title: Assessing the Impact of Mental Health Difficulties on Young People's Daily Lives: Protocol for a Scoping Umbrella Review of Measurement Instruments

abstract:
IntroductionAn important consideration for determining the severity of mental health symptoms is their impact on youths daily lives. Those wishing to assess life impact face several challenges: First, various measurement instruments are available, including of global functioning, health-related quality of life (HRQoL), and well-being. Existing reviews have tended to focus on one of these domains; consequently, a comprehensive overview is lacking. Second, the extent to which such instruments truly capture distinct concepts is unclear. Third, many available scales conflate symptoms and their impact, thus undermining much needed analyses of associations between the two.

Methods and analysisA scoping umbrella review will examine existing reviews of life impact measures for use with 6-24-year-olds in the context of mental health and well-being research. We will systematically search five bibliographic databases (MEDLINE, Embase, APA PsycINFO, CINAHL, Web of Science), and conduct systematic record screening, data extraction and charting based on methodological guidance by the Joanna Briggs Institute (JBI). Data synthesis will involve the tabulation of scale characteristics, feasibility, and measurement properties, and the use of summary statistics to synthesize how these instruments operationalize life impact.

Ethics and disseminationThis study will provide a comprehensive road map for researchers and clinicians seeking to assess life impact in youth mental health, providing guidance in navigating available measurement options. We will seek to publish the findings in a leading peer-reviewed journal in the field. Formal research ethics approval will not be required.

Registration detailsThis protocol was registered prospectively with the Open Science Framework (osf.io/jfqdv).

Strengths and Limitations of this StudyO_LIUmbrella review methodology will enable a higher-level synthesis of existing review efforts, thus generating a comprehensive map of available measurement instruments and research findings about their properties.
C_LIO_LIOur methodological approach is based on the JBI guidelines for scoping reviews, umbrella reviews, and psychometric reviews.
C_LIO_LIThis review is based on a rigorous systematic search developed and executed by a health science librarian.
C_LIO_LIWe will only include studies published in the English language since 1990.
C_LIO_LIAs this is a scoping umbrella review designed to map available measurement instruments, the quality and risk of bias of included review articles will not be systematically assessed.
C_LI


title: Threshold concepts in medical education: A scoping review protocol

abstract: Threshold concepts are attracting increasing attention as a framework for improving medical education practice. A growing number of studies in recent years have explored the role of threshold concepts in knowledge and skill acquisition amongst medical students and physicians. However, no review has utilised a systematic approach to examine the literature in this area. The author therefore proposes to undertake a scoping review to explore and describe the current research regarding threshold concepts in medical education and identify gaps in the existing literature. Medical and education databases will be searched for studies exploring threshold concepts in undergraduate, graduate and continuing medical education contexts. The findings will be presented in the form of a descriptive numerical summary and a narrative synthesis. The review will provide a comprehensive overview of how the threshold concept framework is currently being utilised and applied, and provide recommendations for how medical educators can employ the framework in their own practice. Exploration of the research approaches being used, and identification of gaps in the literature, will help inform future research, including determining focus for future systematic reviews.

category: medical education


title: Novel Insights on Genetic and Environmental Factors in Parkinson's Disease from a regional Swedish Case-Control Cohort

abstract:
BACKGROUNDRisk factors for Parkinsons disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology.

OBJECTIVEWe aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort.

METHODSPD patients (n=929) and matched population-based controls (n=935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores.

RESULTSThe cohort is a representative PD case-control cohort (64% men, mean age at diagnosis=67 years, median Hoehn and Yahr score=2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA. In addition, we nominate an unconfirmed and potentially population-specific genome-wide significant association in the PLPP4 locus (rs12771445).

CONCLUSIONSThis work provides an in-depth description of a new PD case-control cohort from southern Sweden, giving insights into environmental and genetic risk factors of PD in the Swedish population.

category: neurology


title: Insights on Genetic and Environmental Factors in Parkinson's Disease from a regional Swedish Case-Control Cohort


title: A Delphi study to establish a consensus definition and clinical reporting guidelines for Mesenchymal Stromal Cells.

abstract:
IntroductionDespite being more than two decades of research, Mesenchymal Stromal Cell (MSC) treatments are still struggling to cross the translational gap. Two key issues that likely contribute to these failures are i) the lack of clear definition for MSC and ii) poor quality of reporting in MSC clinical studies. To address these issues, we propose a modified Delphi study to establish a consensus definition for MSC and clinical reporting guidelines for MSC.

Methods and analysisWe will conduct a three-round international modified Delphi Survey. Findings from a recent scoping review examining how MSC are defined and reported in preclinical and clinical studies were used to draft the initial survey for round one of our Delphi. Participants will include a  core group of individuals as well as researchers whose work was captured in our scoping review. The core group will include stakeholders from different research fields including developmental biology, translational science, research methods, regulatory practices, scholarly journal editing, and industry. The first two survey rounds will be online, and the final round will take place in person. Each participant will be asked to rate their agreement on potential MSC definition characteristics and reporting items using a Likert scale. After each round, we will analyse data to determine which items have reached consensus for inclusion/exclusion, and then develop a revised questionnaire for any new items, or items that did not reach consensus.

Ethics and disseminationThis study received ethical approval from the Ottawa Health Research Network Research Ethics Board. To support the dissemination of our findings, we will use an evidence-based  integrated knowledge translation approach to engage knowledge users from the inception of the research. This will allow us to develop a tailored end-of-project knowledge translation plan to support and ensure dissemination and implementation of the Delphi results.

Strengths and limitations of this studyO_LIWe proposed to address the current limitations in MSC experimental and clinical research with a rigorous and methodological consensus building method (Delphi method) that will allow for structured communication on controversial issues.
C_LIO_LITo support dissemination and implementation of our results, we will engage stakeholders and end-users from the inception of the project - such as patient partners - and will develop a tailored end of project knowledge translation plan (integrated knowledge translation approach) in order to overcome historical issues related to community uptake.
C_LIO_LITo address the main limitations of a Delphi method (e.g., lack of participation, no in-person interaction or information exchange), we use a modified Delphi survey with a Core group of stakeholders and a face-to-face meeting.
C_LI

category: health systems and quality improvement


title: Temporal changes in mental response and prevention patterns, and their impact from uncertainty stress during the transition in China from the COVID-19 epidemic to sporadic infection

abstract:
ObjectiveThis prospective observational study examined changing trends of mental responses and prevention patterns, and their impact from uncertainty stress during the transition in China from the COVID-19 epidemic to sporadic infection.

SettingA prospective longitudinal observation design was utilized in this study.

ParticipantsWe recruited participants for an online panel survey from chat groups on Chinese social media platforms.

Data collectionThere were 7 waves of interviews. Data were obtained by an online survey. A special administrative WeChat group was established to manage the follow-up data collection.

MeasuresSeveral mental responses and prevention patterns were each measured by single questionnaire items. Uncertainty stress was measured by 5-point scale. An irrational beliefs about prevention variable was comprised 5 common misconceptions, which manifested during the COVID-19 epidemic in China.

AnalysisSixty-two participants completed all observation points and were included in the study. The Mann-Kendall Test was used to assess changing trends across the seven observation points. The nonparametric linear mixed effects model was used to examine the association between uncertainty stress and mental and behavioral responses.

ResultsThe mean uncertainty stress did not change significantly over the observation period (T:-0.911, P>0.05). This trend was also true for perceived risk (T: -0.141, P>0.05), perceived severity (T: 1.010, P>0.05), self-efficacy for prevention (T: 0.129, P>0.05), and prevention behavior (T: 0.728, P>0.05). There was a statistically significant downwards trend in irrational beliefs about prevention (T: -4.993, p < 0.01), sleep (T: -2.499, p < 0.05), emotions (T: -5.650, p < 0.01), and lifestyle (T:-5.978, p < 0.01). The results showed that uncertainty stress was positively associated with irrational beliefs ({beta}: 0.16298, p<0.01). The more uncertainty stress, the worse was their sleep ({beta}: 0.02070, p<0.05), emotions ({beta}: 0.03462, p<0.01), and lifestyle({beta}: 0.02056, p<0.05). High levels of uncertainty stress was negatively associated with self-efficacy for prevention and prevention behavior, {beta}value was =-1.33210 (p<0.01) and -0.82742 (p<0.01), respectively.

ConclusionAs the COVID-19 virus spreads around the globe, it is currently in epidemic status in some countries, in sporadic status in another countries, and it will eventually transition to a sporadic infection status. This study provides new information on changing trends of mental responses and prevention patterns from the COVID-19 epidemic as the transition to a sporadic infection period takes place. These results may have important policy and disease prevention in post-epidemic times.

category: infectious diseases


title: T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire

abstract:
AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T-cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 280 unique vaccine recipients aged 18-85 years who enrolled in the phase 2/3 COV002 trial. Total spike-specific CD4+ T cell helper type 1 (Th1) and CD8+ T-cell responses were significantly increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following AZD1222 vaccination were not detected. Furthermore, AZD1222-specific Th1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T-cell receptor (TCR) {beta} sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for the AZD1222-induced CD4+ and CD8+ T-cell responses. Overall, AZD1222 vaccination induced a robust, polyfunctional Th1-dominated T-cell response, with broad CD4+ and CD8+ T-cell coverage across the SARS-CoV-2 spike protein.

One Sentence SummaryPolyfunctional CD4+ and CD8+ T-cell responses are elicited against the SARS-CoV-2 spike protein following vaccination with AZD1222


title: Date of introduction and epidemiologic patterns of SARS-CoV-2 in Mogadishu, Somalia: estimates from transmission modelling of 2020 excess mortality data

abstract:
IntroductionIn countries with weak surveillance systems confirmed COVID-19 deaths are likely to underestimate the death toll of the pandemic. Many countries also have incomplete vital registration systems, hampering excess mortality estimation. Here, we fitted a dynamic transmission model to satellite imagery data on burial patterns in Mogadishu, Somalia during 2020 to estimate the date of introduction, transmissibility and other epidemiologic characteristics of SARS-CoV-2 in this low-income, crisis-affected setting.

MethodsWe performed Markov chain Monte Carlo (MCMC) fitting with an age-structured compartmental COVID-19 model to provide median estimates and credible intervals for the date of introduction, the basic reproduction number (R0) and the effect of non-pharmaceutical interventions in Mogadishu up to September 2020.

ResultsUnder the assumption that excess deaths in Mogadishu February-September 2020 were directly attributable to SARS-CoV-2 infection we arrived at median estimates of October-November 2019 for the date of introduction and low R0 estimates (1.3-1.5) stemming from the early and slow rise of excess deaths. The effect of control measures on transmissibility appeared small.

ConclusionSubject to study assumptions, a very early SARS-CoV-2 introduction event may have occurred in Somalia. Estimated transmissibility in the first epidemic wave was lower than observed in European settings.


title: Clinical profiles at the time of diagnosis of COVID-19 in Costa Rica during the pre-vaccination period using a machine learning approach

abstract:
BackgroundThe clinical manifestations of COVID-19 disease, caused by the SARS-CoV-2 virus, define a large spectrum of symptoms that are mainly dependent on the human host conditions. In Costa Rica, almost 319 000 cases have been reported during the first third of 2021, contrasting to the 590 000 fully vaccinated people. In the pre-vaccination period (the year 2020), this country accumulated 169 321 cases and 2185 deaths.

MethodsTo describe the clinical presentations at the time of diagnosis of COVID-19 in Costa Rica during the pre-vaccination period, we implemented a symptom-based clustering using machine learning to identify clusters or clinical profiles among 18 974 records of positive cases. Profiles were compared based on symptoms, risk factors, viral load, and genomic features of the SARS-CoV-2 sequence.

ResultsA total of seven COVID-19 clinical profiles were identified, which were characterized by a specific composition of symptoms. In the comparison between clusters, a lower viral load was found for the asymptomatic group, while the risk factors and the SARS-CoV-2 genomic features were distributed among all the clusters. No other distribution patterns were found for age, sex, vital status, and hospitalization.

ConclusionDuring the pre-vaccination time in Costa Rica, the clinical manifestations at the time of diagnosis of COVID-19 were described in seven profiles. The host co-morbidities and the SARS-CoV-2 genotypes are not specific of a particular profile, rather they are present in all the groups, including asymptomatic cases. In further analyses, these results will be compared against the profiles of cases during the vaccination period.

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title: Small-molecule metabolome identifies potential therapeutic targets against COVID-19

abstract:
BackgroundRespiratory viruses are transmitted and acquired via the nasal mucosa, and thereby may influence the nasal metabolome composed of biochemical products produced by both host cells and microbes. Studies of the nasal metabolome demonstrate virus-specific changes that sometimes correlate with viral load and disease severity. Here, we evaluate the nasopharyngeal metabolome of COVID-19 infected individuals and report several small molecules that may be used as potential therapeutic targets. Specimens were tested by qRT-PCR with target primers for three viruses: Influenza A (INFA), respiratory syncytial virus (RSV), and SARS-CoV-2, along with asymptomatic controls. The nasopharyngeal metabolome was characterized using an LC-MS/MS-based small-molecule screening kit capable of quantifying 141 analytes. A machine learning model identified 28 discriminating analytes and correctly categorized patients with a viral infection with an accuracy of 96% (R2=0.771, Q2=0.72). A second model identified 5 analytes to differentiate COVID19-infected patients from those with INFA or RSV with an accuracy of 85% (R2=0.442, Q2=0.301). Specifically, LysoPCaC18:2 concentration was significantly increased in COVID19 patients (P< 0.0001), whereas beta-hydroxybutyric acid, Met SO, succinic acid, and carnosine concentrations were significantly decreased (P< 0.0001). This study demonstrates that COVID19 infection results in a unique NP metabolomic signature with carnosine and LysoPCaC18:2 as potential therapeutic targets.

Significance StatementEfforts to elucidate how SARS-CoV-2 interacts with the host has become a global priority. To identify biomarkers for potential therapeutic interventions, we used a targeted metabolomics approach evaluating metabolite profiles in the nasal mucosa of COVID-19 patients and compared metabolite profiles to those of other respiratory viruses (influenza A, RSV). We identified a COVID-19-specific signature characterized by changes to LysoPCaC18:2, beta-hydroxybutyric acid, Met SO, succinic acid, and carnosine. Carnosine is a promising potential target against SARS-CoV-2 as it has been shown to interfere with binding of SARS-CoV-2 to the ACE2 receptor. This study provides compelling evidence for the use of metabolomics as an avenue for the identification of novel drug targets for viral respiratory infections in the nasopharynx.


title: White Blood Cell and Platelet Dynamics Define Human Inflammatory Recovery

abstract:
Inflammation is the physiologic reaction to cellular and tissue damage caused by pathologic processes including trauma, infection, and ischemia1. Effective inflammatory responses integrate molecular and cellular functions to prevent further tissue damage, initiate repair, and restore homeostasis, while futile or dysfunctional responses allow escalating injury, delay recovery, and may hasten death2. Elevation of white blood cell count (WBC) and altered levels of other acute phase reactants are cardinal signs of inflammation, but the dynamics of these changes and their resolution are not established3,4. Patient responses appear to vary dramatically with no clearly defined signs of good prognosis, leaving physicians reliant on qualitative interpretations of laboratory trends4,5.

We retrospectively, observationally studied the human acute inflammatory response to trauma, ischemia, and infection by tracking the longitudinal dynamics of cellular and serum markers in hospitalized patients. Unexpectedly, we identified a conserved pattern of recovery defined by co-regulation of WBC and platelet (PLT) populations. Across all inflammatory conditions studied, recovering patients followed a consistent WBC-PLT trajectory shape that is well-approximated by exponential WBC decay and delayed linear PLT growth. This recovery trajectory shape may represent a fundamental archetype of human physiologic response at the cellular population scale, and provides a generic approach for identifying high-risk patients: 32x relative risk of adverse outcomes for cardiac surgery patients, 9x relative risk of death for COVID-19, and 5x relative risk of death for myocardial infarction.

category: intensive care and critical care medicine


title: AKI Risk Score (AKI-RiSc): Developing an Interpretable Clinical Score for Early Identification of Acute Kidney Injury for Patients Presenting to the Emergency Department

abstract:
BackgroundAcute kidney injury (AKI) in hospitalised patients is a common syndrome associated with poorer patient outcomes. Clinical risk scores can be used for the early identification of patients at risk of AKI.

MethodsWe conducted a retrospective study using electronic health records of Singapore General Hospital emergency department patients who were admitted from 2008 to 2016. The primary outcome was inpatient AKI of any stage within 7 days of admission based on Kidney Disease Improving Global Outcome (KDIGO) 2012 guidelines. AutoScore, a machine learning based algorithm, was used to generate point based clinical scores from the study sample which was divided into training, validation and testing cohorts. Model performance was evaluated using area under the curve (AUC).

ResultsAmong the 119,468 admissions, 10,693 (9.0%) developed AKI. 8,491 were stage 1 (79.4%), 906 stage 2 (8.5%) and 1,296 stage 3 (12.1%). The AKI Risk Score (AKI-RiSc) was a summation of the integer scores of 6 variables: serum creatinine, serum bicarbonate, pulse, systolic blood pressure, and diastolic blood pressure. AUC of AKI-RiSc was 0.730 (95% CI: 0.713 - 0.747), outperforming an existing AKI Prediction Score model which achieved AUC of 0.665 (95% CI: 0.646 - 0.679) when evaluated on the same test cohort. At a cut-off of 4 points, AKI-RiSc had a sensitivity of 82.5% and specificity of 46.7%.

ConclusionAKI-RiSc is a simple point based clinical score that can be easily implemented on the ground for early identification of AKI in high-risk patients and potentially be applied in healthcare settings internationally.

category: emergency medicine


title: SARS-CoV-2 under an elimination strategy in Hong Kong

abstract:
Hong Kong utilized an elimination strategy with intermittent use of public health and social measures and increasingly stringent travel regulations to control SARS-CoV-2 transmission. By analyzing >1700 genome sequences representing 17% of confirmed cases from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases, two of which circulated cryptically for weeks while less stringent measures were in place. We found that SARS-CoV-2 within-host diversity was most similar among transmission pairs and epidemiological clusters due to a strong transmission bottleneck through which similar genetic background generates similar within-host diversity.

One sentence summaryOut of the 170 detected introductions of SARS-CoV-2 in Hong Kong during 2020, three introductions caused 90% of community cases.

category: epidemiology


title: Predicting COVID-19 incidence in French hospitals using human contact network analytics

abstract:
Coronavirus disease (COVID-19) was detected in Wuhan, China in 2019 and spread worldwide within few weeks. The COVID-19 epidemic started to gain traction in France in March 2020. Sub-national hospital admissions and deaths were then recorded daily and served as the main policy indicators. Concurrently, mobile phone positioning data have been curated to determine the frequency of users being colocalized within a given distance. Contrarily to individual tracking data, these can provide a proxy of human contact networks between subnational administrative units. Motivated by numerous studies correlating human mobility data and disease incidence, we developed predictive time series models of hospital incidence between July 2020 and April 2021. Adding human contact network analytics such as clustering coefficients, contact network strength, null links or curvature as regressors, we found that predictions can be improved substantially (more than 50%) both at the national and sub-national for up to two weeks. Our sub-national analysis also revealed the importance of spatial structure, as incidence in colocalized administrative units improved predictions. This original application of network analytics from co-localisation data to epidemic spread opens new perspectives for epidemics forecasting and public health.

HighlightsO_LIWe use novel human contact network analytics based on colocation data of mobile app users to follow the dynamics of disease incidence and interventions of COVID-19 in France.
C_LIO_LITime series predictions of hospital incidence are greatly improved by adding these analytics as regressors.
C_LIO_LISub-national analysis highlights both spatial correlations of incidence and network analytics to obtain high-precision predictions.
C_LI


title: Two-Month Follow-up of Persons with SARS-CoV-2 Infection: Zambia, September 2020

abstract:
BackgroundCOVID-19 is often characterized by an acute upper respiratory tract infection. However, information on longer-term clinical sequelae following acute COVID-19 is emerging. We followed a group of persons with COVID-19 in Zambia at two months to assess persistent symptoms.

MethodsIn September 2020, we re-contacted participants from SARS-CoV-2 prevalence studies conducted in Zambia in July 2020 whose PCR tests were positive. Participants with valid contact information were interviewed using a structured questionnaire that captured demographics, pre-existing conditions, and types and duration of symptoms. We describe the frequency and duration of reported symptoms and used chi-square tests to explore variability of symptoms by age group, gender, and underlying conditions.

ResultsOf 302 participants, 155 (51%) reported one or more acute COVID-19-related symptoms in July 2020. Cough (50%), rhinorrhoea (36%) and headache (34%) were the most frequently reported symptoms proximal to diagnosis. The median symptom duration was 7 days (IQR: 3-9 days). At a median follow up of 54 days (IQR: 46-59 day), 27 (17%) symptomatic participants had not yet returned to their pre-COVID-19 health status. These participants most commonly reported cough (37%), headache (26%) and chest pain (22%). Age, sex, and pre-existing health conditions were not associated with persistent symptoms.

ConclusionA notable percentage of persons with SARS-CoV-2 infection in July still had symptoms nearly two months after their diagnosis. Zambia is implementing  post-acute COVID-19 clinics to care for patients with prolonged symptoms of COVID-19, to address their needs and better understand how the disease will impact the population over time.


title: Antibiotic Use and Outcomes in Young Children Hospitalized with Uncomplicated Community-Acquired Pneumonia

abstract:
ObjectivesTo compare children aged 36 months or younger hospitalized with uncomplicated community-acquired pneumonia (CAP) that are not treated with antibiotics to those treated with antibiotics in terms of clinical features and outcome measures.

MethodsAdministrative data and medical record review were used to identify patients from 3-36 months of age hospitalized from 2011-2019 with uncomplicated CAP. Patients were considered treated if they received antibiotics for more than 2 inpatient days and/or at discharge, and not treated if they received 2 or fewer inpatient days and no antibiotics at discharge. Demographic features, clinical characteristics, radiologic findings, viral testing, illness severity, length of stay and 30-day hospital readmissions were assessed and compared according to antibiotic treatment.

Results322 CAP cases were included. 266/322 (83%) received antibiotics for more than 48 hours and/or at discharge. 56 patients received 2 or fewer inpatient days of antibiotics and no antibiotics at discharge; the majority received no inpatient antibiotics. There were no differences between the two groups in illness severity, length of stay or hospital readmissions. The proportion of patients treated with antibiotics decreased from 88% (2011-2013) to 66% during the most recent years studied (2017-2019).

ConclusionThere was no difference in outcome of uncomplicated CAP in previously healthy children less than 36 months of age between those treated and not treated with antibiotics. Additional tools are needed to facilitate identification of viral CAP in young children and decrease unnecessary antibiotic use.

category: pediatrics


title: PREVALENCE AND INCIDENCE OF ANTIBODIES AGAINST SARS-COV-2 AMONG PRIMARY HEALTHCARE PROVIDERS IN BELGIUM DURING ONE YEAR OF THE COVID-19 EPIDEMIC: PROSPECTIVE COHORT STUDY PROTOCOL

abstract:
IntroductionNational severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence data provides essential information about population exposure to the virus and helps predict the future course of the epidemic. Early cohort studies have suggested declines in levels of antibodies in individuals, associated with, for example, illness severity, age and co-morbidities. This protocol focuses on the seroprevalence among primary health care providers (PHCPs) in Belgium. They manage the vast majority of COVID-19 patients in addition to other patients and therefore play an essential role in the efficient organisation of health care. Currently, evidence is lacking on 1. how many PHCPs get infected with SARS-CoV-2 in Belgium, 2. the rate at which this happens, 3. their clinical spectrum, 4. their risk factors, 5. the effectiveness of the measures to prevent infection and 6. the accuracy of the serology-based point-of-care test in a primary care setting.

Methods and analysisThis study will be set up as a prospective cohort study. General practitioners (GPs) and other PHCPs (working in a GP practice) will be recruited via professional networks and professional media outlets to register online to participate. Registered GPs and other PHCPs will be asked at each testing point (n=9) to perform a capillary blood sample antibody point-of-care test (OrientGene(R)) and complete an online questionnaire. The primary outcomes are the prevalence and incidence of antibodies against SARS-CoV-2 in PHCPs during a 12-month follow-up period. Secondary outcomes include the longevity of antibodies against SARS-CoV-2.

Ethics and disseminationEthical approval has been granted by the Ethics Committee of the University Hospital Antwerp/University of Antwerp (Belgian registration number: 3002020000237). Alongside journal publications, dissemination activities include the publication of monthly reports to be shared with the participants and the general population through the publicly available website of the Belgian health authorities (Sciensano).

RegistrationTrial registration number: NCT04779424

Article summaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIThis large cohort study will provide regular, timely and precise data at national level on prevalence and incidence of antibodies against SARS-CoV-2 among primary health care providers (PHCPs) managing the vast majority of COVID-19 and other patients and therefore essential to organise health care efficiently.
C_LIO_LIThis study will familiarise PHCPs with the use of serology-based point-of-care tests (POCTs) and validate the POCT in a primary care setting.
C_LIO_LIMissing data points and the use of a convenience sample could limit the validity of the study results.
C_LI

category: primary care research


title: A Malaria Knowledge, Attitudes and Practice Survey in a Rural Community in Guinea.

abstract: Malaria is the top public health problem in the Republic of Guinea. In 2016, we conducted a cross-sectional household survey in Timbi-Touni, Guinea using community workers. The survey included respondent demographic characteristics, child health, child health promotion related to malaria knowledge, water and sanitation, and health services access. Majority of our respondents were women (89.41%) and had never been to school (71.18%). Slightly more than half the children were reported to have ever had malaria and 45% reported to have ever had diarrhea. We did not find any statistically significant association between gender or level of education and malaria knowledge. Eighty six percent of respondents had received a free bednet during national campaigns and 61% slept under a bednet the night before the survey. We found a statistically significant association between receiving information on malaria prevention and sleeping under a bednet. There was no statistically significant association between drinking water source and malaria or diarrhea. Both malaria and diarrhea were considered to be serious illnesses for adults and children by nearly all respondents. Insights from our detailed KAP survey can guide policy makers and practitioners who design and implement malaria control and prevention measures in Guinea.

category: public and global health


title: Quantifying T- and B-cell immune receptor distribution diversity to uncover their clinical relevance in clear cell renal cell carcinoma

abstract: Immune-modulating systemic therapies are often used to treat advanced cancer such as metastatic clear cell renal cell carcinoma (ccRCC). Used alone, sequence-based biomarkers neither accurately capture patient dynamics nor the tumor immune microenvironment. To better understand the tumor ecology of this immune microenvironment, we quantified tumor infiltration across two distinct ccRCC patient tumor cohorts using complementarity determining region-3 (CDR3) sequence recovery counts in tumor-infiltrating lymphocytes and a generalized diversity index (GDI) for CDR3 sequence distributions. GDI can be understood as a curve over a continuum of diversity scales which allows sensitive characterization of distributions to capture sample richness, evenness, and subsampling uncertainty, along with other important metrics that characterize tumor heterogeneity. For example, richness quantified the total unique sequence count, while evenness quantified similarities across sequence frequencies. Significant differences in receptor sequence diversity across gender and race revealed that patients with larger and more clinically aggressive tumors had increased richness of recovered tumoral CDR3 sequences, specifically in those from T-cell receptor alpha and B-cell immunoglobulin lambda light chain. The GDI inflection point (IP) allowed for a novel and robust measure of distribution evenness. High IP values associated with improved overall survival, suggesting that normal-like sequence distributions lead to better outcomes. These results propose a new quantitative tool that can be used to better characterize patient-specific differences related to immune cell infiltration, and to identify unique characteristics of tumor-infiltrating lymphocyte heterogeneity in ccRCC and other malignancies.

category: oncology


title: Quantification of T- and B-cell immune receptor distribution diversity characterizes immune cell infiltration and lymphocyte heterogeneity in clear cell renal cell carcinoma


title: Big Data Analysis of Electronic Health Records: Clinically interpretable representations of older adult inpatient trajectories using time-series numerical data and Hidden Markov Models

abstract: The implementation of Electronic Health Records (EHR) in UK hospitals provides new opportunities for clinical  big data analysis. The representation of observations routinely recorded in clinical practice is the first step to use these data in several research tasks. Anonymised data were extracted from 11 158 first emergency admission episodes (AE) in older adults. Irregular records from 23 laboratory blood tests and vital signs were normalized and regularised into daily bins and represented as numerical multivariate time-series (MVTS). Unsupervised Hidden Markov Models (HMM) were trained to represent each day of each AE as one of 17 state spaces. The visual clinical interpretation of these states showed remarkable differences between patients who died at the end of the AE and those who were discharged. All states had marked features that allowed their clinical interpretation and differentiation between those associated with the patients disease burden, their physiological response to this burden or the stage of admission. The most evident relationships with hold-out clinical information were also confirmed by Chi-square tests, with two states strongly associated with inpatient mortality (IM) and 12 states (71%) associated with at least one admission diagnosis. The potential of these data representations on prediction of hospital outcomes was also explored using Logistic Regression (LR) and Random Forest (RF) models, with higher prediction performance observed when models were trained with MVTS data compared to HMM state spaces. However, the outputs of generative and discriminative analyses were complementary. For example, highest ranking features of the best performing RF model for IM (ROC-AUC 0.85) resembled the laboratory blood test and vital sign variables characterising the  Early Inflammatory Response-like state, itself strongly associated with IM. These results provide evidence of the capability of generative models to extract biological signals from routinely collected clinical data and their potential to represent interpretable patients trajectories for future research in hypothesis generation or prediction modelling.

category: health informatics


title: Seroprevalence of SARS-CoV-2 infection in the Colombo Municipality region, Sri Lanka

abstract:
BackgroundAs the Municipality Council area in Colombo (CMC) experienced the highest number of cases until end of January 2021, in Sri Lanka, we carried out a serosurvey prior to initiation of the vaccination program to understand the extent of the SARS-CoV-2 outbreak.

MethodsSARS-CoV-2 seropositivity was determined in 2547 individuals between the ages of 10 to 86 years, by the Wantai total antibody ELISA. We also compared to seroprevalence using the haemagglutination test (HAT) to evaluate its usefulness in carrying out serosurveys.

ResultsThe overall seropositivity rate was 24.46%, while seropositivity by HAT was 18.9%. Although the SARS-CoV-2 infection detection rates by PCR were highest in the population between the ages of 20 to 60 years of age, the seropositivity rates were equal among all age groups. The seropositivity rate was highest in the 10 to 20 age group (34.03%), whereas the PCR positivity rates was 9.8%. Differences in the PCR positivity rates and seropositivity rates were also seen in 60- to 70-year-olds (8.9% vs 30.4%) and in individuals >70 year (4.1% vs 1.2%). The seropositivity rates of the females was 29.7% (290/976), which was significantly higher (p<0.002) than in males 21.2% (333/1571).

ConclusionsA high seroprevalence rate (24.5%) was seen in all age groups in the CMC suggesting that a high level of transmission was seen during this area. The PCR positivity rates, appear to underestimate the true extent of the outbreak and the age groups which were infected.


title: Molecular Genetic Analysis of SARS-CoV-2 Lineages in Armenia

abstract: Sequencing of SARS-CoV-2 provides essential information into viral evolution, transmission, and epidemiology. Short-read next-generation sequencing platforms are currently the gold-standard approaches characterized by the highest accuracy. Meanwhile, Oxford Nanopores long-read sequencing devices show great promise, offering comparable accuracy, fast turnaround time, and reduced cost. In this study, we performed whole-genome sequencing and molecular-genetic characterization of SARS-CoV-2 from clinical specimens using an amplicon-based nanopore sequencing approach. Lineage and phylogenetic analysis identified the most prevalent lineages at different time points (B.1.1.163, B.1.1.208, B.1.1, and since March 2021 - B.1.1.7). In addition, we evaluated the possible effect of identified mutations on the efficacy of recommended primers and probes used for PCR detection of SARS-CoV-2. In summary, a high-quality SARS-CoV-2 genome can be acquired by nanopore sequencing and it can serve as an efficient and affordable alternative to short-read next-generation sequencing and be used for epidemiologic surveillance and molecular-genetic analyses of the virus.


title: Systematic single-variant and gene-based association testing of 3,700 phenotypes in 281,850 UK Biobank exomes

abstract: Genome-wide association studies have successfully discovered thousands of common variants associated with human diseases and traits, but the landscape of rare variation in human disease has not been explored at scale. Exome sequencing studies of population biobanks provide an opportunity to systematically evaluate the impact of rare coding variation across a wide range of phenotypes to discover genes and allelic series relevant to human health and disease. Here, we present results from systematic association analyses of 3,700 phenotypes using single-variant and gene tests of 281,850 individuals in the UK Biobank with exome sequence data. We find that the discovery of genetic associations is tightly linked to frequency as well as correlated with metrics of deleteriousness and natural selection. We highlight biological findings elucidated by these data and release the dataset as a public resource alongside a browser framework for rapidly exploring rare variant association results.

category: genetic and genomic medicine


title: Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial -- BCPP/ Ya Tsie trial

abstract: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV- intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana (estimated trial population: 175,664). Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly-aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 - 56.7] versus 3% [0.1 - 27.3]) than at baseline (7% [1.5 - 25.3] versus 5% [0.9 - 22.9]) compatible with a benefit from treatment-as-prevention. Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies.

category: hiv aids


title: First identification of SARS-CoV-2 Lambda (C.37) variant in Southern Brazil

abstract: In June 15, 2021, the lineage Lambda (C.37) of SARS-CoV-2 was considered a variant of interest (VOI) by the World Health Organization. This lineage has high prevalence in some South America countries but it was described only occasionally in Brazil. Here we describe the first report of the SARS-CoV-2 Lambda variant in Southern Brazil. The sequence described in this paper presented all the eight C.37 defining lineage mutations (ORF1a gene: {Delta}3675-3677; Spike gene: {Delta}246-252, G75V, T76I, L452Q, F490S, D614G, and T859N) in addition to other 19 mutations. Considering that this VOI has been associated with high rates of transmissibility, the possible spread in the Southern Brazilian community is a matter of concern.


title: The statistical analysis of daily data associated with different parameters of the New Coronavirus COVID-19 pandemic in Georgia and their short-term interval prediction in spring 2021

abstract:
The lockdown introduced in Georgia on November 28, 2020 brought positive results. There are clearly positive tendencies in the spread of COVID-19 to February - first half of March 2021. However, in April-May 2021 there was a significant deterioration in the epidemiological situation.

In this work results of the next statistical analysis of the daily data associated with New Coronavirus COVID-19 infection of confirmed (C), recovered (R), deaths (D) and infection rate (I) cases of the population of Georgia in the period from March 01, 2021 to May 31, 2021 are presented. It also presents the results of the analysis of two-week forecasting of the values of C, D and I. The information was regularly sent to the National Center for Disease Control & Public Health of Georgia and posted on the Facebook page https://www.facebook.com/Avtandil1948/.

The analysis of data is carried out with the use of the standard statistical analysis methods of random events and methods of mathematical statistics for the non-accidental time-series of observations. In particular, the following results were obtained.

Georgias ranking in the world for Covid-19 monthly mean values of infection and deaths cases in spring 2021 (per 1 million population) was determined. Among 156 countries with population [≥] 1 million inhabitants in May 2021 Georgia was in the 11 place on new infection cases and in the 14 place on Death.

A comparison between the daily mortality from Covid-19 in Georgia in spring 2021 with the average daily mortality rate in 2015-2019 shows, that the largest share value of D from mean death in 2015-2019 was 25.3 % (22.05.2021), the smallest 1.42 % (15.03.2021).

Data about infection rate of the population of Georgia with Covid-19 according to traffic light system shown, that Georgia in April and May 2021 was in the red zone.

The statistical analysis of the daily and decade data associated with coronavirus COVID-19 pandemic of confirmed, recovered, deaths cases and infection rate of the population of Georgia are carried out. Maximum daily values of investigation parameters are following: C = 2171 (05.05.2021), R = 2038 (17.05.2021), D = 33 (22.05.2021), I = 8.05 % (04.05.2020). Maximum mean decade values of investigation parameters are following: C = 1258 (3 Decade of April 2021), R = 1283 (2 Decade of May 2021), D = 24 (2 Decade of May 2021), I = 6.54 % (1 Decade of May 2021).

It was found that as with September 2020 to February 2021 [8], in spring 2021 the regression equations for the time variability of the daily values of C, R and D have the form of a tenth order polynomial.

Mean values of speed of change of confirmed -V(C), recovered - V(R), deaths - V(D) and infection rate V(I) coronavirus-related cases in different decades of months in the spring 2021 were determined. Maximum mean decade values of investigation parameters are following: V(C) = +37 cases/day (1 Decade of April 2021), V(R) = +36 cases/day (3 Decade of April 2021), V(D) = +0.6 cases/day (3 Decade of April 2021), V(I) = + 0.17 %/ day (2 and 3 decades of April 2021).

Cross-correlations analysis between confirmed COVID-19 cases with recovered and deaths cases shows, that the maximum effect of recovery is observed 9 and 13 days after infection, and deaths - after 12-17 days.

Comparison of real and calculated predictions data of C, D and I in Georgia are carried out. It was found that two-week daily and mean two-week real values of C, D and I practically fall into the 67% - 99.99% confidence interval of these predicted values for the specified time periods.

The comparison of data about C and D in Georgia (GEO) with similar data in Armenia (ARM), Azerbaijan (AZE), Russia (RUS), Turkey (TUR) and in the World (WRL) is also carried out.


title: The mental health of NHS staff during the COVID-19 pandemic: a two-wave cohort study

abstract:
BackgroundHealth and social care workers(HSCWs) are at risk of experiencing adverse mental health (MH) outcomes (e.g., higher levels of anxiety and depression) as a result of the COVID-19 pandemic. This can have a detrimental impact on quality of care, the national response to the pandemic and its aftermath.

AimsA longitudinal design provided follow-up evidence on the MH(changes in the prevalence of disease over time) of NHS staff working in a remote health board in Scotland during the COVID-19 pandemic and investigated the determinants of MH outcomes over time.

MethodA two-wave longitudinal study was conducted from July to September 2020. Participants self-reported levels of depression(PHQ-9), anxiety(GAD-7), and mental well-being(WEMWBS) at baseline and again 1.5 months later.

ResultsThe analytic sample of 169 participants, working in community(43%) and hospital(44%) settings reported substantial levels of probable clinical depression, anxiety and low mental well-being(MWB) at baseline(depression:30.8%, anxiety:20.1%, low-MWB:31.9%). Whilst the MH of participants remained mostly constant over time, the proportion of participants meeting the threshold for clinical anxiety increased to 27.2% at follow-up. Multivariable modelling indicated that working with, and disruption due to COVID-19 were associated with adverse MH changes over time.

ConclusionsHSCWs working in a remote area with low COVID-19 prevalence, reported similar levels of substantial anxiety and depression as those working in areas of the UK with high rates of COVID-19 infections. Efforts to support HSCW MH must remain a priority and should minimize the adverse effects of working with, and the disruption caused by the COVID-19 pandemic.

category: psychiatry and clinical psychology


title: Safe in my heart: resting heart rate variability longitudinally predicts emotion regulation, worry and sense of safeness during COVID-19 lockdown

abstract: Due to its ability to reflect the capacity to engage in context-appropriate responses, tonic heart rate variability (HRV) is considered a putative biomarker of stress resilience. However, most studies are cross-sectional, precluding causal inferences. The high levels of uncertainty and fear at a global level that characterize the COVID-19 pandemic offer a unique opportunity to investigate the longitudinal role of HRV in stress resilience. The present study examined whether HRV, measured about 2 years earlier (Time 0), could predict emotion regulation strategies and daily affect in healthy adults during the May 2020 lockdown (Time 1). Moreover, we evaluated the association between HRV measures, emotion regulation strategies, subjective perception of COVID-19 risk, and self-reported depressive symptoms at Time 1. Higher tonic HRV at Time 0 resulted a significant predictor of a stronger engagement in more functional emotion regulation strategies, as well as of higher daily feelings of safeness and reduced daily worry at Time 1. Moreover, depressive symptoms negatively correlated with HRV and positively correlated with the subjective perception of COVID-19 risk at Time 1. Current data support the view that HRV might be not only a marker but also a precursor of resilience under stressful times.


title: Genomic evidence for prisons as amplifiers of community tuberculosis epidemics

abstract:
BackgroundGlobally, prisons are high-incidence settings for tuberculosis. Yet the role of prisons as reservoirs of M. tuberculosis, propagating epidemics through spillover from prisons to surrounding communities, has been difficult to measure directly.

Methods and FindingsTo quantify the role of prisons in driving wider community M. tuberculosis transmission, we conducted prospective genomic surveillance in Central West Brazil from 2014 to 2019. We whole genome sequenced 1,152 M. tuberculosis isolates collected during active and passive surveillance inside and outside prisons and linked genomes to detailed incarceration histories. We applied multiple phylogenetic and genomic clustering approaches and inferred timed transmission trees. We found that M. tuberculosis sequences from incarcerated and non-incarcerated people were closely related in a maximum likelihood phylogeny. The majority (70.8%; 46/65) of genomic clusters including people with no incarceration history also included individuals with a recent history of incarceration. Among cases in individuals with no incarceration history, 50.6% (162/320) were in clusters that included individuals with recent incarceration history, suggesting that transmission chains often span prisons and communities. We identified a minimum of 18 highly probable spillover events, M. tuberculosis transmission from people with a recent incarceration history to people with no prior history of incarceration, occurring in the states four largest cities and across sampling years. We additionally found that frequent transfers of people between the states prisons creates a highly connected prison network that likely disseminates M. tuberculosis across the state.

ConclusionsWe developed a framework for measuring spillover from high-incidence environments to surrounding communities by integrating genomic and spatial information to reconstruct tuberculosis transmission chains. Our findings indicate that, in this setting, prisons serve not only as disease reservoirs, but also disseminate M. tuberculosis across highly connected prison networks, both amplifying and propagating M. tuberculosis risk in surrounding communities.


title: The role of prisons in disseminating tuberculosis in Brazil: a genomic epidemiology study


title: An empirical assessment of influenza intensity thresholds obtained from the moving epidemic and WHO methods

abstract: The moving epidemic method (MEM) and the WHO method are widely used to determine intensity levels for seasonal influenza. The two approaches are conceptually similar, but differ in two aspects. Firstly, the MEM involves a log transformation of incidence data, while the WHO method operates on the original scale. Secondly, the MEM uses more than one observation from each past season to compute intensity thresholds, fixing the total number to include. The WHO method uses only the highest value from each season. To assess the impact of these choices on thresholds we perform simulation studies which are based on re-sampling of ILI data from France, Spain, Switzerland and the US. When no transformation is applied, a rather large proportion of season peaks are classified as high or very high intensity. This can be mitigated by a logarithmic transformation. When fixing the total number of included past observations, thresholds increase the more seasons are available. When only few are available, there is a high chance of classifying new season peaks as high or very high intensity. We therefore suggest using one observation per season and a log transformation, i.e. a hybrid of the default settings of the MEM and WHO methods.


title: Voice of the patient: Emergence of new motor and non-motor symptoms in early Parkinsons Disease?

abstract:
ObjectiveTo explore the utility of using patient reported emergence of new symptoms (ES) as an outcome measure during the early phase of the disease.

MethodsWe analyzed data from MDS-UPDRS Part IB and Part II from the Safety, Tolerability, and Efficacy Assessment of Isradipine for PD (STEADY-PD3) study, with at least one annual follow-up over two years. We divided the sample into categories of follow-up visit (between 0 and 12-months, and 13 and 24-months) and the number of ES for each part of the scale between participants who started symptomatic treatment and those who did not (STx-yes/no). We assessed ES differences between participants STx in each follow-up visit using Mann-Whitney U test, and the Kaplan-Meier analyses.

ResultsOf 331 participants observed for months 0 to 12, 288 (87%) developed ES, and 182 (55%) started STx. For Part IB, the median number of ES did not significantly differ between the STx groups (Z=-0.86, p = 0.39), while for Part 2, the number of ES was significantly higher for the STx-yes group (Z=-2.38, p=0.02). Of 148 participants who continued to be observed for months 13 to 24, 114 (77%) developed ES, and 62 (42%) started STx. For Part IB, the median number of ES did not significantly differ between the STx groups (Z=-0.33, p = 0.74), while for Part 2, the number of ES was significantly higher for the STx-yes group (Z=-2.25, p=0.02).

ConclusionsAssessing ES among patient-reported experiences of daily living may provide a useful marker for tracking PD progression.


title: Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistanis and Bangladeshis

abstract:
BackgroundIndividuals with South Asian ancestry have higher risk of heart disease than other groups in Western countries; however, most genetic research has focused on European-ancestry (EUR) individuals. It is unknown whether reported genetic loci and polygenic scores (PGSs) for cardiometabolic traits are transferable to South Asians, and whether PGSs have utility in clinical settings.

MethodsUsing data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort (G&H), we conducted genome-wide association studies (GWAS) and characterised the genetic architecture of coronary artery disease (CAD), body mass index (BMI), lipid biomarkers and blood pressure. We applied a new technique to assess the extent to which loci from GWAS in EUR samples were transferable. We tested how well existing findings from EUR studies performed in genetic risk prediction and Mendelian randomisation in G&H.

ResultsTrans-ancestry genetic correlations between G&H and EUR samples for the tested traits were not significantly lower than 1, except for BMI (rg=0.85, p=0.02). We found evidence for transferability for the vast majority of loci from EUR discovery studies that were sufficiently powered to replicate in G&H. PGSs showed variable transferability in G&H, with the relative accuracy compared to EUR (ratio of incremental r2/AUC) [≥]0.95 for HDL-C, triglycerides, and blood pressure, but lower for BMI (0.78) and CAD (0.42). We observed significant improvement in categorical net reclassification in G&H (NRI=3.9%; 95% CI 0.9-7.0) when adding a previously developed CAD PGS to clinical risk factors (QRISK3). We used transferable loci as genetic instruments in trans-ancestry Mendelian randomisation and found evidence of an increased CAD risk for higher LDL-C and BMI, and for lower HDL-C in G&H, consistent with our findings for EUR samples.

ConclusionsThe genetic loci for CAD and its risk factors are largely transferable from EUR studies to British Pakistanis and Bangladeshis, whereas the transferability of PGSs varies greatly between traits. Our analyses suggest clinical utility for addition of PGS to existing clinical risk prediction tools for this population.

Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIThis is the first study to explore the transferability of GWAS findings and PGSs for CAD and related cardiometabolic traits in British Pakistani and Bangladeshi individuals from a cohort with real-world electronic clinical data.
C_LIO_LIWe propose a new approach to assessing transferability of GWAS loci between populations, which can serve as a new methodological standard in this developing field.
C_LIO_LIWe find evidence of overall high transferability of GWAS loci in British Pakistanis and Bangladeshis. BMI, lipids and blood pressure show the highest transferability of loci, and CAD the lowest.
C_LIO_LIThe transferability of PGSs varied between traits, being high for HDL-C, triglycerides and blood pressure but more modest for CAD, BMI and LDL-C.
C_LIO_LIOur results suggest that, for some traits, the use of transferable GWAS loci improves the robustness of Mendelian randomisation estimates in non-Europeans.
C_LI

What are the clinical implications?O_LIThe polygenic score for CAD derived from genetic studies of European individuals improves reclassification on top of clinical risk factors in British Pakistanis and Bangladeshis. The improvement was driven by identification of more cases in younger individuals (25-54 years old), and of controls in older individuals (55-84 years old).
C_LIO_LIIncorporation of the polygenic score for CAD into risk prediction models is likely to prevent cardiovascular events and deaths in this population.
C_LI


title: Social return on investment of home exercise and community referral for people with early dementia

abstract:
BackgroundExercise can improve physical function and slow the progression of dementia. However, uncertainty exists around the cost-effectiveness of exercise programmes for people with early dementia.

ObjectiveThe aim is to determine whether a home-based supervised exercise programme (PrAISED - promoting activity, independence, and stability in early dementia) can generate a positive social return on investment (SROI).

MethodsSROI was conducted as part of a randomised controlled feasibility trial comparing PrAISED with usual care. Wellbeing valuation was used to compare the costs of the programme with the monetised benefits to participants, carers, and healthcare service providers.

ResultsThe PrAISED programme generated SROI ratios ranging from {pound}3.46 to {pound}5.94 for every {pound}1 invested. Social value was created from improved physical activity, increased confidence, more social connection and PrAISED participants using healthcare services less often than usual care.

ConclusionHome-based supervised exercise programmes can generate a positive SROI for people with early dementia.

Trial registrationClinicalTrials.gov: NCT02874300 (first posted 22nd August 2016), ISRCTN: 10550694 (date assigned 31st August 2016)

category: geriatric medicine


title: Validation of the 4C Deterioration Model for COVID-19 in a UK teaching hospital during Wave 2

abstract: The 4C Deterioration model was developed and validated on data collected in UK hospitals until August 26, 2020, but has not yet been validated in the presence of SARS-CoV-2 variants and novel treatment regimens that have emerged subsequently. In this first validation study of the 4C Deterioration model on patients admitted between August 27, 2020 and April 16, 2021 we found, despite a slightly overestimation of risk, that the discrimination (area under the curve 0.75, 95% CI 0.71-0.78) and calibration of the model remained consistent with the development study, strengthening the evidence for adopting this model into clinical practice.


title: Selective tweeting of COVID-19 articles: Does title or abstract positivity influence dissemination?

abstract:
BackgroundPrevious research has shown that articles may be cited more frequently on the basis of title or abstract positivity. Whether a similar selective sharing practice exists on Twitter is not well understood. The objective of this study was to assess if COVID-19 articles with positive titles or abstracts were tweeted more frequently than those with non-positive titles or abstracts.

MethodsCOVID-19 related articles published between January 1st and April 14th, 2020 were extracted from the LitCovid database and all articles were screened for eligibility. Titles and abstracts were classified using a list of positive and negative words from a previous study. A negative binomial regression analysis controlling for confounding variables (2018 impact factor, open access status, continent of the corresponding author, and topic) was performed to obtain regression coefficients, with the p values obtained by likelihood ratio testing.

ResultsA total of 3752 COVID-19 articles were included. Of the included studies, 44 titles and 112 abstracts were positive; 1 title and 7 abstracts were negative; and 3707 titles and 627 abstracts were neutral. Articles with positive titles had a lower tweet rate relative to articles with non-positive titles, with a regression coefficient of -1.10 (P < .001), while the positivity of the abstract did not impact tweet rate (P = .2218).

ConclusionCOVID-19 articles with non-positive titles are preferentially tweeted, while abstract positivity does not influence tweet rate.


title: Trends in COVID-19 vaccination intent, determinants and reasons for vaccine hesitancy: results from repeated cross-sectional surveys in the adult general population of Greece during November 2020-June 2021

abstract:
BackgroundVaccine hesitancy is a major barrier to achieve large-scale COVID-19 vaccination. We report trends in vaccination intention and associated determinants from surveys in the adult general population in Greece.

MethodsFour cross-sectional phone surveys were conducted in November 2020, February, April and May 2021 on nationally representative samples of adults in Greece. Multinomial logistic regression was used on the combined data of the surveys to evaluate independent predictors of vaccination unwillingness/uncertainty.

ResultsVaccination intention increased from 67.6% in November 2020 to 84.8%. in May 2021. Individuals aged 65 years or older were more willing to get vaccinated (May 2021: 92.9% vs. 79.5% in 18-39 years, p<0.001) but between age-groups differences decreased over time. Vaccination intention increased substantially in both sexes, though earlier among men than women and was higher in individuals with postgraduate studies (May 2021: 91.3% vs. 84.0% up to junior high). From multivariable analysis, unwillingness and/or uncertainty to get vaccinated was associated with younger age, female gender (in particular in the April 2021 survey), lower educational level and living with a child [≤]12 years old. Among those with vaccine hesitancy, concerns about vaccine effectiveness declined over time (21.6% in November 2020 vs. 9.6% in May 2021, p=0.014) and were reported more often by men; safety concerns remained stable over time (66.3% in November 2020 vs. 62.1% in May 2021, p=0.658) and were reported more often by women.

ConclusionsVaccination intention increased substantially over time. Tailored communication is needed to address vaccine hesitancy and concerns regarding vaccine safety.

FundingThe phone surveys were conducted with the kind support of the Greek Shipowners Social Welfare Company SYN-ENOSIS

Conflicts of interest statementThe authors have no conflict of interest related to this article


title: Correlates of Protection against symptomatic and asymptomatic SARS-CoV-2 infection

abstract:
BackgroundAlthough 6 COVID-19 vaccines have been approved by the World Health Organisation as of 16th June 2021, global supply remains limited. An understanding of the immune response associated with protection could facilitate rapid licensure of new vaccines.

MethodsData from a randomised efficacy trial of ChAdOx1 nCoV-19 (AZD1222) vaccine in the UK was analysed to determine the antibody levels associated with protection against SARS-CoV-2. Anti-spike and anti-RBD IgG by multiplex immunoassay, pseudovirus and live neutralising antibody at 28 days after the second dose were measured in infected and non-infected vaccine recipients. Weighted generalised additive models for binary data were applied to symptomatic and asymptomatic SARS-CoV-2 infection data from ChAdOx1 nCoV-19 recipients. Cubic spline smoothed log antibody levels, and weights were applied to account for potential selection bias in sample processing. Models were adjusted for baseline risk of exposure to SARS-CoV-2 infection.

ResultsHigher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Vaccine efficacy of 80% against primary symptomatic COVID-19 was achieved with an antibody level of 40923 (95% CI: 16748, 125017) and 63383 (95% CI: 16903, not computed (NC)) for anti-spike and anti-RBD, and 185 (95% CI: NC, NC) and 247 (95% CI: 101, NC) for pseudo- and live-neutralisation assays respectively. Antibody responses did not correlate with overall protection against asymptomatic infection.

ConclusionsCorrelates of protection can be used to bridge to new populations using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where large efficacy trials cannot be conducted. More work is needed to assess correlates for emerging variants.


title: Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers with no Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial

abstract:
IntroductionThe extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute.

MethodsThis four-arm parallel-group, randomized placebo-controlled trial took place at two academic medical centers in USA (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N=520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8 or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization.

ResultsAt 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI=1.9-104.9] and 3.5 [95% CI=1.2-10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130).

ConclusionsWhen smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute.

IMPLICATIONSThe extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.

category: addiction medicine


title: Reduction in severity of all-cause gastroenteritis requiring hospitalisation in children vaccinated against rotavirus in Malawi

abstract:
BackgroundRotavirus is the major cause of severe gastroenteritis in children aged <5 years. Introduction of Rotarix(R) rotavirus vaccine (RV1) in Malawi in 2012 has reduced rotavirus-associated hospitalisations and diarrhoeal mortality. However, RV1 impact on gastroenteritis severity remains unknown. We conducted a hospital-based surveillance study to assess RV1 impact on gastroenteritis severity in children aged <5 years, in Malawi.

MethodsStool samples were collected from children hospitalised with acute gastroenteritis from December 2011 - October 2019. Gastroenteritis severity was determined using Ruuska and Vesikari scores. Rotavirus was detected in stool using Enzyme Immunoassay. Rotavirus genotypes were determined using nested RT-PCR. Associations between RV1 vaccination and gastroenteritis severity were investigated using adjusted linear regression.

ResultsIn total, 3,159 children were recruited. After adjusting for Mid-Upper Arm Circumference, age, weight, gender and receipt of other vaccines, all-cause gastroenteritis severity scores were 2.21 units lower (95% CI 1.85, 2.56; p<0.001) among RV1-vaccinated (n=2,224) compared to RV1-unvaccinated children (n=935); the decrease was comparable between rotavirus-positive and rotavirus-negative cases in all age groups. The reduction in severity score was observed against every rotavirus genotype, although the magnitude was smaller among those infected with G12P[6] compared to the remaining genotypes (p=0.011). Other than RV1 vaccination, age was the only variable associated with gastroenteritis severity. Each one-year increment in age was associated with a decrease of 0.43 severity score (95% CI 0.26, 0.60; p<0.001).

ConclusionOur findings provide additional evidence of RV1 impact in a high disease burden, low-income country, lending further support to Malawis rotavirus vaccine programme.

SummaryIn a long-term hospital-based surveillance study in Malawi, we found evidence of the reduction in gastroenteritis severity among hospitalised RV1-vaccinated children infected with both homotypic and heterotypic rotavirus strains and off-target RV1 vaccine effects against non-rotavirus diarrhoeal severity.

category: gastroenterology


title: Population disruption: estimating changes in population distribution in the UK during the COVID-19 pandemic

abstract: Mobility data have demonstrated major changes in human movement patterns in response to COVID-19 and associated interventions in many countries. This can involve sub-national redistribution, short-term relocations as well as international migration. In this paper, we combine detailed location data from Facebook measuring the location of approximately 6 million daily active Facebook users in 5km2 tiles in the UK with census-derived population estimates to measure population mobility and redistribution. We provide time-varying population estimates and assess spatial population changes with respect to population density and four key reference dates in 2020 (First lockdown, End of term, Beginning of term, Christmas). We also show how the timing and magnitude of observed population changes can impact the size of epidemics using a deterministic model of COVID-19 transmission. We estimate that between March 2020 and March 2021, the total population of the UK has declined and we identify important spatial variations in this population change, showing that low-density areas have experienced lower population decreases than urban areas. We estimate that, for the top 10% highest population tiles, the population has decreased by 6.6%. Further, we provide evidence that geographic redistributions of population within the UK coincide with dates of non-pharmaceutical interventions including lockdowns and movement restrictions, as well as seasonal patterns of migration around holiday dates. The methods used in this study reveal significant changes in population distribution at high spatial and temporal resolutions that have not previously been quantified by available demographic surveys in the UK. We found early indicators of potential longer-term changes in the population distribution of the UK although it is not clear how these changes may persist after the COVID-19 pandemic.


title: Signature transcriptome analysis of stage specific atherosclerotic plaques of patients

abstract:
BackgroundInflammation plays an important role in all the stages of atherosclerotic plaque development. The current study aimed at assessing the altered expression of genes functioning in inflammation within the early stage (ES)and advanced stage (AS) atherosclerotic plaques obtained from patients undergoing coronary artery bypass grafting (CABG) surgery and identifying biomarker panel/sthat may detect the status of plaque stages using peripheral blood samples.

MethodsA section of ES and ASplaques and normal left internal mammary arteries (LIMA) were obtained from 8 patients undergoing theCABG surgery. Total RNA isolated was analysed for mRNA and miRNAexpression profile by Affymetrix arrays. Significant number of mRNAs was found to be differentially expressed in ES and ASplaque tissues relative to LIMA. The pathway analysis of differentially expressed mRNAs in the two plaque stages was also performed using DAVID Bioinformatics Database.

ResultsThe mRNAs were found to be involved in critical inflammatory processes such as Toll-like receptor signalling pathway and cytokine-cytokine receptor interaction. Few miRNAs targeting these mRNAs were also altered in the two plaque conditions. QRT-PCR results showedsimilar expression pattern of few of themRNAs and miRNAsin peripheral blood of same patients relative to healthy controls.

ConclusionChanges in mRNA and miRNA expression associated with various inflammatory processes occur in different atherosclerotic stage plaques as well as peripheral blood. Detection of such variations in patients blood can be used as a possible prognostic tool to detect and/or predict the risk and stage of atherosclerosis.

category: cardiovascular medicine


title: Delay of molecular SARS-CoV-2 testing and turnaround time in Mexico and Colombia

abstract:
ObjectiveTo quantify the delay in SARS-CoV-2 real time polymerase chain reaction (RT-PCR) testing and test result reporting in Mexico and Colombia, and to assess the relation between margination status and these delays.

MethodsWe quantified time in days from symptom onset until testing (latency one) and delay in test results report (latency two) using freely available country-wide open data from Mexico and Colombia. Directed acyclic graphs were built to determine which associations were appropriate to assess. Stratification by margination status, state and hospitalization status was used to determine corresponding associations.

ResultsIn almost all the study period latency two was longer than latency one. Median latency one was 3 (IQR 0-6) days and latency two 7 (IQR 4-11) days in Colombia, while in Mexico they were 3 (IQR 1-5) days and 4 (IQR 3-6) days. In Colombia, worse margination status prolonged latency two. In Mexico, a lower number and percentage of point-of-care (POC) tests in areas with worse margination.

ConclusionPOC tests must be used as a widespread means to reduce latency two, and until then should be prioritized in areas with longer latency two. An unequal distribution of this resource should be avoided.


title: Optimal Selection of COVID-19 Vaccination Sites at the Municipal Level

abstract: In this work, we present an approach to determine the optimal location of coronavirus disease (COVID-19) vaccination sites at the municipal level. We assume that each municipality or town is subdivided into smaller administrative units, which we refer to as villages or barangays. The proposed method solves a minimization problem arising from a facility location problem, which is formulated based on the proximity of the vaccination sites to the villages, number of COVID-19 cases, and population densities of the villages. We present a numerical scheme to solve the optimization problem and give a detailed description of the algorithm, which is coded in Python. To make the results reproducible, the codes used in this study are uploaded to a public repository, which also contains complete instructions on how to use them. As an illustration, we apply our method in determining the optimal location of vaccination sites in San Juan, a town in the province of Batangas, in the Philippines. We hope that this study may guide the local government units in coming up with strategic plans for the COVID-19 vaccine rollout.


title: The effect of Health Literacy on COVID-19 Vaccine Hesitancy: The Moderating Role of Stress

abstract:
BackgroundThe COVID-19 vaccine is an essential means to establish group immunity and prevent the spread of the pandemic. However, the publics hesitation has created major difficulties to the promotion of the vaccine. By investigating the relationship between health literacy and COVID-19 vaccine hesitancy, as well as the potential moderating role of stress, the present study would provide critical insights for tailoring vaccine-promotion strategies.

ObjectiveThe two-fold research purpose is: i) address the effect of health literacy on peoples attitude toward COVID-19 vaccine, ii) clarify the role of stress in this effect.

MethodsWith structured questionnaires, an online survey was conducted to evaluate general publics COVID-19 vaccine hesitancy, health literacy, and perceived stress. In total, 560 responses were collected, and moderated regression analysis was conducted to test the effect of health literacy on vaccine hesitancy among people with different levels of stress.

ResultsA total of 560 participants aged over 18 years were included in this study. About 39.8% of the respondents reported vaccine hesitancy, and this rate is higher among those aged 20-30 years old (83%) and female (71.3%). The results showed people with higher level of health literacy are less likely to have vaccine hesitancy ({beta} =-2.00, 95%CI= [-3.00[~] -0.99]). However, this effect was only among those with lower to moderate level of stress ({beta} =-3.43, p<0.001), among the people with high stress, no significant effect of health literacy was found ({beta} =-0.53, p>0.05).

ConclusionsBy focusing on the effect of health literacy on COVID-19 vaccine hesitancy, the findings showed education program increasing individuals health literacy may also effectively reduce the publics vaccine hesitancy and promote accepting attitude. However, for people with high level of stress, other health programs need to be developed to enhance their positive attitude toward the COVID-19 vaccine. In conclusion, promotion strategies should be tailored for different populations, with considering individual factors such as health literacy and stress.


title: OVARIAN GRANULOSA CELLS FROM WOMEN WITH PCOS EXPRESS LOW LEVELS OF SARS-COV-2 RECEPTORS AND CO-FACTORS

abstract:
PurposeSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is global pandemic with more than 3 million deaths so far. Female reproductive tract organs express coronavirus-associated receptors and factors (SCARFs); suggesting they may be susceptible to SARS-CoV-2 infection however the susceptibility of ovary/follicle/oocyte to the same is still elusive. Co-morbidities like obesity, type-2 diabetes mellitus, cardiovascular disease etc. increase the risk of SARS-CoV-2 infection. These features are common in women with polycystic ovary syndrome (PCOS), warranting further scope to study SCARFs expression in ovary of these women.

Materials and methodsSCARFs expression in ovary and ovarian tissues of women with PCOS and healthy women was explored by analyzing publically available microarray datasets. Transcript expression of SCARFs were investigated in mural and cumulus granulosa cells (MGCs and CGCs) from control and PCOS women undergoing in vitro fertilization (IVF).

ResultsMicroarray data revealed that ovary expresses all genes necessary for SARS-CoV-2 infection. PCOS women mostly showed down-regulated/unchanged levels of SCARFs. MGCs and CGCs from PCOS women showed lower expression of receptors ACE2, BSG and DPP4 and protease CTSB than in controls. MGCs showed lower expression of protease CTSL in PCOS than in controls. Expression of TMPRSS2 was not detected in both cell types.

ConclusionsHuman ovarian follicle may be susceptible to SARS-CoV-2 infection. Lower expression of SCARFs in PCOS indicate that the risk of SARS-CoV-2 infection to the ovary may be lesser in these women than controls. This knowledge may help in safe practices at IVF settings in the current pandemic.

category: sexual and reproductive health


title: Improving prediction of amyloid deposition in Mild Cognitive Impairment with a timed motor task

abstract: Cortical amyloid deposition is one of the hallmark biomarkers of Alzheimers disease. However, given how cost- and time-intensive amyloid imaging can be, there is a continued need for a low-cost, non-invasive, and accessible enrichment strategy to pre-screen individuals for their likelihood of amyloid prior to imaging. Previous work supports the use of coordinated limb movement as a potential screening tool, even after controlling for cognitive and daily function. Thirty-six patients diagnosed with amnestic Mild Cognitive Impairment over the age of 65 underwent 18F-Flutemetamol amyloid-positron emission tomography imaging, then completed a timed motor task involving upper limb coordination. This task takes [~]5 minutes to administer and score. Multivariate linear regression and Receiver Operator Characteristic analyses showed that including motor task performance improved model prediction of amyloid burden. Results support the rationale for including functional upper extremity motor assessment as a cost- and time-effective means to screen participants for amyloid deposition.

category: neurology


title: The impact of legislation on Covid-19 mortality in a Brazilian federative unit was mediated by social isolation.

abstract:
BackgroundThis study aimed to estimate the effect of restrictive laws on actual social isolation and COVID-19 mortality. Moreover, we evaluated how community adherence, measured with an index of social isolation, would mediate the lockdown effect on COVID-19 mortality.

MethodsThis ecological study assessed the legislations published until June 30, 2020, in the Brazilian state of Ceara. We performed a systematic review and classification of restrictive norms and estimated their immediate effect on social isolation, measured by an index based on mobile data, and the subsequent impact on COVID-19 mortality (three weeks later). A mediation analysis was performed to estimate the effect of rigid lockdown on mortality that was explained for effective social isolation.

ResultsThe social isolation index showed an increase of 11.9% (95% CI: 2.9% - 21%) during the days in which a rigid isolation norm (lockdown) was implemented. Moreover, this rigid lockdown was associated with a reduction of 26% (95% CI: 21% - 31%) in the three-week-delayed mortality. We also calculated that the rigid lockdown had the indirect effect, i.e., mediated by adherence to social isolation, of reducing COVID-19 mortality by 38.24% (95% CI: 21.64% to 56.07%). Therefore, the preventive effect of this norm was fully explained by the actual population adherence, reflected in the social isolation index. On the other hand, mandatory mask use was associated with 11% reduction in COVID-19 mortality (95% CI: 8% -13%).

ConclusionsWe estimated the effect of quarantine regulations on social isolation and evidenced that a rigid lockdown law led to a reduction of COVID-19 mortality in one state of Brazil. In addition, the mandatory masks norm was an additional determinant of the reduction of this outcome.


title: Point-of-care testing in a high-income country paediatric emergency department: a qualitative study in Sweden

abstract:
ObjectivesIn many resource-limited health systems, point-of-care tests (POCTs) are the only means for clinical patient sample analyses. However, the speed and simplicity of POCTs also makes their use appealing to clinicians in high-income countries (HICs), despite their having greater laboratory accessibility. Although also part of the clinical routine in HICs, the utility of POCTs is relatively unknown in such settings as compared to others.

In a Swedish paediatric emergency department (PED) where POCT use is routine, we aimed to characterize health care providers perspectives on the clinical utility of POCTs and explore their implementation in the local setting; to compare such experiences to those reported in other settings; and finally, to gather requests for ideal novel POCTs.

DesignQualitative study using focus group discussions. A data-driven content analysis approach was used for analysis.

SettingThe PED of a secondary paediatric hospital in Stockholm, Sweden.

ParticipantsTwenty-four health care providers clinically active at the PED were enrolled in six focus groups.

ResultsA range of POCTs was routinely used. The emerging theme Utility of POCTs is double-edged illustrated the perceived utility of POCTs. While POCT services were considered to have clinical and social value, the local testing practice was named to distract from the care for patients. Requests were made for novel POCTs and their implementation.

ConclusionDespite their clinical integration, deficient implementation routines limit the benefits of POCT services to this well-resourced paediatric clinic. As such deficiencies are shared with other settings, it is suggested that some characteristics of POCTs and of their utility are less related to resource level and more to policy deficiency. To address this, we propose the appointment of skilled laboratory personnel as ambassadors to hospital clinics offering POCT services, to ensure higher utility of such services.

ARTICLE SUMMARYO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIThis is the first study to present the use and utility of POCTs in a HIC paediatric hospital setting, directly from the perspective of its clinical staff.
C_LIO_LIOur main finding is that deficient implementation routines limit benefit of POCT services in this well-resourced setting, strongly indicating that such deficiencies are irrespective of resource level, and more related to policy deficiency.
C_LIO_LIThe findings of the relatively small study size may be contextual, yet we believe our main conclusions to be generalizable as most of our findings are compatible with those reported in other settings.
C_LIO_LIThe study is strengthened by the diversity of its participants, corresponding to the multi-professional staffing of the PED.
C_LI


title: Hidden fraction of Polish population immune to SARS-CoV-2 in May 2021

abstract:
Population immunity (herd immunity) to SARS-CoV-2 derives from two well-defined and controlled sources: vaccinations or diagnosed and registered cases of the disease. It may however also result from asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered cases from which patients recovered at home. Here we present a population screening for SARS-CoV-2 specific IgG and IgA antibodies in Polish citizens (N=501) who had never been positively diagnosed with or vaccinated against SARS-CoV-2. Serum samples were collected in Wrocaw (Lower Silesia) on 15th and 22nd May 2021. Sera from hospitalized COVID-19 patients (N=22) or from vaccinated citizens (N=14) served as positive controls.

Sera were tested with Microblot-Array COVID-19 IgG and IgA (quantitative) that contain specific SARS-CoV-2 antigens: NCP, RBD, Spike S2, E, ACE2, PLPro protein, and antigens for exclusion cross-reactivity with other coronaviruses: MERS-CoV, SARS-CoV, HCoV 229E Np, HCoV NL63 Np.

Within the investigated population of healthy individuals who had never been positively diagnosed with or vaccinated against SARS-CoV-2, we found that 35.5% (178 out of 501) were positive for SARS-CoV-2-specific IgG and 52.3% (262 out of 501) were positive for SARS-CoV-2-specific IgA; 21.2% of the investigated population developed virus-specific IgG or IgA while being asymptomatic. Anti-RBD IgG, which represents virus-neutralizing potential, was found in 25.6% of individuals (128 out of 501).

These patients, though positive for anti-SARS-CoV-2 antibodies, cannot be identified in the public health system as convalescents due to undiagnosed infections, and they are considered unaffected by SARS-CoV-2. Their contribution to population immunity against COVID-19 should however be considered in predictions and modeling of the COVID-19 pandemic. Of note, the majority of the investigated population still lacked anti-RBD IgG protection (74.4%); thus vaccination against COVID-19 is still of the most importance for controlling the pandemic.

category: infectious diseases


title: The serological diversity of serum IgG/IgA/IgM against the SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan

abstract:
ObjectivesTo compare the temporal changes of IgM, IgG, and IgA antibodies against the SARS-CoV-2 nucleoprotein, S1 subunit, and receptor binding domain and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with COVID-19.

MethodsA total of five patients in Nissan Tamagawa Hospital, Tokyo, Japan confirmed COVID-19 from August 8, 2020 to August 14, 2020 were investigated. Serum samples were acquired multiple times from 0 to 76 days after symptom onset. Using a fully automated CLIA analyzer, we measured the levels of IgG, IgA, and IgM against the SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2.

ResultsThe levels of IgG antibodies against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA antibodies increasing before IgG and IgM in 3/5 cases. The NAb levels against SARS-CoV-2 increased and kept above 10 AU/mL more than around 70 days after symptom onset in all cases. Furthermore, in the early stage, NAb levels were more than cut off value in 4/5 COVID-19 patients some of whose antibodies against RBD didnt exceed 10 AU/mL.

ConclusionsOur findings indicate that patients with COVID-19 should be examined for IgG, IgA and IgM antibodies against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 in addition to conventional antibody testing methods for SARS-CoV-2 (IgG and IgM kits) to analyze the diversity of patients immune mechanisms.


title: Adopting an American framework to optimize nursing admission documentation in an Australian health organization

abstract:
ObjectiveApply and modify the American Essential Clinical Dataset (ECD) approach to optimize the data elements of an electronic nursing admission assessment form in a metropolitan Australian local health district.

Materials and MethodsWe used the American ECD approach but made modifications. Our approach included 1) a review of data, 2) a review of current admission practice via consultations with nurses, 3) a review of evidence and policies, 4) workshops with nursing and informatics teams in partnership with the eMR vendor, and 5) team debrief sessions to consolidate findings and decide what data elements should be kept, moved, or removed from the admission form.

ResultsOf 165 data elements in the form, 32% (n=53) had 0% usage, while 25% (n=43) had 100% usage. Nurses perceptions of the forms purpose varied. Eight policy documents specifically prescribed data to be noted at admission. Workshops revealed risks of moving or removing data elements, but also uncovered ways of streamlining the form. Consolidation of findings from all phases resulted in a recommendation to reduce 91% of data elements.

DiscussionApplication of a modified ECD approach allowed the team to identify opportunities for significantly reducing and reorganizing data elements in the eMR to enhance the utility, quality, visibility, and value of nursing admission data.

ConclusionWe found the modified ECD approach effective for identifying data elements and work processes that were unnecessary and duplicated. Our findings and methodology can inform improvements in nursing clinical practice, information management, and governance in a digital health age.


title: Expert Opinion on COVID-19 Vaccination and the Use of Cladribine Tablets in Clinical Practice

abstract:
BackgroundGaps in current evidence and guidance leave clinicians with unanswered questions on the use of cladribine tablets for the treatment of multiple sclerosis (MS) in the era of the COVID-19 pandemic, in particular relating to COVID-19 vaccination.

ObjectiveWe describe a consensus-based program led by international MS experts with the aim of supplementing current guidelines and treatment labels by providing timely recommendations relating to COVID-19 vaccination and the use of cladribine tablets in clinical practice.

MethodsA steering committee (SC) of 10 international MS experts identified seven clinical questions to answer concerning the use of cladribine tablets and COVID-19 vaccination, which addressed issues relating to patient selection, timing and efficacy, and safety. Clinical recommendations to address each question were drafted using available evidence combined with expert opinion from the SC. An extended faculty of 28 MS experts, representing 19 countries, in addition to the 10 SC members, voted on the recommendations. Consensus on recommendations was achieved when [≥]75% of respondents expressed an agreement score of 7-9, on a 9-point scale.

ResultsConsensus was achieved on all 13 recommendations. Clinical recommendations are provided on whether all patients with MS receiving cladribine tablets should be vaccinated against COVID-19, and whether they should be prioritized; the timing of vaccination around dosing of cladribine tablets (i.e., before and after a treatment course); and the safety of COVID-19 vaccination for these patients.

ConclusionsThese expert recommendations provide timely guidance on COVID-19 vaccination in patients receiving cladribine tablets, which is relevant to everyday clinical practice.