title: Are we back to normal yet? The impact of the COVID-19 pandemic on mental health with a specific focus on schizotypal traits in the general population of Germany and the UK, comparing responses from April/May vs. September/October

abstract: Studies reported a strong impact on mental health during the first wave of the COVID-19 pandemic in March-June, 2020. In this study, we assessed the impact of the pandemic on mental health in general and on schizoptypal traits in two independent general population samples of the UK (May sample N: 239, October sample N: 126; participation at both timepoints: 21) and in two independent general population samples of Germany (May sample N: 543, October sample N: 401; participation at both timepoints: 100) using online surveys. Whereas general psychological symptoms (global symptom index, GSI) and percentage of responders above clinical cut-off for further psychological investigation were higher in the May sample compared to the October sample, schizotypy scores (Schizotypal Personality Questionnaire) were higher in the October sample. We investigated potential associations, using general linear regression models (GLM). For schizotypy scores, we found that loneliness, use of drugs, and financial burden were more strongly corrected with schizotypy in the October compared to the May sample. We identified similar associations for GSI, as for schizotypy scores, in the May and October samples. We furthermore found that living in the UK was related to higher schizotypal scores or GSI. However, individual estimates of the GLM are highly comparable between the two countries. In conclusion, this study shows that while the general psychological impact is lower in the October than the May sample, potentially showing a normative response to an exceptional situation; schizotypy scores are higher at the second timepoint, which may be due to a stronger impact of estimates of loneliness, drug use, and financial burden. The ongoing, exceptional circumstances within this pandemic might increase the risk for developing psychosis in some individuals. The development of general psychological symptoms and schizotypy scores over time requires further attention and investigation.

category: psychiatry and clinical psychology


title: Subjective impact of the COVID-19 pandemic on schizotypy and general mental health in Germany and the UK, for independent samples in May and in October 2020


title: Impacts of COVID-19 on long-term health and health care use

abstract:
AimTo explore the temporal impact of mild COVID-19 on need for primary and specialist health care services.

MethodsIn all persons tested for SARS-CoV-2 in Norway March 1st 2020 to February 1st 2021 (N=1 401 922), we contrasted the monthly all-cause health care use before and up to 6 months after the test (% relative difference), for patients with a positive test for SARS-CoV-2 (non-hospitalization, i.e. mild COVID-19) and patients with a negative test (no COVID-19).

ResultsWe found a substantial short-term elevation in primary care use in all age groups, with men generally having a higher relative increase (men 20-44 years: 522%, 95%CI=509-535, 45-69 years: 439%, 95%CI=426-452, [≥] 70 years: 199%, 95%CI=180-218) than women (20-44 years: 342, 95%CI=334-350, 45-69 years=375, 95%CI=365-385, [≥] 70 years: 156%, 95%CI=141-171) at 1 month following positive test. At 2 months, this sex difference was less pronounced, with a (20-44 years: 21%, 95%CI=13-29, 45-69 years=38%, 95%CI=30-46, [≥] 70 years: 15%, 95%CI=3-28) increase in primary care use for men, and a (20-44 years: 30%, 95%CI=24-36, 45-69 years=57%, 95%CI=50-64, [≥] 70 years: 14%, 95%CI=4-24) increase for women. At 3 months after test, only women aged 45-70 years still had an increased primary care use (14%, 95%CI=7-20). The increase was due to respiratory- and general/unspecified conditions. We observed no long-term (4-6 months) elevation in primary care use, and no elevation in specialist care use.

ConclusionMild COVID-19 gives an elevated need for primary care that vanishes 2-3 months after positive test. Middle-aged women had the most prolonged increased primary care use.

category: public and global health


title: Teaching an Old Dog New Tricks: Serum Troponin T as a Biomarker in Amyotrophic Lateral Sclerosis

abstract:
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Diagnosis, management and therapeutic trials are hampered by a lack of informative biomarkers. Troponins (Tn) are components of skeletal and cardiac muscles. Acute elevation of cardiac isoforms of troponin I (cTnI) and T (cTnT) in serum indicates myocardial injury. Case reports suggested that serum levels of cTnT, but not cTnI are chronically elevated in ALS and other neuromuscular disorders.

Using standard clinical laboratory methodologies we studied serum troponin levels in a multicentric cross-sectional cohort of 75 ALS patients and sixty controls (DESCRIBE-ALS cohort) and in a real-world cohort of 179 consecutive patients from our ALS clinic at the University Hospital Bonn.

We found that serum cTnT, is elevated in >60% of ALS patients while cTnI is always normal. Serum cTnT levels increase over time and correlate with disease severity as measured with the revised ALS FRS score. There was no correlation with the phosphorylated neurofilament heavy chain (pNfH) levels in the cerebrospinal fluid. We propose that cTnT elevations in ALS are of non-cardiac origin and may serve as a proxy of lower motor neuron or skeletal muscle involvement. They potentially help to stratify patients according to lower motoneuron involvement. Further research will determine the biological origin of the cTnT elevation and its validity as a diagnostic and/or prognostic marker. Our finding also serves as a reminder to interpret cTnT with caution elevations in patients with neuromuscular diseases.

category: neurology


title: Use of Convalescent Plasma Therapy among Hospitalized Coronavirus Disease 2019 (COVID-19) Patients: A Single-Center Experience

abstract:
COVID-19 Disease has strained our healthcare system. Convalescent plasma has been used to treat emerging infectious diseases -Influenza A/B, SARS-CoV, Ebola virus and now SARS-CoV 2.

OBJECTIVEThis study aims to determine the outcome and clinical course of COVID-19 patients who received convalescent plasma transfusion at Cardinal Santos Medical Center.

METHODSThis is a retrospective cohort analytical study of 75 patients who received convalescent plasma.

RESULTSMedian time from admission to CP transfusion was 3 days. Majority of patients received additional therapies including dexamethasone (100%); Remdesivir (95%); antibiotics (100%), tocilizumab (65%); hemoperfusion (88%) or combination of these. Among the survivors, the median LOS was 15 days while non-survivors have a median LOS of 6 days. One patient (1.33%) had mild transfusion reaction. Four patients (5.33%) developed DVT despite anti-coagulation. There was improvement in the inflammatory markers (LDH pvalue 0.04, CRP pvalue 0.00, Ferritin pvalue 0.0001). There was improvement in the pulmonary parameters -increase in mean PaO2, mean SaO2, and mean PFR; and decrease in mean FiO2 and mean RR post-treatment. Median LOS is 14 days for the CP group vs 11 days for the non-CP group. Mortality rate among the CP group is 25.33% while the non-CP group was 26.67%. LOS and mortality rate did not reach statistical significance.

CONCLUSIONSThere was no significant difference in mortality and length of hospital stay in patients given CP vs controls. CP might have a role in the improvement of inflammatory markers and pulmonary status.

category: hematology


title: The efficacy and safety of Favipiravir in treatment of COVID-19: A systematic review and meta-analysis of clinical trials

abstract: The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved and marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy and safety of Favipiravir in treatment of COVID-19 patients through a systematic review and meta-analysis. This systematic review and meta-analysis were reported in accordance with the PRISMA statement. We registered the protocol in the PROSPERO (CRD42020180032). All clinical trials which addressed the safety and efficacy of Favipiravir in comparison to other control groups for treatment of patients with confirmed infection with SARS-CoV2 were included. We searched electronic databases including LitCovid hub/PubMed, Scopus, ISI web of Sciences, Cochrane, and Scientific Information Database up to 31 December 2020. We assessed the risk of bias of the included studies using Cochrane Collaboration criteria. All analyses were performed using the Comprehensive Meta-Analysis software version 2, and the risk ratio index was calculated. Egger and Begg test was used for assessing publication bias. Nine studies were included in our meta-analysis. The results of the meta-analysis revealed a significant clinical improvement in the Favipiravir group versus the control group during seven days after hospitalization (RR=1.24, 95% CI: 1.09-1.41; P=0.001). Viral clearance was more in 14 days after hospitalization in Favipiravir group than control group, but this finding marginally not significant (RR=1.11, 95% CI: 0.98-1.25; P=0.094). Requiring supplemental oxygen therapy in the Favipiravir group was 7% less than the control group, (RR=0.93, 95% CI: 0.67-1.28; P=0.664). Transferred to ICU and adverse events were not statistically different between two groups. The mortality rate in the Favipiravir group was approximately 30% less than the control group, but this finding not statistically significant. Favipiravir possibly exerted no significant beneficial effect in the term of mortality in the general group of patients with mild to moderate COVID-19. We should consider that perhaps the use of antiviral once the patient has symptoms is too late and this would explain their low efficacy in the clinical setting.

category: infectious diseases


title: Protocol for Safe, Affordable, and Reproducible Isolation and Quantitation of SARS-CoV-2 RNA from Wastewater

abstract: The following protocol describes our workflow for processing wastewater with the goal of detecting the genetic signal of SARS-CoV-2. The steps include pasteurization, virus concentration, RNA extraction, and quantification by RT-qPCR. We include auxiliary steps that provide new users with tools and strategies that will help troubleshoot key steps in the process. This protocol is one of the safest, cheapest, and most reproducible approaches for the detection of SARS-CoV-2 RNA in wastewater. Furthermore, the RNA obtained using this protocol, minus the pasteurization step, can be sequenced both using a targeted approach sequencing specific regions or the whole genome. The protocol was adopted by the New York City Department of Environmental Protection in August 2020 to support their efforts in monitoring SARS-CoV-2 prevalence in wastewater in all five boroughs of the city. Owing to a pasteurization step, it is safe for use in a BSL1+ facility. This step also increases the genetic signal of the virus while making the protocol safe for the personnel involved. This protocol could be used to isolate a variety of other clinically relevant viruses from wastewater and serve as a foundation of a wastewater surveillance strategy for monitoring community spread of known and emerging viral pathogens.


title: Overall burden and characteristics of COVID-19 in the United States during 2020

abstract: The COVID-19 pandemic disrupted health systems and economies throughout the world during 2020 and was particularly devastating for the United States. Many of epidemiological features that produced observed rates of morbidity and mortality have not been thoroughly assessed. Here we use a data-driven model-inference approach to simulate the pandemic at county-scale in the United States during 2020 and estimate critical, time-varying epidemiological properties underpinning the dynamics of the virus. The pandemic in the US during 2020 was characterized by an overall ascertainment rate of 21.6% (95% credible interval (CI):18.9 - 25.5%). Population susceptibility at years end was 68.8% (63.4 - 75.3%), indicating roughly one third of the US population had been infected. Community infectious rates, the percentage of people harboring a contagious infection, rose above 0.8% (0.6 - 1.0%) before the end of the year, and were as high as 2.4% in some major metropolitan areas. In contrast, the infection fatality rate fell to 0.3% by years end; however, community control of transmission, estimated from trends of the time-varying reproduction number, Rt, slackened during successive pandemic waves. In the coming months, as vaccines are distributed and administered and new more transmissible virus variants emerge and spread, greater use of non-pharmaceutical interventions will be needed.


title: Polygenic risk, lifestyle, and cardiovascular mortality: a prospective population-based UK Biobank study

abstract:
OBJECTIVETo assess the prognostic ability of polygenic risk scores (PRSs) for coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) for cardiovascular (CV) mortality, independent of traditional risk factors, and further investigate the additive effect between lifestyle behavior and PRS on CV mortality.

DESIGNProspective population-based cohort study.

SETTINGUK Biobank.

PARTICIPANTSA total 377,909 unrelated participants of white British descent were included in the analyses from the UK Biobank cohort.

MAIN OUTCOME MEASURESGenome-wide PRSs were constructed using >6 million genetic variants. We stratified patients into four PRS risk groups: low (0 to 19th percentile), intermediate (20 to 79th percentile), high (80 to 98th percentile), and very high (99th percentile). We defined a favorable and unfavorable lifestyle with four modifiable lifestyle components, including smoking, obesity, physical activity, and diet. Cox proportional hazard models were used to analyze the relationship between PRS and CV mortality with stratification by age, sex, disease status, and lifestyle behavior.

RESULTSOf 377,909 UK Biobank participants having European ancestry, 3,210 (0.8%) died due to CV disease during a median follow-up of 8.9 years. CV mortality risk was significantly associated with CAD PRS (low vs. very high genetic risk groups, CAD PRS hazard ratio [HR] 2.61 [2.02 to 3.36]) and T2DM PRS (HR 2.08 [1.58 to 2.73]), respectively. These relationships remained significant even after adjustment for a comprehensive range of demographic and clinical factors. In the very high genetic risk group, adherence to an unfavorable lifestyle was further associated with a substantially increased risk of CV mortality (favorable versus unfavorable lifestyle with very high genetic risk for CAD PRS, HR 8.31 [5.12 to 13.49]; T2DM PRS, HR 5.84 [3.39 to 10.04]). Across all genetic risk groups, 32.1% of CV mortality was attributable to lifestyle behavior (population attributable fraction [PAF] 32.1% [95% CI 28.8 to 35.3%]) and 14.1% was attributable to smoking (PAF 14.1% [95% CI 12.4 to 15.7%]). There was no evidence of significant interaction between PRSs and age, sex, or lifestyle behavior in predicting the risk of CV mortality.

CONCLUSIONPRSs for CAD or T2DM and lifestyle behaviors are independent predictive factors for future CV mortality in the white, middle-aged population. PRS-based risk assessment could be useful to identify individuals who need intensive behavioral or therapeutic interventions to reduce the risk of CV mortality.

Summary BoxO_ST_ABSWhat is already known on this topicC_ST_ABSPolygenic risk scores quantify the inherited risk conferred by the cumulative impact of common variants into a quantitative risk estimate.

Previous studies primarily targeted the ability of polygenic risk scores to predict a specific disease, and only a few studies have investigated the association between genetic risk scores and cardiovascular mortality.

The majority of previous analyses calculated polygenic risk scores from only a small number of genetic variants or adjusted for only a few risk factors, and no studies have examined whether the association of polygenic risk score with cardiovascular mortality differs by lifestyle behavior.

What this study addsGenetic risk and lifestyle are independent predictive factors for cardiovascular mortality, even after adjustment for a comprehensive range of demographic and clinical factors.

A healthy lifestyle is associated with relative risk reduction for cardiovascular mortality across all genetic risk categories, a finding that indicates the potential benefit of intensive lifestyle modification in overcoming genetic risk for cardiovascular mortality.

category: cardiovascular medicine


title: Seroprevalence of anti-SARS-CoV-2 IgG antibodies among truck drivers and assistants in Kenya

abstract: In October 2020, anti-SARS-CoV-2 IgG seroprevalence among truck drivers and their assistants (TDA) in Kenya was 42.3%, higher than among other key populations. TDA transport essential supplies during the COVID-19 pandemic, placing them at increased risk of being infected and of transmitting SARS-CoV-2 infection over a wide geographical area.

category: epidemiology


title: Epidemiological dynamics of the incidence of COVID-19 in children and the relationship with the opening of schools in Catalonia (Spain)

abstract: Here we analyse the epidemiological trend of the incidence of COVID-19 in children in Catalonia (Spain) during the first 20 weeks of the 2020-2021 school year. This study demonstrates that while schools were open the incidence rate among children remained significantly lower than in general population, despite a greater diagnostic effort in children. These results suggest that schools have not played a significant role in the SARS-CoV-2 dissemination in Catalonia.


title: COVID-19 European Regional Tracker

abstract: This Tracker presents data on daily COVID-19 cases at the sub-national level for 26 European countries from January 2020 till present. Country-level data sources are identified and processed to form a homogenized panel at the NUTS 3 or NUTS 2 level, the two lowest standardized administrative units of Europe. The strengths and weaknesses of each country dataset are discussed in detail. The raw data, spatial layers, the code, and the final homogenized files are provided in an online repository for replication. The data highlights the spatial distribution of cases both within and across countries that can be utilized for a disaggregated analysis on the impacts of the pandemic. The Tracker is updated monthly to expand its coverage.


title: COVID-19 European regional tracker


title: Should We Delay the Second COVID-19 Vaccine Dose?

abstract:
ObjectivesWith vaccination shortage persisting in many countries, adopting an optimal vaccination program is of crucial importance. Given the slow pace of vaccination campaigns globally, a very relevant and burning public health question is whether it is better to delay the second COVID-19 vaccine shot until all priority group people have received at least one shot. Currently, many countries are looking to administer a third dose (booster shot), which raises the question of how to distribute the available daily doses to maximize the effectively vaccinated population.

MethodsWe formulate a generalized optimization problem with a total of [Formula] vaccine doses, that have to be optimally distributed between n different sub-populations, where sub-population ui represents people receiving the i-th dose of the vaccine with efficacy i. The particular case where n = 2 is solved first, followed by the general case of n dose regimen.

ResultsIn the case of a two dose regimen, if the efficacy of the second dose is less than (or equal to) twice the efficacy of the first dose, the optimal strategy to maximize the number of effectively vaccinated people is to delay the second vaccine as much as possible. Otherwise, the optimal strategy would consist of administering the second dose as quickly as possible. In the general case, the optimal vaccination strategy would be to administer the k-th dose corresponding to the index providing the maximum inter-dose efficacy difference (i - i-1) for all possible values of i [isin] {1, ..., n}, with 0 = 0.

ConclusionOur results suggest that although extending the interval between doses beyond 12 weeks was likely optimal earlier in the pandemic, the reduced single dose efficacy of vaccines against the delta variant make this approach no longer viable.


title: Should We Delay the Second COVID-19 Vaccine Dose in Order to Optimize Rollout? A Mathematical Perspective.


title: Are there significant correlations between climate factors and the spread of COVID-19 for less densely populated and less polluted regions?

abstract:
This study analyzes the correlation between the spread of COVID-19 and meteorological variables (air temperature, relative humidity, wind speed, and precipitation) in urban-rural cities located in southeastern Brazil. Spearmans correlation coefficients were used for the statistical analysis. Results show that air temperature and wind speed were positively correlated with COVID-19 cases, while air relative humidity showed negative correlation. As seen in several recent studies, climate factors and the spread of COVID-19 seem to be related. Our study corroborates this hypothesis for less densely populated and less polluted regions. We hope that our findings help worldwide scientific efforts towards understanding this disease and how it spreads in different regions.

HighlightsO_LIClimate and COVID-19s spread were also correlated in less-densely populated regions.
C_LIO_LIBoth maximum and minimum temperatures are strongly correlated with cases of covid-19.
C_LIO_LIOne hypothesis for the strong association could be the high minimum temperatures in the subtropical region.
C_LIO_LIWind speed is also positively correlated with COVID-19, while air humidity is negatively related.
C_LIO_LIMitigation policies against the spread of COVID-19 should be based on local climate profiles.
C_LI


title: The Phenome-wide Consequences of Anorexia Nervosa Genes

abstract:
Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional GWAS studies produce principal evidence for the association of genetic variants with disease, and provide a jumping-off point for downstream functional analyses. Transcriptomic imputation (TI) allows for the translation of SNPs into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a more broad setting through the use of phenome-wide association studies (PheWAS) in large and diverse clinical biobank populations with electronic health record (EHR) phenotypes. Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe Biobank and performed PheWAS on over 2000 clinical outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of BMI on AN-GReX clinical associations.

Our S-PrediXcan analysis identified 47 genes associated with AN, including what is, to our knowledge, the first genetic association of AN with the Major Histocompatibility Complex (MHC). AN-GReX was associated with autoimmune, anthropometric, metabolic, psychiatric and gastrointestinal diagnoses in our biobank cohort, as well as measures of anthropometry, substance use, and pain score. Our analyses reveal that AN-GReX associations with measures of weight and substance use are modified by BMI, and indicate potential avenues of functional mechanism to investigate further.

category: genetic and genomic medicine


title: Evaluation of a fully automated high-throughput SARS-CoV-2 multiplex qPCR assay with build-in screening functionality for DelHV69/70- and N501Y variants such as B.1.1.7

abstract:
1BackgroundNew SARS-CoV-2 variants with increased transmissibility, like B.1.1.7 from England or B1.351 from South Africa, have caused considerable concern worldwide. In order to contain the spread of these lineages, it is of utmost importance to have rapid, sensitive and high-throughput detection methods at hand.

MethodsAnalytical sensitivity was assessed for both wild-type SARS-CoV-2 and B.1.1.7 lineage by serial dilution. A total of 141 clinical samples were subjected to the test and results compared to a commercial manual typing-PCR assay and NGS.

ResultsThe multiplex assay is highly sensitive for detection of SARS-CoV-2 RNA in clinical samples, with an LoD of 25.82 cp/ml (CI: 11.61 - 57.48). LoDs are slightly higher for the HV68/70 deletion (111.36 cp/ml; CI: 78.16 - 158.67) and the N501Y SNP (2548.04 cp/ml, CI: 1592.58 - 4076.73). A total of 141 clinical samples were tested with the assay, including 16 samples containing SARS-CoV-2 of the B.1.1.7 lineage. Three non-B.1.1.7 samples contained a HV69/70 deletion. All were correctly identified by the multiplex assay.

ConclusionWe describe here a highly sensitive, fully automated multiplex PCR assay for the simultaneous detection of del-HV69/70 and N501Y that can distinguish between lineages B.1.1.7 and B1.351. The assay allows for high-throughput screening for relevant variants in clinical samples prior to sequencing.


title: Hexosylceramides and glycerophosphatidylcholine GPC(36:1) increase in Multi Organ Dysfunction Syndrome patients with Pediatric Intensive Care Unit Admission over 8 day hospitalization

abstract: Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients, undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting criteria for MODS were screened, consented (n=24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n=4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. 61 patient samples over 3 time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63% - 3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (P-value [≤]0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.

category: intensive care and critical care medicine


title: Systematic Review and Scientific Rating of Commercial Apps Available in India for Diabetes Prevention

abstract:
BACKGROUNDScientific evidence for digital health applications (apps) which claim to help in the prevention and management of Type 2 diabetes (T2D) is limited.

OBJECTIVESWe aimed to evaluate the quality of currently available health apps for prevention of T2D amongst Asian Indians.

METHODSUsing the keywords,  diabetes prevention,  healthy lifestyle and  fitness, a total of 1486 apps available in India via Google Play were assessed for eligibility by two independent reviewers. After initial screening using specific inclusion and exclusion criteria, 50 apps underwent a pre-specified rating based on user reviews, number of downloads and app size. Sixteen apps that scored [≥] 9 were shortlisted for further review using the Mobile App Rating Scale (MARS). MARS contains 2 main categories: Category I (Application Quality) and Category II (Application Subjective Quality). The mean MARS scores were used to identify the top ranked apps.

RESULTSThe mean score for Category I of MARS rating was highest for  Google Fit: Health and Activity Tracking (4.55/5). This was followed by  Healthifyme - Diet Plan, Health and Weight Loss (4.45/5). For Category II of MARS,  Diabetes M,  Google Fit: Health and Activity Tracking and Calorie Counter- My fitness pal,  Healthifyme - Diet plan, Health and Weight Loss all scored equally well. On comparing the advantages and disadvantages of each of these applications,  Google Fit: Health and Activity Tracking and  Healthifyme - Diet plan, Health and Weight Loss again ranked the best.

CONCLUSIONSOur review identifies two commercially available apps  Google Fit: Health and Activity Tracking and  Healthifyme - Diet plan, Health and Weight Loss as being user friendly and good quality. Although encouraging, further research is needed to evaluate the efficacy of these apps for prevention of diabetes.

category: endocrinology


title: Characterization of SARS-CoV-2 genetic structure and infection clusters in a large German city based on integrated genomic surveillance, outbreak analysis, and contact tracing

abstract: Viral genome sequencing can address key questions about SARS-CoV-2 evolution and viral transmission. Here, we present an integrated system of genomic surveillance in the German city of Dusseldorf, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) analysis of hospital outbreaks, d) integration of public health authority contact tracing data, and e) a user-friendly dashboard application as a central data analysis platform. The generated surveillance sequencing data (n = 320 SARS-CoV-2 genomes) showed that the development of the local viral population structure from August to December 2020 was consistent with European trends, with the notable absence of SARS-CoV-2 variants 20I/501Y.V1/B.1.1.7 and B.1.351 until the end of the local sampling period. Against a background of local surveillance and other publicly available SARS-CoV-2 data, four putative SARS-CoV-2 outbreaks at Dusseldorf University Hospital between October and December 2020 (n = 44 viral genomes) were investigated and confirmed as clonal, contributing to the development of improved infection control and prevention measures. An analysis of the generated surveillance sequencing data with respect to infection clusters in the population based on a greedy clustering algorithm identified five candidate clusters, all of which were subsequently confirmed by the integration of public health authority contact tracing data and shown to be represent transmission settings of particular relevance (schools, care homes). A joint analysis of outbreak and surveillance data identified a potential transmission of an outbreak strain from the local population into the hospital and back; and an in-depth analysis of one population infection cluster combining genetic with contact tracing data enabled the identification of a previously unrecognized population transmission chain involving a martial arts gym. Based on these results and a real-time sequencing experiment in which we demonstrated the feasibility of achieving sample-to-turnaround times of <30 hours with the Oxford Nanopore technology, we discuss the potential benefits of routine ultra-fast sequencing of all detected infections for contact tracing, infection cluster detection, and, ultimately, improved management of the SARS-CoV-2 pandemic.


title: Optimal Allocation of COVID-19 Vaccines in the Philippines

abstract: Vaccine allocation is a national concern especially for countries such as the Philippines that have limited resources in acquiring COVID-19 vaccines. As such, certain groups are suggested to be prioritized for vaccination to protect the most vulnerable before vaccinating others. Our model suggests an allocation of vaccines such that COVID-19 deaths are minimized while the prioritization framework is satisfied. Results of the model show that a vaccine coverage of at least 50 to 70% of the population can be enough for a community with limited supplies, and an increase in vaccine supply is beneficial if initial coverage is less than the specified target range. Also, among the vaccines considered in the study, the one with 89.9% effectiveness and has a 183 Philippine peso (Php) price per dose projected the least number of deaths. Compared to other model variations and common allocation approaches, the model has achieved both an optimal and equitable allocation. This will be helpful for policymakers in determining a vaccine distribution for a resource-constrained community.


title: A disproportionate epidemic: COVID-19 cases and deaths among essential workers in Toronto, Canada

abstract: Shelter-in-place mandates and closure of non-essential businesses have been central to COVID-19 response strategies including in Toronto, Canada. Approximately half of the working population in Canada are employed in occupations that do not allow for remote work suggesting potentially limited impact of some of the strategies proposed to mitigate COVID-19 acquisition and onward transmission risks and associated morbidity and mortality. We compared per-capita rates of COVID-19 cases and deaths from January 23, 2020 to January 24, 2021, across neighborhoods in Toronto by proportion of the population working in essential services. We used person-level data on laboratory-confirmed COVID-19 community cases (N=74,477) and deaths (N=2319), and census data for neighborhood-level attributes. Cumulative per-capita rates of COVID-19 cases and deaths were 3-fold and 2.5-fold higher, respectively, in neighborhoods with the highest versus lowest concentration of essential workers. Findings suggest that the population who continued to serve the essential needs of society throughout COVID-19 shouldered a disproportionate burden of transmission and deaths. Taken together, results signal the need for active intervention strategies to complement restrictive measures to optimize both the equity and effectiveness of COVID-19 responses.


title: COVID-19 Associated Stroke--A Single Centre Experience

abstract:
Background and PurposeVarious neurological complications have been reported in association with COVID-19. We report our experience of COVID-19 with stroke at a single center over a period of eight months spanning 1 March to 31 October 2020.

MethodsWe recruited all patients admitted to Internal Medicine with an acute stroke, who also tested positive for COVID-19 on RTPCR. We included all stroke cases in our analysis for prediction of in-hospital mortality, and separately analyzed arterial infarcts for vascular territory of ischemic strokes.

ResultsThere were 62 stroke cases among 3923 COVID-19 admissions (incidence 1.6%). Data was available for 58 patients {mean age 52.6 years; age range 17-91; F/M=20/38; 24% (14/58) aged [≤]40; 51% (30/58) hypertensive; 36% (21/58) diabetic; 41% (24/58) with O2 saturation <95% at admission; 32/58 (55.17 %) in-hospital mortality}. Among 58 strokes, there were 44 arterial infarcts, seven bleeds, three arterial infarcts with associated cerebral venous sinus thrombosis, two combined infarct and bleed, and two of indeterminate type. Among the total 49 infarcts, Carotid territory was the commonest affected (36/49; 73.5%), followed by vertebrobasilar (7/49; 14.3%) and both (6/49; 12.2%). Concordant arterial block was seen in 61% (19 of 31 infarcts with angiography done).  Early stroke (within 48 hours of respiratory symptoms) was seen in 82.7% (48/58) patients. Patients with poor saturation at admission were older (58 vs 49 years) and had more comorbidities and higher mortality (79% vs 38%). Mortality was similar in young strokes and older patients, although the latter required more intense respiratory support. Logistic regression analysis showed that low GCS and requirement for increasing intensity of respiratory support predicted in-hospital mortality.

ConclusionsWe had a 1.6% incidence of COVID-19 related stroke of which the majority were carotid territory infarcts. In-hospital mortality was 55.17%, predicted by low GCS at admission.


title: Excess Mortality in Suicide caused by COVID-19 in Japan

abstract:
BackgroundCountermeasures against COVID-19 outbreak such as lockdown and voluntary restrictions against going out adversely affect human stress and economic activity. Particularly, this stress might lead to suicide.

ObjectWe examined excess mortality attributable to suicide caused by COVID-19. Method: We applied the NIID model to suicide deaths from October 2009 through September, 2021 for the whole of Japan by gender. Effects of the great earthquake that struck in eastern Japan on March 11, 2011 were incorporated into the estimation model. Results: Significant excess mortality in suicide was found between July, 2020 and July, 2021 for both genders. However, in August and September, 2021, excess mortality in suicide was detected only in female. It was greater among females than among males. In total, 2950 excess cases of mortality were identified.

Discussion and ConclusionExcess mortality during the four months was more than two times greater than the number of COVID-19 deaths confirmed by PCR testing. Countermeasures against COVID-19 should be chosen carefully in light of suicide effects.


title: Excess Mortality by Suicide associated with COVID-19 in Japan through August, 2021


title: Serum Markers Predict Brain Death Due to Trauma and Hypoxia Within 32 hours of Injury

abstract:
BackgroundPrediction of which traumatic and hypoxic brain injuries will progress to brain death is currently based predominantly on history, physical examination and radiographic findings. We investigated how accurately purely objective measures including three neurologic serum markers and algorithmic CT (computed tomograph) scan analysis can predict brain death and differentiate its etiology.

MethodsThis prospective observational study enrolled 51 isolated trauma subjects and 19 clinically brain dead subjects that were further divided by mechanism of injury into high-velocity trauma with presumed diffuse axonal injury, cardiopulmonary/respiratory arrest, and found down groups. Levels of glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 Calcium-Binding Protein B (S100B) were compared, and algorithmic analysis of CT scan imaging was performed using an open-source deep learning software (BLAST-CT).

FindingsThe prognostic value of various biomarker combinations in identifying subjects progressing to brain death was assessed using machine learning. Prediction accuracy for GFAP, UCH-L1, and S100B and algorithmic CT analysis in combination to predict brain death from among all other cohorts yielded an area under the receiver operator curve of 0.98 versus all other brain injury subjects. This model was also able to distinguish brain death attributed to cardiopulmonary/respiratory arrest from combined non-trauma controls and diffuse axonal injury with an area under the curve of 0.99.

InterpretationSerum concentrations of GFAP, UCH-L1, and S100B measured within 32 hours of traumatic and hypoxic brain injury (cardiopulmonary/respiratory arrest) and algorithmic CT analysis have utility in prognosticating brain death and predicting its mechanism of injury as either hypoxic or traumatic/unknown (diffuse axonal injury/found down).

FundingAbbott Labs and the Minnesota State Office of Higher Education.


title: Machine Learning with Objective Serum Markers and Algorithmic Deep Learning CT Scan Analysis Predicts Brain Death Due to Trauma and Hypoxia


title: Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers

abstract:
BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) reduce child stunting and provide many of the fatty acids and micronutrients that are necessary for rapid brain development that occurs during infancy and early childhood. Positive effects of SQ-LNS on developmental outcomes have been found in some trials, but not others.

ObjectivesOur objectives were to generate pooled estimates of the effect of SQ-LNS, compared to control groups that received no intervention or an intervention without any nutritional supplement, on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.

MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 intervention versus control group comparisons in 13 randomized trials of SQ-LNS provided to infants and young children age 6 to 24 months in 9 low- or middle-income countries (total n=30,024). We generated study-specific estimates of SQ-LNS vs. control groups (including main effects and subgroup estimates for individual-level effect modifiers) and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.

ResultsIn 11-13 intervention versus control group comparisons (n=23,588-24,561), SQ-LNS increased mean language (mean difference: 0.07 standard deviations; 95% CI: 0.04, 0.10), social-emotional (0.08; 0.05, 0.11), and motor scores (0.08; 0.05, 0.11) and reduced the prevalence of children in the lowest decile of these scores by 17% (prevalence ratio: 0.83, 95% CI 0.76, 0.91), 19% (0.81; 0.74, 0.90), and 16% (0.84; 0.77, 0.92), respectively. SQ-LNS also increased the prevalence of children walking without support at 12 months by 9% (1.09; 1.05, 1.14). Effects of SQ-LNS on language, social-emotional, and motor outcomes were larger among study populations with a higher burden ([≥] 35%) of child stunting at 18 months (mean difference 0.11-0.13 SD; 8-9 comparisons) than in populations with lower stunting burden (estimates near zero). At the individual level, greater effects of SQ-LNS were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socio-economic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).

ConclusionsSQ-LNS provided daily to children in the range of 6-24 months of age can be expected to result in modest, but potentially important, developmental gains, particularly in populations with high child stunting burden. Certain groups of children who experience higher risk environments, such as those from poor households or with poor baseline nutritional status, have greater potential to benefit from SQ-LNS in developmental outcomes. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

category: nutrition


title: Small-quantity lipid-based nutrient supplements for prevention of child malnutrition and promotion of healthy development: Overview of individual participant data meta-analysis and programmatic implications

abstract: Small-quantity lipid-based nutrient supplements (SQ-LNS) were designed to provide multiple micronutrients within a food base that also provides energy, protein and essential fatty acids, and were targeted towards the prevention of malnutrition in low- and middle-income countries. Previous meta-analyses have demonstrated beneficial effects of SQ-LNS on child growth, anemia and mortality. To further examine efficacy and effectiveness of SQ-LNS, and explore study-level and individual-level modifiers of the effects, we conducted an individual participant data (IPD) meta-analysis of 14 randomized controlled trials of SQ-LNS provided to infants and young children 6 to 24 mo of age (n > 37,000). We examined growth, development, anemia and micronutrient status outcomes. Children who received SQ-LNS had a 12-14% lower prevalence of stunting, wasting and underweight, were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development, and had a 16% lower prevalence of anemia and 64% lower prevalence of iron-deficiency anemia, compared to control group children. For most outcomes, beneficial effects of SQ-LNS were evident regardless of study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact or average reported compliance with SQ-LNS. For certain outcomes, targeting based on population-level socioeconomic status or undernutrition may be worthwhile, as the benefits of SQ-LNS for iron status, anemia and child development were larger in sub-groups with a greater potential to benefit. A greater impact of SQ-LNS might be possible by co-packaging it with interventions that reduce constraints on response, such as prevention and control of pre-and postnatal infections, improving maternal nutrition, improving health care access, and promotion of early child development. Policy-makers and program planners should consider including SQ-LNS in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency and developmental impairments. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971 and CRD42020156663.


title: Experimental quantification of soft tissue deformation in quasi-static single leg flexion using biplanar imaging

abstract:
Soft tissue deformation(STD) causes the most prominent source of error in skin marker (SM) based motion analysis, commonly referred to as Soft Tissue Artifact (STA). To compensate for its effect and to accurately assess in vivo joint kinematics, quantification of STD in three-dimension (3D) is essential. In the literature, different invasive and radiological approaches have been employed to study how STA propagates in joint kinematics. However, there is limited reference data extensively reporting distribution of the artifact itself in 3D.

The current study was thus aimed at quantifying STD in 10 subjects along three anatomical directions. Biplanar X-ray system was used to determine true bone and SM positions while the subjects underwent quasi-static single leg flexion.

STD exhibited inter-subject similarity. A non-uniform distribution was observed at the pelvis, thigh and shank displaying maximum at the thigh (up to 18.5 mm) and minimum at the shank (up to 8 mm). STD at the pelvis and thigh displayed inter-marker similarity. STD at the pelvis was found direction independent, showing similar distribution in all the 3 directions. However, the thigh and shank exhibited higher STD in the proximal-distal direction of the bone embedded anatomical reference frame. These findings may provide more insights while interpreting motion analysis data as well to effectively strategize STA compensation methods.

category: orthopedics


title: Genome-wide association studies of 27 accelerometry-derived physical activity measurements identifies novel loci and genetic mechanisms

abstract: Physical inactivity (PA) is an important risk factor for a wide range of diseases. Previous genome-wide association studies (GWAS), based on self-reported data or a small number of phenotypes derived from accelerometry, have identified a limited number of genetic loci associated with habitual PA and provided evidence for involvement of central nervous system in mediating genetic effects. In this study, we derived 27 PA phenotypes from wrist accelerometry data obtained from 88,411 UK Biobank study participants. Single-variant association analysis based on mixed-effects models and transcriptome-wide association studies (TWAS) together identified 5 novel loci that were not detected by previous studies of PA, sleep duration and self-reported chronotype. For both novel and previously known loci, we discovered associations with novel phenotypes including active-to-sedentary transition probability, light-intensity PA, activity during different times of the day and proxy phenotypes to sleep and circadian patterns. Follow-up studies including TWAS, colocalization, tissue-specific heritability enrichment, gene-set enrichment and genetic correlation analyses indicated the role of the blood and immune system in modulating the genetic effects and a secondary role of the digestive and endocrine systems. Our findings provided important insights into the genetic architecture of PA and its underlying mechanisms.


title: Development and validation of a dynamic 48-hour in-hospital prognostic risk stratification for COVID-19 in a UK teaching hospital: a retrospective cohort study

abstract:
ObjectivesTo develop a disease stratification model for COVID-19 that updates according to changes in a patients condition while in hospital to facilitate patient management and resource allocation.

DesignIn this retrospective cohort study we adopted a landmarking approach to dynamic prediction of all cause in-hospital mortality over the next 48 hours. We accounted for informative predictor missingness, and selected predictors using penalised regression.

SettingAll data used in this study was obtained from a single UK teaching hospital.

ParticipantsWe developed the model using 473 consecutive patients with COVID-19 presenting to a UK hospital between March 1 and September 12, 2020; and temporally validated using data on 1119 patients presenting between September 13, 2020 and March 17, 2021.

Primary and secondary OutcomesThe primary outcome is all-cause in-hospital mortality within 48 hours of the prediction time. We accounted for the competing risks of discharge from hospital alive and transfer to a tertiary Intensive Care Unit for extracorporeal membrane oxygenation.

ResultsOur final model includes age, Clinical Frailty Scale score, heart rate, respiratory rate, SpO2/FiO2 ratio, white cell count, presence of acidosis (pH < 7.35) and Interleukin-6. Internal validation achieved an AUROC of 0.90 (95% CI 0.87-0.93) and temporal validation gave an AUROC of 0.86 (95% CI 0.83-0.88).

ConclusionOur model incorporates both static risk factors (e.g. age) and evolving clinical and laboratory data, to provide a dynamic risk prediction model that adapts to both sudden and gradual changes in an individual patients clinical condition. Upon successful external validation, the model has the potential to be a powerful clinical risk assessment tool.

Trial RegistrationThe study is registered as "researchregistry5464" on the Research Registry (www.researchregistry.com).

Article Summary- Our dynamic prediction model is able to incorporate patient data as it accumulates throughout a hospital visit.
- We use the established statistical landmarking approach to dynamic prediction; account for competing risks for the primary outcome of in-hospital mortality; and the potentially-informative availability of clinical and laboratory data.
- The sample size of the first wave of patients admitted with severe COVID-19 was relatively low, due to the lower incidence in Cambridgeshire, but increased significantly during the winter months of 2020/21, providing the opportunity to temporally validate the model.
- As a single centre study, the presented model will require external validation to assess its performance in other cohorts; and also if there are significant changes in the characteristics of new variants or the management thereof.
- Our work also highlights the adaptability of the statistical landmarking framework to be used to model individual patient outcomes using densely-collected hospital data.

category: health informatics


title: SARS-CoV-2 Seroprevalence Survey Among District Residents Presenting for Serologic Testing at Three Community Based Test Sites in Washington, DC, July to August, 2020

abstract:
BackgroundThe District of Columbia (DC), a major metropolitan area, continues to see community transmission of SARS-CoV-2. While serologic testing does not indicate current SARS-CoV-2 infection, it can indicate prior infection and help inform local policy and health guidance. The DC Department of Health (DC Health) conducted a community-based survey to estimate DCs SARS-CoV-2 seroprevalence and identify seropositivity-associated factors.

MethodsA mixed-methods cross-sectional serology survey was conducted among a convenience sample of DC residents during July 27-August 21, 2020. Free serology testing was offered at three public test sites. Participants completed an electronic questionnaire on household and demographic characteristics, COVID-like illness (CLI) since January 1, 2020, comorbidities, and SARS-CoV-2 exposures. Univariate and bivariate analyses were conducted to describe the sample population and assess factors associated with seropositivity.

ResultsAmong a sample of 671 participants, 51 individuals were seropositive, yielding an estimated seroprevalence of 7.6%. More than half (56.9%) of the seropositive participants reported no prior CLI; nearly half (47.1%) had no prior SARS-CoV-2 testing. Race/ethnicity, prior SARS-CoV-2 testing, prior CLI, employment status, and contact with confirmed COVID-19 cases were associated with seropositivity (P<0.05). Among those reporting prior CLI, loss of taste or smell, duration of CLI, fewer days between CLI and serology test, or prior viral test were associated with seropositivity (P[≤]0.006).

ConclusionsThese findings indicate many seropositive individuals reported no symptoms consistent with CLI since January or any prior SARS-CoV-2 testing. This underscores the potential for cases to go undetected in the community and suggests wider-spread transmission than previously reported in DC.

What is already known on this subject?Traditional case-based detection and syndromic surveillance efforts might not identify mildly symptomatic or asymptomatic SARS-CoV-2 infections. This is particularly true among people in the general population who do not have increased risk of severe illness or might not be tested otherwise. Consequently, the true population prevalence of prior SARS-CoV-2 infections might not be known.

What this study adds?A community-based seroprevalence survey conducted in Washington, DC, during July 27-August 21, 2020 estimated that 7.6% of the convenience sample had antibodies to SARS-CoV-2, indicating prior infection. At the time of this survey, most of the participants reported that they had not been previously infected with or tested for SARS-CoV-2. These findings highlight both the value of serologic surveillance in complementing other surveillance methods, and the importance of continued prevention and mitigation measures, such as maintaining physical distances of at least 6 feet, avoiding crowds and poorly ventilated spaces, practicing frequent hand hygiene, and wearing face masks properly and consistently around people who do not live with you.


title: Mapping of SARS-CoV-2 Brain Invasion and Histopathology in COVID-19 Disease

abstract: The coronavirus SARS-CoV-2 (SCV2) causes acute respiratory distress, termed COVID-19 disease, with substantial morbidity and mortality. As SCV2 is related to previously-studied coronaviruses that have been shown to have the capability for brain invasion, it seems likely that SCV2 may be able to do so as well. To date, although there have been many clinical and autopsy-based reports that describe a broad range of SCV2-associated neurological conditions, it is unclear what fraction of these have been due to direct CNS invasion versus indirect effects caused by systemic reactions to critical illness. Still critically lacking is a comprehensive tissue-based survey of the CNS presence and specific neuropathology of SCV2 in humans. We conducted an extensive neuroanatomical survey of RT-PCR-detected SCV2 in 16 brain regions from 20 subjects who died of COVID-19 disease. Targeted areas were those with cranial nerve nuclei, including the olfactory bulb, medullary dorsal motor nucleus of the vagus nerve and the pontine trigeminal nerve nuclei, as well as areas possibly exposed to hematogenous entry, including the choroid plexus, leptomeninges, median eminence of the hypothalamus and area postrema of the medulla. Subjects ranged in age from 38 to 97 (mean 77) with 9 females and 11 males. Most subjects had typical age-related neuropathological findings. Two subjects had severe neuropathology, one with a large acute cerebral infarction and one with hemorrhagic encephalitis, that was unequivocally related to their COVID-19 disease while most of the 18 other subjects had non-specific histopathology including focal {beta}-amyloid precursor protein white matter immunoreactivity and sparse perivascular mononuclear cell cuffing. Four subjects (20%) had SCV2 RNA in one or more brain regions including the olfactory bulb, amygdala, entorhinal area, temporal and frontal neocortex, dorsal medulla and leptomeninges. The subject with encephalitis was SCV2-positive in a histopathologically-affected area, the entorhinal cortex, while the subject with the large acute cerebral infarct was SCV2-negative in all brain regions. Like other human coronaviruses, SCV2 can inflict acute neuropathology in susceptible patients. Much remains to be understood, including what viral and host factors influence SCV2 brain invasion and whether it is cleared from the brain subsequent to the acute illness.


title: FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system

abstract: Large Phase 3 clinical trials of the two FDA-authorized COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,138 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st 2020 and February 8th 2021. Our retrospective analysis contrasts 31,069 individuals receiving at least one dose of either vaccine with 31,069 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. 8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose. Administration of two COVID-19 vaccine doses was 88.7% effective in preventing SARS-CoV-2 infection (95% CI: 68.4-97.1%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.


title: Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

abstract: Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of globally circulating variants, we evaluated the neutralization potency of 48 sera from BNT162b2 and mRNA-1273 vaccine recipients against pseudoviruses bearing spike proteins derived from 10 strains of SARS-CoV-2. While multiple strains exhibited vaccine-induced cross-neutralization comparable to wild-type pseudovirus, 5 strains harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was weak and comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.


title: Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity


title: Artificial Intelligence Applications for COVID-19 in Intensive Care and Emergency Settings: A Systematic Review

abstract:
BackgroundLittle is known about the role of artificial intelligence (AI) as a decisive technology in the clinical management of COVID-19 patients. We aimed to systematically review and critically appraise the current evidence on AI applications for COVID-19 in intensive care and emergency settings, focusing on methods, reporting standards, and clinical utility.

MethodsWe systematically searched PubMed, Embase, Scopus, CINAHL, IEEE Xplore, and ACM Digital Library databases from inception to 1 October 2020, without language restrictions. We included peer-reviewed original studies that applied AI for COVID-19 patients, healthcare workers, or health systems in intensive care, emergency or prehospital settings. We assessed predictive modelling studies using PROBAST (prediction model risk of bias assessment tool) and a modified TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) statement for AI. We critically appraised the methodology and key findings of all other studies.

ResultsOf fourteen eligible studies, eleven developed prognostic or diagnostic AI predictive models, all of which were assessed to be at high risk of bias. Common pitfalls included inadequate sample sizes, poor handling of missing data, failure to account for censored participants, and weak validation of models. Studies had low adherence to reporting guidelines, with particularly poor reporting on model calibration and blinding of outcome and predictor assessment. Of the remaining three studies, two evaluated the prognostic utility of deep learning-based lung segmentation software and one studied an AI-based system for resource optimisation in the ICU. These studies had similar issues in methodology, validation, and reporting.

ConclusionsCurrent AI applications for COVID-19 are not ready for deployment in acute care settings, given their limited scope and poor quality. Our findings underscore the need for improvements to facilitate safe and effective clinical adoption of AI applications, for and beyond the COVID-19 pandemic.


title: Quantification of the tradeoff between test sensitivity and test frequency in COVID-19 epidemic - a multi-scale modeling approach

abstract: Control strategies that employ real time polymerase chain reaction (RT-PCR) tests for the diagnosis and surveillance of COVID-19 epidemic are inefficient in fighting the epidemic due to high cost, delays in obtaining results, and the need of specialized personnel and equipment for laboratory processing. Cheaper and faster alternatives, such as antigen and paper-strip tests, have been proposed. They return results rapidly, but have lower sensitivity thresholds for detecting virus. To quantify the effects of the tradeoffs between sensitivity, cost, testing frequency, and delay in test return on the overall course of an outbreak, we built a multi-scale immuno-epidemiological model that connects the virus profile of infected individuals with transmission and testing at the population level. We investigated various randomized testing strategies and found that, for fixed testing capacity, lower sensitivity tests with shorter return delays slightly flatten the daily incidence curve and delay the time to the peak daily incidence. However, compared with RT-PCR testing, they do not always reduce the cumulative case count at half a year into the outbreak. When testing frequency is increased to account for the lower cost of less sensitive tests, we observe a large reduction in cumulative case counts, from 57% to as low as 1.5% half a year into the outbreak and to 3.2% three years into the outbreak. The improvement is preserved even when the testing budget is reduced by one half or one third. Our results predict that surveillance testing that employs low-sensitivity tests at high frequency is an effective tool for epidemic control.


title: Effects of visual attention modulation on dynamic effective connectivity and visual fixation during own-face viewing in body dysmorphic disorder

abstract:
BackgroundIn individuals with body dysmorphic disorder (BDD), selective attention biases and aberrant visual scanning patterns may cause imbalances in global vs. detailed visual processing, contributing to perceptual distortions for appearance. The mechanistic effects of modifying visual attention on brain function in BDD, which may be critical to developing perceptual-based treatments, have not been explored. This study tested the effects of visual-attention modulation on dorsal and ventral visual stream activation and connectivity, and eye behaviors.

MethodsWe acquired functional magnetic resonance imaging data in 37 unmedicated adults with BDD and 30 controls. Participants viewed their faces under two conditions: a) unconstrained (naturalistically), and b) holding their gaze on the center of the image (visual-attention modulation), monitored with an eye-tracking camera. We analyzed activation and dynamic effective connectivity in dorsal and ventral visual streams and visual fixation duration.

ResultsVisual-attention modulation resulted in longer fixation duration and reduced activation in dorsal and ventral visual streams in both groups compared with naturalistic viewing. Longer fixation duration was associated with greater effective connectivity from V1 to early dorsal visual stream during the second naturalistic viewing, across groups. During naturalistic viewing, there was greater V1 to early dorsal visual stream connectivity after, compared with before, visual-attention modulation.

ConclusionsWhen viewing ones face, longer visual fixation may confer greater communication in dorsal visual system, facilitating global/holistic visual processing. The finding that reduction in visual scanning while viewing ones face results in persistent effects during unconstrained viewing has implications for perceptual retraining treatment design for BDD.


title: Severe SARS-CoV-2 infection induces a distinct nasal cytokine profile

abstract: Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we comprehensively characterise patients hospitalised with suspected or confirmed COVID-19, and healthy community controls. PCR-confirmed COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-/IgG+ and PCR-/IgG-participants. PCR-/IgG+ participants exhibited a nasal and systemic cytokine signature analogous to PCR-confirmed COVID-19 participants, but increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. We did not find evidence that HIV co-infection in COVID-19 participants was associated with mortality or altered cytokine responses. The nasal immune signature in PCR-/IgG+ and PCR-confirmed COVID-19 participants was distinct and predominated by chemokines and neutrophils. In addition, PCR-/IgG+ individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.

category: respiratory medicine


title: In depth analysis of patients with severe SARS-CoV-2 in sub-Saharan Africa demonstrates distinct clinical and immunological profiles


title: ClinGen Variant Curation Interface: A Variant Classification Platform for the Application of Evidence Criteria from ACMG/AMP Guidelines

abstract:
BackgroundIdentification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments in next-generation sequencing technologies. However, the infrastructure and accessible comprehensive curation tools necessary for analyzing an individual patient genome and interpreting genetic variants to inform healthcare management have been lacking.

ResultsHere we present the ClinGen Variant Curation Interface (VCI), a global open-source variant classification platform for supporting the application of evidence criteria and classification of variants based on the ACMG/AMP variant classification guidelines. The VCI is among a suite of tools developed by the NIH-funded Clinical Genome Resource (ClinGen) Consortium, and supports an FDA-recognized human variant curation process. Essential to this is the ability to enable collaboration and peer review across ClinGen Expert Panels supporting users in comprehensively identifying, annotating, and sharing relevant evidence while making variant pathogenicity assertions. To facilitate evidence-based improvements in human variant classification, the VCI is publicly available to the genomics community and is available at https://curation.clinicalgenome.org. Navigation workflows support users providing guidance to comprehensively apply the ACMG/AMP evidence criteria and document provenance for asserting variant classifications.

ConclusionThe VCI offers a central platform for clinical variant classification that fills a gap in the learning healthcare system, and facilitates widespread adoption of standards for clinical curation.


title: Project DELTA - integrateD diagnostic solution forEarLy deTection of oesophageal cAncer: a study protocol for data mining and risk prediction algorithm development

abstract:
IntroductionOesophageal cancer is the sixth most common cause for cancer related deaths with over 450,000 new cases and 400,000 resulting deaths per year globally. Most cases in the UK are adenocarcinoma with some of the poorest outcomes from this cancer type in Europe -- mainly due to late diagnosis. The main risk factor for oesophageal adenocarcinoma is chronic reflux disease and due to the high prevalence and non-specific nature of these symptoms most patients are often managed with acid-reflux medications (e.g. Proton Pump Inhibitors (PPIs)) without referral for endoscopy. For those patients that are referred the endoscopy is normal in over 70% of cases, and there is not enough capacity within the NHS for endoscopy especially considering colon cancer screening.

The primary aim of this project is to improve early identification of individuals at risk of oesophageal cancer and reduce over-use of prescription antacids.

Methods and analysisWe will conduct a longitudinal cohort study consisted of adults 40 years and over who are free of oesophageal cancer at study entry, using the QResearch database for data gathered between 2000 and 2020. The main exposure is the use of prescription antacids which includes PPI, H2RA, and other aluminium and magnesium containing antacids. The exposure will be categorised based on active ingredients, dose, and duration of use and will be modelled as a time-varying covariate.

Ethics and disseminationEthical approval for this project was obtained from the QResearch Scientific Committee [Ref: OX39, project title "DELTA - integrated Diagnostic solution for Early detection of Oesophageal cAncer"]. This project has been supported by patient and public involvement panels. We intend to submit the findings for peer-reviewed publication in an academic journal and disseminate them to the public.

Strength and limitations of this studyO_LIThis is an open cohort study comprising a nationally representative sample of English population.
C_LIO_LIThe cohort consists of GP clinic data linked to hospital records, the English national cancer registry and English national death registry.
C_LIO_LIThis study has access to detailed information on acid-suppressant prescriptions, allowing analysis with consideration of the specific compound, dose, and duration of exposure.
C_LIO_LIThis study is limited by high rates of missing data for cancer grade and stage, although completeness has improved in recent years, this will be accounted for using appropriate multiple imputation techniques.
C_LI

category: primary care research


title: Epidemiology of COVID-19 infection amongst workers in Primary Healthcare in Qatar

abstract:
BackgroundCOVID-19 transmission was significant amongst Healthcare workers worldwide.

AimThis study aims to estimate the risk of exposure for COVID-19 across Primary Healthcare workers in the State of Qatar. Methods: A cross-sectional descriptive study was conducted to study the burden of COVID-19 among staff working at PHCC during the COVID-19 pandemic from March 1 to October 31, 2020.

Results1,048 (87.4%)of the infected HCWs belonged to the age group below 45 years, and 488 (40.7%) HCWs were females. 450 (37.5%) were HCWs clinical staff working in one of the 27 PHCC HCs; Despite the increased patient footfall and risk environment, the COVID HCs had an attack rate of 10.1%, which is not significantly different from the average attack rate of 8.9% among staff located in other HCs (p-value =0.26). Storekeepers, engineering & maintenance staff, housekeeping staff, support staff, and security staff (outsourced positions) had the highest positivity rates, 100%, 67.2%, 47.1%, 32.4%, and 29.5% respective positivity rates.

ConclusionsThe elevated risk of infection amongst outsourced healthcare workers can be explained by environmental factors such as living conditions. On the other hand, better containment within clinical healthcare workers can be attributed to strict safety training and compliance with preventative measures which is recommended to be implemented across all settings.


title: Fat-enlarged Axillary Lymph Nodes are Associated with Node-Positive Breast Cancer in Obese Patients

abstract:
PurposeObesity-associated fat infiltration of organ systems is accompanied by organ dysfunction and poor cancer outcomes. Obese women demonstrate variable degrees of fat infiltration of axillary lymph nodes (LNs), and they are at increased risk for node-positive breast cancer. However, the relationship between enlarged axillary nodes and axillary metastases has not been investigated. The purpose of this study is to evaluate the association between axillary metastases and fat-enlarged axillary nodes visualized on mammograms and breast MRI in obese women with a diagnosis of invasive breast cancer.

MethodsThis retrospective case-control study included 431 patients with histologically confirmed invasive breast cancer. The primary analysis of this study included 306 patients with pre-operative MRI and body mass index (BMI) > 30 (201 node-positive cases and 105 randomly selected node-negative controls) diagnosed with invasive breast cancer diagnosed between April 1, 2011, and March 1, 2020. The largest visible LN was measured in the axilla contralateral to the known breast cancer on breast MRI. Multivariate logistic regression models were used to assess the association between node-positive status and LN size adjusting for age, BMI, tumor size, tumor grade, tumor subtype, and lymphovascular invasion.

ResultsA strong likelihood of node-positive breast cancer was observed among obese women with fat-expanded lymph nodes (adjusted OR for the 4th vs. 1st quartile for contralateral LN size on MRI: 9.70; 95% CI: 4.26, 23.50; p < 0.001). The receiver operating characteristic curve for size of fat-enlarged nodes in the contralateral axilla identified on breast MRI had an area under the curve of 0.72 for predicting node-positive breast cancer and this increased to 0.80 when combined with patient and tumor characteristics.

ConclusionFat expansion of axillary lymph nodes was associated with a high likelihood of axillary metastases in obese women with invasive breast cancer independent of BMI and tumor characteristics.

category: oncology


title: Retrospective study of the first wave of COVID-19 in Spain: analysis of counterfactual scenarios

abstract:
One of the most important questions on the COVID-19 pandemic is ascertaining the correct timing to introduce non-pharmaceutical interventions (NPIs), based mainly on mobility restrictions, to control the rising of the daily incidence in a specific territory. Here, we make a retrospective analysis of the first wave of the epidemic in Spain and provide a set of useful insights to optimize actions in the near future. We have reconstructed the exposure times, from infection to detectability, to correctly estimate the reproduction number Rt. This enables us to analyze counterfactual scenarios to understand the impact of earlier or later responses, decoupling containment measures from natural immunity. Our results quantify the differences in the number of fatalities for earlier and later responses to the epidemic in Spain.

Teaser"We propose a backward analysis of pandemic incidence in a region to determine the correct timing of authorities non-pharmaceutical interventions to fight COVID-19"


title: Accuracy of Smartphone Integrated Pulse Oximetry Meets Full FDA Clearance Standards for Clinical Use.

abstract:
BackgroundPulse oximetry is used as an assessment tool to gauge the severity of COVID-19 infection and identify patients at risk of poor outcomes. 1,2,3,4 The pandemic highlights the need for accurate pulse oximetry, particularly at home, as infection rates increase in multiple global regions including the UK, USA and South Africa 5. Over 100 million Samsung smartphones containing dedicated biosensors (Maxim Integrated Inc, San Jose, CA) and preloaded Apps to perform pulse oximetry, are in use globally. We performed detailed in human hypoxia testing on the Samsung S9 smartphone to determine if this integrated hardware meets full FDA/ISO requirements for clinical pulse oximetry.

MethodsThe accuracy of integrated pulse oximetry in the Samsung 9 smartphone during stable arterial oxygen saturations (SaO2) between 70% and 100% was evaluated in 12 healthy subjects. Inspired oxygen, nitrogen, and carbon dioxide partial pressures were monitored and adjusted via a partial rebreathing circuit to achieve stable target SaO2 plateaus between 70% and 100%. Arterial blood samples were taken at each plateau and saturation measured on each blood sample using ABL-90FLEX blood gas analyzer. Bias, calculated from smartphone readings minus the corresponding arterial blood sample, was reported as root mean square deviation (RMSD).

FindingsThe RMSD of the over 257 data points based on blood sample analysis obtained from 12 human volunteers tested was 2.6%.

InterpretationEvaluation of the smartphone pulse oximeter performance is within requirements of <3.5% RMSD blood oxygen saturation (SpO2) value for FDA/ISO clearance for clinical pulse oximetry. This is the first report of smartphone derived pulse oximetry measurements that meet full FDA/ISO accuracy certification requirements. Both Samsung S9 and S10 contain the same integrated pulse oximeter, thus over 100 million smartphones in current global circulation could be used to obtain clinically accurate spot SpO2 measurements to support at home assessment of COVID-19 patients.


title: A New Hematological Prognostic Index For Covid-19 Severity

abstract:
Backgroundsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or Covid-19 is a nationwide public health emergency with significant impact on human life.

ObjectiveTo develop a new simple hematological prognostic index for Covid-19 severity state.

Patients and methodsThis observational cross sectional study was conducted on 250 patients with Covid-19 disease. Age, gender, and severity of Covid -19 were recorded. Complete blood count and lactate dehydrogenase were measured.

New index: COVID-19 severity-Iraqi-index = CSI index to predict COVID-19 severity.

CSI index is monocyte/lymphocyte absolute counts multiplied by LDH (lactate dehydrogenase)/upper normal reference laboratory range of LDH value.

ResultsMean age of patients was 50.4 + 15.1 years. Majority of patients were Males 148 (59.2%)..Most of patients were in stage 2 and 3 (> 94%). There was a significant difference between means of White Blood Cells, lymphocytes and Monocytes among the different stages of the disease (P = 0.0001, 0.036, 0.012). There was a significant moderate correlation between the prognostic index and the stage of the disease (r=0.41, p=0.0001).

ConclusionsCSI index is a new simple predictor of clinical outcome in patients with covid-19 during early stage of the disease.


title: Investigation and public health response to a COVID-19 outbreak in a rural resort community--Blaine County, Idaho, 2020

abstract:
Blaine County, Idaho, a rural area with a renowned resort, experienced an outbreak of novel coronavirus disease (COVID-19). We undertook an epidemiologic investigation to describe the outbreak and guide public health action. Confirmed cases of COVID-19 were identified from reports of SARS-CoV-2-positive laboratory test results to South Central Public Health District.

Information on symptoms, hospitalization, recent travel, healthcare worker status, and close contacts was obtained by medical record review and patient interviews. Viral sequence analysis was conducted on a subset of available specimens. During March 13-April 10, 2020, a total of 451 COVID-19 cases occurred among Blaine County residents (1,959 cases per 100,000 population). An additional 37 cases occurred in out-of-state residents. Among the 451 COVID-19 patients, the median age was 51 years (Interquartile range [IQR]: 37-63), 52 (11.5%) were hospitalized, and 5 (1.1%) died. The median duration between specimen collection and a positive laboratory result was 9 days (IQR: 4-10). Forty-four (9.8%) patients reported recent travel. Healthcare workers comprised 56 (12.4%) cases; 33 of whom worked at the only hospital in the county, leading to a 15-day disruption of hospital services. Of 562 close contacts monitored by public health authorities, 22 (3.9%) had laboratory-confirmed COVID-19 and an additional 29 (5.2%) experienced compatible symptoms. Sequencing results from 34 Idaho specimens supported epidemiologic findings indicating travel as a source of SARS-CoV-2, and identified multiple lineages among hospital workers. Community mitigation strategies included school and resort closure, stay-at-home orders, and restrictions on incoming travelers. COVID-19 outbreaks in rural communities can disrupt health services. Lack of local laboratory capacity led to long turnaround times for COVID-19 test results. Rural communities frequented by tourists should consider implementing restrictions on incoming travelers among other mitigation strategies to reduce COVID-19 transmission.


title: Sensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay as an aid in determining previous exposure to SARS-CoV-2

abstract:
BackgroundThe Elecsys(R) Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Roche Diagnostics International Ltd) was developed for the in vitro qualitative detection of antibodies to SARS-CoV-2. We evaluated the sensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in samples from a diverse cross-section of patients across multiple sites and compared results against commercially available comparators.

MethodsSensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay was evaluated using anonymised, frozen, residual single and sequential serum and plasma samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Point estimates and 95% confidence intervals (CIs) were calculated and method comparisons performed versus the following comparator assays: Euroimmun Anti-SARS-CoV-2 IgG, Abbott ARCHITECT SARS-CoV-2 IgG, Siemens ADVIA Centaur SARS-CoV-2 Total, and YHLO iFlash SARS-CoV-2 IgG and IgM.

ResultsOverall sensitivity for the Elecsys Anti-SARS-CoV-2 immunoassay in 219 samples drawn [≥]14 days post-PCR confirmation was 93.6% (95% CI 89.5-96.5). Across the three study sites, sensitivity in samples drawn [≥]14 days post-PCR confirmation ranged from 85.7-98.9%. Sensitivity was significantly higher for the Elecsys Anti-SARS-CoV-2 immunoassay compared with the YHLO iFlash SARS-CoV-2 IgM assay for samples drawn [≥]14 days post-PCR confirmation (86.3% [95% CI 76.7-92.9] versus 33.8% [95% CI 23.6-45.2]). Both Siemens ADVIA Centaur SARS-CoV-2 Total and YHLO iFlash SARS-CoV-2 IgG assays had a significantly higher sensitivity compared with the Elecsys Anti-SARS-CoV-2 immunoassay for samples drawn [≥]14 days post-PCR confirmation (95.1% [95% CI 87.8-98.6] versus 85.2% [95% CI 75.6-92.1]; 93.8% [95% CI 86.0-97.9] versus 86.3% [95% CI 76.7-92.9]). Differences in sensitivity between the Elecsys Anti-SARS-CoV-2 immunoassay and the Euroimmun Anti-SARS-CoV-2 IgG (90.3% [95% CI 83.7-94.9] versus 95.2% [95% CI 89.8-98.2]) and Abbott ARCHITECT SARS-CoV-2 IgG (84.8% [95% CI 75.0-91.9] versus 87.3% [95% CI 78.0-93.8]) assays for samples drawn [≥]14 days post-PCR confirmation were not significant.

ConclusionsThe Elecsys Anti-SARS-CoV-2 immunoassay demonstrated high sensitivity in samples collected [≥]14 days post-PCR confirmation of SARS-CoV-2 infection, and comparable sensitivity to several commercially available comparator assays across multiple sites, supporting the use of this assay as a tool to aid in determination of previous exposure to SARS-CoV-2.

Required information for submission systemO_ST_ABSEthical guidelinesC_ST_ABSThe study was conducted in accordance with the study protocol provided by Roche Diagnostics and in accordance with the principles of the Declaration of Helsinki. All human samples utilised at the three study sites in Germany (Augsburg, Heidelberg, Berlin) were anonymised, frozen, residual samples, therefore no ethical approval or waiver was required in accordance with local legislation from ZEKO (Central Ethics Commission at the German Medical Association). A statement was obtained from the Ethics Committee of the Landesarztekammer Bayern confirming that there are no objections to the coherent use of anonymised residual samples.

Research reporting guidelinesPlease see separate STARD checklist.

Data availability statementQualified researchers may request access to individual patient level data through the clinical study data request platform (https://vivli.org/). Further details on Roches criteria for eligible studies are available here: https://vivli.org/members/ourmembers/. For further details on Roches Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm


title: Glaucoma patient screening from online retinal fundus images via Artificial Intelligence

abstract:
ObjectivesTo design and evaluate a novel automated glaucoma classifier from retinal fundus images.

MethodsWe designed a novel Artificial Intelligence (AI) automated tool to detect glaucoma from retinal fundus images. We then downloaded publicly available retinal fundus image datasets containing healthy patients and images with verified glaucoma labels. Two thirds of the images were used to train the classifier. The remaining third of the images was used to create several cross-validation evaluation sets with a realistic glaucoma prevalence, to evaluate the classifiers performance in a screening scenario.

Results10,658 retinal fundus images from seven different sources were found and downloaded. They were randomly divided into 7,106 for training and 3,551 for validation. Glaucoma prevalence was 24%. Using the validation set, we created 50 random sets of 1,000 images with a 5% glaucoma prevalence. On these sets, the classifier reached a detection rate of 84.1% (CI 95=+-1.1%) and 95.8% (CI 95=+-0.2%) specificity.

ConclusionsA novel glaucoma classifier from retinal fundus images showed promising results as screening tool on a large cohort of patients. A large clinical study is needed to confirm these results.

category: ophthalmology


title: Using DNA to predict behaviour problems from preschool to adulthood

abstract:
BackgroundOne goal of the DNA revolution is to predict problems in order to prevent them. We tested here if the prediction of behaviour problems from genome-wide polygenic scores (GPS) can be improved by creating composites across ages and across raters and by using a multi-GPS approach that includes GPS for adult psychiatric disorders as well as for childhood behaviour problems.

MethodOur sample included 3,065 genotyped unrelated individuals from the Twins Early Development Study who were assessed longitudinally for hyperactivity, conduct, emotional problems and peer problems as rated by parents, teachers and children themselves. GPS created from 15 genome-wide association studies were used separately and jointly to test the prediction of behaviour problems composites (general behaviour problems, externalizing and internalizing) across ages (from age 2 to age 21) and across raters in penalized regression models. Based on the regression weights, we created multi-trait GPS reflecting the best prediction of behaviour problems. We compared GPS prediction to twin heritability using the same sample and measures.

ResultsMulti-GPS prediction of behaviour problems increased from less than 2% of the variance for observed traits to up to 6% for cross-age and cross-rater composites. Twin study estimates of heritability mirrored patterns of multi-GPS prediction as they increased from less than 40% to up to 83%.

ConclusionsThe ability of GPS to predict behaviour problems can be improved by using multiple GPS, cross-age composites and cross-rater composites, although the effect sizes remain modest, up to 6%. Our results can be used in any genotyped sample to create multi-trait GPS predictors of behaviour problems that will be more predictive than polygenic scores based on a single age, rater or GPS.

Key pointsO_LIGenome-wide polygenic scores (GPS) can be used to predict behaviour problems in childhood, but the effect sizes are generally less than 3.5%.
C_LIO_LIDNA-based prediction models of achieve greater accuracy if holistic approaches are employed, that is cross-trait, longitudinal and trans-situational approaches.
C_LIO_LIThe prediction of childhood behaviour problems can be improved by using multiple GPS to predict composites that aggregate behaviour problems across ages and across raters.
C_LIO_LIOur results yield weights that can be applied to GPS in any study to create multi-trait GPS predictors of behaviour problems based on cross-age and cross-rater composites.
C_LIO_LIAs compared to individuals in the lowest multi-trait GPS decile, nearly three times as many individuals in the highest internalizing multi-trait GPS decile were diagnosed with anxiety disorder and 25% more individuals in the highest general behaviour problems and externalizing multi-trait GPS deciles have taken medication for mental health.
C_LI


title: Size and duration of COVID-19 clusters go along with a high SARS-CoV-2 viral load : a spatio-temporal investigation in Vaud state, Switzerland

abstract:
To understand the geographical and temporal spread of SARS-CoV-2 during the first wave of infection documented in the canton of Vaud, Switzerland, we analysed clusters of positive cases using the precise place of residence of 33651 individuals tested (RT-PCR) between January 10 and June 30, 2020. We identified both space-time (SaTScan) and transmission (MST-DBSCAN) clusters; we estimated their duration, their transmission behavior (emergence, growth, reduction, etc.) and relative risk. For each cluster, we computed the within number of individuals, their median age and viral load.

Among 1684 space-time clusters identified, 457 (27.1%) were significant (p [≤] 0.05), i.e. harboring a higher relative risk of infection, as compared to other regions. They lasted a median of 11 days (IQR 7-13) and included a median of 12 individuals per cluster (IQR 5-20). The majority of significant clusters (n=260; 56.9 %) had at least one person with an extremely high viral load (above 1 billion copies/ml). Those clusters were considerably larger (median of 17 infected individuals, p < 0.001) than clusters with subjects showing a viral load lower than 1 million copies/ml (median of 3 infected individuals). The highest viral loads were found in clusters with the lowest average age, while clusters with the highest average age had low to middle viral load. Interestingly, in 20 significant clusters the viral load of three first cases were all below 100000 copies/ml suggesting that subjects with less than 100000 copies/ml may still have been contagious. Noteworthy, the dynamics of transmission clusters made it possible to identify three diffusion zones, which mainly differentiated rural from urban areas, the latter being more prone to last and spread in a new nearby clusters.

The use of geographic information is key for public health decision makers to mitigate the spread of the virus. This study suggests that early localization of clusters help implementing targeted protective measures limiting the spread of the SARS-CoV-2 virus.


title: Increased hazard of mortality in cases compatible with SARS-CoV-2 variant of concern 202012/1 - a matched cohort study

abstract:
ObjectivesTo establish whether there is any change in mortality associated with infection of a new variant of SARS-CoV-2 (VOC-202012/1), first detected in UK in December 2020, compared to that associated with infection with circulating SARS-CoV-2 variants.

DesignMatched cohort study. Cases are matched by age, gender, ethnicity, index of multiple deprivation, lower tier local authority region, and sample date of positive specimen, and differing only by detectability of the spike protein gene using the TaqPath assay - a proxy measure of VOC-202012/1 infection.

SettingUnited Kingdom, Pillar 2 COVID-19 testing centres using the taqPath assay.

Participants54,773 pairs of participants testing positive for SARS-CoV-2 in Pillar 2 between 1st October 2020 and 29th January 2021.

Main outcome measures - Death within 28 days of first positive SARS-CoV-2 test.

ResultsThere is a high probability that the risk of mortality is increased by infection with VOC-202012/01 (p <0.001). The mortality hazard ratio associated with infection with VOC-202012/1 compared to infection with previously circulating variants is 1.7 (95% CI 1.3 - 2.2) in patients who have tested positive for COVID-19 in the community. In this comparatively low risk group, this represents an increase of deaths from 1.8 in 1000 to 3.1 in 1000 detected cases.

ConclusionsIf this finding is generalisable to other populations, VOC-202012/1 infections have the potential to cause substantial additional mortality over and previously circulating variants. Healthcare capacity planning, national and international control policies are all impacted by this finding, with increased mortality lending weight to the argument that further coordinated and stringent measures are justified to reduce deaths from SARS-CoV-2.


title: Molecular diagnosis of causality in T cell mediated severe cutaneous adverse drug reactions

abstract:
BackgroundOne of the most severe forms of T cell mediated cutaneous adverse drug reactions is  drug reaction with eosinophilia and systemic symptoms (DRESS), hence subsequent avoidance of the causal drug is imperative. However, attribution of drug culpability in DRESS is challenging and standard skin allergy tests are not recommended due to for patient safety reasons. We sought to identify potential biomarkers for development of a diagnostic test.

MethodsPeripheral blood mononuclear cells (PBMCs) from a  discovery cohort (n=5) challenged to drug or control were analysed for transcriptomic profile. A signature panel of genes was then tested in a validation cohort (n=6), and compared to tolerant controls and other inflammatory conditions which can clinically mimic DRESS. A scoring system to identify presence of drug hypersensitivity was developed based on gene expression alterations of this panel.

ResultsWhole transcriptome analysis identified 4 major gene clusters including those regulating T cell activation via NFAT and cytokine receptor activity. 22 differentially expressed gene transcripts were identified as a DRESS signature including Type 1 interferon pathways and Th2 activation. The DRESS transcriptomic panel identified antibiotic-DRESS cases in a validation cohort but was not altered in other inflammatory conditions. Machine learning or differential expression selection of a biomarker panel showed high sensitivity and specificity (100% and 85.7-100% respectively) for identification of the culprit drug in DRESS.

ConclusionTranscriptomic analysis of DRESS revealed important insights into the key activated pathways and identified a transcriptional signature which shows potential as a test with high sensitivity for drug culpability attribution.

category: dermatology


title: Lockdown and non-COVID-19 deaths: Cause-specific mortality during the first wave of the 2020 pandemic in Norway. A population-based register study

abstract:
ObjectiveTo explore the potential impact of the first wave of COVID-19 pandemic on all cause and cause-specific mortality in Norway.

DesignPopulation based register study.

SettingThe Norwegian cause of Death Registry and the National Population Register of Norway.

ParticipantsAll recorded deaths in Norway during March to May from 2010 to 2020.

Main outcome measuresRate (per 100 000) of all-cause mortality and causes of death in the EU Shortlist for Causes of Death March to May 2020. The rates were age-standardised and adjusted to a 100% register coverage and compared with a 95% prediction interval (PI) based on corresponding rates for 2010-2019.

Results113 710 deaths were included, of which 10 226 from 2020. We did not observe any deviation from predicted total mortality. There were fewer than predicted deaths from chronic lower respiratory diseases excluding asthma (11.4, 95% PI 11.8 to 15.2) and from other non-ischemic, non-rheumatic heart diseases (13.9, 95% PI 14.5 to 20.2). The death rates were higher than predicted for Alzheimers disease (7.3, 95% PI 5.5 to 7.3) and diabetes mellitus (4.1, 95% PI 2.1 to 3.4).

ConclusionsThere was no significant difference in the frequency of the major causes of death in the first wave of the 2020 COVID-19 pandemic in Norway. An increase in diabetes mellitus deaths and reduced mortality due to some heart and lung conditions may be linked to infection control measures.