title: Insulin Resistance and Metabolic Comorbidities in Alzheimers Disease

abstract: Alzheimers disease affects 50 million people worldwide and just like any modern lifestyle disease, it is steadily increasing. Unfortunately, a cure has not yet been found, despite decades of research. The pathophysiology of Alzheimers disease is extraordinarily complex and involves many different factors. Despite it being a protein misfolding disease, a lot of evidence currently point to insulin resistance, impaired glucose metabolism and comorbidities with other metabolic disorders such as obesity, elevated blood lipids, and non-alcoholic fatty liver disease, as a potential root cause. Genetics aside, it seems like poor metabolic functioning affects the brain and central nervous system a great deal: affecting mood, behaviour, and cognitive performance. Even mood disorders are interlinked with metabolic disorders and increase the risk for Alzheimers disease later in life. This is a summary of objectively chosen original research articles, published between 2011-2021 and with insulin resistance as the main objective for cognitive impairment and Alzheimers disease.


title: Environmental determinants of E. coli, link with the diarrheal diseases, and indication of vulnerability criteria in tropical area (Kapore, Burkina Faso)

abstract:
In 2017, diarrheal diseases were responsible for 606 024 deaths in Sub-Saharan Africa. This situation is due to domestic and recreational use of polluted surface waters, deficits in hygiene, access to healthcare and drinking water, and to weak environmental and health monitoring infrastructures.

Escherichia coli (E. coli) is an indicator for the enteric pathogens that cause many diarrheal diseases. The links between E. coli, diarrheal diseases and environmental parameters have not received much attention in West Africa, and few studies have assessed health risks by taking into account hazards and socio-health vulnerabilities. This case study, carried out in Burkina Faso (Bagre Reservoir), aims at filling this knowledge gap by analyzing the environmental variables that play a role in the dynamics of E. coli, cases of diarrhea, and by identifying initial criteria of vulnerabilities. A particular focus is given to satellite-derived parameters to assess whether remote sensing can provide a useful tool to assess health hazard.

Samples of surface water were routinely collected to measure E. coli, enterococci and suspended particulate matter (SPM) at a monitoring point (Kapore) during one year. In addition, satellite data were used to estimate precipitation, water level, Normalized Difference Vegetation Index (NDVI) and SPM. Monthly epidemiological data for cases of diarrhea from three health centers were also collected and compared with microbiological and environmental data. Finally, semi-structured interviews were carried out to document the use of water resources, contacts with elements of the hydrographic network, health behaviors and conditions, and water and health policy and prevention in order to identify the initial vulnerability criteria.

A positive correlation between E. coli and enterococci in surface waters was found indicating that E. coli is an acceptable indicator of fecal contamination in this region.

E. coli and diarrheal diseases were strongly correlated with monsoonal precipitation, in situ SPM, and Near Infra-Red (NIR) band between March and November. Partial least squares regression showed that E. coli concentration was strongly associated with precipitation, Sentinel-2 reflectance in the NIR and SPM, and that the cases of diarrhea were strongly associated with precipitation, NIR, E. coli, SPM, and to a lesser extent with NDVI.

Moreover, the use of satellite data alone allowed to reproduce the dynamics of E. coli, particularly from February to mid-December (R{superscript 2} = 0.60) and those of cases of diarrhea throughout the year (R{superscript 2} = 0.76). This implies that satellite data could provide an important contribution to water quality monitoring.

Finally, the vulnerability of the population is found to increase during the rainy season due to reduced accessibility to healthcare and drinking water sources and increased use of water of poor quality. At this period, surface water is used because it is close to habitations, free and easy to use irrespective of monetary or political constraints. This vulnerability particularly impacts the Fulani, whose concessions are often close to surface water (river, lake) and far from health centers, a situation aggravated by marginality.

Author summaryIn 2017, diarrheal diseases were responsible for 1.57 million deaths, principally in Sub-Saharan Africa. Many diarrheal diseases are caused by the presence of enteric pathogens in surface water including Escherichia coli (E. coli), a frequently used indicator of the presence of these pathogens. Yet, few studies have been carried out in West Africa to verify this link or to study the relationship between diarrheal diseases, E. coli and environmental parameters. These diarrheal diseases also depend on socio-health vulnerabilities. This case study addresses the dynamics of E. coli along with another fecal indicator bacteria, enterococci, as well as diarrheal diseases (from three health centers) and socio-health vulnerability (from three villages and Fulani settlements) and their relationship with hydro-meteorological parameters derivable by satellite. The study site is located in the Bagre reservoir in Burkina Faso where Suspended Particulate Matter (SPM) and E. coli were monitored over one year. Water was generally polluted by bacteria of fecal origin throughout the year and more so during the rainy season. We observed a significant relationship between E. coli and enterococci. E. coli concentrations were strongly correlated to, and predicted by, precipitation, satellite reflectance in the NIR band by Sentinel-2, and SPM measured in-situ. Diarrheal diseases were also strongly correlated with these variables as well as E. coli. Vulnerability of the population to diarrhea increases during the rainy season. The microbiological health risk is more important during the rainy season, from June to September, and especially concerns the Fulani settlements.

category: occupational and environmental health


title: Stress and Depression in the Workplace of Educators in the Philippines

abstract: Workplace Stress and depression should be treated properly in order to maintain productive teaching as the noblest profession. Unmanaged stress and depression could lead to a serious outcome that affects the happy environment in the classroom. Thus, managing stress and avoiding depression in the workplace is one of the important situations that a teacher should aim in order to succeed. This study aims to determine the level of workplace stress and depression of the educators in the Philippines by gathering their profile, workplace stress, and the state of depression. A correlation was investigated if there is a significant difference in the profile to the workplace stress and state of depression. Based on the result of the study, teachers sometimes experience stress in the workplace, while some experience depression at some point in time. It is recommended that teachers should understand how to practice stress management and avoiding depression.


title: An emerging role of microplastics in the etiology of lung ground glass nodules

abstract:
Pulmonary ground glass nodules (GGNs) have been increasingly identified in past decades and is becoming an important clinical dilemma in oncology. Meanwhile, humans persistently inhale microplastics which are dominant in the air. However, the retention of "non-self" microplastics in human lung and its correlation with pulmonary GGNs remains elusive. In this study, we firstly demonstrated the presence of microfibers and microplastics in human lung, with higher detection rates in GGNs in comparison to those in normal tissue. Moreover, both types and colors of microfibers in tumor were richer than those in normal tissues. Intriguingly, high risk of microfibers exposure predisposes the formation of pulmonary GGN. Further, increased roughness surface was observed in microfibers isolated in human lung, indicating the possible link of surface roughness to the formation of pulmonary GGN. Collectively, our findings reveal an emerging role of environmental microplastics exposure in the etiology of pulmonary GGN.

One Sentence SummaryThe exposure of environmental microplastics is a risk factor of pulmonary GGN.

category: oncology


title: Immunogenetics of resistance to SARS-CoV-2 infection in discordant couples

abstract:
BackgroundDespite the high number of individuals infected by SARS-CoV-2 who develop COVID-19 symptoms worldwide, many exposed individuals remain asymptomatic and/or stay uninfected. This could be explained by a combination of environmental (exposure, previous infection), epigenetic, and genetic factors. Aiming to identify genetic variants involved in SARS-CoV-2 resistance, we analyzed 86 discordant Brazilian couples where one was infected and symptomatic while the partner remained asymptomatic and seronegative despite sharing the same bedroom during the infection. The discordant partners had comparable ages, and genetic ancestry proportions.

MethodsWhole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic MHC and LRC.

ResultsWe observed a minor impact in antigen-presentation genes and KIR genes associated with resistance. Interestingly, genes related to immune modulation, mainly involved in NK cell killing activation/inhibition harbor variants potentially contributing to infection resistance. We hypothesize that individuals prone to produce higher amounts of MICA (possibly soluble), LILRB1, LILRB2, and low amounts of MICB, would be more susceptible to infection.

ConclusionAccording to this hypothesis, quantitative differences in these NK activity-related molecules could contribute to resistance to COVID-19 down regulating NK cell cytotoxic activity in infected individuals but not in resistant partners.

category: genetic and genomic medicine


title: Analysis and Augmentation of Small Datasets with Unsupervised Machine Learning

abstract: Analysis of small datasets presents a number of essential challenges not in the least due to insufficient sampling of characteristic patterns in the data making confident conclusions about the unknown distribution elusive and resulting in lower statistical confidence and higher error. In this work, a novel approach to augmentation of small datasets is proposed based on an ensemble of neural network models of unsupervised generative self-learning. Applying generative learning with an ensemble of individual models allowed to identify stable clusters of data points in the latent representations of the observable data. Several techniques of augmentation based on identified latent cluster structure were applied to produce new data points and enhance the dataset. The proposed method can be used with small and extremely small datasets to identify characteristics patterns, augment data and in some cases, improve accuracy of classification in the scenarios with strong deficit of labels.

category: health informatics


title: NeMoR: a New Method Based on Data-Driven for Neonatal Mortality Rate Forecasting

abstract:
Reduction in child mortality is one of the United Nations Sustainable Development Goals for 2030. In Brazil, despite recent reduction in child mortality in the last decades, the neonatal mortality is a persistent problem and it is associated with the quality of prenatal, childbirth care and social-environmental factors. In a proper health system, the effect of some of these factors could be minimized by the appropriate number of newborn intensive care units, number of health care units, number of neonatal incubators and even by the correct level of instruction of mothers, which can lead to a proper care along the prenatal period. With the intent of providing knowledge resources for planning public health policies focused on neonatal mortality reduction, we propose a new data-driven machine leaning method for Neonatal Mortality Rate forecasting called NeMoR, which predicts neonatal mortality rates for 4 months ahead, using NeoDeathForecast, a monthly base time series dataset composed by these factors and by neonatal mortality rates history (2006-2016), having 57,816 samples, for all 438 Brazilian administrative health regions. In order to build the model, Extra-Tree, XGBoost Regressor, Gradient Boosting Regressor and Lasso machine learning regression models were evaluated and a hyperparameters search was also performed as a fine tune step. The method has been validated using Sao Paulo city data, mainly because of data quality. On the better configuration the method predicted the neonatal mortality rates with a Mean Square Error lower than 0.18. Besides that, the forecast results may be useful as it provides a way for policy makers to anticipate trends on neonatal mortality rates curves, an important resource for planning public health policies.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/21255916v1_ufig1.gif" ALT="Figure 1">
View larger version (26K):
org.highwire.dtl.DTLVardef@db40f3org.highwire.dtl.DTLVardef@854b67org.highwire.dtl.DTLVardef@1197d69org.highwire.dtl.DTLVardef@78b48e_HPS_FORMAT_FIGEXP  M_FIG C_FIG HighlightsO_LIProposition of a new data-driven approach for neonatal mortality rate forecast, which provides a way for policy-makers to anticipate trends on neonatal mortality rates curves, making a better planning of health policies focused on NMR reduction possible;
C_LIO_LIa method for NMR forecasting with a MSE lower than 0.18;
C_LIO_LIan extensive evaluation of different Machine Learning (ML) regression models, as well as hyperparameters search, which accounts for the last stage in NeMoR;
C_LIO_LIa new time series database for NMR prediction problems;
C_LIO_LIa new features projection space for NMR forecasting problems, which considerably reduces errors in NRM prediction.
C_LI


title: COVID-19 vaccination beliefs, attitudes, and behaviours among health and social care workers in the UK: a mixed-methods study

abstract:
BackgroundThe UK began delivering its COVID-19 vaccination programme on 8 December 2020, with health and social care workers (H&SCWs) given high priority for vaccination. Despite well- documented occupational exposure risks, however, there is evidence of lower uptake among some H&SCW groups.

MethodsWe used a mixed-methods approach - involving an online cross-sectional survey and semi- structured interviews - to gain insight into COVID-19 vaccination beliefs, attitudes, and behaviours amongst H&SCWs in the UK by socio-demographic and employment variables. 1917 people were surveyed - 1658 healthcare workers (HCWs) and 261 social care workers (SCWs). Twenty participants were interviewed.

FindingsWorkplace factors contributed to vaccination access and uptake. SCWs were more likely to not be offered COVID-19 vaccination than HCWs (OR:1.453, 95%CI: 1.244 - 1.696). SCWs specifically reported uncertainties around how to access COVID-19 vaccination. Participants who indicated stronger agreement with the statement  I would recommend my organisation as a place to work were more likely to have been offered COVID-19 vaccination (OR:1.28, 95%CI: 1.06 - 1.56). Those who agreed more strongly with the statement  I feel/felt under pressure from my employer to get a COVID-19 vaccine were more likely to have declined vaccination (OR:1.75, 95%CI: 1.27- 2.41). Interviewees that experienced employer pressure to get vaccinated felt this exacerbated their vaccine concerns and increased distrust.

In comparison to White British and White Irish participants, Black African and Mixed Black African participants were more likely to not be offered (OR:2.011, 95%CI: 1.026 - 3.943) and more likely to have declined COVID-19 vaccination (OR:5.55, 95%CI: 2.29 - 13.43). Reasons for declining vaccination among Black African participants included distrust in COVID-19 vaccination, healthcare providers, and policymakers.

ConclusionH&SCW employers are in a pivotal position to facilitate COVID-19 vaccination access, by ensuring staff are aware of how to get vaccinated and promoting a workplace environment in which vaccination decisions are informed and voluntary.

category: health systems and quality improvement


title: RELIABILITY METHODS FOR ANALYZING COVID-19 PANDEMIC SPREADING BEHAVIOR, LOCKDOWN IMPACT AND INFECTIOUSNESS

abstract:
In 2021, the COVID-19 pandemic continues to challenge the globalized world. Restrictions on the public life and lockdowns of different characteristics define the life in many countries. This paper focuses on the first year of the COVID-19 pandemic (01-28-2020 to 01-15-2021). As a transfer of methods used in reliability engineering for analyzing occurrence of infection, Weibull distribution models are used to evaluate the spreading behavior of COVID-19.

Key issues of this study are the differences of spreading behavior in first and second pandemic phase and the various impacts of lockdown measures with different characteristics (hard, light). Therefore, the occurrence of infection in normed time periods with and without lockdown measures are analyzed in detail on the example of Germany representing the spreading behavior in Europe. Additional information in comparison to classical infection analyzes models like SIR model is generated by the application of Weibull distribution models with easy interpretable parameters and the dynamic development of COVID-19 is outlined.

In a further step, the occurrence of infection of COVID-19 is put into the context of other common infectious diseases in Germany like Influenza or Norovirus to evaluate the infectiousness. Differences in spreading behavior of COVID-19 in comparison to these well-known infectious diseases are underlined for different pandemic phases.

category: infectious diseases


title: Transmission characteristics of SARS-CoV-2 variants of concern: Rapid Scoping Review

abstract:
BackgroundAs of March 2021, three SARS-CoV-2 variants of concern (VOC) have been identified (B.1.1.7, B.1.351 and P.1) and been detected in over 111 countries. Despite their widespread circulation, little is known about their transmission characteristics. There is a need to understand current evidence on VOCs before practice and policy decisions can be made. This study aimed to map the evidence related to the transmission characteristics of three VOCs.

MethodsA rapid scoping review approach was used. Seven databases were searched on February 21, 2021 for terms related to VOCs, transmission, public health and health systems. A grey literature search was conducted on February 26, 2021. Title/abstracts were screened independently by one reviewer, while full texts were screened in duplicate. Data were extracted using a standardized form which was co-developed with infectious disease experts. A second data extractor verified the results. Studies were included if they reported on at least one of the VOCs and transmissibility. Animal studies and modeling studies were excluded. The final report was reviewed by content experts.

ResultsOf the 1796 articles and 67 grey literature sources retrieved, 16 papers and 7 grey sources were included. Included studies used a wide range of designs and methods. The majority (n=20) reported on B.1.1.7. Risk of transmission, reported in 15 studies, was 45-71% higher for B.1.1.7 compared to non-VOCs, while R0 was 75-78% higher and the reported Rt ranged from 1.1-2.8. There was insufficient evidence on the transmission risk of B.1.35.1 and P.1. Twelve studies discussed the mechanism of transmission of VOCs. Evidence suggests an increase in viral load among VOCs based on cycle threshold values, and possible immune evasion due to increased ACE2 binding capacity of VOCs. However, findings should be interpreted with caution due to the variability in study designs and methods.

ConclusionVOCs appear to be more transmissible than non-VOCs, however the mechanism of transmission is unclear. With majority of studies focusing on the B.1.1.7 VOC, more research is needed to build upon these preliminary findings. It is recommended that decision-makers continue to monitor VOCs and emerging evidence on this topic to inform public health policy.


title: Evaluation of the sensitivity, accuracy and currency of the Cochrane COVID-19 Study Register for supporting rapid evidence synthesis production

abstract:
IntroductionThe Cochrane COVID-19 Study Register (CCSR) is a public, continually updated, curated database of COVID-19 study references. The aim of this study-based register is to support rapid and living evidence synthesis, including a project to build an evidence ecosystem of COVID-19 research (CEOsys). In November and December 2020 we conducted an evaluation of the CCSR for CEOsys, measured its performance and identified areas for improvement.

MethodsFor the evaluation we generated a purposive sample of 286 studies from 20 reviews to calculate the CCSRs sensitivity (comprehensiveness), accuracy (correctly classified and linked studies) and currency (time to publish and process references).

ResultsThe CCSR had an overall sensitivity of 77.2%, with the highest sensitivity for interventional studies (94.4%) and lowest sensitivity for modelling studies (63.6%). The study register had 100% sensitivity for trial registry records, 86.5% for journal articles and 52.4% for preprints. 98.3% of references were correctly classified with regard to study type, and 93.4% with regard to study aim. 89% of studies were correctly linked. 81.4% of references were published to the register in under 30 days, with 0.5 day (median) for trial registry records, 2 days for journal articles and 56 days for preprints.

ConclusionThe CCSR had high sensitivity, accurate study classifications and short publishing times for journal articles and trial registry records. We identified that the CCSRs coverage and publishing times for preprints needed improvement. Finally, the evaluation illustrated the value of a study-based register for identifying additional study references for analysis in evidence synthesis.


title: Risk Profile of Thanksgiving Gatherers and Subsequent SARS-CoV2 Testing and Diagnosis

abstract:
BackgroundDuring Fall 2020 in the United States (U.S.), despite high COVID-19 case numbers and recommendations from public health officials not to travel and gather with individuals outside ones household, millions of people gathered for Thanksgiving. The objective of this study was to understand if individuals behaviors and risk perceptions influenced their decision to gather, and if they did gather, their subsequent test seeking and diagnoses.

MethodsParticipants were part of the CHASING COVID Cohort study - a U.S. national prospective cohort. The study sample consisted of participants who completed routine questionnaires before and after Thanksgiving. Non-pharmaceutical interventions (NPIs) use informed behavioral risk scores and a score of perceived risk of COVID-19 were assigned to each participant. Multinomial logistic regression models were used to assess the association between higher risk behaviors and gathering with other households, and the association of gathering with subsequent testing and test positivity.

ResultsA total of 1,932 (40.5%) cohort participants spent Thanksgiving with individuals from at least one other household. Participants with higher behavioral risk scores had greater odds of gathering with one other household (aOR: 2.35, 95% CI: 2.0, 2.7), two other households (aOR: 4.54, 95% CI: 3.7, 5.6), and three or more other households (aOR: 5.44, 95% CI: 4.1, 7.2). Participants perceiving COVID-19 as a low-risk to themselves and others had greater odds of gathering with one other household (aOR: 1.12, 95% CI: 0.97, 1.3), two other households (aOR: 1.39, 95% CI: 1.1, 1.7), and three or more other households (aOR: 1.86, 95% CI: 1.4, 2.4). Those who spent Thanksgiving with one or more other households had 1.23 times greater odds (95% CI: 1.1, 1.4) of having a COVID-19 test afterward. There was no association between gathering for Thanksgiving and subsequent COVID-19 test positivity or developing COVID-19 symptoms.

ConclusionsThose who gathered with other households for Thanksgiving tended to engage in higher-risk activities. Thanksgiving gathering with other households was not associated with subsequently testing positive for COVID-19, but only a small proportion obtained post-travel testing. Public health messaging should emphasize behavior change strategies that promote safer gathering.


title: Exploring the Behavioral Determinants of COVID-19 Vaccine Acceptance among an Urban Population in Bangladesh: Implications for Behavior Change Interventions

abstract:
BackgroundWhile vaccines ensure individual protection against COVID-19 infection, delay in receipt or refusal of vaccines will have both individual and community impacts. The behavioral factors of vaccine hesitancy or refusal are a crucial dimension that need understanding to implicate appropriate interventions. The aim of this study was to assess the behavioral determinants of COVID-19 vaccine acceptance and to provide recommendations to increase the uptake of COVID-19 vaccines in Bangladesh.

MethodsWe employed a Barrier Analysis (BA) approach to examine twelve potential behavioral determinants (drawn from the Health Belief Model and Theory of Reasoned Action [TRA]) of intended vaccine acceptance. We conducted 45 interviews with those who intended to take the vaccine (Acceptors) and another 45 interviews with those who did not have that intention (Non-acceptors). We performed data analysis to find statistically significant differences and to identify which beliefs were most highly associated with acceptance and non-acceptance with COVID-19 vaccines.

ResultsCOVID-19 vaccine Acceptors in Dhaka were different from Non-acceptors in terms of many of their beliefs and responses. The behavioral determinants associated with the behavior included perceived social norms, perceived safety of COVID-19 vaccines and trust in them, perceived risk/susceptibility, perceived self-efficacy, perceived positive and negative consequences, perceived action efficacy, perceived severity of COVID-19, access, and perceived divine will. In line with the Health Belief Model, beliefs about the disease itself were highly correlated with vaccine acceptance, although not the only determinant. Other responses of Acceptors provide clues such as providing vaccination through government health facilities, schools, and kiosks, and having vaccinators maintain proper COVID-19 health and safety protocols as to ways to make it easier to boost acceptance.

ConclusionAn effective behavior change strategy for COVID-19 vaccines uptake will need to address multiple beliefs and behavioral determinants, reducing barriers and leveraging enablers identified in this study. The national plans on COVID-19 vaccination should adopt culturally and community label acceptable and appropriate evidence-based behavior change interventions strategies to promote high vaccination coverage and acceptance in all societal structures across the country.


title: Optimal health and economic impact of non-pharmaceutical intervention measures prior and post vaccination in England: a mathematical modelling study

abstract:
BackgroundEven with good progress on vaccination, SARS-CoV-2 infections in the UK may continue to impose a high burden of disease and therefore pose substantial challenges for health policy decision makers. Stringent government-mandated physical distancing measures (lockdown) have been demonstrated to be epidemiologically effective, but can have both positive and negative economic consequences. The duration and frequency of any intervention policy could, in theory, could be optimised to maximise economic benefits while achieving substantial reductions in disease.

MethodsHere we use a pre-existing SARS-CoV-2 transmission model to assess the health and economic implications of different strengths of control through time in order to identify optimal approaches to non-pharmaceutical intervention stringency in the UK, considering the role of vaccination in reducing the need for future physical distancing measures. The model is calibrated to the COVID-19 epidemic in England and we carry out retrospective analysis of the optimal timing of precautionary breaks in 2020 and the optimal relaxation policy from the January 2021 lockdown, considering the willingness to pay for health improvement.

ResultsWe find that the precise timing and intensity of interventions is highly dependent upon the objective of control. As intervention measures are relaxed, we predict a resurgence in cases, but the optimal intervention policy can be established dependent upon the willingness to pay (WTP) per QALY loss avoided. Our results show that establishing an optimal level of control can result in a reduction in net monetary loss of billions of pounds, dependent upon the precise WTP value.

ConclusionsIt is vital, as the UK emerges from lockdown, but continues to face an on-going pandemic, to accurately establish the overall health and economic costs when making policy decisions. We demonstrate how some of these can be quantified, employing mechanistic infectious disease transmission models to establish optimal levels of control for the ongoing COVID-19 pandemic.


title: A Spatial Analysis of Hypertension Prevalence in Rural and Urban Malawi

abstract:
BackgroundNon-communicable diseases (NCD) represent a large and rapidly growing disease burden in Malawi and the wider sub-Saharan Africa region. National and regional NCD prevalence estimates and mapping, establishment of associated risk factors, and trend monitoring are vital for sustaining hard-won gains in well-being and life expectancy from the successful management of infectious diseases.

MethodsBetween 2012 and 2016, blood pressure was measured in a population-representative sample of 29,628 Malawian adults (18+ years) residing in two locations; the southern part of rural Karonga district and urban Area 25 in Lilongwe city. Each location was divided into approximately 200 zones with individuals assigned the zone in which their home was located. A conditional autoregressive (CAR) model was fitted to estimate zonal hypertension prevalence. Estimates were plotted on regional maps featuring key amenities, healthcare facilities, and transport links. Individual-level economic and lifestyle covariates were then incorporated to assess how much of the variation could be explained by those covariates.

ResultsVariation in hypertension prevalence was observed in both the rural and urban location (P < 0.0005), with high-prevalence zones clustering in areas near to major transport links and/or concentrations of amenities. Covariates explained most of the variation in both sites (P > 0.14).

ConclusionsIn rural and urban Malawi, hypertension prevalence is higher among those of relatively high wealth, those who are closer to local amenities, or a combination of these two factors. More detailed data are needed to determine if these associations are explained by wealth-consequent behaviours such as sedentary occupations and deleterious lifestyle choices.

category: epidemiology


title: Impact of national and regional lockdowns on COVID-19 epidemic waves: Application to the 2020 spring wave in France

abstract: Several countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like "where" and "when" still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increases. However, the public health costs associated with these delays tend to grow exponentially with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality and stress on the healthcare system.


title: Cross-classification between self-rated health and health status: longitudinal analyses of all-cause mortality and leading causes of death in the UK

abstract:
BackgroundRisk stratification is an important public health priority that is central to clinical decision making and resource allocation. The aim of the present study was to examine how different combinations of self-rated and objective health status predict (i) all-cause mortality and (ii) cause-specific mortality from leading causes of death in the UK.

MethodsThe UK Biobank study recruited >500,000 participants, aged 37-73, between 2006-2010. The health cross-classification examined incorporated self-rated health (poor, fair, good or excellent) and health status derived from medical history and current disease status, including 81 cancer and 443 non-cancer illnesses. We examined all-cause mortality and six specific causes of death: ischaemic heart disease, cerebrovascular disease, influenza and pneumonia, dementia and Alzheimers disease, chronic lower respiratory disease and malignant neoplasm.

ResultsAnalyses included >370,000 middle-aged and older adults with a median follow-up of 11.75 (IQR = 1.4) years, yielding 4,320,270 person years of follow-up. Compared to excellent self-rated health and favourable health status, all other levels of the health cross-classification were associated with a greater risk of mortality, with hazard ratios ranging from 1.22 (95% CI 1.15-1.29, pBonf. < 0.001) for good self-rated health and favourable health status to 7.14 (95% CI 6.70-7.60, pBonf. < 0.001) for poor self-rated health and unfavourable health status.

ConclusionsOur findings highlight that self-rated health captures additional health-related information and should be more widely assessed across settings. The cross-classification between health status and self-rated health represents a straightforward metric for risk stratification, with applications to population health, clinical decision making and resource allocation.


title: Maternal and child outcomes reported by breastfeeding women following mRNA COVID-19 vaccination

abstract:
Table of Contents SummaryO_ST_ABSWhats known on this subjectC_ST_ABSOne published U.S. study with 31 breastfeeding women who were vaccinated with either of the two available mRNA COVID-19 vaccines found that 67% experienced any side effects after dose one and 61% after dose two of the vaccine.

What this study addsMore than 85% of 180 breastfeeding women who received an mRNA COVID-19 vaccine reported local or systemic symptoms, with higher frequency following the second dose. Few symptoms were reported in their breastfed children. No serious adverse events were noted.

Contributors Statement PageDr. Chambers and Ms. Bertrand designed the study and supervised the collection of data used in the study. Mr. Honerkamp-Smith performed the statistical analysis. All authors were involved in preparing the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

category: pediatrics


title: Prevalence of traumatic psychological stress reactions in children and parents following paediatric surgery: a systematic review and meta-analysis

abstract:
BackgroundChildren undergoing surgery, and their parents, are at risk of developing post-traumatic stress reactions. We systematically reviewed the literature to understand the prevalence of this issue, as well as potential risk factors.

MethodsWe conducted a systematic review and meta-analysis, using PubMed, PsycInfo, Web of Science and Google Scholar, with searches conducted in February 2021. Papers were included if they measured post-traumatic stress in children and/or parents following paediatric surgery, and were excluded if they did not use a validated measure of post-traumatic stress. Data was extracted from published reports.

FindingsOur search yielded a total of 1,672 papers, of which 16 of met our inclusion criteria. In meta-analysis, pooled studies of children estimated an overall prevalence of 16% meeting criteria for post-traumatic stress disorder post-surgery (N= 187, 95% CI : 5-31%, I2 = 80%). After pooling studies of parents, overall prevalence was estimated at 23% (N= 1444, 95% CI 16-31%, I2 = 91%). Risk factors reported within studies included length of stay, level of social support and parental mental health.

InterpretationThere is consistent evidence of traumatic stress following surgery in childhood which warrants further investigation. Those delivering surgical care to children would benefit from a raised awareness of the potential for post-traumatic stress in their patients and their families, including offering screening and support.

FundingWe did not seek or receive any funding for this study.


title: A systematic review on Multisystem Inflammatory Syndrome in Children (MIS-C) with COVID-19: Development of a scoring system for clinical diagnosis

abstract:
BackgroundThere is growing evidence of Multisystem Inflammatory Syndrome in Children (MIS-C) resembling Kawasaki disease in children infected with SARS-CoV-2. The review was undertaken to evaluate the case definition, the spectrum of clinical presentations and current management practices in children with COVID-19 presenting with or without MIS-C.

MethodsThe individual patient data from 119 studies accounting for 333 children were analyzed. We devised a scoring system as per WHO criteria to classify the patients as MIS-C or without MIS-C. A score of 3 was given for the presence of fever (>24h) and a score of 1 for lab-confirmed diagnosis of SARS-CoV-2. Additionally, a score of 1 was given for a) rash or conjunctivitis or muco-cutaneous inflammation signs, b) hypotension or shock, c) diarrhea, vomiting or abdominal pain, d) features of myocardial dysfunction as determined by abnormal eco-cardiography or elevated Troponin or N-terminal pro B-type Natriuretic Peptide (NT-proBNP), e) evidence of coagulopathy as evidenced by elevated levels of prothrombin time PT, partial thromboplastin time PTT or D-dimer, f) laboratory evidence of inflammation as determined by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) or procalcitonin. A negative score of (-3) was given when there was a diagnosis of sepsis, staphylococcal or streptococcal shock syndrome. Based on these criteria, a minimum score of 6 was essential to classify the child as MIS-C.

ResultsBased on this score, 18% (52/289) of cases were identified to be MIS-C. A greater proportion of children with MIS-C had cardiac involvement (MIS-C 80% vs Non-MIS-C 20%) and gastrointestinal involvement (MIS-C 71% vs Non-MIS-C 12%). Lymphopenia was commonly reported in MIS-C (MIS-C 54.2% vs Non-MIS-C 29.7%). In addition to routine inflammatory markers, significantly greater proportion of children with MIS-C had elevated Ferritin, LDH, Fibrinogen and IL-6. Children with MIS-C were less likely to have respiratory symptoms like cough (MIS-C 25% vs Non-MIS-C 75%) and rhinorrhea (MIS-C 4% vs Non-MIS-C 22.8%). A greater proportion of children with MIS-C required intensive care and aggressive treatment; and mortality rates were also higher in MIS-C group (MIS-C 10% vs Non-MIS-C 1%).

ConclusionThe children with COVID-19 having cardiac and/or gastrointestinal involvement are more likely to develop MIS-C. The children with MIS-C have higher mortality rates. The scoring system developed herein will aid clinicians in patient diagnosis and timely management.


title: Evaluating the Perceived Utility of an Artificial Intelligence-Powered Clinical Decision Support System for Depression Treatment Using a Simulation Centre

abstract: Aifred is a clinical decision support system (CDSS) that uses artificial intelligence to assist physicians in selecting treatments for major depressive disorder (MDD) by providing probabilities of remission for different treatment options based on patient characteristics. We evaluated the utility of the CDSS as perceived by physicians participating in simulated clinical interactions. Twenty psychiatry and family medicine staff and residents completed a study in which each physician had three 10-minute clinical interactions with standardized patients portraying mild, moderate, and severe episodes of MDD. During these scenarios, physicians were given access to the CDSS, which they could use in their treatment decisions. The perceived utility of the CDSS was assessed through self-report questionnaires, scenario observations, and interviews. 60% of physicians perceived the CDSS to be a useful tool in their treatment-selection process, with family physicians perceiving the greatest utility. Moreover, 50% of physicians would use the tool for all patients with depression, with an additional 35% noting they would reserve the tool for more severe or treatment-resistant patients. Furthermore, clinicians found the tool to be useful in discussing treatment options with patients. The efficacy of this CDSS and its potential to improve treatment outcomes must be further evaluated in clinical trials.

category: psychiatry and clinical psychology


title: Epidemiology of COVID-19 and effect of public health interventions, Chennai, India, March - October 2020

abstract:
ObjectivesTo describe the public health strategies and their effect in controlling the COVID-19 pandemic from March to October 2020 in Chennai, India.

SettingChennai, a densely populated metropolitan city in Southern India, was one of the five cities which contributed to more than half of the COVID-19 cases in India.

ParticipantsWe collected the de-identified line list of all the 192,450 COVID-19 case-patients reported from 17 March to 31 October 2020 in Chennai and their contacts for the analysis. We defined a COVID-19 case-patient based on the RT-PCR positive test in one of the Government approved labs.

Outcome measuresThe primary outcomes of interest were incidence of COVID-19 per million population, case fatality ratio, deaths per million and the effective reproduction number (Rt). We also analysed the indicators for surveillance, testing, contact tracing and isolation.

ResultsOf the 192,450 RT-PCR confirmed COVID-19 case-patients reported in Chennai from 17 March-31 October 2020, 114,889 (60%) were males. The highest incidence was 41,064 per million population among the 61-80 years. The incidence peaked during June 2020 at 5239 per million and declined to 3,627 per million in October 2020. The city reported 3,543 deaths, with a case fatality ratio (CFR) of 1.8% and the crude death rate was 431 per million. When lockdown began, Rt was high (4.2) in March and fluctuated from April to June 2020. The Rt dropped below one by the first week of July and remained so until October 2020, even with the relaxation of restrictions

ConclusionThe combination of public health strategies controlled the COVID-19 epidemic in a large, densely populated city in India. We recommend continuing the interventions to prevent resurgence, even as vaccination is being rolled out.

StrengthsO_LIWe did a comprehensive analysis of COVID-19 strategies and outcome in a large, densely populated metropolitan city in India.
C_LIO_LIWe documented that the community-centric public health strategies were feasible and effective in controlling the COVID-19 outbreak even in a large, thickly populated city
C_LIO_LIThe lessons learnt are relevant to similar settings in low-and middle-income countries. Given the ongoing multiple waves of COVID-19 and the difficulty in controlling the transmission, our experience and lessons learnt will be valuable for policymakers and scientific advisors globally
C_LI

LimitationsO_LIWe analysed the data available from the GCC database and not from the hospitals where patients with moderate to severe illness were admitted. Hence, we could not report the severity of illness among admitted patients.
C_LIO_LISecond, the COVID-19 incidence might have been underestimated while testing was low during the early phase of the epidemic
C_LI

category: public and global health


title: COVID-19 Vaccine Hesitancy among the Adult Population in Bangladesh: A Nationally Representative Cross-sectional Survey

abstract:
IntroductionThe study related to the COVID-19 vaccine hesitancy is scanty in the context of Bangladesh, despite the growing necessity of understanding the mass peoples vaccination-related behavior. Thus, the present study was conducted to assess the prevalence of the COVID-19 vaccine hesitancy and its associated factors in Bangladesh to fill the knowledge gap.

MethodologyThis study adopted a cross-sectional study design to collect data from 1497 respondents using online (Google forms) and face-to-face interviews. We employed descriptive statistics and multiple hierarchical linear regression analysis.

FindingsThe prevalence of vaccine hesitancy was 41.1%. Men had less hesitancy ({beta} = -0.046, p = 0.030) than women. The Muslims ({beta} = 0.057, p = 0.009) and the respondents living in the city corporation areas ({beta} = 0.132, p <0.001) had more hesitancy. There was significant variation in vaccine hesitancy by administrative divisions (geographic regions). The vaccine hesitancy tended to decrease with increasing knowledge about the vaccine ({beta} = -0.072, p=0.001) and the vaccination process ({beta}= -0.058, p = 0.018). On the other hand, hesitancy increased with the increased negative attitudes towards vaccine ({beta} = 0.291, p <0.001) and conspiracy beliefs towards the COVID-19 vaccine ({beta} = 0.105, p=0.004). The perceived severity of the COVID-19 ({beta} = -0.079, p=0.002) and perceived benefits of COVID-19 vaccination ({beta} = -0.180, p=0.001) were negatively associated with hesitancy, while perceived barriers ({beta} = 0.180, p <0.001) were positively associated. The participants were more hesitant to accept the vaccine from a specific manufacturer.

ConclusionThis study emphasizes that negative attitudes and conspiracies towards the COVID-19 vaccine should be reduced through effective communications and contracting with additional vaccine manufacturers should be prioritized. The barriers like online registration for receiving the COVID-19 vaccination need to be removed, and initiatives like text message service using the mobile phone operator can be introduced.

HighlightsO_LIAbout 41% of the respondents had had hesitancy to accept the COVID-19 vaccine.
C_LIO_LIThe hesitancy increased with negative attitudes about vaccines and conspiracy beliefs.
C_LIO_LIPerceived barriers to receive the vaccine were increasing vaccine hesitancy.
C_LIO_LIPerceived severity of the COVID-19 decreased the vaccine hesitancy.
C_LIO_LIPerceived benefits of receiving the COVID-19 vaccine decreased the vaccine hesitancy.
C_LI


title: Effects of the COVID-19 Pandemic on Park Use in U.S. Cities

abstract:
IntroductionThe COVID-19 pandemic focused attention on city parks as important public resources. However, it is unknown how city park use in 2020 compared to prior years and whether COVID-19 may have exacerbated racial/ethnic inequities in access. Moreover, traditional methods of measuring park use present major drawbacks.

MethodsWe analyzed monthly mobility data derived from a large panel of smartphone devices, cross-referenced with a database of parks locations sourced from local agencies. We assessed park use trends in 44 of the 50 most populous U.S. cities from January 2018 to November 2020 using interrupted time series regressions. We also compared parks to other city amenities (e.g., gyms and libraries).

ResultsBased on a sample of 5,559 city parks, park visits declined by 14.6% (95% CI [9.2, 19.7], p < 0.001) from March through November 2020, compared to prior levels and trends. When we segmented the COVID-19 period by time of widespread closures (March-April) and partial-to-full reopenings (May-November), we estimated a larger reduction during closures (35.7% reduction, 95% CI [33.5, 37.8], p < 0.001) compared to the reduction during reopenings (8.0% reduction, 95% CI [1.9, 13.7], p = 0.001). Reductions for other amenities were more prolonged. In park service areas where a greater proportion of residents were White, reopening was associated with more visits, suggesting that racial privilege influenced access.

ConclusionsSmartphone mobility data can address a data availability gap for monitoring park use. Park use only declined modestly in 2020. Opportunities exist to make access more racially equitable.

Significance statementParks are public resources that promote health. Little is known about how parks have been used during the COVID-19 pandemic, when parks have become particularly important public spaces. This study introduces an approach to monitor park use over time, using location data from smartphones. This approach enabled the authors to evaluate trends in park use during the pandemic, including major gaps in visits to parks according to whether they mostly served White residents or residents of color. This big data approach offers advantages over traditional methods for monitoring park use and can help city officials to identify and address inequities in park access.


title: Efficacy of universal masking for source control and personal protection from simulated cough and exhaled aerosols in a room

abstract: Face masks reduce the spread of infectious respiratory diseases such as COVID-19 by blocking aerosols produced during coughs and exhalations ("source control"). Masks also slow and deflect cough and exhalation airflows, which changes the dispersion of aerosols. Factors such as the directions in which people are facing (orientation) and separation distance also affect aerosol dispersion. However, it is not clear how masking, orientation, and distance interact. We placed a respiratory aerosol simulator ("source") and a breathing simulator ("recipient") in a 3 m x 3 m chamber and measured aerosol concentrations for different combinations of masking, orientation, and separation distance. When the simulators were front-to-front during coughing, masks reduced the 15-minute mean aerosol concentration at the recipient by 92% at 0.9 and 1.8 m separation. When the simulators were side-by-side, masks reduced the concentration by 81% at 0.9 m and 78% at 1.8 m. During breathing, masks reduced the aerosol concentration by 66% when front-to-front and 76% when side-by-side at 0.9 m. Similar results were seen at 1.8 m. When the simulators were unmasked, changing the orientations from front-to-front to side-by-side reduced the cough aerosol concentration by 59% at 0.9 m and 60% at 1.8 m. When both simulators were masked, changing the orientations did not significantly change the concentration at either distance during coughing or breathing. Increasing the distance between the simulators from 0.9 m to 1.8 m during coughing reduced the aerosol concentration by 25% when no masks were worn but had little effect when both simulators were masked. During breathing, when neither simulator was masked, increasing the separation reduced the concentration by 13%, which approached significance, while the change was not significant when both source and recipient were masked. Our results show that universal masking reduces exposure to respiratory aerosol particles regardless of the orientation and separation distance between the source and recipient.


title: Imputation of PaO2 from SpO2 values from the MIMIC-III Critical Care Database Using Machine-Learning Based Algorithms

abstract:
BackgroundThe partial pressure of oxygen (PaO2)/fraction of oxygen delivered (FIO2) ratio is the reference standard for assessment of hypoxemia in mechanically ventilated patients. Non-invasive monitoring with the peripheral saturation of oxygen (SpO2) is increasingly utilized to estimate PaO2 because it does not require invasive sampling. Several equations have been reported to impute PaO2/FIO2 from SpO2 /FIO2. However, machine-learning algorithms to impute the PaO2 from the SpO2 has not been compared to published equations.

Research QuestionHow do machine learning algorithms perform at predicting the PaO2 from SpO2 compared to previously published equations?

MethodsThree machine learning algorithms (neural network, regression, and kernel-based methods) were developed using 7 clinical variable features (n=9,900 ICU events) and subsequently 3 features (n=20,198 ICU events) as input into the models from data available in mechanically ventilated patients from the Medical Information Mart for Intensive Care (MIMIC) III database. As a regression task, the machine learning models were used to impute PaO2 values. As a classification task, the models were used to predict patients with moderate-to-severe hypoxemic respiratory failure based on a clinically relevant cut-off of PaO2/FIO2 [≤] 150. The accuracy of the machine learning models was compared to published log-linear and non-linear equations. An online imputation calculator was created.

ResultsCompared to seven features, three features (SpO2, FiO2 and PEEP) were sufficient to impute PaO2/FIO2 ratio using a large dataset. Any of the tested machine learning models enabled imputation of PaO2/FIO2 from the SpO2/FIO2 with lower error and had greater accuracy in predicting PaO2/FIO2 [≤] 150 compared to published equations. Using three features, the machine learning models showed superior performance in imputing PaO2 across the entire span of SpO2 values, including those [≥] 97%.

InterpretationThe improved performance shown for the machine learning algorithms suggests a promising framework for future use in large datasets.

category: respiratory medicine


title: Attenuated alpha oscillations as an index of cortical hyperexcitability: Evidence from migraine patients

abstract: Anomalous phantom visual perceptions coupled to an aversion to some visual patterns has been associated with aberrant cortical hyperexcitability in migraine patients. Previous literature has found fluctuations of alpha oscillation (8-14 Hz) over the visual cortex to be associated with the gating of the visual stream. In the current study, we examined whether alpha activity was differentially modulated in migraineurs in anticipation of an upcoming stimulus as well as post-stimulus periods. We used EEG to examine the brain activity in a group of 28 migraineurs (17 with aura/11 without) and 29 non-migraineurs and compared the modulations of alpha power in the pre/post-stimulus period relative to onset of stripped gratings of 3 spatial frequencies 0.5, 3, and 13 cycles per degree (cpd). Overall, we found that that migraineurs had significantly less alpha power prior to the onset of the stimulus relative to controls. Moreover, relative to the control group, migraineurs had significantly greater post-stimulus alpha suppression (i.e event-related desynchronization) induced by the 3 cpd grating at the 2nd half of the experiment, the stimulus most often reported to induce visual disturbances. These findings taken together provide strong support of the presence of elevated cortical excitability in the visual cortex of migraine sufferers. We speculate that cortical hyperexcitation could be the consequence of impaired perceptual learning driven by the dysfunction of GABAergic inhibitory mechanism.

category: neurology


title: Whole genome sequencing as an investigational device for return of hereditary disease risk and pharmacogenomic results as part of the All of Us Research Program

abstract: The All of Us Research Program (AoURP,  the program) is an initiative, sponsored by the National Institutes of Health (NIH), that aims to enroll one million people (or more) across the United States. Through repeated engagement of participants, a research resource is being created to enable a variety of future observational and interventional studies. The program has also committed to genomic data generation and returning important health-related information to participants. To do so, whole genome sequencing (WGS), variant calling processes, data interpretation, and return-of-results procedures had to be created and receive an Investigational Device Exemption (IDE) from the United States Food and Drug Administration (FDA). The performance of the entire workflow was assessed through the largest known cross-center, WGS-based, validation activity that was refined iteratively through interactions with the FDA over many months. The accuracy and precision of the WGS process as a device for the return of certain health-related genomic results was determined to be sufficient, and an IDE was granted. We present here both the process of navigating the IDE application process with the FDA and the results of the validation study as a guide to future projects which may need to follow a similar path. Future supplements to the IDE will be submitted to support additional variant classes, sample types, and any expansion to the reportable regions.


title: Point of Care Testing using rapid automated Antigen Testing for SARS-COV-2 in Care Homes; an exploratory safety, usability and diagnostic agreement evaluation

abstract:
IntroductionSuccessful adoption of POCTs (Point-of-Care tests) for COVID-19 in care homes requires the identification of ideal use cases and a full understanding of contextual and usability factors that affect test results and minimise biosafety risks. This paper presents findings from a scoping-usability and test performance study of a microfluidic immunofluorescence assay for COVID-19 in care homes.

MethodsA mixed-methods evaluation was conducted in four UK care homes to scope usability and to assess the agreement with qRT-PCR. A dry run with luminescent dye was carried out to explore biosafety issues.

ResultsThe agreement analysis was carried out on 227 asymptomatic participants (159 staff and 68 residents) and 14 symptomatic participants (5 staff and 9 residents). Asymptomatic specimens showed 50% (95% CI: 1.3%-98.7%) positive agreement and 96% (95% CI: 92.5%-98.1%) negative agreement with overall prevalence and bias-adjusted Kappa (PABAK) of 0.911 (95% CI: 0.857-0.965). Symptomatic specimens showed 83.3% (95% CI: 35.9%-99.6%) positive agreement and 100% (95% CI: 63.1%-100%) negative agreement with overall prevalence and bias-adjusted Kappa (PABAK) of 0.857 (95% CI: 0.549-1).

The dry run showed four main sources of contamination that led to the modification of the standard operating procedures. Simulation after modification showed no further evidence of contamination.

ConclusionCareful consideration of biosafety issues and contextual factors associated with care home are mandatory for safe use the POCT. Whilst POCT may have some utility for ruling out COVID-19, further diagnostic accuracy evaluations are needed to promote effective adoption.


title: Safety and efficacy of Pulmonary physiotherapy in hospitalized patients with severe COVID-19 pneumonia (PPTCOVID): A prospective, randomised, single-blind, controlled trial

abstract:
BackgroundPulmonary physiotherapy (PPT) is an important treatment in the management of patients with different types of pulmonary disorders. We aimed to evaluate safety and efficacy of PPT in hospitalized patients with severe COVID-19 pneumonia.

MethodsIn this randomised, single-blind, controlled trial, we enrolled hospitalized, non-intubated patients (18 to 75 years with oxygen saturation (Spo2) in free-air breathing [≤]90%) with COVID-19 pneumonia at a referral hospital. Participants were randomly assigned (1:1) to receive PPT (six sessions PPT with breathing exercises and airway clearance techniques) or basic care. The primary outcomes were venous blood O2 (pO2) and CO2 (pCO2) pressures, Spo2, and three-minute walking test (3MWT) that were assessed before and end of sixth session. Secondary outcomes included level of dyspnea, venous blood PH, one-month mortality, three-month mortality and short form-36 (SF-36) after one and three months. The assessor was blinded to the assignment. This trial is registered with ClinicalTrials.gov (NCT04357340).

FindingsIn April-May 2020, 40 participants were randomly assigned to PPT or basic care groups. While at the end of intervention, pO2 (adjusted mean difference to baseline measure (AMD) 6.43 mmHg [95%CI 2.8, 10.07], P<0.01), Spo2 (AMD 4.43% [95%CI 2.04, 6.83], P=0.0011), and 3MTW (AMD 91.44 m [95%CI 68.88, 113.99], P<0.01) were higher in PPT group and basic care group, pCO2 was not improved (AMD -2.1 mmHg [95%CI-6.36, 2.21], P=0.33). Mortality rate was 20% (OR adjusted to baseline Spo2 .19 [95%CI .03, 1.30], P=.09) and 25% (OR adjusted to baseline Spo2 .16 [95%CI .26, 1.05], P=.056) lower in the PPT group at three-month at one-month and three-month, respectively. There were no significant differences in most SF-36 domains scores after one and three months. No serious adverse event was observed during PPT sessions.

ConclusionEarly PPT can be considered a safe and effective therapeutic choice for patients with severe COVID-19.

category: rehabilitation medicine and physical therapy


title: Safety and efficacy of Pulmonary physiotherapy in hospitalized patients with severe COVID-19 pneumonia (PPTCOVID Study): A prospective, randomised, single-blind, controlled trial


title: Surveillance of potential pathogens and antibiotic resistance in wastewater and surface water from Boston, USA and Vellore, India using long-read metagenomic sequencing

abstract: Environmental sampling (wastewater) could be an efficient surveillance strategy to capture global emerging trends in the spread of antibiotic resistance. Long-read DNA sequencing can resolve the genetic context of antibiotic resistance genes (ARGs) and is a promising tool for non-culture-based monitoring of antibiotic-resistant pathogens and ARGs in environmental samples, but has not been rigorously validated against conventional methods. We tested long-read sequencing using the portable Nanopore MinION for surveying pathogens, ARGs, and antibiotic-resistant pathogens in municipal wastewater, hospital wastewater, and surface water collected from Boston, USA and Vellore, India. We compared detection of enteric pathogens by assembly of long reads, with and without short-read polishing, and unassembled raw long reads for ARGs to multiplex real-time PCR. Using real-time PCR as a benchmark, long-read metagenomics was 49% sensitive and 75% specific at pathogen detection in assembled contigs, and 16% sensitive and 100% specific at detecting 28 clinically relevant resistance genes in raw long reads. Short-read polishing did not substantially improve pathogen identification or impact ARG identification in the assembled contigs, demonstrating that short-read polishing is not required, which greatly reduces costs. The high specificity of ARG detection supports portable long-read sequencing as a valuable tool to profile ARGs and antibiotic-resistant pathogens for environmental surveillance programs.


title: Resting-state functional MRI signal fluctuations are correlated with brain amyloid-β deposition

abstract:
Mounting evidence suggests that amyloid-{beta} (A{beta}) and vascular etiologies are intertwined in the pathogenesis of Alzheimers disease. Spontaneous fluctuations of the brain blood-oxygen-level-dependent (BOLD) signal, as measured by resting-state functional MRI (rs-fMRI), have been shown to be associated with neuronal activities as well as cerebrovascular hemodynamics. Nevertheless, it is unclear if rs-fMRI BOLD fluctuations are associated with brain A{beta} deposition in individuals with an elevated risk of Alzheimers disease.

We recruited 33 patients with amnestic mild cognitive impairment who underwent rs-fMRI and positron emission tomography (PET). The A{beta} standardized uptake value ratio (SUVR) was calculated with cortical white matter as the reference region to improve sensitivity for cortical A{beta} quantification. We calculated the amplitudes of low-frequency fluctuations (ALFF) of local BOLD signals in the frequency band of 0.01-0.08 Hz. Applying physiological/vascular signal regression in stepwise increasing levels on the rs-fMRI data, we examined whether local correlations between ALFF and brain A{beta} deposition were driven by vascular hemodynamics, spontaneous neuronal activities, or both.

We found that ALFF and A{beta} SUVR were negatively correlated in brain regions involving the default-mode and visual networks, with peak correlation at the precuneus, and angular, lingual, and fusiform gyri. Regions with higher ALFF had less A{beta} accumulation. The correlated cluster sizes in MNI space were reduced from 3018 mm3 with no physiological/vascular regression to 1072 mm3 with strong physiological/vascular regression, with mean cluster r values at approximately -0.47.

Results demonstrate that both vascular hemodynamics and neuronal activities, as reflected by BOLD fluctuations, are negatively associated with brain A{beta} deposition. These findings further imply that local brain blood fluctuations due to either vascular hemodynamics or neuronal activities can affect A{beta} homeostasis.

category: radiology and imaging


title: Role of non-aerosols activities in the transmission of SARS-Cov-2 infection among health care workers.

abstract:
BackgroundSince the emergence of SARS-CoV-2, health care workers (HCWs) have been on the front line in caring for COVID-19 patients. Better knowledge of risk factors for SARS-CoV-2 infection is crucial for the prevention of disease among this population.

MethodsWe conducted a seroprevalence survey among HCWs in a French university hospital after the first wave (May-June 2020), based on a validated lateral flow immuno-assay test (LFIAT) for SARS-CoV-2. Demographic characteristics as well as data on the working characteristics of COVID-19 and non-COVID-19 wards and 23 care activities were systematically recorded. The effectiveness of protective equipment was also estimated, based on self-declaration of mask use. SARS-CoV-2 IgG status was modelled by multiple imputations approach, accounting for the performance of the test and data on serum validation ELISA immunoassay.

FindingsAmong the 3,234 enrolled HCWs, the prevalence of SARS-CoV-2 IgG was 3.8%. Contact with relatives or HCWs who developed COVID-19 were risk factors for SARS-CoV-2 infection, but not contact with COVID-19 patients. In multivariate analyses, suboptimal use of protective equipment during naso-pharyngeal sampling, patient mobilisation, clinical and eye examination was associated with SARS-CoV-2 infection. In addition, patients washing and dressing and aerosol-generating procedures were risk factors for SARS-CoV-2 infection with or without self-declared appropriate use of protective equipment.

InterpretationMain routes of transmission of SARS-CoV-2 IgG among HCWs were i) contact with relatives or HCWs with COVID-19, ii) close or prolonged contact with patients, iii) aerosol-generating procedures.


title: Genetic analyses on the health impacts of testosterone highlights effects on female-specific diseases and sex differences

abstract:
Testosterone (T) is linked with diverse characteristics of human health, yet, whether these associations reflect correlation or causation remains debated. Here, we provide a broad perspective on the role of T on complex diseases in both sexes leveraging genetic and health registry data from the UK Biobank and FinnGen (total N=625,650).

We find genetically predicted T affects sex-biased and sex-specific traits, with a particularly pronounced impact on female reproductive health. We show T levels are intricately involved in metabolism, sharing many associations with sex hormone binding globulin (SHBG), but report lack of direct causality behind most of these associations. Across other disease domains, including behavior, we find little evidence for a significant contribution from normal variation in T levels. Highlighting Ts unique biology, we show T associates with antagonistic effects on stroke risk and reproduction in males and females.

Overall, we underscore the involvement of T in both male and female health, and the complex mechanisms linking T levels to disease risk and sex differences.


title: Genetic analyses on the health impacts of testosterone highlight effects on female-specific diseases and sex differences


title: Tocilizumab and mortality in hospitalised patients with covid-19. A systematic review comparing randomised trials with observational studies

abstract:
ObjectiveTo summarise and compare evidence from randomised controlled trials and observational studies of the effect of tocilizumab on in-hospital mortality in patients with covid-19.

DesignSystematic review and meta-analysis.

Data sourcesSearches conducted in Embase and PubMed from July 2020 until 1 March 2021.

Study SelectionObservational studies and randomised controlled trials (RCTs) assessing in-hospital mortality in patients receiving tocilizumab compared with standard care or placebo.

Data extractionThe primary outcome was in-hospital mortality at 30 days. The risk of bias in observational studies was assessed using the ROBINS-I tool. A fixed effect meta-analysis was used to combine relative risks, with random effects and risk of bias as a sensitivity analysis.

ResultsOf 5,792 publications screened for inclusion, eight RCTs and 35 observational studies were identified. The RCTs showed an overall relative risk reduction in in-hospital mortality at 30 days of 0.86 (95% CI 0.78 to 0.96) with no statistically significant heterogeneity. 23 of the observational studies had a severe risk of bias, 10 of which did not adjust for potential confounders. The 10 observational studies with moderate risk of bias reported a larger reduction in mortality at 30-days (relative risk 0.72, 95% CI 0.64 to 0.81) but with significant heterogeneity (P<0.01).

ConclusionThis meta-analysis provides strong evidence from RCTs that tocilizumab reduces the risk of mortality in hospitalised covid-19 patients. Observational studies with moderate risk of bias exaggerated the benefits on mortality two-fold and showed heterogeneity. Collectively observational studies provide a less reliable evidence base for evaluating treatments for covid-19.

Summary boxO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIEarly case reports suggested that tocilizumab might produce clinical and biochemical improvement in covid-19. This was followed by observational studies using retrospective data, largely supporting clinicians impressions of benefit.
C_LIO_LIThis led to wider use of tocilizumab, despite failure to show benefit on all-cause mortality from early underpowered randomised controlled trials (RCTs) in severe covid-19. The RECOVERY trial, the largest trial, has recently shown clear overall benefit in hospitalised patients with covid-19.
C_LI

What this study addsO_LIThis meta-analysis provides strong evidence from RCTs that tocilizumab reduces the risk of mortality in hospitalised covid-19 patients.
C_LIO_LIObservational studies with moderate risk of bias exaggerated the benefits on mortality by two-fold.
C_LIO_LICollectively observational studies provide a less reliable evidence base for evaluating treatments for covid-19.
C_LI

category: pharmacology and therapeutics


title: Indirect Effects of COVID-19 on Maternal, Neonatal, Child, Sexual and Reproductive Health Services in Kampala, Uganda

abstract:
BackgroundCOVID-19 impacted global maternal, neonatal and child health outcomes. We hypothesised that the early, strict lockdown which restricted individuals movements in Uganda limited access to services.

MethodsAn observational study, using routinely collected data from Electronic Medical Records was carried out, in Kawempe district, Kampala. An interrupted time series analysis assessed the impact on maternal, neonatal, child, sexual and reproductive health services from July 2019 to December 2020. Descriptive statistics summarised the main outcomes before (July 2019 - March 2020), during (April 2020 - June 2020) and after the national lockdown (July 2020 - December 2020).

ResultsBetween 1st July 2019 and 31st December 2020 there were 14,401 antenatal clinic attendances, 33,499 deliveries, 111,658 childhood service attendances and 57,174 for sexual health. All antenatal and vaccination services ceased in lockdown for four weeks. During the three-month lockdown, the number of antenatal attendances significantly decreased, and remain below pre-COVID levels (370 fewer/month). Attendances for prevention of mother-to-child transmission of HIV dropped then stabilised. Increases during lockdown and immediately postlockdown included the number of women treated for high blood pressure, eclampsia and pre-eclampsia (218 more/month), adverse pregnancy outcomes (stillbirths, low-birth-weight and premature infant births), the rate of neonatal unit admissions, neonatal deaths and abortions. Maternal mortality remained stable. Immunisation clinic attendance declined whilst neonatal death rate rose (from 39-49/1000 livebirths). The number of children treated for pneumonia, diarrhoea and malaria decreased during lockdown.

ConclusionThe Ugandan response to COVID-19 negatively impacted maternal, child and neonatal health, with an increase seen in pregnancy complications, and fetal and infant outcomes, likely due to delayed care-seeking behaviour. Decreased vaccination clinic attendance leaves a cohort of infants unprotected, affecting all vaccine-preventable diseases. Future pandemic responses must consider impacts of movement restrictions and access to preventative services to protect maternal and child health.

O_TEXTBOXKEY QUESTIONS

What is already known?O_LIThe response to COVID-19 has been shown to have indirectly impacted on maternal, child, neonatal, sexual, and reproductive health.
C_LIO_LIThis is largely related to access to services and fear of contracting COVID-19 in outpatient departments.
C_LIO_LIThere has been very little data published on the health impacts of the COVID-19 response in Uganda.
C_LI

What are the new findings?O_LIAntenatal attendances decreased dramatically in April, followed by increased numbers low-birthweight infants and neonatal deaths.
C_LIO_LINewborn immunisations against polio, tetanus, diphtheria, hepatitis B, haemophilus influenzae, rotavirus and pneumococcus decreased significantly.
C_LIO_LISexual, and reproductive health services were reduced in number.
C_LI

What do the new findings imply?O_LIAlthough Uganda has been less affected directly by COVID-19 infections in the first wave, the indirect impacts are far-reaching and will have future influences on population health.
C_LIO_LIThere is a degree of resilience within the healthcare service, but many services were adversely affected by the lockdown leading to poorer pregnancy and neonatal outcomes.
C_LIO_LIAntenatal and vaccination services are of particular importance in ensuring the safety of mother and child and must be prioritised in the responses to future pandemics.
C_LI

C_TEXTBOX


title: Estimation of local time-varying reproduction numbers in noisy surveillance data

abstract: 1A valuable metric in understanding local infectious disease dynamics is the local time-varying reproduction number, i.e. the expected number of secondary local cases caused by each infected individual. Accurate estimation of this quantity requires distinguishing cases arising from local transmission from those imported from elsewhere. Realistically, we can expect identification of cases as local or imported to be imperfect. We study the propagation of such errors in estimation of the local time-varying reproduction number. In addition, we propose a Bayesian framework for estimation of the true local time-varying reproduction number when identification errors exist. And we illustrate the practical performance of our estimator through simulation studies and with outbreaks of COVID-19 in Hong Kong and Victoria, Australia.


title: Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers: an observational cohort study.

abstract:
BackgroundThe SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the UK National Health Service (NHS). During the first wave of SARS-CoV-2 transmission in UK, SARS-CoV-2 NHS diagnostic test availability was limited to self-isolating symptomatic staff. The burden of symptomatic and asymptomatic infection in healthcare workers (HCW) attending work was unknown.

MethodsWe conducted an observational cohort study of SARS-CoV-2 infection in HCW working in an acute NHS Trust during the first wave of the COVID-19 pandemic, using serial self-collected saliva and nasopharyngeal (NP) samples. We also collected self-assessed symptom profiles and isolation behaviours. We retrospectively compared SARS-CoV-2 detection by RT-PCR from saliva (weekly) and NP swabs (twice weekly) from 85 individuals in this cohort and evaluated the association with symptoms.

FindingsOver a 12-week period from 30th March 2020, 40% (n=34/85, CI95% 31.3-51.8%) HCWs had evidence of SARS-CoV-2 infection by surveillance NP swab and/or saliva RT-qPCR. Agreement between paired saliva and NP swabs was poor (28.6%, CI95% 13.2-48.7%) with both methods detecting symptomatic and asymptomatic infections. Symptoms were reported by 47.1% (n=40) and self-isolation by 25.9% participants (n=22). Only 41.2% (n=14/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of the infection.

InterpretationHCWs are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections in HCW. Saliva is an easily accessible fluid sample for screening for SARS-CoV-2 infection and in addition to NP swab, facilitated ascertainment of symptomatic and asymptomatic cases in this setting. Combined saliva and NP testing would improve detection of SARS-CoV-2 for surveillance. Better understanding of transmissibility from asymptomatic staff using transmission-based infection precautions, is required to inform policy.


title: Transmission of SARS-CoV-2 within households: a prospective cohort study in the Netherlands and Belgium - Interim results

abstract:
BackgroundHousehold transmission studies are useful to obtain granular data on SARS-CoV-2 transmission dynamics and to gain insight into the main determinants. In this interim report we investigated secondary attack rates (SAR) by household and subject characteristics in the Netherlands and Belgium.

MethodsHouseholds with a real-time reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 index case were enrolled <48 hours following report of the positive test result. Daily symptom follow-up, standardized nose-throat sampling at enrollment and at new-onset acute respiratory illness (ARI) and paired dried blood spots (DBS) were collected from each participant. Children 0-2 years of age were additionally requested to collect a stool sample 7 days after enrollment and at new-onset of ARI. Swabs and stool samples were tested by RT-PCR for virus detection and DBS by multiplex protein microarray for detection of SARS-CoV-2 antibodies. The SAR was calculated 1) per-household as the proportion of households with [≥]1 secondary SARS-CoV-2 case and 2) per-person as the probability of infection in household members at risk. We explored differences in SARs by household and subject characteristics.

ResultsThis analysis includes 117 households that completed follow-up between April-December 2020. Among 382 subjects, 74 secondary infections were detected, of which 13 (17.6%) were asymptomatic and 20 (27.0%) infections were detected by seroconversion only. Of cases detected by RT-PCR, 50 (67.6%) were found at enrollment. The household SAR was 44.4% (95%-CI: 35.4-53.9%) and was higher for index cases meeting the ARI case definition (52.3%; 95%-CI 41.4-62.9%) compared to mildly symptomatic (22.2%; 95%-CI: 9.4-42.7%) and asymptomatic index cases (0.0%; 95%-CI: 0.0-80.2%). The per-person SAR was 27.9% (95%-CI: 22.7-33.8%). Transmission was lowest from child to parent (9.1%; 95%-CI: 2.4-25.5%) and highest from parent to child (28.1%; 95%-CI: 19.7-38.4%) and in children 6-12 years (34.2%; 95%-CI: 20.1-51.4%). Among 141 subjects with RT-PCR confirmed SARS-CoV-2 infections, seroconversion was detected in 111 (78.7%).

ConclusionWe found a high household SAR, with the large majority of transmissions detected early after identification of the index case. Our findings confirm differential SAR by symptom status of the index. In almost a quarter of RT-PCR positive cases, no antibodies were detected. Other factors influencing transmission will be further explored as more data accumulate.


title: Reduced Reflex Autonomic Responses following Intradetrusor OnabotulinumtoxinA Injections: A pre/post study in Individuals with Cervical and Upper Thoracic Spinal Cord Injury

abstract:
ImportanceUrodynamic studies (UDS) can provoke autonomic dysreflexia (AD) in individuals with spinal cord injury (SCI) at and above the sixth thoracic (T6) spinal segment potentially leading to profound vagally mediated heart rate reductions. Intradetrusor onabotulinumtoxinA injections have been shown to reduce AD events during UDS in this cohort but evidence is lacking whether this treatment can improve reflex autonomic responses.

ObjectiveTo assess the effects of intradetrusor onabotulinumtoxinA injections on heart rate variability (HRV) responses to UDS in individuals, 18-65 years of age, with chronic (>1-year) SCI at or above T6 with confirmed neurogenic detrusor overactivity and AD during UDS.

Design, Setting, and ParticipantsThis cohort study used participants from our recent prospective phase IV clinical trial. Individuals were screened at an academic medical centre between November 2014 and December 2019. After enrollment, participants underwent UDS prior to (i.e., baseline) and one month after intradetrusor onabotulinumtoxinA injections (post-treatment).

InterventionsOnabotulinumtoxinA (200 U) was injected into the detrusor muscle at 20 sites (10 U/site).

Main Outcomes and MeasuresContinuous electrocardiogram (ECG) and blood pressure (BP) recordings were used to assess RR-interval, time and frequency domain metrics of HRV (a surrogate marker of autonomic nervous system activity), and AD pre- and post-intervention.

ResultsA total of 19 participants with SCI (5 women; mean [SD] age 42 [8.3] years) with complete ECG and BP data sets were suitable for autonomic analysis. During baseline UDS, an increase in RR-interval (adjusted mean difference, -0.08; 95% CI, -0.14 to -0.03; P=0.002) as well as time and frequency domain metrics of HRV were detected. Vagally mediated increases in high frequency (HF) power during UDS were larger in participants with cervical SCI compared to upper thoracic SCI (adjusted mean difference, 20.3; 95% CI, 3.3 to 37.2; P=0.013). Intradetrusor onabotulinumtoxinA injections significantly reduced time domain metrics of HRV and HF power (adjusted mean difference, 9.1; 95% CI, 3.1 to 15.1, P<0.01) responses to UDS across all participants.

Conclusions and RelevanceChanges in HRV during UDS could be a potential indicator of improved autonomic cardiovascular function following interventions such as intradetrusor onabotulinumtoxinA injections.

Trial RegistrationClinicalTrials.gov Identifier: NCT02298660

category: cardiovascular medicine


title: A Novel Evidence-Based Predictor Tool for Hospitalization and Length of Stay: Insights from COVID19 Patients in New York City

abstract:
BackgroundCoronavirus disease 2019 (COVID-19) has evolved into a true global pandemic infecting more than 30 million people worldwide. Predictive models for key outcomes have the potential to optimize resource utilization and patient outcome as outbreaks continue to occur worldwide. We aimed to design and internally validate a web-based calculator predictive of hospitalization and length of stay (LOS) in a large cohort of COVID-19 positive patients presenting to the Emergency Department (ED) in a New York City health system.

MethodsThe study cohort consisted of consecutive adult (>18 years) patients presenting to the ED of one of the Mount Sinai Health System hospitals between March, 2020 and April, 2020 who were diagnosed with COVID-19. Logistic regression was utilized to construct predictive models for hospitalization and prolonged (>3 days) LOS. Discrimination was evaluated using area under the receiver operating curve (AUC). Internal validation with bootstrapping was performed, and a web-based calculator was implemented.

ResultsThe cohort consisted of 5859 patients with a hospitalization rate of 65% and a prolonged LOS rate of 75% among hospitalized patients. Independent predictors of hospitalization included older age (OR=6.29; 95% CI [1.83-2.63], >65 vs. 18-44), male sex (OR=1.35 [1.17-1.55]), chronic obstructive pulmonary disease (OR=1.74; [1.00-3.03]), hypertension (OR=1.39; [1.13-1.70]), diabetes (OR=1.45; [1.16-1.81]), chronic kidney disease (OR=1.69; [1.23-2.32]), elevated maximum temperature (OR=4.98; [4.28-5.79]), and low minimum oxygen saturation (OR=13.40; [10.59-16.96]). Predictors of extended LOS included older age (OR=1.03 [1.02-1.04], per year), chronic kidney disease (OR=1.91 [1.35-2.71]), elevated maximum temperature (OR=2.91 [2.40- 3.53]), and low minimum percent oxygen saturation (OR=3.89 [3.16-4.79]). AUCs of 0.881 and 0.770 were achieved for hospitalization and LOS, respectively. A calculator was made available under the following URL: https://covid19-outcome-prediction.shinyapps.io/COVID19_Hospitalization_Calculator/

ConclusionThe prediction tool derived from this study can be used to optimize resource allocation, guide quality of care, and assist in designing future studies on the triage and management of patients with COVID-19.

category: emergency medicine


title: The urgency of resuming disrupted dog rabies vaccination campaigns: a modeling and cost-effectiveness analysis

abstract:
OBJECTIVEDog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the 2019 dog vaccination campaign did not include the capital city, and the 2020 campaign was cancelled because of COVID-19 lockdown restrictions and redirection of funds. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios.

METHODSWe modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005-2025. We compared model outputs to surveillance data on human rabies deaths from 2005-2020 and animal rabies cases from 2018-2020. We then estimated the human health and cost implications of restarting dog vaccination programs in either 2021 or 2022.

FINDINGSModel predictions and animal surveillance data from Haiti both suggest a 5-to 8-fold increase in animal rabies cases has occurred in the capital city between Fall 2019 and Fall 2020. We estimate that restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6,541 human rabies exposures over a five-year period and may decrease program costs due to reduced need for human post-exposure prophylaxis.

CONCLUSIONSA one-year delay in resuming dog vaccination in Haiti, from 2021 to 2022, could cost hundreds of lives over the next 5 years. Interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.


title: Increased Interregional Travel to Shopping Malls and Restaurants in Response to Differential COVID-19 Restrictions in the Greater Toronto Area

abstract:
BackgroundIn the fall of 2020, the government of Ontario, Canada adopted a 5-tier, regional framework of public health measures for the COVID-19 pandemic. During the second wave of COVID-19 in Ontario, the urban core of the Greater Toronto Area (Toronto and Peel) were the first regions in the province to enter the highest restriction tier ("lockdown") on November 23, 2020, which closed restaurants to in-person dining and limited non-essential businesses, including shopping malls, to curbside pickup. The peripheral regions of the Greater Toronto Area (York, Durham, Halton) would not enter lockdown until later the following month. In this analysis, we examine whether the implementation of differentially timed restrictions in a highly interconnected metropolitan area led to increased interregional travel, potentially driving further transmission of SARS-CoV-2.

MethodsWe used anonymized smartphone data to estimate the number of visits by residents of regions in the urban core to shopping malls and restaurants in peripheral regions in the week before compared to the week after the November 23 lockdown.

ResultsResidents of Toronto and Peel took fewer trips to shopping malls and restaurants in the week following lockdown. This was entirely driven by reductions in visits within the locked down regions themselves, as there was a significant increase in trips to shopping malls in peripheral regions by these residents in the same period (Toronto: +40.7%, Peel: +65.5%). Visits to restaurants in peripheral regions also increased slightly (Toronto: +6.3%, Peel: +11.8%).

DiscussionHeterogeneous restrictions may undermine lockdowns in the urban core as well as driving residents from zones of higher transmission to zones of lower transmission. These concerns are likely generalizable to other major metropolitan areas, which often comprise interconnected but administratively independent regions.


title: Regional opening strategies with commuter testing and containment of new SARS-CoV-2 variants

abstract:
BackgroundDespite the vaccination process in Germany, a large share of the population is still susceptible to SARS-CoV-2. In addition, we face the spread of novel variants. Until we overcome the pandemic, reasonable mitigation and opening strategies are crucial to balance public health and economic interests.

MethodsWe model the spread of SARS-CoV-2 over the German counties by a graph-SIR-type, metapopulation model with particular focus on commuter testing. We account for political interventions by varying contact reduction values in private and public locations such as homes, schools, workplaces, and other. We consider different levels of lockdown strictness, commuter testing strategies, or the delay of intervention implementation. We conduct numerical simulations to assess the effectiveness of the different intervention strategies after one month. The virus dynamics in the regions (German counties) are initialized randomly with incidences between 75-150 weekly new cases per 100,000 inhabitants (red zones) or below (green zones) and consider 25 different initial scenarios of randomly distributed red zones (between 2 and 20 % of all counties). To account for uncertainty, we consider an ensemble set of 500 Monte Carlo runs for each scenario.

ResultsWe find that the strength of the lockdown in regions with out of control virus dynamics is most important to avoid the spread into neighboring regions. With very strict lockdowns in red zones, commuter testing rates of twice a week can substantially contribute to the safety of adjacent regions. In contrast, the negative effect of less strict interventions can be overcome by high commuter testing rates. A further key contributor is the potential delay of the intervention implementation. In order to keep the spread of the virus under control, strict regional lockdowns with minimum delay and commuter testing of at least twice a week are advisable. If less strict interventions are in favor, substantially increased testing rates are needed to avoid overall higher infection dynamics.

ConclusionsOur results indicate that local containment of outbreaks and maintenance of low overall incidence is possible even in densely populated and highly connected regions such as Germany or Western Europe. While we demonstrate this on data from Germany, similar patterns of mobility likely exist in many countries and our results are, hence, generalizable to a certain extent.


title: Regional opening strategies with commuter testing and containment of new SARS-CoV-2 variants in Germany


title: Predicting the end of Covid-19 infection for various countries using a stochastic agent-based model taking into account vaccination rates and the new mutant

abstract: Using a stochastic, agent-based model, the course of infection since the first occurrence of a Covid-19 infection is simulated for various countries, taking into account the new, more infectious mutant and the vaccinations. The simulation shows that the course of infection for the United Kingdom (UK) and Israel is surprisingly good. For the other countries, an end date for the infection can be predicted based on the course of the simulation. For Germany, the course is calculated in a second scenario, assuming a higher vaccination rate.


title: A Mobile App for Prolonged Grief among Bereaved Parents: Study Protocol for a Randomized Controlled Trial

abstract:
IntroductionBereaved parents have elevated risk to develop mental health problems, yet, few studies have evaluated the effect of psychosocial interventions developed for bereaved parents. Cognitive behavioral therapy (CBT), both face-to-face or digitally delivered, has shown to be an effective intervention for prolonged grief symptoms. Self-help mobile apps offer various advantages and studies show improved mental health after app interventions. No app has yet been evaluated targeting prolonged grief in bereaved parents. Therefore, the aim of this planned study is to develop and examine the effectiveness of a CBT-based mobile app, called My Grief, in reducing symptoms of prolonged grief, as well as other psychological symptoms, in bereaved parents. Another aim is to assess users experiences and adverse events of My Grief.

Methods and analysisWe will conduct a two-armed randomized waitlist-controlled trial. Parents living in Sweden, who lost a child to cancer between one and ten years ago, with elevated symptoms of prolonged grief, will be recruited to participate in the trial. The content of My Grief covers four main domains (Learn; Self-monitoring; Exercises; Get support) and builds on principles of CBT and the proven-effective PTSD Coach app. Participants in the intervention group will fill out online questionnaires at baseline and at 3-, 6- and 12-months follow-ups, and the waitlist-controls at baseline and at 3 months. The primary outcome will be prolonged grief symptoms at the 3 months follow-up. Secondary outcomes are posttraumatic stress and depression symptoms, quality of life, and cognitive behavioral variables (i.e., avoidance, rumination, negative cognitions).

Ethics and disseminationEthical approval has been received from the Swedish Ethical Review Authority (project no. 2021-00770). If the app is shown to be effective, the app will be made publicly accessible on app stores, so that it can benefit other bereaved parents.

Trial registrationClinicaltrials.gov, identifier: NCT04552717.

STRENGTHS AND LIMITATIONSO_LIThis is the first study to examine whether access of a self-help app can have beneficial effect on bereaved parents mental health, quality of life
C_LIO_LIThis study will examine the effect of the app on cognitive-behavioral processes proposed to underlie the development of prolonged grief.
C_LIO_LIGeneralizability of findings from this study may be limited as parents who want to participate in such study may experience fewer barriers to talk about the loss and seek help for their grief.
C_LIO_LIThis study includes parents who have lost a child to cancer, hence the findings may not be generalizable to other causes.
C_LIO_LIThis study uses self-report questionnaires, hence we do not establish formal diagnosis of prolonged grief disorder.
C_LI


title: Depression and Anxiety Symptoms in Young Adults Before and During the Covid-19 Pandemic: Evidence from a Canadian Population-Based Cohort

abstract:
ObjectivesConcerns have been raised that the COVID-19 pandemic could increase risk for adverse mental health outcomes, especially in young adults, a vulnerable age group. We investigated changes in depression and anxiety symptoms (overall and severe) from before to during the pandemic, as well as whether these changes are linked to COVID-19 related stressors and pre-existing vulnerabilities in young adults followed in the context of a population-based cohort.

MethodParticipants (n=1039) from the Quebec Longitudinal Study of Child Development reported on their depression and anxiety symptoms and completed a COVID-19 questionnaire during the first wave of the COVID-19 pandemic in the summer of 2020 (age 22 years). Assessments at age 20 (2018) were used to estimate pre-pandemic depression and anxiety symptom severity.

ResultsWhile overall levels of depression and anxiety symptoms did not change, there was an increase in rates of severe depression (but not severe anxiety) from before (6.1%) to during (8.2%) the pandemic. Depressive and anxiety symptoms increased from before to during the COVID-19 pandemic among young adults with the lowest levels of symptoms before the pandemic, while they decreased among those with the highest levels of pre-existing symptoms. Youth who were living alone experienced an increase in depressive symptoms. Other COVID-19 related variables (e.g., loss of education/occupation, frequent news-seeking) and pre-existing vulnerabilities (e.g., low SES, low social support) were not associated with changes in depression or anxiety symptoms.

ConclusionDepression and anxiety symptoms in young adults from Quebec in Summer 2020 were comparable to symptoms reported in 2018. Most COVID-19 related stressors and pre-existing vulnerabilities were not associated with changes in symptoms. However, the increased rate of severe depression and the increase in depression and anxiety symptoms among young adults with the least mental health symptoms before the COVID-19 pandemic are concerning.