented breadth and depth of health outcomes, geographical resolutions, types of mask mandates, early versus later waves and controlling for other government interventions, mobility testing rate and weather. We show that mask mandates are associated with a statistically significant decrease in new cases (-3.55 per 100K), deaths (-0.13 per 100K), and the proportion of hospital admissions (-2.38 percentage points) up to 40 days after the introduction of mask mandates both at the state and county level. These effects are large, corresponding to 14% of the highest recorded number of cases, 13% of deaths, and 7% of admission proportion. We also find that mask mandates are linked to a 23.4 percentage point increase in mask adherence in four diverse states. Lastly, using a large novel survey dataset of almost half a million people in 68 countries, we introduce the novel results that community mask adherence and community attitudes towards masks are associated with a reduction in COVID-19 cases and deaths. Our results have policy implications for reinforcing the need to maintain and encourage mask-wearing by the public, especially in light of some states starting to remove their mask mandates.


title: Clinical Associations of Functional Dyspepsia with Gastric Dysrhythmia on Electrogastrography: A Comprehensive Systematic Review and Meta-Analysis

abstract:
BackgroundFunctional dyspepsia (FD) is a common gastroduodenal disorder, yet its pathophysiology remains poorly understood. Bioelectrical gastric slow wave abnormalities are thought to contribute to its multifactorial pathophysiology. Electrogastrography (EGG) has been used to record gastric electrical activity, however the clinical associations require further evaluation.

AimsThis study aimed to systematically assess the clinical associations of EGG in FD.

MethodsMEDLINE, EMBASE, and CENTRAL databases were systematically searched for articles using EGG in adults with FD. Primary outcomes were percentage normal vs abnormal rhythm (bradygastria, normogastria, tachygastria). Secondary outcomes were dominant power, dominant frequency, percentage coupling and the meal responses.

Results1751 FD patients and 555 controls from 47 studies were included. FD patients spent less time in normogastria while fasted (SMD -0.74; 95%CI -1.22 - -0.25) and postprandially (-0.86; 95%CI -1.35 - -0.37) compared to controls. FD patients also spent more fasted time in bradygastria (0.63; 95%CI 0.33 - 0.93) and tachygastria (0.45; 95%CI 0.12 - 0.78%). The power ratio (-0.17; 95%CI -0.83 - 0.48), and dominant frequency meal-response ratio (0.06; 95%CI -0.08 - 0.21) were not significantly different to controls. Correlations between EGG metrics and the presence and timing of FD symptoms were inconsistent. EGG methodologies were diverse and variably applied.

ConclusionAbnormal gastric slow wave rhythms are a consistent abnormality present in FD, as defined by EGG, and therefore likely play a role in pathophysiology. The aberrant electrophysiology identified in FD warrants further investigation, including into underlying mechanisms, associated spatial patterns, and symptom correlations.


title: The Association of COVID-19 Incidence with Sport and Face Mask Use in United States High School Athletes

abstract:
PurposeTo evaluate the influence of sport characteristics and face mask use on COVID-19 incidence among high school athletes.

MethodsSurveys were distributed to high school athletic directors throughout the United States regarding sport re-initiation, COVID-19 cases, and risk reduction procedures in fall 2020.

Separate mixed effects Poisson regression models were developed to evaluate the associations between reported COVID-19 incidence and 1) sport characteristics (contact/non-contact, individual/team, indoor/outdoor) and 2) face mask use while playing (yes/no).

Results991 schools had restarted fall sports, representing 152,484 athletes on 5,854 teams. 2,565 cases of COVID-19 were reported, representing a case rate of 1,682 cases per 100,000 athletes and an incidence rate of 24.6 cases per 100,000 player-days. COVID-19 incidence was lower among outdoor versus indoor sports (incidence rate ratio [IRR]=0.54, 95% CI=0.49-0.60, p<0.001) and non-contact versus contact sports (IRR=0.78 [0.70-0.87], p<0.001), but not team versus individual sports (IRR=0.96 [0.84-1.1], p=0.49). Face mask use was associated with a decreased incidence in girls volleyball (IRR=0.53 [0.37-0.73], p<0.001), boys basketball (IRR=0.53 [0.33-0.83], p=0.008) and girls basketball (IRR=0.36 [0.19-0.63], p<0.001), and approached statistical significance in football (IRR=0.79 [0.59-1.04], p=0.10) and cheer/dance (IRR=0.75 [0.53-1.03], p=0.081).

ConclusionsIn this nationwide survey of US high school athletic directors representing 152,484 athletes, lower COVID-19 incidence was independently associated with participation in outdoor versus indoor and non-contact versus contact sports, but not team versus individual sports. Face mask use was associated with decreased COVID-19 incidence among indoor sports, and may be protective among outdoor sports with prolonged close contact between participants.

category: sports medicine


title: Evaluating the Long-Term Efficacy of COVID-19 Vaccines

abstract:
Large-scale deployment of safe and durably effective vaccines can curtail the COVID-19 pandemic.1-3 However, the high vaccine efficacy (VE) reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about two months4-5 and thus does not pertain to long-term efficacy. To evaluate the duration of protection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross participants over from the placebo arm to the vaccine arm according to priority groups. Here, we show how to estimate potentially time-varying placebo-controlled VE in this type of staggered vaccination of participants. In addition, we compare the performance of blinded and unblinded crossover designs in estimating long-term VE.

Authors InformationDan-Yu Lin, Ph.D., is Dennis Gillings Distinguished Professor of Biostatistics, and Donglin Zeng, Ph.D., is Professor of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599-7420, USA. Peter B. Gilbert, Ph.D., is Member, Vaccine and Infectious Disease Division, Fred Hutch, Seattle, WA 98109-1024, USA.

SummaryWe show how to estimate the potentially waning long-term efficacy of COVID-19 vaccines using data from randomized, placebo-controlled clinical trials with staggered enrollment of participants and sequential crossover of placebo recipients.


title: The psychosocial impact of the COVID-19 pandemic on 4,378 UK healthcare workers and ancillary staff: initial baseline data from a cohort study collected during the first wave of the pandemic.

abstract:
ObjectivesThis study reports preliminary findings on the prevalence of, and factors associated with, mental health and wellbeing outcomes of healthcare workers during the early months (April-June) of the COVID-19 pandemic in the UK.

MethodsPreliminary cross-sectional data were analysed from a cohort study (n=4,378). Clinical and non-clinical staff of three London-based NHS Trusts (UK), including acute and mental health Trusts, took part in an online baseline survey. The primary outcome measure used is the presence of probable common mental disorders (CMDs), measured by the General Health Questionnaire (GHQ-12). Secondary outcomes are probable anxiety (GAD-7), depression (PHQ-9), Post-Traumatic Stress Disorder (PTSD) (PCL-6), suicidal ideation (CIS-R), and alcohol use (AUDIT). Moral injury is measured using the Moray Injury Event Scale (MIES).

ResultsAnalyses showed substantial levels of CMDs (58.9%, 95%CI 58.1 to 60.8), and of PTSD (30.2%, 95%CI 28.1 to 32.5) with lower levels of depression (27.3%, 95%CI 25.3 to 29.4), anxiety (23.2%, 95%CI 21.3 to 25.3), and alcohol misuse (10.5%, 95%CI, 9.2 to 11.9). Women, younger staff, and nurses tended to have poorer outcomes than other staff, except for alcohol misuse. Higher reported exposure to moral injury (distress resulting from violation of ones moral code) was strongly associated with increased levels of CMDs, anxiety, depression, PTSD symptoms, and alcohol misuse.

ConclusionsOur findings suggest that mental health support for healthcare workers should consider those demographics and occupations at highest risk. Rigorous longitudinal data are needed in order to respond to the potential long-term mental health impacts of the pandemic.

HighlightsO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LILarge-scale population studies report increased prevalence of depression, anxiety, and psychological distress during the COVID-19 pandemic.
C_LIO_LIEvidence from previous epidemics indicates a high and persistent burden of adverse mental health outcomes among healthcare workers.
C_LI

What are the new findings?O_LISubstantial levels of probable common mental disorders and post-traumatic stress disorder were found among healthcare workers.
C_LIO_LIGroups at increased risk of adverse mental health outcomes included women, nurses, and younger staff, as well as those who reported higher levels of moral injury.
C_LI

How might this impact on policy or clinical practice in the foreseeable future?O_LIThe mental health offering to healthcare workers must consider the interplay of demographic, social, and occupational factors.
C_LIO_LIAdditional longitudinal research that emphasises methodological rigor, namely with use of standardised diagnostic interviews to establish mental health diagnoses, is necessary to better understand the mental health burden, identify those most at risk, and provide appropriate support without pathologizing ordinary distress responses.
C_LI

category: psychiatry and clinical psychology


title: Prevalence of malnutrition among children at primary cleft surgery: A cross-sectional analysis of a global database

abstract:
BackgroundOrofacial clefts are common birth defects requiring prompt feeding support and timely surgery. Little information exists about the impact of inadequate care provision in poor-resource settings. We aimed to estimate the burden of malnutrition in children from 101 low- and middle-income countries (LMICs) using cleft surgery records collected by one cleft NGO.

MethodsWe conducted a cross-sectional study using anonymised records of children [≤]5 years who underwent cleft surgery between 2008 and 2018. The data included birth date, gender, weight at surgery, ethnicity, country of origin, and date of primary surgery and was analysed using descriptive statistics. The prevalence of malnutrition was derived from the generation of weight-for-age z scores and described in relation to cleft type, gender, and ethnicity/geography. For purpose of comparison, the most recent prevalence estimates for underweight in children under-5 were extracted from publicly available national surveys.

FindingsThe analysis included 602,568 children. The overall prevalence of underweight at the time of primary cleft surgery was 28{middle dot}6% - a figure well above the global underweight prevalence in under-5 children without cleft estimated at about 13{middle dot}5%. The prevalence of underweight varied with the age at primary surgery and the type of cleft, as well as with gender, ethnicity, and region of origin, and was positively correlated with country-specific estimates of underweight prevalence in children without cleft.

InterpretationOur findings support the need for advancing universal health coverage with special efforts to increase timely nutrition care and access to surgery for the most disadvantaged children.

FundingNone.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSRegardless of the setting, infants born with an orofacial cleft have a heightened risk of failure to thrive (FTT), especially when their ability to suck and swallow is compromised.(1-3) Timely identification of feeding problems and appropriate nutrition support are essential to ensure healthy child development.(4-6) Limited access to (specialist) care in LMICs increases the risk of FTT in babies with unrepaired cleft, yet limited research has described the extent of the problem in these settings.

We searched Medline and Google Scholar up to April 2020 for studies that estimated the scale of malnutrition in children with cleft born in limited-resource settings. A 2019 systematic review of the literature identified seven cross-sectional or case-control studies conducted in LMICs (three in Africa(7-9), three in Latin America(10-12), one in Iran(13)).(14) We excluded one study in Brazil(10) which did not estimate undernutrition and found one additional cross-sectional study from South Africa.(15) Overall, seven hospital-based studies published between 1999 and 2017 included a total of 2,300 children <5 years old. They all provided evidence of malnutrition in this population, yet none was designed to give a global prevalence estimate.

Added value of this studyThis study is the first that attempted to provide a global prevalence estimate of malnutrition in children with unrepaired cleft in LMICs. Using pre-surgery clinical records from over 600,000 of patients operated by Smile Trains global partners, we identified underweight in 28{middle dot}6% of children [≤]5 years. Country-specific figures ranging from 6{middle dot}9% in Kazakhstan to 48{middle dot}2% in Chad were above national statistics on the prevalence of underweight in children in the general populations. Cleft epidemiology contributes to variations in malnutrition rates across LMIC settings but do not explain health disparities between children with cleft and those without cleft within countries.

Implications of all the available evidenceThere is an urgent need to identify and/or address the barriers that prevent children with cleft from receiving immediate feeding and nutritional support and timely reparative surgery. Current health services and nutrition programmes in LMICs should consider opportunities to help meet the health care needs of these children. Poor early-life nutrition has well-documented detrimental consequences on child physical, functional, and cognitive development. Accordingly, a higher prevalence of malnutrition in children born with a cleft means that this population likely experiences higher rates of morbidity and mortality - even if they are eventually operated.

category: nutrition


title: Symptoms of anxiety and depression in relation to work patterns during the first wave of the COVID-19 epidemic in Philadelphia PA: a cross-sectional survey

abstract:
ObjectiveWe investigated whether patterns of work during COVID-19 pandemic altered by effort to contain the outbreak affected anxiety and depression.

MethodsWe conducted a cross-sectional online survey of 911 residents of Philadelphia, inquiring about their working lives during early months of the epidemic, symptoms of anxiety and depression, plus demographics, perceived sources of support, and general health.

ResultsOccupational contact with suspected COVID-19 cases was associated with anxiety. Concerns about return to work, childcare, lack of sick leave, and loss/reduction in work correlated with anxiety and depression, even when there was no evidence of occupational contact with infected persons; patterns differed by gender.

ConclusionsHeightened anxiety and depression during COVID-19 pandemic can be due to widespread disruption of working lives, especially in "non-essential" low-income industries, on par with experience in healthcare.

The significance to clinical practice of the information being presented: Anxiety and depression symptoms that emerged during COVID-19 pandemic may be related to disruption of working lives even among people who are not the "essential" workers with one-one-one contact with infected persons. Clinicians may find this evidence of occupational correlates and articulated specific worries useful in treating such patients.

category: occupational and environmental health


title: Exploring support needs of people living with diabetes during the coronavirus COVID-19 pandemic: insights from a UK survey.

abstract:
BackgroundThe coronavirus COVID-19 pandemic has radically compromised healthcare for people living with chronic conditions such as diabetes. Government-imposed restrictions to contain the spread of the virus has forced people to suddenly adjust their lifestyle. This study aimed to capture the impact of the pandemic on people living with diabetes and the views of these individuals on ways in which the information, advice and support they are receiving could be improved.

Research design and methodsAn online anonymous survey was distributed across the UK during the first lockdown and initial easing. The survey comprised questions about confidence in diabetes self-management, resources used to obtain information, advice and support, and opinions on how these could be improved. Open-ended captured subjective experiences.

ResultsThe survey was completed by 773 adults living with diabetes (69.2% type 1, 28.5% type 2). There was notable variability in the impact of the pandemic on confidence in self-management, with confidence having deteriorated most commonly in the ability to take care of own mental wellbeing (37.0% respondents) and improved most commonly in maintaining a healthy weight (21.1% respondents). 41.2% of respondents living alone reported not receiving any outside support. The quality of information, advice and support received from the healthcare team was rated poorly by 37.2%. Respondents sought greater communication and tailored advice from their care team, clear and consistent information from the government and news channels, and improved understanding of diabetes and its challenges from their personal networks and employers.

ConclusionAdjusting to the COVID-19 pandemic has strained the mental health and wellbeing of people living with diabetes. Diabetes care teams must receive assistance to support these individuals without risking further inequalities in access to healthcare. Equipping personal networks and employers with knowledge on diabetes and skills to support self-management may reduce the burden on the NHS.

O_TEXTBOXSignificance of this study

O_LIWhat is already known about this subject?
O_LIThe COVID-19 pandemic has posed multiple challenges to the everyday life of people across the world.
C_LIO_LIPeople living with diabetes mellitus, particularly those with poor blood glucose are more vulnerable to developing the severe outcomes of COVID-19.
C_LIO_LINHS prioritisation of COVID-19 has disrupted the availability of care for patients with chronic health conditions, including diabetes mellitus.
C_LI
C_LIO_LIWhat are the new findings?
O_LIThe pandemic generated a decrease in confidence in diabetes self-management, particularly regarding mental wellbeing (37.0%) and adhering to physical activity recommendations (32.0%) and a healthy eating pattern (29.6%). Greater access to the healthcare team and services, strategies to adjust self-care (with greater focus on mental health) and more external support are deemed as important to reinstate diabetes self-management.
C_LIO_LICancellation of appointments reduced patients access to knowledge on their glucose control and their confidence in diabetes self-management, it generated difficulties in switching between treatments and resulted in impoverished mental health and motivation to self-manage.
C_LIO_LI41.2% of respondents living alone report not receiving support from outside their household.
C_LIO_LIQuality of information, advice and support received from the government and healthcare teams were perceived most poorly (% of respondents giving a rating of poor or very poor: 39.0% and 37.2% respectively). There is a request for greater transparency, higher quality information, improved contact, and an increased understanding of the condition by others.
C_LI
C_LIO_LIHow might these results change the focus of research or clinical practice?
O_LIThere is a need to ensure equitable contact between healthcare teams and their patients, both for diabetes self-management and overall wellbeing.
C_LIO_LIA shift to remote consultations should include training practitioners to detect emotional distress in patients and the ability to refer patients to NHS or community-led mental health support.
C_LIO_LIA collective effort is needed to produce more stratified and consistent guidance, with clear messaging to minimise uncertainty and distress.
C_LIO_LIFurther research and policy are needed to help patients identify a support network outside their direct care team and equip them with the knowledge and skills to provide adequate support.
C_LIO_LIGreater understanding on how some individuals were able to adjust their self-management successfully could assist care teams, relevant charities and policy makers to provide better support for those individuals who are struggling.
C_LI
C_LI

C_TEXTBOX

category: health policy


title: Early detection of SARS-CoV-2 infection cases or outbreaks at nursing homes by targeted wastewater tracking

abstract:
ObjectivesNear-source tracking of SARS-CoV-2 RNA in the sewage drains serving particular buildings may allow rapid identification of SARS-CoV-2 infection cases or local outbreaks. In this pilot study, we investigated whether this was the case for nursing homes (NH).

MethodsThe study involved five NH (from A to E) affiliated to the Clinico-Malvarrosa Health Department, Valencia (Spain). These were nursing or mixed nursing/care homes of different sizes, altogether providing care for 472 residents attended by a staff of 309. Near-source sewage samples were screened for presence of SARS-CoV-2 RNA by RT-qPCR at least 5 days per week during the study period. SARS-CoV-2 RNA testing in nasopharyngeal swabs from residents and staff was performed with the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Massachusetts, USA).

ResultsSARS-CoV-2 RNA was detected in wastewater samples from four of the five NH. SARS-CoV-2 infection cases were documented in three of these four NH. Of the two NH without SARS-CoV-2 infection cases, no SARS-CoV-2 RNA was detected in sewer samples from one facility, while it was repeatedly detected in samples from the other. Presence of SARS-CoV-2 RNA in sewage preceded identification of isolated cases among residents or staff or outbreak declaration in two NH, with lag times ranging from 5 to 19 days.

ConclusionOur study demonstrated that intermittent or persistent detection of SARS-CoV-2 RNA in NH sewers can provide an early warning of subsequent individual cases or outbreaks in these facilities.


title: Extending influenza surveillance to detect non-influenza respiratory viruses of public health relevance: analysis of surveillance data, 2015-2019, Belgium

abstract:
BACKGROUNDSeasonal influenza-like illness (ILI) affects millions of people yearly. Severe acute respiratory infections (SARI), mainly caused by influenza, are a leading cause of hospitalisation and mortality. Increasing evidence indicates that non-influenza respiratory viruses (NIRVs) also contribute to the burden of SARI. In Belgium, SARI surveillance by a network of sentinel hospitals is ongoing since 2011.

AIMHere, we report the results of using in-house multiplex PCRs for the detection of a flexible panel of viruses in respiratory ILI and SARI samples and the estimated incidence rates of SARI associated to each virus.

METHODSILI was defined as an infection with onset of fever and cough or dyspnoea. SARI was defined as an infection requiring hospitalization with onset of fever and cough or dyspnoea within the previous 10 days. Samples were collected during four winter seasons and tested by multiplex RT-qPCRs for influenza virus and NIRVs. Using catchment population estimates, incidence rates of SARI associated to each virus were calculated.

RESULTSOne third of the SARI cases were positive for NIRVs, reaching 49.4% among children under fifteen. In children under five, incidence rates of NIRV-associated SARI were double that of influenza (103.4 versus 57.6 per 100000 person-months), with NIRV co-infections, respiratory syncytial viruses, human metapneumoviruses and picornaviruses contributing the most (33.1, 13.6, 15.8 and 18.2 per 100000 person-months, respectively).

CONCLUSIONEarly testing for NIRVs could be beneficial to clinical management of SARI patients, especially in children under five, for whom the burden of NIRV-associated disease exceeds that of influenza.


title: REACT-1 round 8 interim report: SARS-CoV-2 prevalence during the initial stages of the third national lockdown in England

abstract:
BackgroundHigh prevalence of SARS-CoV-2 virus in many northern hemisphere populations is causing extreme pressure on healthcare services and leading to high numbers of fatalities. Even though safe and effective vaccines are being deployed in many populations, the majority of those most at-risk of severe COVID-19 will not be protected until late spring, even in countries already at a more advanced stage of vaccine deployment.

MethodsThe REal-time Assessment of Community Transmission study-1 (REACT-1) obtains throat and nose swabs from between 120,000 and 180,000 people in the community in England at approximately monthly intervals. Round 8a of REACT-1 mainly covers a period from 6th January 2021 to 15th January 2021. Swabs are tested for SARS-CoV-2 virus and patterns of swab-positivity are described over time, space and with respect to individual characteristics. We compare swab-positivity prevalence from REACT-1 with mobility data based on the GPS locations of individuals using the Facebook mobile phone app. We also compare results from round 8a with those from round 7 in which swabs were collected from 13th November to 24th November (round 7a) and 25th November to 3rd December 2020 (round 7b).

ResultsIn round 8a, we found 1,962 positives from 142,909 swabs giving a weighted prevalence of 1.58% (95% CI, 1.49%, 1.68%). Using a constant growth model, we found no strong evidence for either growth or decay averaged across the period; rather, based on data from a limited number of days, prevalence may have started to rise at the end of round 8a. Facebook mobility data showed a marked decrease in activity at the end of December 2020, followed by a rise at the start of the working year in January 2021. Between round 7b and round 8a, prevalence increased in all adult age groups, more than doubling to 0.94% (0.83%, 1.07%) in those aged 65 and over. Large household size, living in a deprived neighbourhood, and Black and Asian ethnicity were all associated with increased prevalence. Both healthcare and care home workers, and other key workers, had increased odds of swab-positivity compared to other workers.

ConclusionDuring the initial 10 days of the third COVID-19 lockdown in England in January 2021, prevalence of SARS-CoV-2 was very high with no evidence of decline. Until prevalence in the community is reduced substantially, health services will remain under extreme pressure and the cumulative number of lives lost during this pandemic will continue to increase rapidly.


title: Redeployment and training of healthcare professionals to Intensive Care during COVID-19: a systemic review

abstract:
BackgroundA rapid influx of patients to intensive care and infection control measures during the COVID-19 pandemic required the rapid development of innovative redeployment and training strategies.

MethodsWe conducted a systematic search of 9 databases including key terms related to intensive care AND training AND redeployment AND healthcare workers. Analysis consisted of a narrative synthesis of quantitative study outputs, and a framework-based thematic analysis of qualitative study outputs and grey literature. These results were then combined applying an interpretative synthesis.

ResultsTwenty papers were analysed. These took place primarily in the UK (N=8, 40%) and USA (N=5, 25%). Themes included in the results are Redeployment: Implementation strategies and learnings; Redeployed staff experience and strategies to address their needs; Redeployed staff learning needs; Training formats offered and training evaluations; and Future redeployment and training concerns. Some of the redeployment implementation and training strategies documented in this review are: Skills-based redeployment, buddy support systems, and agreeing on locally-specific principles, rather than strict procedures.

ConclusionThe COVID-19 pandemic presented unique challenges to deliver training promptly while following infection control recommendations and develop flexible redeployment strategies. This study synthesises original approaches to tackle these challenges which are relevant to inform the development of targeted and adaptative training and redeployment plans.

category: intensive care and critical care medicine


title: Redeployment and training of healthcare professionals to Intensive Care during COVID-19: a systematic review


title: Clinical prediction rule for SARS-CoV-2 infection from 116 U.S. emergency departments

abstract:
ObjectivesAccurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction rule for SARS-CoV-2 infection that uses simple criteria widely available at the point of care.

MethodsData came from the Registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical predictors and 30-day outcomes were abstracted from medical records of 19,850 emergency department (ED) patients tested for SARS-CoV-2. The criterion standard for diagnosis of SARS-CoV-2 required a positive molecular test from a swabbed sample or positive antibody testing within 30 days. The prediction rule was derived from a 50% random sample (n=9,925) using unadjusted analysis of 107 candidate variables as a screening step, followed by stepwise forward logistic regression on 72 variables.

ResultsMultivariable regression yielded a 13-variable score, which was simplified to 13-point rule: +1 point each for age>50 years, measured temperature>37.5{degrees}C, oxygen saturation<95%, Black race, Hispanic or Latino ethnicity, household contact with known or suspected COVID-19, patient reported history of dry cough, anosmia/dysgeusia, myalgias or fever; and -1 point each for White race, no direct contact with infected person, or smoking. In the validation sample (n=9,975), the score produced an area under the receiver operating character curve of 0.80 (95% CI: 0.79-0.81), and this level of accuracy was retained across patients enrolled from the early spring to summer of 2020. In the simplified rule, a score of zero produced a sensitivity of 95.6% (94.8-96.3%), specificity of 20.0% (19.0-21.0%), likelihood ratio negative of 0.22 (0.19-0.26). Increasing points on the simplified rule predicted higher probability of infection (e.g., >75% probability with +5 or more points).

ConclusionCriteria that are available at the point of care can accurately predict the probability of SARS-CoV-2 infection. These criteria could assist with decision about isolation and testing at high throughput checkpoints.

Key pointsO_ST_ABSQuestionC_ST_ABSCan clinical criteria, derived solely from interview and vital signs accurately estimate the probability of infection from the novel coronavirus (SARS-CoV-2) that causes COVID-19?

FindingsFrom derivation sample (n=9,925), we derived a set of 13 clinical criteria that produced an area under the receiver operating characteristic curve of 0.80 (0.79-0.81) in a validation sample (n=9,925). At a score of zero, the simplified version of the criteria produced sensitivity of 95.6% (94.8 to 96.3%), and specificity of 20.0% (19.0 to 21.0%).

MeaningClinical criteria can estimate the probability of SARS-CoV-2 infection.

category: emergency medicine


title: Clinical effectiveness of convalescent plasma in hospitalized patients with COVID-19: a systematic review and meta-analysis

abstract:
Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients with diagnosis of COVID-19.

We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement.

A total of 50 studies were retrieved from the databases. Four articles were finally included in the data extraction, qualitative and quantitative synthesis of results. The meta-analysis suggests that there is no benefit of convalescent plasma compared to standard care or placebo in the reduction of the overall mortality and in the ventilation requirement; but there could be a benefit for the clinical improvement in patients treated with plasma.

We can conclude that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed.


title: Longitudinal trends and risk factors for depressed mood among Canadian adults during the first wave of COVID-19

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBO_SCPLOWACKGROUNDC_SCPLOWC_ST_ABSThe COVID-19 pandemic has raised serious concerns about the mental health impact of people directed and indirectly affected by the virus. Because this is a rapidly evolving situation, our goal was to explore potential risk factors and trends in feelings of anxiety and depression among the general population in Canada over the first five months of the pandemic.

MO_SCPLOWETHODSC_SCPLOWWe completed on-line surveys of 3,127 unique individuals representative of the Canadian general population at 4 discreet periods every 6 weeks from April 15th to July 28th 2020. We assessed feelings of anxiety, depression and loss of interest with the interRAI self-reported mood scale using a multivariable generalized estimating equation model to examine factors associated with having a 5+ score on the scale (indicating potentially depressed mood). We also investigated potential longitudinal trends to examine temporal changes in mood scores.

RO_SCPLOWESULTSC_SCPLOWMore than 30% of participants felt highly anxious, depressed, and disinterested in everyday activities in the first survey (April), but this number decreased to about 20% over 4 months. Feeling lonely, younger age, feeling overwhelmed by ones health needs, having financial concerns, and living outside of Quebec were significantly associated with depressed mood.

IO_SCPLOWNTERPRETATIONC_SCPLOWThe prevalence of depressed mood during the pandemic was between 2 and 3 times the pre-pandemic rate (especially among young people), but it can change rapidly in response to social changes. Thus, monitoring of psychological distress among vulnerable groups that may benefit from additional supports should be a priority.


title: A cross-sectional analysis of demographic and behavioral risk factors of SARS-CoV-2 antibody positivity among a sample of U.S. college students

abstract:
BackgroundColleges and universities across the United States are developing and implementing data-driven prevention and containment measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Identifying risk factors for SARS-CoV-2 seropositivity could help to direct these efforts.

ObjectiveTo estimate the associations between demographic factors and social behaviors and SARS-CoV-2 seropositivity and self-reported positive SARS-CoV-2 diagnostic test.

MethodsIn September 2020, we randomly sampled Indiana University Bloomington (IUB) undergraduate students. Participants completed a cross-sectional, online survey about demographics, SARS-CoV-2 testing history, relationship status, and risk behaviors. Additionally, during a subsequent appointment, participants were tested for SARS-CoV-2 antibodies using a fingerstick procedure and SARS-CoV-2 IgM/IgG rapid assay kit. We used unadjusted modified Poisson regression models to evaluate the associations between predictors of both SARS-CoV-2 seropositivity and self-reported positive SARS-CoV-2 infection history.

ResultsOverall, 1,076 students were included in the serological testing analysis, and 1,239 students were included in the SARS-CoV-2 infection history analysis. Current seroprevalence of SARS-CoV-2 was 4.6% (95% CI: 3.3%, 5.8%). Prevalence of self-reported SARS-CoV-2 infection history was 10.3% (95% CI: 8.6%, 12.0%). Greek membership, having multiple romantic partners, knowing someone in ones immediate environment with SARS-CoV-2 infection, drinking alcohol more than 1 day per week, and hanging out with more than 4 people when drinking alcohol increased both the likelihood of seropositivity and SARS-CoV-2 infection history.

ConclusionOur findings have implications for American colleges and universities and could be used to inform SARS-C0V-2 prevention and control strategies on such campuses.


title: Age-dependent heterogeneity of lymph node metastases and survival: A population-based study.

abstract:
BackgroundFor several cancers, including those of the breast, young age at diagnosis is associated with an adverse prognosis. Although this effect is often attributed to heritable mutations such as BRCA1/2, the relationship between pathologic features, young age of onset, and prognosis for breast cancer remains unclear. In the present study, we highlight links between age of onset and lymph node metastasis (NM) in US women with breast cancer.

MethodsCase listings from Surveillance, Epidemiology, and End Result (SEER) 18 registry data for women with breast cancer, which include information on race, were used. NM and its associated outcomes were evaluated for a subset of women with receptor subtype information and then compared against a larger, pre-subtype validation set of data from the same registry. Age of diagnosis was a 5-category variable; under 40 years, 40-49 years, 50-59 years, 60-69 years and 70+ years. Univariate and adjusted multivariate survival models were applied to both sets of data.

ResultsAs determined with adjusted logistic regression models, women under 40 years old at diagnosis had 1.55 times the odds of NM as women 60-69 years of age. The odds of NM for (HR = hormone receptor) HR+/HER2+, HR-/HER2+, and triple-negative breast cancer subtypes were significantly lower than those for HR+/HER2-. In subtype-stratified adjusted models, age of diagnosis had a consistent trend of decreasing odds of NM by age category, most noticeable for HR+ subtypes of luminal A and B. Univariate 5-year survival by age was worst for women under 40 years, with NM attributable for 49% of the hazard of death from cancer in adjusted multivariate models.

ConclusionsLymph node metastasis is age-dependent, yet not all molecular subtypes are clearly affected by this relationship. For <40-yr-old women, NM is a major cause for shorter survival. When stratified by subtype, the strongest associations were in HR+ groups, suggesting a possible hormonal connection between young age of breast cancer onset and NM.


title: Age-dependent heterogeneity of lymph node metastases and survival in breast cancer: A population-based study.


title: Incentivizing Multiple Objectives in Active Surveillance for Urban Disease Vectors

abstract: Large-scale vector control campaigns have successfully reduced infectious disease incidence around the world. In addition to preventing new infections, these campaigns produce a wealth of information about the distribution and density of insect vectors, which can be incorporated into risk maps. These maps can effectively communicate risk map data to technicians on the ground, although encouraging them to use the data remains a challenge. We carried out a series of rolling trials in which we evaluated risk map use under different incentive schemes. Participants in the studies were trained field technicians tasked with house-to-house surveillance for insect vectors of Chagas disease in Arequipa, Peru. A novel incentive scheme based on poker best achieved a dual objective: to encourage technicians to preferentially visit higher-risk houses while surveilling evenly across the search zone. The poker incentive structure may be well-suited to improve entomological surveillance activities and other complex multi-objective tasks.


title: Air passenger travel and international surveillance data predict spatiotemporal variation in measles importations to the United States

abstract: Measles incidence in the United States has grown dramatically, as vaccination rates are declining and transmission internationally is on the rise. Measles virus is highly infectious and can cause severe symptoms and even death. Because imported cases are necessary drivers of outbreaks in non-endemic settings, predicting measles outbreaks in the US depends on predicting imported cases. To assess the predictability of imported measles cases, we performed a regression of imported measles cases in the US against an inflow variable that combines air travel data with international measles surveillance data. To understand the contribution of each data type to these predictions, we repeated the regression analysis with alternative versions of the inflow variable that replaced each data type with averaged values and with versions of the inflow variable that used modeled inputs. We assessed the performance of these regression models using correlation, coverage probability, and area under the curve statistics, including with resampling and cross-validation. Our regression model had good predictive ability with respect to the presence or absence of imported cases in a given state in a given year (AUC = 0.78) and the magnitude of imported cases (Pearson correlation = 0.84). By comparing alternative versions of the inflow variable averaging over different inputs, we found that both air travel data and international surveillance data contribute to the models ability to predict numbers of imported cases, and individually contribute to its ability to predict the presence or absence of imported cases. Predicted sources of imported measles cases varied considerably across years and US states, depending on which countries had high measles activity in a given year. Our results emphasize the importance of the relationship between global connectedness and the spread of measles.


title: Improving Fabric Face Masks: Impact of Design Features on the Protection Offered by Fabric Face Masks

abstract:
ObjectiveWith much of the public around the world depending on fabric face masks to protect themselves and others, it is essential to understand how the protective ability of fabric masks can be enhanced. This study evaluated the protection offered by eighteen fabric masks designs. In addition, it assessed the benefit of including three design features: insert filters, surgical mask underlayers, and nose wires.

MethodsQuantitative fit tests were conducted on different masks and with some additional design features. An array of fabric masks were tested on a single participant to account for variability in face shapes. The effects of insert filters, surgical mask underlayers and nose wires were also assessed.

ResultsAs expected, the fabric masks offered low degrees of protection; however, alterations in design showed significant increase in their protective ability. The most effective designs were multi-layered masks that fit tightly to the face and lacked dead space between the user and mask. Also, low air-resistance insert filters and surgical mask underlays provided the greatest increase in protection.

ConclusionsOur findings indicate substantial heterogeneity in the protection offered by various fabric face masks. We also note some design features which may enhance the protection these masks offer.


title: Simulating the impact of different vaccination policies on the COVID-19 pandemic in New York City

abstract:
PurposeTo analyze potential COVID-19 epidemic outcomes in New York City under different SARS-CoV-2 virus circulation scenarios and vaccine rollout policies from early Jan 2021 to end of June 2021.

Key findingsIn anticipation of the potential arrival and dominance of the more infectious SARS-CoV-2 variant:

O_LIMass-vaccination would be critical to mitigating epidemic severity (26-52% reduction in infections, hospitalizations, and deaths, compared to no vaccination, provided the new UK variant supplants currently circulating variants).
C_LIO_LIPrioritizing key risk groups for earlier vaccination would lead to greater reductions in hospitalizations and deaths than infections. Thus, in general this would be a good strategy.
C_LIO_LICurrent vaccination prioritization policy is suboptimal. To avert more hospitalizations and deaths, mass-vaccination of all individuals 65 years or older should be done as soon as possible. For groups listed in the same phase, 65+ year-olds should be given first priority ahead of others.
C_LIO_LIAvailable vaccine doses should be given to the next priority groups as soon as possible without awaiting hesitant up-stream groups.
C_LIO_LIWhile efficacy of vaccination off-protocol is unknown, provided immune response following a first vaccine dose persists, delaying the 2nd vaccine dose by [~]1 month (i.e. administer the two doses 8 weeks apart) can substantially reduce infections, hospitalizations, and deaths compared to the 3-week apart regimen. Across all scenarios tested here, delaying the 2nd vaccine dose leads to the largest reduction in severe epidemic outcomes (e.g. hospitalizations and deaths). Therefore, to protect as many people as possible, this strategy should be considered if rapid increases in infections, hospitalization or deaths and/or shortages in vaccines were to occur.
C_LI


title: Apolipoprotein E genotype and MRI-detected brain alterations pertaining to neurodegeneration: A systematic review

abstract:
IntroductionThe effect of apolipoprotein E (APOE) genotype, particularly APOE {varepsilon}4, the main genetic risk factor for late-onset Alzheimers disease (LOAD), has been widely explored in neuroimaging studies pertaining to older adults. The goal of this systematic review was to review the literature on the relationship between carriage of the APOE {varepsilon}4 allele and grey matter (GM) changes across various age groups and its influence on neurodegeneration as evidenced by structural magnetic resonance imaging (MRI).

MethodsA search of the electronic databases Pubmed, Scopus, Ovid and Cochrane was carried out till March 2020. Only studies published in English were included. Risk of bias of each study was assessed using the modified Newcastle-Ottawa Scale.

ResultsA total of 115 articles met the inclusion criteria. Methodological quality varied from poor to good. There is moderate evidence of reduced GM volume in the middle frontal gyrus, precuneus, hippocampus, hippocampal subfields, amygdala, parahippocampal gyrus, middle temporal lobe, whole temporal lobe, temporal pole, and posterior cingulate cortex in APOE {varepsilon}4 carriers.

ConclusionThe present data supports the utility of the hippocampal GM volume to evaluate early structural neurodegenerative changes that occurs in APOE {varepsilon}4 positive elderly individuals who are at increased risk of developing LOAD. Furthermore, the evidence supports serial measurements and comparison of hippocampal volume based on age group, to track the progression of neurodegeneration in APOE {varepsilon}4 carriers. Additional longitudinal studies are necessary to confirm whether the combination of MRI-detected hippocampal atrophy with APOE {varepsilon}4 carrier status, can better predict the development of LOAD in cognitively normal individuals.

category: radiology and imaging


title: Plasma biomarkers of Alzheimer's disease predict cognitive decline and could improve clinical trials in the cognitively unimpaired elderly

abstract: Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly indviduals. We therefore tested if plasma measurements of amyloid-{beta} (A{beta})42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 {+/-}1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in the cognition (Pre-Alzheimers Clinical Composite; R2=0.14, 95% CI [0.12-0.17]; P<0.0001) and subsequent AD dementia (AUC=0.82, 95% CI [0.77-0.91], P<0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54-81]; P<0.001) with cognition as trial endpoint, and by 63% (95% CI [53-70], P<0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.


title: Excess mortality associated with the COVID-19 pandemic among Californians 18-65 years of age, by occupational sector and occupation: March through October 2020

abstract:
BackgroundThough SARS-CoV-2 outbreaks have been documented in occupational settings and though there is speculation that essential workers face heightened risks for COVID-19, occupational differences in excess mortality have, to date, not been examined. Such information could point to opportunities for intervention, such as workplace modifications and prioritization of vaccine distribution.

Methods and findingsUsing death records from the California Department of Public Health, we estimated excess mortality among Californians 18-65 years of age by occupational sector and occupation, with additional stratification of the sector analysis by race/ethnicity. During the COVID-19 pandemic, working age adults experienced a 22% increase in mortality compared to historical periods. Relative excess mortality was highest in food/agriculture workers (39% increase), transportation/logistics workers (28% increase), facilities (27%) and manufacturing workers (23% increase). Latino Californians experienced a 36% increase in mortality, with a 59% increase among Latino food/agriculture workers. Black Californians experienced a 28% increase in mortality, with a 36% increase for Black retail workers. Asian Californians experienced an 18% increase, with a 40% increase among Asian healthcare workers. Excess mortality among White working-age Californians increased by 6%, with a 16% increase among White food/agriculture workers.

ConclusionsCertain occupational sectors have been associated with high excess mortality during the pandemic, particularly among racial and ethnic groups also disproportionately affected by COVID-19. In-person essential work is a likely venue of transmission of coronavirus infection and must be addressed through strict enforcement of health orders in workplace settings and protection of in-person workers. Vaccine distribution prioritizing in-person essential workers will be important for reducing excess COVID mortality.


title: Potential contribution of climate conditions on COVID-19 pandemic transmission over West and North African countries

abstract: The COVID-19 disease, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a very contagious disease that has killed many people around the world. According to the World Health Organization (WHO) data, the spread of the disease appears to be slower in Africa. Although a number of studies have been published on the relationship between meteorological parameters and COVID-19 transmission, the effects of climate conditions on COVID-19 remain largely unexplored and without consensus following the main research finding over Africa (often based on a single country or city). Here, using available epidemiological data over 275 days (i.e., from March 1 to November 30, 2020) taken from the European Center for Disease Prevention and Control of the European Union database and daily data of surface air temperature and humidity from the National Center for Environmental Prediction (NCEP), this paper investigates the potential contributions of climate conditions on COVID-19 transmission over 16 countries selected from three bioclimatic regions of Africa (i.e., Sahel, Maghreb and Gulf of Guinea). On average, our main findings highlight statistically significant inverse correlations between COVID-19 cases and temperature over the Maghreb and the Gulf of Guinea regions, whereas positive correlations are found in the Sahel, especially over the central part including Niger and Mali. Correlations with specific humidity and water vapor parameters display significant and positive values over the Sahelian and the Gulf of Guinean countries and negative values over the Maghreb countries. In other word, results imply that the COVID-19 pandemic transmission is influenced differently across the three bioclimatic regions: i) cold and dry environmental conditions over the Maghreb; ii) warm and humid conditions over the Sahel iii) cold and humid conditions over the Gulf of Guinea. These findings could be useful for decision-makers who plan public health and control measures in affected African countries and would have substantial implications for directing respiratory disease surveillance activities.


title: Associations between indicators of socioeconomic position and DNA methylation: A systematic review

abstract: Socioeconomic position (SEP) is a major determinant of health across the life course. Yet, little is known about the biological mechanisms explaining this relationship. One possible explanation is through an epigenetic process called DNA methylation (DNAm), wherein the socioeconomic environment causes no alteration in the DNA sequence but modifies gene activity, gene expression, and therefore long-term health. To understand the evidence supporting a potential SEP-DNAm link, we performed a systematic review of published empirical findings on the association between SEP (from prenatal development to adulthood) and DNAm measured across the life course, with an eye toward evaluating how the timing, duration, and type of SEP exposure influenced DNAm. Across the 37 studies we identified, there was some evidence for the effect of SEP timing and duration on DNAm, with early-life SEP and persistently low SEP being particularly strong indicators of DNAm. Different indicators of SEP also had some unique associations with DNAm profiles, suggesting that SEP is not a singular concept, but rather that different aspects of the socioeconomic environment can shift DNAm patterns through distinct pathways. These differences with respect to SEP timing, duration, and type were notable because they were detected even among heterogenous study designs. Overall, findings from this review underscore the importance of analyzing SEP timing, duration, and type, given the complex relationship between SEP and DNAm across the lifespan. To guide future research, we highlight current limitations in the literature and propose recommendations for overcoming some of these challenges.

category: genetic and genomic medicine