title: Estimating the effectiveness of first dose of COVID-19 vaccine against mortality in England: a quasi-experimental study

abstract:
BackgroundEstimating real-world vaccine effectiveness is vital to assess the impact of the vaccination programme on the pandemic and inform the ongoing policy response. However, estimating vaccine effectiveness using observational data is inherently challenging because of the non-randomised design and the potential for unmeasured confounding.

MethodsWe used a Regression Discontinuity Design (RDD) to estimate vaccine effectiveness against COVID-19 mortality in England, exploiting the discontinuity in vaccination rates resulting from the UKs age-based vaccination priority groups. We used the fact that people aged 80 or over were prioritised for the vaccine roll-out in the UK to compare the risk of COVID-19 and non-COVID-19 death in people aged 75-79 and 80-84.

FindingsThe prioritisation of vaccination of people aged 80 or above led to a large discrepancy in vaccination rates in people 80-84 compared to those 75-79 at the beginning of the vaccination campaign. We found a corresponding difference in COVID-19 mortality, but not in non-COVID-19 mortality, suggesting that our approach appropriately addresses the issue of unmeasured confounding factors. Our results suggest that the first vaccine dose reduced the risk of COVID-19 death by 52.6% (95% Cl 26.6-84.2) in those aged 80.

InterpretationsOur results support existing evidence that a first dose of a COVID-19 vaccine has a strong protective effect against COVID-19 mortality in older adults. The RDD estimate of vaccine effectiveness is comparable to previously published studies using different methods, suggesting that unmeasured confounding factors are unlikely to substantially bias these studies.

FundingOffice for National Statistics.

Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for studies reporting on the  real-world effectiveness of the COVID-19 vaccination on risk of death using terms such as "COVID-19", "vaccine effectiveness", "mortality" and "death". The relevant published studies on this topic report vaccine effectiveness estimates against risk of death ranging from 64.2% to 98.7%, for varying times post-vaccination. All of these are observational studies and therefore potentially subject to bias from unmeasured confounding. We found no studies that used a quasi-experimental method such as regression discontinuity design, which is not subject to bias from unmeasured confounding, to calculate the effectiveness of the COVID-19 vaccination on risk of COVID-19 death, or on other outcomes such as hospitalisation or infection.

Added value of this studyThe estimates of vaccine effectiveness based on observational data may be biased by unmeasured confounding. This study uses a regression discontinuity design to estimate vaccine effectiveness, exploiting the fact that the vaccination campaign in the UK was rolled out following age-based priority groups. This enables the calculation of an unbiased estimate of the effectiveness of the COVID-19 vaccine against risk of death.

The vaccine effectiveness estimate of 52.6% (95% Cl 26.6-84.2) is slightly lower but similar to previously published estimates, therefore suggesting that these estimates are not substantially affected by unmeasured confounding factors and confirming the effectiveness of the COVID-19 vaccine against risk of COVID-19 death.

Implications of all the available evidenceObtaining an unbiased estimate of COVID-19 vaccine effectiveness is of vital importance in informing policy for lifting COVID-19 related measures. The regression discontinuity design provides confidence that the existing estimates from observational studies are unlikely to be substantially biased by unmeasured confounding.


title: Evaluation of lymphocyte subtypes in COVID-19 patients

abstract:
BackgroundAlthough the many aspects of COVID-19 have not been yet recognized, it seems that the dysregulation of the immune system has a very important role in the progression of the disease. In this study the lymphocyte subsets were evaluated in COVID-19 patients with different severity.

MethodsIn this prospective study, the levels of peripheral lymphocyte subsets (CD3+, CD4+, CD8+ T cells; CD19+ and CD20+ B cells; CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were measured in 67 confirmed patients with COVID-19 on the first day of admission.

ResultsThe mean age of cases was 51.3 {+/-} 14.8 years. Thirty-two patients (47.8%) were classified as severe cases and 11 (16.4%) patients were categorized as critical. The frequency of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells; and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, CD16+56+ lymphocytes were lower in more severe cases in comparison to milder cases. Percentages of lymphocytes, T cells, and NK cells were significantly lower inthe patients who died (p= 0.002 and P= 0.042, p=0.006, respectively).

ConclusionFindings of this cohort study suggests that the frequency of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells were difference in the severe COVID-19 patients. Moreover, lower frequency of, T cells, and NK cells are predictors of mortality of these patients.

category: infectious diseases


title: Homologous and Variant-Specific Memory B-Cell and Antibody Responses after SARS-CoV-2 mRNA Vaccination

abstract:
ImportanceA better understanding of the immune memory and functional humoral immunity directed at the emerging Variants of Concern (VoC) strains after SARS-CoV-2 vaccination is essential for predicting the longevity of heterotypic protection.

ObjectiveThe aim of our study was to characterize functional humoral immunity (including memory B cell response) after COVID-19 mRNA vaccination and to determine/compare the reactivity of COVID-19 vaccine-induced memory B cells to the emerging SARS-CoV-2 Variants of Concern (VoC).

Design, setting, participants and interventionsWe designed an exploratory longitudinal observational (convenience sample-based) study at Mayo Clinic, Rochester, MN that enrolled and followed naive subjects and recovered COVID-19 subjects from Olmsted County, MN and surrounding areas after COVID-19 vaccination in January-June 2021. The study enrolled 17 relatively healthy subjects, 59% females and 94% White/Non-Hispanic or Latino with median age at enrollment 41 years. The subjects received either the BNT162b2 (Pfizer/BioNtech) or mRNA-1273 (Moderna) vaccine (n=3) and provided a blood sample at baseline, at [~]3 weeks after their first vaccine dose/before the second dose, and at [~]2 weeks after the receipt of their second vaccine dose.

Main outcomes and measuresSpike-specific humoral and memory B cells responses were assessed over time after vaccination against the original Wuhan-Hu-1/vaccine and against emerging VoC strains/antigens.

ResultsWe observed a robust neutralizing antibody response after COVID-19 mRNA vaccination, but a reduction in the functional antibody activity to several of the emerging SARS-CoV-2 VoC. Consistent with this, we also found differences in the number of isotype-switched/IgG+ MBCs responding to homologous and variant receptor-binding domain/RBDs after vaccination. We found a reduction of MBCs reactive to RBDs of Beta, Gamma and Delta SARS-CoV-2 VoC strains.

Conclusion and relevanceIn this exploratory study in subjects following receipt of COVID-19 mRNA vaccine, we found differences in antibody titers observed for VoCs after vaccination that are accompanied with, and can partially be explained by, decreased MBC reactivity against the VoCs. This can further attenuate the generated recall humoral immune response upon exposure to these variants.

Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the reactivity of COVID-19 vaccine-induced memory B cells to the emerging SARS-CoV-2 Variants of Concern (VoC)?

FindingsIn this longitudinal cohort study of subjects receiving COVID-19 mRNA vaccine we assessed memory B cell response and functional antibody titers. We found statistically significant differences between the frequencies of memory B cells responding to homologous and VoC receptor-binding domain/RBDs after vaccination.

MeaningIn concert with the lowered antibody response, the reduced memory B-cell response to VoC could translate to an increased susceptibility to the emerging SARS-CoV-2 variant strains in the face of waning immunity.


title: Convergent epitope-specific T cell responses after SARS-CoV-2 infection and vaccination

abstract: Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 memory T cells is poorly understood. Here, we utilize DNA-barcoded MHC-multimers combined with scRNAseq and scTCRseq to capture the ex vivo profile of SARS-CoV-2-responsive T cells within a cohort of individuals with one, two, or three antigen exposures, including vaccination, primary infection, and breakthrough infection. We found that the order of exposure determined the relative distribution between spike- and non-spike-specific responses, with vaccination after infection leading to further expansion of spike-specific T cells and differentiation to a CCR7-CD45RA+ effector phenotype. In contrast, individuals experiencing a breakthrough infection mount vigorous non-spike-specific responses. In-depth analysis of over 4,000 epitope-specific T cell receptor sequences demonstrates that all types of exposures elicit diverse repertoires characterized by shared, dominant TCR motifs, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and that current vaccination protocols continue to expand and differentiate spike-specific memory responses.


title: SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells


title: The required size of cluster randomized trials of non-pharmaceutical interventions in epidemic settings

abstract: To control the SARS-CoV-2 pandemic and future pathogen outbreaks requires an understanding of which non-pharmaceutical interventions are effective at reducing transmission. Observational studies, however, are subject to biases, even when there is no true effect. Cluster randomized trials provide a means to conduct valid hypothesis tests of the effect of interventions on community transmission. While they may only require a short duration, they often require large sample sizes to achieve adequate power. However, the sample sizes required for such tests in an outbreak setting are largely undeveloped and the question of whether these designs are practical remains unanswered. We develop approximate sample size formulae and simulation-based sample size methods for cluster randomized trials in infectious disease outbreaks. We highlight key relationships between characteristics of transmission and the enrolled communities and the required sample sizes, describe settings where cluster randomized trials powered to detect a meaningful true effect size may be feasible, and provide recommendations for investigators in planning such trials. The approximate formulae and simulation banks may be used by investigators to quickly assess the feasibility of a trial, and then more detailed methods may be used to more precisely size the trial. For example, we show that community-scale trials requiring 220 clusters with 100 tested individuals per cluster are powered to identify interventions that reduce transmission by 40% in one generation interval, using parameters identified for SARS-CoV-2 transmission. For more modest treatment effects, or settings with extreme overdispersion of transmission, however, much larger sample sizes are required.


title: Performance of antigenic detection of SARS-CoV-2 in nasopharyngeal samples

abstract:
ObjectivesSARS-CoV-2 virus detection on nasopharyngeal specimens to infected individuals has become a challenge for the COVID-19 pandemic outbreak. We aim at comparing the performance of antigenic detection of SARS-CoV-2 in nasopharyngeal samples via an immunochromatographic method to molecular detection via qRT-PCR.

Materials and Methods47 nasopharyngeal exudates were collected from suspicious COVID-19 cases. The samples were performed both via the qualitative immuno-chromatographic method for S protein detection in the SARS-CoV-2 structure, using fluorescent labelled anti-protein S antibodies and via qRT-PCR test for the qualitative detection of the screening gene E and the specific ORF1ab region of the RNA-SARS-CoV-2.

ResultsThere was a fair correlation between the positive antigen tests and the positive PCR assays measured through threshold cycle ORF1ab region (Ct orf). A better correlation was obtained between the antigen test results and the Ct orf when including patients with Ct orf below 25.

ConclusionsUsing antigen tests as screening tests is useful on symptomatic persons during the viral replication period, therefore during the contagious period. A positive test shows a high predictive value for infection, while a negative antigen test result via immuno-chromatography must be confirmed by a qRT-PCR test.


title: Intravenous Iron Decreases Rehospitalizations but Does not Change mortality in Patients Admitted with Acute Heart Failure and Iron Deficiency: A Systematic review and Meta-analysis

abstract:
IntroductionThe role of intravenous (IV) iron in chronic heart failure has been well studied, however, its role in acute heart failure (AHF) is less well-known. Including the recent AFFIRM-HF trial, we performed a systematic review and meta-analysis to highlight the role of IV iron in AHF with iron deficiency.

HypothesisWe hypothesized that IV iron doesnt change mortality or heart failure re-hospitalization rates in patients with AHF with iron deficiency.

MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies published from inception till June 30, 2021. We searched PubMed, MEDLINE, EMBASE (embase.com), and Cochrane database including only RCTs and Cohort studies. We also included one prospective and one retrospective Cohort studies and two RCTs in our meta-analysis. Eligible studies included adults with AHF, left ventricular ejection fraction less than 40%-50%, and able to receive IV iron therapy. Outcomes included re-hospitalization rates and overall mortality from 30 days to 52 weeks post randomization (in one RCT). We used random-effects model calculating Risk Ratio (RR) with 95% confidence interval (95% CI) using Review Manger 5.4 software. I2statistics was used to assess heterogeneity.

ResultsThere were total 1561 participants in both groups (IV iron and placebo/control) of four studies. The controls were comparable in both cohort studies and both the RCTs were well matched. Our results showed re-hospitalization in 278 of 833 (33.37%) patients in the IV iron/exposure group and 337 of 728 (0.46%) patients in the placebo/control group. The pooled result showed that the risk of rehospitalization was comparable across both groups (RR 0.85, 95%CI 0.62-1.17; I2=45%, P=0.14). However, subgroup analysis, including RCTs only showed that IV iron decreases re-hospitalization rate by 28% compared to placebo (RR 0.72, 95% CI: 0.64, 0.82, I2=0%, P<0.00001) but didnt improve mortality when compared to placebo (RR 0.97, 95% CI: 0.73, 1.30, I2 =0%).

ConclusionsIV iron showed significant improvement in re-hospitalization rate for AHF hospitalizations in iron deficient patients but didnt improve overall mortality. We need larger RCTs to further validate its effect on mortality.

category: cardiovascular medicine


title: Apple Watch and Withings Evaluation of Symptoms, Treatment, and Rhythm in those Undergoing Cardioversion (AWE STRUCk): A Pragmatic Randomized Controlled Trial

abstract:
IntroductionPersonal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilization are sparse. Among a population of patients with atrial fibrillation undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and electrocardiogram features of the Apple Watch on quality of life and healthcare utilization.

Methods and analysisWe are conducting a prospective, open-label multicenter pragmatic randomized clinical trial, leveraging a unique patient-centered health data sharing platform for enrollment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation (or atrial flutter, if they have a history of atrial fibrillation) will be randomized 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) global score at six months post-cardioversion. Secondary outcomes include inpatient and outpatient healthcare utilization. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold standard data obtained in routine clinical care settings.

Ethics and disseminationThe Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians, and patients about the impact of the heart rate, irregular rhythm notification, and electrocardiogram features of widely used personal digital devices on patient quality of life and healthcare utilization. Findings will be disseminated to study participants, at professional society meetings, and in peer-reviewed journals.

Trial registration numberNCT04468321

Strengths and limitations of this studyO_LIThis randomized clinical trial will use a patient-centered health data sharing platform for study enrollment and follow-up, leveraging patient ownership over health data and patient engagement with researchers.
C_LIO_LIThis is the first study to examine the impact of electrocardiogram and irregular rhythm notification features of personal digital technologies on patient-reported quality-of-life among patients with atrial fibrillation.
C_LIO_LIDue to costs of personal digital devices, our study is powered to identify a difference of 8.8 on the primary outcome of Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) global score, which is greater than the minimal clinically important difference of 5.
C_LIO_LIOur study focuses on a subset of patients with atrial fibrillation, and the findings may not be generalizable to those who do not have atrial fibrillation.
C_LI


title: Significant Disruptions in the International Incidence of Hepatitis Delta Virus

abstract:
Background & AimsThe international incidence of Hepatitis Delta Virus (HDV) is challenging to accurately estimate due to limited testing and lack of active surveillance for this rare infectious disease. These limitations prevent the detection of low-level and/or geographically dispersed changes in the incidence of HDV diagnoses. A study was designed to enable international active tracking and analyses of HDV epidemiology by aggregating international HDV and Hepatitis B Virus (HBV) diagnoses datasets.

MethodsPublicly accessible datasets containing yearly incidence for HDV and HBV diagnoses were mined from government publications for Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Finland, Germany, Macao, Netherlands, New Zealand, Norway, Sweden, Taiwan, Thailand, United Kingdom, and United States. The Bayesian Information Criterion (BIC) was used to determine the best-fitting breakpoint model for the number of breakpoints and the break dates identified using the determined model.

ResultsAggregated analysis of these HDV and HBV datasets spanning 1999-2020 identified structural breaks in the timeline of HDV incidence in 2002, 2012, and 2017. A significant increase in the international HDV incidence, relative to reported HBV diagnoses, occurred in 2013-2017. Secondary analysis identified four distinct temporal clusters of HDV incidence, including Cluster I (Macao, Taiwan), Cluster II (Argentina, Brazil, Germany, Thailand), Cluster III (Bulgaria, Netherlands, New Zealand, United Kingdom, United States), and Cluster IV (Australia, Austria, Canada, Finland, Norway, Sweden).

ConclusionRe-evaluation of the testing paradigm for HDV in HBV-positive patients and an active surveillance status of HDV are warranted to define the etiology of the structural breaks in HDV incidence timelines.

category: epidemiology


title: Significant Structural Breaks in the International Incidence of Hepatitis Delta Virus


title: An Open Repository of Real-Time COVID-19 Indicators

abstract: The COVID-19 pandemic presented enormous data challenges in the United States. Policy makers, epidemiological modelers, and health researchers all require up-to-date data on the pandemic and relevant public behavior, ideally at fine spatial and temporal resolution. The COVIDcast API is our attempt to fill this need: operational since April 2020, it provides open access to both traditional public health surveillance signals (cases, deaths, and hospitalizations) and many auxiliary indicators of COVID-19 activity, such as signals extracted from de-identified medical claims data, massive online surveys, cell phone mobility data, and internet search trends. These are available at a fine geographic resolution (mostly at the county level) and are updated daily. The COVIDcast API also tracks all revisions to historical data, allowing modelers to account for the frequent revisions and backfill that are common for many public health data sources. All of the data is available in a common format through the API and accompanying R and Python software packages. This paper describes the data sources and signals, and provides examples demonstrating that the auxiliary signals in the COVIDcast API present information relevant to tracking COVID activity, augmenting traditional public health reporting and empowering research and decision-making.


title: Harnessing the Wisdom of the Crowd to Forecast Incident and Cumulative COVID-19 Mortality in the United States

abstract:
BackgroundForecasting models have played a pivotal role in health policy decision making during the coronavirus disease-2019 (COVID-19) pandemic. A combined forecast from multiple models will be typically more accurate than an individual forecast, but there are few examples of studies of combined forecasts of COVID-19 data, focusing mainly on simple mean and median  ensembles and involving short forecast evaluation periods. We aimed to investigate the accuracy of different ways of combining probabilistic forecasts of weekly COVID-19 mortality data, including two weighted methods that we developed previously, on an extended dataset and new dataset, and evaluate over a period of 52 weeks.

MethodsWe considered 95% interval and point forecasts of weekly incident and cumulative COVID-19 mortalities between 16 May 2020 and 8 May 2021 in multiple locations in the United States. We compared the accuracy of simple and more complex combining methods, as well as individual models.

ResultsThe average of the forecasts from the individual models was consistently more accurate than the average performance of these models (the mean combination), which provides a fundamental motivation for combining. Weighted combining performed well for both incident and cumulative mortalities, and for both interval and point forecasting. Our inverse score with tuning method was the most accurate overall. The median combination was a leading method in the last quarter for both mortalities, and it was consistently more accurate than the mean combination for point forecasting. For interval forecasts of cumulative mortality, the mean performed better than the median. The best performance of the leading individual model was in point forecasting.

ConclusionsCombining forecasts can improve the contribution of probabilistic forecasting to health policy decision making during epidemics, and, when there are sufficient historical data on forecast accuracy, weighted combining provides the most accurate method.


title: Forecasts of weekly incident and cumulative COVID-19 mortality in the United States: A comparison of combining methods


title: Understanding genetic risk factors for common side effects of antidepressant medications

abstract: Major depression is one of the most disabling health conditions internationally. In recent years, new generation antidepressant medicines have become very widely prescribed. While these medicines are efficacious, side effects are common and frequently result in discontinuation of treatment. Compared with specific pharmacological properties of the different medications, the relevance of individual vulnerability is understudied. We used data from the Australian Genetics of Depression Study to gain insights into the aetiology and genetic risk factors to antidepressant side effects. As expected, the most commonly reported longer-term side effects were reduced sexual function and weight gain. Importantly, participants reporting a specific side effect for one antidepressant were more likely to report the same side effect for other antidepressants, suggesting the presence of shared individual or pharmacological factors. Depression Polygenic Risk Scores (PRS) were associated with side effects that overlapped with depressive symptoms, including suicidality and anxiety. Body Mass Index PRS were strongly associated with weight gain from all medications. PRS for headaches were associated with headaches from sertraline. Insomnia PRS showed some evidence of predicting insomnia from amitriptyline and escitalopram. Our results suggest a set of common factors underlying the risk for antidepressant side effects. These factors seem to be, at least in part, explained by genetic liability related to depression severity and the nature of the side effect. Future studies on the genetic aetiology of side effects will enable insights into their underlying mechanisms and the possibility of risk stratification and prophylaxis strategies.

category: psychiatry and clinical psychology


title: Olfactory detection of human odorant signatures in Covid patients by trained dogs

abstract: The objective of the study was to verify the ability of specially trained dogs to detect the odour of people ill with COVID-19 and, at the same time, to use the outcome of this research in the future, whether in combatting a similar pandemic or in the field of medicine in the shape of a biological detector in uncovering different diseases. Our key assumption was that the disease will change the active odour signature of the individuals just like other diseases (TBC, malaria, tumours, etc.). The pilot study was conducted in two places, based on the same protocolar methods, and it included four specially trained detection dogs in total. For the first phase of the project, we obtained 156 positive and 72 negative odour samples primarily from a hospital. Each detection dog involved in the study was imprinted with the smell samples of Covid-positive people. The first experiment only involved two dogs. With the other two dogs, the phase of imprinting a specific smell was longer, possibly because these dogs were burdened with previous training. During a presentation of 100 randomised positive samples, the experimental dogs showed a 95% reliability rate. Data from this pilot study show that specially trained dogs are able to detect and identify the odour samples of people infected with the SARS-CoV-2 coronavirus.

category: public and global health


title: Lessons learned and lessons missed: Impact of the Covid-19 pandemic on all-cause mortality in 40 industrialised countries prior to mass vaccination

abstract: Industrialised countries have varied in their early response to the Covid-19 pandemic, and how they have adapted to new situations and knowledge since the pandemic began. These variations in preparedness and policy may lead to different death tolls from Covid-19 as well as from other diseases. We applied an ensemble of 16 Bayesian probabilistic models to vital statistics data to estimate the impacts of the pandemic on weekly all-cause mortality for 40 industrialised countries from mid-February 2020 through mid-February 2021, before a large segment of the population was vaccinated in any of these countries. Taken over the entire year, an estimated 1,401,900 (95% credible interval 1,259,700-1,572,500) more people died in these 40 countries than would have been expected had the pandemic not taken place. This is equivalent to 140 (126-157) additional deaths per 100,000 people and a 15% (13-17) increase in deaths over this period in all of these countries combined. In Iceland, Australia and New Zealand, mortality was lower over this period than what would be expected if the pandemic had not occurred, while South Korea and Norway experienced no detectable change in mortality. In contrast, the populations of the USA, Czechia, Slovakia and Poland experienced at least 20% higher mortality. There was substantial heterogeneity across countries in the dynamics of excess mortality. The first wave of the pandemic, from mid-February to the end of May 2020, accounted for over half of excess deaths in Scotland, Spain, England and Wales, Canada, Sweden, Belgium and Netherlands. At the other extreme, the period between mid-September 2020 and mid-February 2021 accounted for over 90% of excess deaths in Bulgaria, Croatia, Czechia, Hungary, Latvia, Montenegro, Poland, Slovakia and Slovenia. Until the great majority of national and global populations have vaccine-acquired immunity, minimising the death toll of the pandemic from Covid-19 and other diseases will remain dependent on actions to delay and contain infections and continue routine health and social care.


title: Comparative effectiveness of different exercises on bone mineral density in postmenopausal women: a systematic review and network meta-analysis of randomized controlled trials

abstract:
ObjectiveTo compare and rank different exercise interventions on bone mineral density (BMD) in postmenopausal women.

Data Sources and Study SelectionMEDLINE, EMBASE, CINAHL, AMED, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus and Web of Science were searched from database inception to January 2021 of randomized controlled studies investigating the effect of exercise more than six months on BMD in postmenopausal women.

Data Extraction and SynthesisData at baseline and post intervention (or the change from baseline) were extracted. A Bayesian random-effects network meta-analysis was performed.

Main Outcomes and MeasuresThe primary outcome was the change of BMD (at lumbar spine, femoral neck, and total hip) from baseline values. Effect size measures were mean differences with 95% credible intervals (CrIs).

ResultsWe identified 3324 citations and included 66 studies with a total number of 4336 participants. Associated with BMD at lumbar spine (LS) improve were found for multicomponent exercise, resistance training, mind body exercise, lower impact exercise, high impact exercise, and whole body vibration. With regard to femoral neck (FN), only multicomponent exercise, whole body vibration, and mind body exercise were effective. As for total hip (TH), only multicomponent exercise, resistance training, and flexibility exercise were found to be beneficial. Moreover, no matter the age of postmenopausal women, and the duration of intervention (range between 6 to 18 months), some certain kinds of exercise could be performed to improve BMD at LS and FN.

Conclusions and RelevanceThis NMA confirms that exercise therapy has clear benefits on bone mineral density in postmenopausal women. It also shows that the magnitude of effect varies depending on the outcome of interest, the age of participants, and the duration of intervention. Clinicians might consult the ranking of the exercise intervention presented in this study, when designating an optimal, individualized exercise prescription to improve BMD.

category: rehabilitation medicine and physical therapy


title: Influenza infection, Acute myocardial Infarction, Flu Shot during COVID-19 Pandemic in US population. A Review of Literature.

abstract: Influenza is a major cause of hospitalization in all age groups but can cause more severe infections in specific high-risk population. Novel Corona Virus Disease 2019 (COVID-19) pandemic and Influenza virus infection cause similar illness and coexist. Cardiovascular complications due to influenza are important causes of morbidity and mortality in the US, especially in the elderly population (aged more than 65 years). Acute Myocardial Infarction (AMI) is the most serious among the cardiovascular causes of mortality following the attack of influenza, mainly in patients with various co-morbidities like pre-existing coronary artery disease (CAD), diabetes mellitus (DM), hypertension (HTN), and heart failure (HF). We have reviewed the association between influenza virus infection and AMI and extrapolated the beneficial effects of influenza vaccine in preventing AMI and its grave consequences. We have also highlighted about the importance of flu shot during the COVID-19 pandemic.


title: Combined Anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalized COVID-19 patients: a propensity matched cohort study

abstract:
BackgroundCOVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.

MethodsA retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, ICU admission, or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation.

Results242 patients were included in the study and divided into 4 subgroups: therapeutic anticoagulation (TAC), prophylactic anticoagulation + antiplatelet (PACAP), therapeutic anticoagulation + antiplatelet (TACAP), and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable cox regression analysis and propensity matching were done and showed when compared to PAC, TACAP and TAC were associated with less in-hospital all cause mortality with an adjusted hazard ratio (aHR) of 0.113 (95% confidence interval (CI) 0.028-0.449) and 0.126 (95% CI, 0.028-0.528) respectively. The number needed to treat (NNT) in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI, 0.014-0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission, or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation.

ConclusionThe use of combined anticoagulant and antiplatelet agents or therapeutic anticoagulation alone in hospitalized COVID-19 patients was associated with a better outcome in comparison to prophylactic anticoagulation alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomized controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using therapeutic anticoagulation in the management of patients with COVID-19 infection.

What is already known about this subject ?Covid-19 infection is associated with several complex coagulation disorders resulting in thrombotic, microthrombotic and thromboembolic events. Currently, prophylactic dose anticoagulation is considered the standard of care antithrombotic regimen in hospitalized COVID-19 patients. However, high-quality data about the subject is unavailable.

What does this study add?This is the first adequately sized study in the literature to dwell on the antithrombotic strategy consisting of combination anticoagulant and antiplatelet therapy in the treatment of COVID-19 induced hypercoagulable state. Furthermore, it also challenges the currently recommended prophylactic dosing of anticoagulation used in the treatment of those patients.

How might this impact on clinical practice?Our data suggests for the first time that concurrent use of anticoagulant and antiplatelet therapy is associated with a superior clinical outcome as compared to prophylactic anticoagulation used alone. Furthermore, it solidifies the emerging evidence that therapeutic anticoagulation is linked to better clinical results than prophylactic anticoagulation.


title: Epidemiology and Clinical Characteristics in Individuals with Confirmed SARS-CoV-2 Infection During the Early COVID-19 Pandemic in Saudi Arabia

abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the catastrophic coronavirus disease 2019 (COVID-19) global pandemic. This study aimed to provide epidemiologic and clinical characteristics of patients with confirmed COVID-19 in Saudi Arabia and to determine whether characteristic profiles differ between patients who are symptomatic vs. asymptomatic for the disease. The first 492 consecutive patients diagnosed with SARS-CoV-2 infection at King Faisal Specialist Hospital and Research Centre in Saudi Arabia between March and September 2020 were included in this study. An electronic case report form developed using REDCap was used to collect data for each patient, including demographic characteristics, virus exposure (travel history, and human and animal contact), vaccination history, comorbidities, signs and symptoms, laboratory and radiographic reports, cardiac workup, medications, treatment regimens, and patient outcome. This patient cohort was 54% male, with 20.4% aged more than 60 years, 19.9% aged 31 to 40 years, and 17% aged 41 to 50 years. Most patients (79.2%) were symptomatic. Variables that significantly differed between symptomatic and asymptomatic patients were age, blood oxygen saturation percentage, hemoglobin level, lymphocyte count, neutrophil to lymphocyte (NTL) ratio, alanine aminotransferase (ALT) level, and aspartate aminotransferase (AST) level. Asymptomatic patients were mostly younger, with lower body mass index and ALT and AST levels but higher lymphocyte counts, NTL ratio, and CD4, CD8, natural killer cell, IgG, and IgM levels. The median incubation period reported for this cohort was 16 day, with upper and lower 95% quartiles of 27 and 10 days, respectively. Factors associated with increased risk of mortality were age (older than 42 years) and comorbidities, including specifically diabetes mellitus and hypertension. Patients who were not given an antiviral regimen were associated with better prognosis than patients who received an antiviral regimen (HR, 0.07; 95% CI, 0.011-0.25). Similar to countries worldwide, Saudi Arabia has explored treatment options to save the lives of patients during the COVID-19 pandemic. Our analyses will inform clinicians as well as policy makers to adopt the best strategies for SARS-CoV-2 infection management and treatment options.


title: Results from Canton Grisons of Switzerland Suggest Repetitive Testing Reduces SARS-CoV-2 Incidence (February-March 2021)

abstract: In February 2021, in response to emergence of more transmissible SARS-CoV-2 virus variants, the Canton Grisons launched a unique RNA mass testing program targeting the labour force in local businesses. Employees were offered weekly tests free of charge and on a voluntary basis. If tested positive, they were required to self-isolate for ten days and their contacts were subjected to daily testing at work. Thereby, the quarantine of contact persons could be waved. Here, we evaluate the effects of the testing program on the tested cohorts. We examined 121364 test results from 27514 participants during February-March 2021. By distinguishing different cohorts of employees, we observe a noticeable decrease in the test positivity rate and a statistically significant reduction in the associated incidence rate over the considered period. The reduction in the latter ranges between 18%-50%. The variability is partly explained by different exposures to exogenous infection sources (e.g., contacts with visiting tourists or cross-border commuters). Our analysis provides the first empirical evidence that applying repetitive mass testing to a real population over an extended period of time can prevent spread of COVID-19 pandemic. However, to overcome logistic, uptake, and adherence challenges it is important that the program is carefully designed and that disease incursion from the population outside of the program is considered and controlled.


title: Variants of SARS-COV-2 and the Death Toll

abstract: New variants of SARS-COV-2 have been found in various countries. Especially, the UK has been attacked by Indias Delta Plus, and the spread of infection has been very rapid, since it is extremely infectious. Fortunately, however, the number of deaths has been stayed flat, where deaths are reported to be those who are not yet received a shot of COVID-19 vaccine. In this short not, we would like to consider why the number of deaths is so small, compared with high cases, around the infection peak, when the basic reproduction number is very large.


title: Gut microbiota alterations in patients with persistent respiratory dysfunction three months after severe COVID-19

abstract:
ObjectiveAlthough COVID-19 is primarily a respiratory infection, mounting evidence suggests that the GI tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and could be related to long-term respiratory dysfunction is unknown.

DesignFrom the NOR-Solidarity trial (n=181), plasma was collected during hospital admission and after three months, and analyzed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring diffusing capacity of the lungs for carbon monoxide (DLCO), and rectal swabs for gut microbiota analyses were collected (n= 97) and analysed by sequencing of the 16S rRNA gene.

ResultsGut microbiota diversity was reduced in COVID-19 patients with persistent respiratory dysfunction, defined as DLCO below lower limit of normal three months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Flavonifractor and Veillonella, the latter potentially being linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2/fiO2-(P/F-ratio)<26.6 kPa. LBP levels remained elevated during and after hospitalization, and was associated with low-grade inflammation and persistent respiratory dysfunction after three months.

ConclusionPersistent respiratory dysfunction after COVID-19 is associated with reduced biodiversity and gut microbiota alterations, along with persistently elevated LBP levels. Our results point to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.

Summary boxO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIMounting evidence suggests that the gastrointestinal tract is involved in the pathogenesis of COVID-19, with the putative SARS-CoV-2 receptor ACE 2 ubiquitously expressed in the gut.
C_LIO_LIIn severe COVID-19, the gut-blood barrier is compromised, and leakage of microbial products, such as lipopolysaccharides (LPS), could affect the hosts response to COVID-19 infection.
C_LIO_LICOVID-19 patients exhibit an altered gut microbiota composition, which has been related to disease severity. However, it is currently not known whether dysbiosis or gut barrier dysfunction persist long-term after hospitalization, or whether microbiota-related mechanisms could be related to persistent pulmonary dysfunction.
C_LI

What are the new findings?O_LICOVID-19 patients with persistent respiratory dysfunction after three months had a lower microbial diversity and an altered gut microbiota composition at the same time point.
C_LIO_LIThe microbiota alterations included reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Veillonella and Flavonifractor.
C_LIO_LIDuring hospitalization, increased plasma levels of LBP were strongly associated with respiratory failure.
C_LIO_LILBP levels remained elevated during and after hospitalization, and associated significantly with persistent respiratory dysfunction at three-month follow-up.
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How might it impact on clinical practice in the foreseeable future?Our findings point to a potential gut-lung axis in relation not only to respiratory failure during hospitalization, but also to long-term COVID-19 morbidity. Further studies on gut microbiota composition and gut barrier dysfunction as potential treatment targets and/or disease severity biomarkers in relation to long-term pulmonary dysfunction and long COVID are warranted.

category: gastroenterology


title: Monitoring of COVID-19 Pandemic-related Psychopathology using Machine Learning

abstract: The COVID-19 pandemic has been shown to have major impact on global mental health. We show that the developments in COVID-19 pandemic-related psychopathology can be meaningfully monitored using machine learning methods providing invaluable insights to psychiatric services and of the management of the psychological consequences of the COVID-19 pandemic. The COVID-19 pandemic-related psychopathology among patients with mental illness was found to covary with the pandemic pressure, however, was less pronounced during the second wave compared to the first wave of the pandemic - possibly due to habituation.


title: Inequalities in access to healthcare by local policy model among newly arrived refugees: evidence from population-based studies in two German states

abstract:
BackgroundAccess to healthcare is restricted for newly arriving asylum seekers and refugees (ASR) in many receiving countries, which may lead to inequalities in health. In Germany, regular access and full entitlement to healthcare (equivalent to statutory health insurance, SHI) is only granted after a waiting time of 18 months. During this time of restricted entitlements, local authorities implement different access models to regulate asylum seekers access to healthcare: the electronic health card (EHC) or the healthcare voucher (HV). This paper examines inequalities in access to healthcare by comparing healthcare utilization by ASR under the terms of different local models (i.e., regular access equivalent to SHI, EHC, and HV).

MethodsWe used data from three population-based, cross-sectional surveys among newly arrived ASR (N=863) and analyzed six outcome measures: specialist and general practitioner (GP) utilization, unmet needs for specialist and GP services, emergency department use and avoidable hospitalization. Using logistic regression, we calculated odds ratios (OR) and 95% confidence intervals for all outcome measures, while considering need by adjusting for socio-demographic characteristics and health-related covariates.

ResultsCompared to ASR with regular access, ASR under the HV model showed lower needs-adjusted odds of specialist utilization (OR=0.41 [0.24-0.66]) and a tendency towards lower GP (OR=0.61 [0.33-1.16]) and emergency department utilization (OR=0.74 [0.48-1.14]). ASR under the EHC model showed a tendency toward higher specialist unmet needs (OR= 1.89 [0.98-3.64]) and avoidable hospitalizations (OR=1.69 [0.87-3.30]) compared to ASR with regular access. A comparison between EHC and HV showed higher odds for specialist utilization under the EHC model as compared to the HV model (OR=2.39 [1.03-5.52]).

ConclusionASR using the HV are disadvantaged in their access to healthcare compared to ASR having either an EHC or regular access. Given equal need, they use specialist (and partly also GP) services less. The identified inequalities constitute inequities in access to healthcare that could be reduced by policy change from HV to the EHC model during the initial 18 months waiting time, or by granting ASR regular healthcare access upon arrival. Minor differences in unmet needs, emergency department use and avoidable hospitalization between the models deserve further exploration in future studies.


title: Rare PSAP variants and possible interaction with GBA in REM sleep behavior disorder

abstract: PSAP encodes saposin C, the co-activator of glucocerebrosidase, encoded by GBA. Since GBA mutations are associated with idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of synucleinopathy, we examined the role of PSAP mutations in iRBD. We fully sequenced PSAP and performed Optimized Sequence Kernel Association Test in 1,113 iRBD patients and 2,324 controls. We identified loss-of-function (LoF) mutations, which are very rare in PSAP, in three iRBD patients and none in controls (uncorrected p=0.018). Two variants were stop mutations, p.Gln260Ter p.Glu166Ter, and one was an in-frame deletion, p.332_333del. All three mutations have a deleterious effect on saposin C, based on in silico analysis. In addition, the two carriers of p.Glu166Ter and p.332_333del mutations also carried a GBA variant, p.Arg349Ter and p.Glu326Lys, respectively. The co-occurrence of these extremely rare PSAP LoF mutations in two (0.2%) GBA variant carriers in the iRBD cohort, is unlikely to occur by chance (estimated co-occurrence in the general population based on gnomAD data is 0.00035%). Although none of the three iRBD patients with PSAP LoF mutations have phenoconverted to an overt synucleinopathy at their last follow-up, all manifested initial signs suggestive of motor dysfunction, two were diagnosed with mild cognitive impairment and all showed prodromal clinical markers other than RBD. Their probability of prodromal PD, according to the Movement Disorder Society research criteria was 98% or more. These results suggest a possible role of PSAP variants in iRBD and potential genetic interaction with GBA, which requires additional studies.

category: neurology


title: Self-Reliance, Social Norms, and Self-Stigma as Barriers to Psychosocial Help Seeking Among Rural Cancer Survivors with Cancer-Related Distress

abstract:
ObjectivesEven when technology allows rural cancer survivors to connect with supportive care providers from a distance, uptake of psychosocial referrals is low. During our telemedicine-delivered intervention aimed at identifying rural survivors with high distress and connecting them with psychosocial care, fewer than 1/3 of those with high distress accepted a referral. The purpose of this research was to examine the reasons rural cancer survivors did not accept a psychosocial referral.

MethodsWe utilized a qualitative descriptive design to analyze data from interviews conducted with participants who had been offered a psychosocial referral during the intervention. Interviews were conducted 6 weeks following the intervention (n=14) and 9 months after the completion of the intervention (n=6).

ResultsUltimately, none of the rural cancer survivors in our study engaged with a psychosocial care provider, including those who had originally accepted a referral for further psychosocial care. When explaining their decisions, survivors minimized their distress, emphasizing their self-reliance and the need to handle distress on their own. They expressed a preference for dealing with distress via informal support networks, which was often limited to close family members. No survivors endorsed public stigma as a barrier to accepting psychosocial help, but several suggested that self-stigma associated with not being able to handle their own distress was a reason for not seeking care.

Significance of ResultsRural cancer survivors willingness to accept a psychosocial referral may be mediated by the rural cultural norm of self-reliance, and by self-stigma. Interventions to address referral uptake may benefit from further illumination of these relationships as well as a strength-based approach that emphasizes positive aspects of the rural community and individual self-affirmation.

category: oncology


title: Prevalence of Strabismus in Individuals on the Autism Spectrum: A Meta-analysis

abstract:
Background and ObjectivesStrabismus, a misalignment of the eyes, is an important risk factor for amblyopia and visual impairment in the pediatric population. Several studies have reported an increased likelihood of strabismus in persons on the autism spectrum, but prevalence estimates in this group vary greatly.

MethodsWe searched multiple databases to identify peer-reviewed articles published in English through November 1, 2020 that provided estimates of strabismus prevalence in autistic individuals. Prevalence estimates were synthesized using Bayesian random-effects meta-analysis, and sensitivity analysis was also performed using only the subset of studies that recruited participants from non-ophthalmologic settings and identified strabismus using structured ocular exams. Bayesian meta-regression was used to assess potential moderators of prevalence across studies.

ResultsA total of 151 nonduplicate articles were screened, of which 22 were included in the meta-analysis (k=28 samples, nAUT=113,227). The meta-analytic point prevalence of strabismus in autistic individuals was 13.4% (95% CrI [8.3,19.4]), and sensitivity analysis produced a very similar estimate (14.0% [7.0,22.0], nAUT=581). Esotropia was the predominant subtype of strabismus reported, accounting for approximately 55% of cases. Reported prevalence rates were higher in younger samples (BF10=13.43, R2Het =0.273) and samples recruited from optometry/ophthalmology clinics (BF10=11.47, R2Het =0.238).

ConclusionThis meta-analysis found a high prevalence of strabismus in autistic individuals, with rates 3-10 times that of the general population. As untreated strabismus is a major risk factor for amblyopia in young children, these findings underscore the importance of timely screening and assessment of ocular problems in persons on the autism spectrum.

Whats Known on This SubjectStrabismus has been reported to be more prevalent in individuals on the autism spectrum, but estimates have been very imprecise, ranging from 3-84% across studies.

What This Study AddsThis study performs the first quantitative synthesis of strabismus prevalence in over 100,000 autistic individuals, generating more precise estimates of the prevalence of strabismus in the autistic population. Factors contributing to the large differences between studies are also examined using meta-regression.

category: ophthalmology


title: The Association of Stay-at-Home Orders and the Spread of COVID-19 in Rural and Urban United States

abstract:
BackgroundThroughout the spring of 2020, stay-at-home orders were imposed to curb the spread of COVID-19. There is limited data on the effectiveness of stay-at-home orders, particularly in rural as compared to urban areas.

ObjectiveTo examine the association between stay-at-home order implementation and the incidence of COVID-19 in rural vs. urban counties.

DesignInterrupted time series analysis using a mixed effects zero-inflated Poisson model.

Participants3,142 U.S. counties.

InterventionsStay-at-home orders.

Main MeasuresCOVID-19 daily incidence (primary) and mobility (secondary and intermediate measure of stay-at-home effectiveness)

Key ResultsStay-at-home orders were implemented later (median March 30 vs. March 28) and were shorter (median 35 vs. 54 days) in rural than urban counties. Indoor mobility was, on average, 2.6-6.9% higher in rural than urban counties both during and after stay-at-home orders. Compared to the baseline (pre-stay-at-home) period, the number of new COVID-19 cases increased under stay-at-home by IRR 1.60 (95% CI, 1.57-1.64) in rural and 1.36 (95% CI, 1.30-1.42) in urban counties. For each day under stay-at-home orders, the number of new cases changed by a factor of 0.982 (95% CI 0.981-0.982) in rural and 0.952 (95% CI, 0.951-0.953) in urban counties compared to prior to stay-at-home. Each day after stay-at-home orders expired, the number of new cases changed by a factor of 0.995 (95% CI, 0.994-0.995) in rural and 0.997 (95% CI, 0.995-0.999) in urban counties compared to prior to stay-at-home.

ConclusionStay-at-home orders decreased mobility and slowed the spread of COVID-19, but less effectively in rural than in urban counties. This necessitates a critical reevaluation of how stay-at-home orders are designed, communicated, and implemented in rural areas.

category: health policy


title: Longitudinal monitoring of DNA viral loads in transplant patients using quantitative metagenomic next-generation sequencing

abstract:
IntroductionImmunocompromised patients are prone to reactivations of multiple latent DNA viruses. Viral load monitoring by single-target quantitative PCRs (qPCR) is the current cornerstone for virus quantification. In this study, a metagenomic next-generation sequencing (mNGS) approach was used for identification and load monitoring of transplantation-related DNA viruses.

MethodsLongitudinal plasma samples from six patients that were qPCR-positive for cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyoma virus (BKV, adenovirus (ADV), parvovirus B19 (B19V), and torque teno-virus (TTV) were sequenced using the quantitative metagenomic Galileo Viral Panel Solution (Arc Bio, LLC) reagents and bioinformatics pipeline combination. Qualitative and quantitative performance was analysed with focus on viral load ranges relevant for clinical decision-making.

ResultsAll pathogens identified by qPCR were also identified by mNGS. In addition, BKV, CMV, and HHV6B were detected by mNGS which were not ordered initially but could be confirmed by qPCR. Viral loads determined by mNGS correlated with the qPCR results, with inter-method differences in viral load per virus ranging from 0.19 log10 IU/ml for EBV to 0.90 log10 copies/ml for ADV. TTV, analysed by mNGS in a semi-quantitative way, showed a mean difference of 3.0 log10 copies/ml. Trends over time in viral load determined by mNGS and qPCR were comparable, and clinical thresholds for initiation of treatment were equally indicated by mNGS.

ConclusionThe Galileo Viral Panel for quantitative mNGS performed comparable to qPCR with regard to detection and viral load determination, within clinically relevant ranges of patient management algorithms.


title: Clinical outcomes in vaccinated individuals hospitalized with Delta variant of SARS-CoV-2

abstract: Emerging variants of SARS-CoV-2 with increased transmissibility or immune escape have been causing large outbreaks of COVID-19 infections across the world. As most of the vaccines currently in use have been derived from viral strains circulating in the early part of the pandemic, it becomes imperative to constantly assess the efficacy of these vaccines against emerging variants. In this hospital-based cohort study, we analysed clinical profiles and outcomes of 1161 COVID-19 hospitalized patients (vaccinated with COVISHIELD (ChAdOx1) or COVAXIN (BBV-152), n = 495 and unvaccinated n = 666) in Hyderabad, India between April 24th and May 31st 2021. Viral genome sequencing revealed that >90% of patients in both groups were harbouring the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Vaccinated individuals showed higher neutralizing antibodies (545{+/-}1256 AU/ml Vs 51.1{+/-}296 AU/ml; p<0.001) and significantly decreased Ferritin (392.26 {+/-} 448.4 ng/mL Vs 544.82 {+/-} 641.41 ng/mL; p<0.001) and LDH (559.45 {+/-} 324.05 U/L Vs 644.99 {+/-} 294.03 U/L; p<0.001), when compared to the unvaccinated group. Severity of the disease (3.2% Vs 7.2%; p=0.0039) and requirement of ventilatory support (2.8% Vs 5.9%; p=0.0154) were significantly low in the vaccinated group despite the fact that these individuals had significantly higher age and risk factors. The rate of mortality was about 50% lower (2/132=1.51%) in the completely vaccinated breakthrough infections although mortality in individuals who had received a single dose was similar to the unvaccinated group (9/269=3.35% vs 23/666= 3.45%). Our results demonstrate that both COVISHIELD and COVAXIN are effective in preventing disease severity and mortality against the Delta variant in completely vaccinated hospitalized patients.


title: Rapid and Quantitative Detection of Human Antibodies Against the 2019 Novel Coronavirus SARS CoV2 and its Variants as a Result of Vaccination and Infection

abstract: Measuring the antibody response to 2019 SARS CoV2 is critical for diagnostic purposes, monitoring the prevalence of infection, and for gauging the efficacy of the worldwide vaccination effort COVID-19. In this study, a microchip-based grating coupled fluorescent plasmonic (GC-FP) assay was used to measure antibody levels that resulted from COVID-19 infection and vaccination. In addition, we measured the relative antibody binding towards antigens from variants CoV2 virus variants, strains B.1.1.7 (UK) and B.1.351 (S. African). Antibody levels against multiple antigens within the SARS CoV2 spike protein were significantly elevated for both vaccinated and infected individuals, while those against the nucleocapsid (N) protein were only elevated for infected individuals. GC-FP was effective for monitoring the IgG-based serological response to vaccination throughout the vaccination sequence, and could also resolve acute (within hours) increases in antibody levels. A significant decrease in antibody binding to antigens from the B.1.351 variant, but not B.1.1.7, was observed for all vaccinated subjects when measured by GC-FP as compared to the 2019 SARS CoV2 antigens. These results were corroborated by competitive ELISA assay. Collectively, the findings suggest that GC-FP is a viable, rapid, and accurate method for measuring both overall antibody levels to CoV2 and relative antibody binding to viral variants during infection or vaccination.


title: Persistence of neutralizing antibodies a year after SARS-CoV-2 infection

abstract:
Understanding for how long antibodies persist following Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection provides important insight into estimating the duration of immunity induced by infection.

We assessed the persistence of serum antibodies following wild-type SARS-CoV-2 infection six and twelve months after diagnosis in 367 individuals of whom 13% had severe disease requiring hospitalization. We determined the SARS-CoV-2 spike (S-IgG) and nucleoprotein IgG concentrations and the proportion of subjects with neutralizing antibodies (NAb). We also measured the NAb titers among a smaller subset of participants (n=78) against a wild-type virus (B.1) and three variants of concern (VOCs): Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2).

We found that NAb against the wild-type virus and S-IgG persisted in 89% and 97% of subjects for at least twelve months after infection, respectively. IgG and NAb levels were higher after severe infection. NAb titers were significantly lower against variants compared to the wild-type virus.


title: CLOT STIFFNESS MEASURED BY SEER SONORHEOMETRY AS A MARKER OF POOR PROGNOSIS IN HOSPITALIZED COVID-19 PATIENTS

abstract:
BackgroundHigh incidence of life-threatening thrombotic complications is observed in severely ill COVID-19 patients. D-dimer may help evaluate disease severity and predict outcomes at hospital admission. However, its non-specificity and long analysis times strongly constrain its clinical value. Viscoelastic tests (VET) are widely available rapid point-of-care devices that have been shown to detect a hypercoagulable state (increased clot stiffness and fibrinolysis shutdown) as major contributors of the thrombotic complication in COVID-19. Nevertheless, based on the data obtained so far, definitive conclusions have not been drawn.

ObjectivesWe aim to evaluate the association between VET parameters, standard coagulation tests and inflammation markers assessed in COVID-19 patients at hospital admission with disease severity and outcomes.

Patients/MethodsA total of 69 COVID-19 patients requiring hospitalization were included in the study. The pro-inflammatory and pro-thrombotic state was analyzed by a panel of inflammation markers (IL-6, CRP, LDH, ferritin), routine coagulation tests (PT, aPTT, platelet count, fibrinogen, D-dimer) and a SEER sonorheometry VET profile (Quantra(R) System).

ResultsInflammatory markers IL-6, CRP, LDH and ferritin were elevated in a high percentage of patients (73.6%, 89.2%, 57.1% and 52.4%), as were coagulation-related parameters such as fibrinogen (81.4%) and D-dimer levels (66.2%). Quantra(R) analysis revealed increased clot stiffness (CS) in 34.8%, particularly due to increased fibrinogen contribution (FCS) in 63.7%. Increased clot stability to lysis (CSL) was observed in 32.4%. Age > 65 years, elevated values of fibrinogen, D-dimer, LDH, increased clot stiffness and resistance to clot lysis were significantly associated with worsening disease. The Quantra(R) FCS parameter showed a particularly high prognostic value in distinguishing patients with severe symptomatology.

ConclusionThe global study of hemostasis by the whole blood point-of-care Quantra(R) VET system may be a powerful tool for identifying poor prognosis in COVID-19 patients at hospital admission. In particular, FCS measured by Quantra(R) could be established as a plausible prognostic marker to aid the clinical management of COVID-19 patients.


title: Digitizing ECG image: new fully automated method and open-source software code

abstract:
BackgroundWe aimed to develop and validate an automated, open-source code ECG-digitizing tool and assess agreements of ECG measurements across three types of median beats, comprised of digitally recorded, simultaneous and asynchronous ECG leads and digitized asynchronous ECG leads.

MethodsWe used the data of clinical studies participants (n=230; mean age 30{+/-}15 y; 25% female; 52% had the cardiovascular disease) with available both digitally recorded and printed on paper and then scanned ECGs, split into development (n=150) and validation (n=80) datasets. The agreement between ECG and VCG measurements on the digitally recorded time-coherent median beat, representative asynchronous digitized, and digitally recorded beats was assessed by Bland-Altman analysis.

ResultsAgreement between digitally recorded and digitized representative beat was high [area spatial ventricular gradient (SVG) elevation bias 2.5(95% limits of agreement [LOA] -7.9-13.0){degrees}; precision 96.8%; inter-class correlation [ICC] 0.988; Lins concordance coefficient {rho}c 0.97(95% confidence interval [CI] 0.95-0.98)]. Agreement between digitally recorded asynchronous and time-coherent median beats was moderate for area-based VCG metrics (spatial QRS-T angle bias 1.4(95%LOA -33.2-30.3){degrees}; precision 94.8%; ICC 0.95; Lins concordance coefficient {rho}c 0.90(95%CI 0.82-0.95)], but poor for peak-based VCG metrics of global electrical heterogeneity.

ConclusionsWe developed and validated an open-source software tool for paper-ECG digitization. Asynchronous ECG leads are the primary source of disagreement in measurements on digitally recorded and digitized ECGs.


title: Patterns of SARS-CoV-2 exposure and mortality suggest endemic infections, in addition to space and population factors, shape dynamics across countries

abstract: Some countries have been crippled by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic while others have emerged with few infections and fatalities; the factors underscoring this macro-epidemiological variation is one of the mysteries of this global catastrophe. Variation in immune responses influence SARS-CoV-2 transmission and mortality, and factors shaping this variation at the country level, in addition to other socio-ecological drivers, may be important. Here, we construct spatially explicit Bayesian models that combine data on prevalence of endemic diseases and other socio-ecological characteristics to quantify patterns of confirmed deaths and cases across the globe before mass vaccination. We find that the prevalence of parasitic worms, human immunodeficiency virus and malaria play a surprisingly important role in predicting country-level SARS-CoV-2 patterns. When combined with factors such as population density, our models predict 63% (56-67) and 76% (69-81) of confirmed cases and deaths among countries, respectively. While our findings at this macro-scale are necessarily associative, they highlight a need for studies to consider factors, such as infection by other pathogens, on global SARS-CoV-2 dynamics. These relationships are vital for developing countries that already have the highest burden of endemic disease and are becoming the most affected by the SARS-CoV-2 pandemic.


title: Social risk factors for SARS-CoV-2 acquisition in University students: cross sectional survey

abstract:
ObjectivesTo define risk factors for SARS-CoV-2 infection in University of Cambridge students during a period of increased incidence in October and November 2020.

Study designSurvey

MethodsRoutine public health surveillance identified a marked increase in the numbers of University of Cambridge students with respiratory illness and SARS-CoV-2 positivity in the 10 days after a national lockdown was announced in the UK on 5 November 2020. Cases were identified both through symptom-triggered testing and a universal asymptomatic testing program. An online questionnaire was sent to all University of Cambridge students on 25 November to investigate risk factors for testing positive in the period after 30th October 2020. This asked about symptoms, SARS-CoV-2 test results, in-person teaching settings, other aspects of University life, and attendance at social events in the period just prior to lockdown, from 30th October and 4th November 2020. Univariate and multivariable analyses were undertaken evaluating potential risk factors for SARS-CoV-2 positivity.

ResultsAmong 3,980 students responding to the questionnaire, 99 (2.5%) reported testing SARS-CoV-2 positive in the period studied; 28 (28%) were asymptomatic. We found strong independent associations with SARS-CoV-2 positivity were attendance at two social settings in the City of Cambridge (adjusted odds ratio favouring disease 13.0 (95% CI 6.2,26.9) and 14.2 (95% CI 2.9,70)), with weaker evidence of association with three further social settings. By contrast, we did not observe strong independent associations between disease risk and type of accommodation or attendance at, or participation in, a range of activities associated with the University curriculum.

ConclusionsAttendance at social settings can facilitate widespread SARS-CoV-2 transmission in University students. Constraint of transmission in higher education settings needs to emphasise risks outside University premises, as well as a COVID-safe environment within University premises.

HighlightsO_LIIn a population of University students, a large increase in individuals testing positive for SARS-CoV-2 occurred in the days following a national lockdown.
C_LIO_LIAttendance at particular social gatherings was strongly linked to the development of disease, independent of other risk factors.
C_LIO_LIBy contrast, a range of risk factors including age, gender, ethnicity, accommodation type, shared kitchen facilities, attendance at supermarkets, and attending teaching sessions were not significantly associated with SARS-CoV-2 risk.
C_LIO_LIThese data emphasise the increased risk associated with University students attending social settings with large numbers of others, even when other risks associated with university attendance are well controlled.
C_LI


title: Epidemiology of Atrial Fibrillation in the All of Us Research Program

abstract:
BackgroundThe prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described.

MethodsWe analyzed data from 173,099 participants of the All of Us Research Program recruited in the period 2017-2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR.

ResultsAt enrollment, mean age was 52 years old (range 18-89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF.

ConclusionThe epidemiology of AF in the All of Us Research Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases.


title: Fecal microbiota transplantation increases colonic IL-25 and dampens tissue inflammation in patients with recurrent Clostridioides difficile

abstract:
BackgroundClostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon.

MethodsSubjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT.

ResultsAll 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT.

ConclusionThe increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.


title: Association of the Liver and Plasma Lipidomes with the Histological Stage of Alcohol-Related Liver Disease

abstract:
Background and aimsAlcohol disturbs hepatic lipid synthesis and transport, but the role of lipid dysfunction in the severity of alcohol-related liver disease (ALD) is unclear. We therefore characterised the liver and plasma lipidome in a biopsy-controlled cohort of patients with early ALD.

MethodsWe performed ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry for lipidomics of the liver and plasma from 315 patients, and of plasma from 51 healthy controls matched for age, gender and BMI. We correlated lipid levels with histological fibrosis, inflammation and steatosis, after correction for multiple testing and adjustment for age, gender, statin use, BMI, HbA1c, HOMA-IR, and ongoing drinking. Moreover, we investigated the mechanism of dysregulated sphingolipid metabolism by whole-blood transcriptomics and qPCR sequencing of miRNA.

ResultsWe detected 198 lipids in the liver and 236 lipids in the circulation from 18 lipid classes. Nearly all ceramides, sphingomyelins and lyso-phosphocholines in plasma decreased as fibrosis progressed. This was paralleled by a comparable decrease in the liver. Circulating and liver sphingomyelins were also inversely associated with hepatic inflammation. The lipidomic signature of healthy controls was only comparable to ALD patients with no fibrosis. Three circulating miRNA, highly involved in sphingomyelin metabolism, were dysregulated together with the mRNA expression of enzymes in the sphingomyelin degradation pathway. Mendelian randomization in Finnish and UK population biobanks externally validated our findings, suggesting a causal relationship between genetic disposition to ALD and low sphingolipid levels.

ConclusionsLiver fibrosis severity in alcohol-related liver disease is characterized by selective lipid depletion in blood and liver, indicating profound effects of progressive disease on the bioactive sphingolipids, already from early stages of fibrosis.

Visual Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/21260429v1_ufig1.gif" ALT="Figure 1">
View larger version (39K):
org.highwire.dtl.DTLVardef@ad651org.highwire.dtl.DTLVardef@17c7c95org.highwire.dtl.DTLVardef@1d742f7org.highwire.dtl.DTLVardef@16da292_HPS_FORMAT_FIGEXP  M_FIG C_FIG HighlightsO_LIThe lipidome in the liver and circulation in alcohol-related liver disease (ALD)
C_LIO_LISphingolipid, phospholipid and triacylglycerol levels were lowered in fibrosis
C_LIO_LIExpression and regulation of genes in the sphingolipid pathway were affected
C_LIO_LIALD has a causal link to lowered sphingomyelin levels in blood
C_LI

Lay summaryAlcohol causes a dysfunctional fat metabolism in the liver. In this study, we detected 198 different types of lipids in the liver and 236 in the blood stream of patients with different severity of alcohol-related liver disease. We found that patients with more severe scarring (fibrosis) of the liver, and more severe liver inflammation, had lower levels of sphingolipids both in the circulation and the liver. Sphingolipids regulate cell survival and inflammation, so they may be involved in the mechanism of progressive alcohol-related liver disease.


title: The I-KID Study Protocol: Evaluation of Efficacy, Outcomes and Safety of a New Infant Haemodialysis and Ultrafiltration Machine in Clinical Use: a Randomised Clinical Investigation using a Cluster Stepped-wedge Design.

abstract:
IntroductionThe I-KID study aims to determine the clinical efficacy, outcomes and safety of a novel non-CE-marked infant haemodialysis machine, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared to currently available therapy in the UK. NIDUS is specifically designed for renal replacement therapy in small babies between 0.8 and 8 kilograms.

Methods and analysisThe clinical investigation is taking place in six UK centres. This is a randomised clinical investigation using a cluster stepped-wedge design. The study aims to recruit 95 babies requiring renal replacement therapy in paediatric intensive care units over 20 months.

RegistrationIRAS ID number: 170481

MHRA Reference: CI/2017/0066

ISRCT Number: 13787486

CPMS ID number: 36558

NHS REC reference: 16/NE/0008

Eudamed number: CIV-GB-18-02-023105

Link to full protocol v6.0: https://fundingawards.nihr.ac.uk/award/14/23/26

What is known about this subjectBabies in paediatric intensive care unit (PICU) may develop acute renal failure and require therapeutic support.

Renal replacement options for babies are limited because of their small size and limitations of technology.

Current haemodialysis and filtration systems in use in UK are not recommended or licensed for children under 8kg.

What this study hopes to addRenal replacement methods for infants under 8kg in PICU will be compared.

The efficacy, outcomes and safety of a new infant haemodialysis device will be assessed.

Usability of the new device in normal clinical settings outside of the development centre will be examined.

category: pediatrics


title: Acute phase clinical manifestation of COVID-19 is linked to long-COVID symptoms; A 9-month follow-up study

abstract:
BackgroundThe number of long-COVID is rising but it is not still clear which patients will develop long-covid and what will be the symptoms if they do.We followed up 95 patientswith confirmed COVID-19 after 9 months of the original study to delineate possible long COVID symptoms.

MethodsThe original study included 201 patients who were treated in a large referral center from March to May 2020. Ninty percent of the patients reported physical or psychological symptoms within 9 months post-COVID.

FindingsEasy fatigability was the most common 51.04 % long-COVID symptoms followed by anxiety 38.54 %, dyspnea 38.54 %, and new headache 38.54%. There was no association between COVID-19 severity in the acute phase (admission status) and the number of long-COVID symptoms (F(1, 93) = 0.75, p = 0.45 (n.s.)), chronic fatigue syndrome (CFS) (F(1,93) = -0.49, p = 0.62 (n.s.), MOCA scores (F(1, 90) = 0.073, p = 0.787 (n.s.)) in the future. Being female (F(1, 92) = -2.27, p = 0.02), having a higher number of symptoms in the acute phase(F(1,93) = 2.76, p = 0.0068),and experiencing constitutional neuropsychiatric symptoms(F(1, 93)= 2.529, p = 0.01) in the acute phase were associated with higher occurance of CFS in follow up. Moreover, constitutional neuropsychiatric symptoms in acute phase were associated with cognitive dificits (lower MOCA score) (F(1, 93) = 10.84, p= 0.001) in the follow up.

ConclusionsSeverity of the acute disease does not seem to be related to long-COVID symptoms. However, specific clinical presentations might be predictors of distinct long-COVID symptoms. Constitutional neuropsychiatric symptoms in the acute phase are associated with important and debilitating chronic symptoms including chronic fatigue syndrome, and cognitive deficits. These results might pave the way for findingthe underlying mechanisms of long-COVID and provide additional insight into possible candidate treatments for COVID-19.


title: The Reliability and Validity of the Hebrew Patient Health Questionnaire (PHQ-9) in the General Population

abstract:
ObjectiveTo assess the psychometric properties of the Hebrew version of the Patient Health Questionnaire (PHQ-9) in the general population.

MethodsUsing an online survey, we assessed test-retest reliability with a two-week time interval. A total of 118 participants enrolled in the study, of whom 103 completed the survey twice. Each participant filled out the PHQ-9 and the 12-Item Short Form Survey (SF-12). Our statistical analysis includes Cronbachs alpha, Intraclass Correlation Coefficient (ICC2,1), Spearmans rank correlation coefficient, Standard Error of Measurement (SEM), and Minimal Detectable Change (MDC).

ResultsInternal consistency of the Hebrew version of the PHQ-9 ranged from =0.79-0.83. The test-retest reliability of the questionnaire is good (ICC2,1= 0.81), and it is moderately and negatively correlated to the mental component of the SF-12 (Spearman {rho}= -0.57, p< .05). The SEM of the PHQ-9 is 1.83 points, and the MDC was found to be 5 points.

ConclusionThe Hebrew version of the PHQ-9 is valid and reliable for screening self-reported depressive symptoms online in the general Hebrew-speaking population.


title: Adoption and continued use of mobile contact tracing technology: Multilevel explanations from a three-wave panel survey and linked data

abstract:
ObjectiveTo identify the key individual-level (demographics, attitudes, mobility) and contextual (Covid-19 case numbers, tiers of mobility restrictions, urban districts) determinants of adopting the NHS Covid-19 contact tracing app and continued use over-time.

Design and settingA three-wave panel survey conducted in England in July 2020 (background survey), November 2020 (first measure of mobile app adoption), and March 2021 (continued use of app and new adopters) linked with official data.

Primary outcomeRepeated measures of self-reported app usage.

ParticipantsN = 2,500 adults living in England, representative of Englands population in terms of regional distribution, age, and gender (2011 census).

ResultsWe observe initial app uptake at 41%, 95% CI [0.39,0.43], in November 2020 with a 12% dropout rate by March 2021, 95% CI [0.10,0.14]. We also found that 7% of nonusers as of wave 2 became new adopters by wave 3, 95% CI [0.05,0.08]. Initial uptake (or failure to use) of the app associated with social norms, privacy concerns, and misinformation about third-party data access, with those living in postal districts with restrictions on mobility less likely to use the app. Perceived lack of transparent evidence of effectiveness was associated with drop out of use. In addition, those who trusted the government were more likely to adopt in wave 3 as new adopters.

ConclusionsSuccessful uptake of the contact tracing app should be evaluated within the wider context of the UK Governments response to the crisis. Trust in government is key to adoption of the app in wave 3 while continued use is linked to perceptions of transparent evidence. Providing clear information to address privacy concerns could increase uptake, however, the disparities in continued use among ethnic minority participants needs further investigation as differences are not fully explained via attitudinal measures.

Article summaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIOur data captures reported behaviour at two points to assess within-subject changes over time;
C_LIO_LIResults based on a large, nationally representative sample rather than the convenience, non-probability and/or limited-N samples of previous contact tracing studies;
C_LIO_LIIntegrating demographic/structural and attitudinal explanations relating to technology acceptance with questions adopted from the results of a deliberative poll;
C_LIO_LILimitation: studied population is England (see Section 2.3) where overall mobility is restricted in wave 3 during national lockdown, allowing for limited opportunities for app usage e.g. venue check-ins;
C_LIO_LIDrawing on our findings, an ethnic minority booster sample will in the future allow us to better understand inequalities across and within diverse ethnic populations.
C_LI


title: Neural Correlates of Effects of Internally versus Externally Guided Partnered Rehabilitative Tango for People with Parkinson's Disease

abstract: Restoring function to damaged neural pathways, or promoting compensatory strategies to overcome dysfunctional neural pathways have been topics of inquiry within motor rehabilitation. This study considers these topics in Parkinsons disease (PD), where disruption within the striatal-thalamic-cortical (STC) circuits can cause impairment in internally guided (IG) movements. A related, but separate externally guided (EG) movement network, recruits the intact cerebellar-thalamic-cortical (CTC) loop to facilitate movement in response to sensory cues, and is effective in remediating motor function. Partnered dance with leading and following roles may be used as proxies for training IG and EG strategies respectively, in PD and can test which strategy is more effective in remediating effects of PD. Leaders determine variables associated with IG and communicate step amplitude, timing, and direction to the follower. Followers use an EG strategy to sense and interpret directional pressure cues from the leader and then enact an appropriate movement response. This study examines how IG and EG training strategy affects STC and CTC circuits and their behavioral outcomes to examine whether compensatory or direct entrainment of neural pathways is more effective in PD. Fifty-eight participants were recruited with mild-moderate PD (stages 1-3) and randomly assigned to EG, IG or non-dance education control group and assessed before and after 12 weeks of biweekly interventions. Participants were assessed with standard cognitive and motor behavioral measures and lay in a Magnetic Resonance Imaging (MRI) scanner while they tapped their foot under two conditions: internal (tapping a learned rhythm: IT) and external (participant taps in response to an assistants felt tap on the participants hand: ET) guidance. The foot-tapping data collected with an accelerometer were evaluated by analyzing the frequency spectrum to calculate amplitude and timing of the foot taps. The functional (fMRI) data were pre-processed (AFNI), registered (MNI), and analyzed for changes in activation using a general linear model in SAS and AFNI. Postintervention, both the EG and the IG groups showed clinically significant changes on disease severity, but the EG group showed improvements on cognitive, motor, and mood variables. The EG group also outperformed the IG group in the in-scanner task performance measured by the foot accelerometer. Imaging data revealed a significant increase in the EG group in the primary motor cortex lower limb region and the parts of the cerebellar circuits, particularly right Cerebellar Lobule VIIIa. The control group showed an increase in activity in the putamen compared to the IG and EG groups that could be due to a different compensatory pathway. All findings were corroborated using a region of interest approach examining the same pathways according to an atlas. Our results indicate that the most effective strategy for the PD participants involved external cues that increased activity in the compensatory CTC pathway, the primary motor region, and significant improvements on almost all behavioral measurements.


title: MODERN CONTRACEPTIVE USE AMONG WOMEN IN ZAMBIA: A DESCRIPTIVE SURVEY

abstract:
OBJECTIVEThis study aimed to describe the modern contraceptive use by women of childbearing age in Zambia.

METHODSThe study was retrospective descriptive observational design. Secondary data of 13,683 women aged 15 - 49 who participated in the ZDHS 2018 were analysed. Data were extracted using a data extraction tool and analysed using IBM SPSS Statistics 26. Since the ZDHS 2018 used numeric data, the study was quantitative research. The study examined the association between demographic and socioeconomic characteristics and modern contraceptive use using Pearson, Chi-Square and multiple logistic regression.

RESULTSIn Zambia, the most used type of modern contraception were injectables (52%). Female condom is the most known type of modern contraceptives (55%). The significant factors associated with the use of modern contraceptives were age group 25-29 and 45-49 (AOR=1.41 95% CI=1.05, 1.90) and (AOR=0.41, 95% CI 0.28, 0.62), respectively. Being married and widowed (AOR=2.18, 95% CI 1.75, 2.71), and (AOR=0.50, 95% CI 0.31, 0.78), respectively. The likelihood utilization varied across the gradient of parity, educational attainment, and wealth. Educated and wealthy women were more likely to use modern methods compared to women with no education and in the poor category, respectively.

CONCLUSIONThe study established that factors such as age, marital status, the number of living children (parity), religion, and education level and wealth index remain significant issues in determining modern contraceptive use among childbearing women aged 15 to 49 in Zambia. Therefore, concerted efforts are required to increase use of modern methods of contraception by addressing these determinants.

ARTICLE SUMMARYO_ST_ABSStrengths and limitations of the studyC_ST_ABSO_LIThe study utilized secondary data from the ZDHS 2018 as a proxy to establish the determinants of contraceptive use among women of childbearing age 15-49 in Zambia and therefore added to the body of knowledge.
C_LIO_LIThis study was limited by its cross-sectional nature and hence causal inferences cannot be made.
C_LIO_LIThe study relied on self-report measures, which could be affected by social desirability bias or memory bias
C_LI

category: sexual and reproductive health


title: Does Coaching in the 3rd Year of Medical School Affect Stress, Anxiety and Depression?

abstract:
BackgroundMedical students experience significant stress and anxiety during undergraduate education. Coaching is a possible way of supporting these students throughout this challenging time. To assess the benefits of coaching for medical students, a pilot study providing coaching was performed. This pilot assessed how coaching affected the mental health of medical students and how coaching was received by them.

MethodsTwelve third-year medical students were each given eight 30-60 minute coaching sessions. Each participant took the Hospital Anxiety and Depression Scale (HADS) and the Perceived Stress Scale (PSS) pre-, mid-and post-coaching. After coaching, there were three open-ended questions to measure the reactions to coaching and a scale to determine the likelihood of accessing coaching in the future.

ResultsThere was a significant effect of coaching on perceived stress(p=.023); a trend toward significant effect of coaching on anxiety(p=.057); and no effect of coaching on depression. Qualitative analysis indicated Affective responses (gaining perspective and self-awareness); Cognitive responses (goal setting and working through solving problems); and Skills responses (developing reflection abilities and critical thinking). Attributes of coaching included perceiving coaching as a positive, individualized and supportive experience that students were highly likely to access again.

ConclusionsCoaching holds promise as an intervention offered to medical students to reduce stress and anxiety, and provide positive support for students, preparing them for their professional futures.

Key PointsO_LIAppreciate the stress and anxiety that medical students manage in medical school.
C_LIO_LICoaching is an option that holds promise to support medical students.
C_LIO_LICoaching has possible long-term outcomes that could help future physicians navigate their professional paths more effectively.
C_LIO_LIStudents value individualized, positive support during medical school
C_LI

category: medical education


title: Effect of Criminalization of Drink-Driving on Road Traffic Mortality in China

abstract: To evaluate the national effect of CDD on reducing road traffic mortality, we analyzed crude road traffic mortality rates data collected between 2006 and 2016 through Chinas National Disease Surveillance System. Linear regression models were fit with the pre-CDD data (2006-2011) and used to predict mortality rates in the post-CDD years (2012-2016). It is estimated that the new law was associated with 317,197 (95% CI: 280,425[~]353,968) lives saved in the entire country in the first 5-years of the new law. Similar reduction in mortality rates was observed in both urban and rural areas. The decline in non-occupants was more prominent and occurred earlier than that in occupants, among whom the road traffic mortality rate did not show a statistically significant reduction in the first 4 years of the new law. Our study shows that CDD is particularly effective in protecting non-occupants and is equally effective in both rural and urban areas in China.

category: health economics


title: Fifty Ways to Tag your Pubtypes: Multi-Tagger, a Set of Probabilistic Publication Type and Study Design Taggers to Support Biomedical Indexing and Evidence-Based Medicine

abstract:
ObjectiveIndexing articles according to publication types (PTs) and study designs can be a great aid to filtering literature for information retrieval, especially for evidence syntheses. In this study, 50 automated machine learning based probabilistic PT and study design taggers were built and applied to all articles in PubMed.

Materials and MethodsPubMed article metadata from 1987-2014 were used as training data, with 2015 used for recalibration. The set of articles indexed with a particular study design MeSH term or PT tag was used as positive training sets. For each PT, the rest of the literature from the same time period was used as its negative training set. Multiple features based on each article title, abstract and metadata were used in training the models. Taggers were evaluated on PubMed articles from 2016 and 2019. A manual analysis was also performed.

ResultsOf the 50 predictive models that we created, 44 of these achieved an AUC of [~]0.90 or greater, with many having performance above 0.95. Of the clinically related study designs, the best performing was SYSTEMATIC_REVIEW with an AUC of 0.998; the lowest performing was RANDOM_ALLOCATION, with an AUC of 0.823.

DiscussionThis work demonstrates that is feasible to build a large set of probabilistic publication type and study design taggers with high accuracy and ranking performance. Automated tagging permits users to identify qualifying articles as soon as they are published, and allows consistent criteria to be applied across different bibliographic databases. Probabilistic predictive scores are more flexible than binary yes/no predictions, since thresholds can be tailored for specific uses such as high recall literature search, user-adjustable retrieval size, and quality improvement of manually annotated databases.

ConclusionThe PT predictive probability scores for all PubMed articles are freely downloadable at http://arrowsmith.psych.uic.edu/evidence_based_medicine/mt_download.html for incorporation into user tools and workflows. Users can also perform PubMed queries at our Anne OTate value-added PubMed search engine http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/AnneOTate.cgi and filter retrieved articles according to both NLM-annotated and model-predicted publication types and study designs.

category: health informatics