title: Modeling COVID-19 in Iran using Particle Swarm Optimization algorithm

abstract:
BackgroundThe first confirmed cases of COVID-19 in Iran were reported on February 19, 2020. The coronavirus expanded rapidly in all Iranian provinces and three waves of COVID-19 cases have been observed since the pandemic took effect and the fourth wave of Covid-19 cases will likely be observed soon. This study aimed to model the spread of COVID-19 in Iran and to estimate the epidemic parameters and to predict the short-term future trend of COVID-19 in Iran.

MethodsWe proposed a modified SEIR epidemic spreading model and we used data from February 20, 2020, to April 9, 2021, on the number of cases reported by Iranian governments to fit the proposed model on the reported data. Particle Swarm Optimization (PSO) algorithm was employed to estimate the parameters of the proposed model and the numerical simulation results were obtained by Runge-Kutta method. The estimated parameters were employed to calculate the effective reproduction number and to predict the short-term future trends of COVID-19 cases.

ResultsThe results indicated that the effective reproduction number has increased during Nowruz (Persian New Year) and it was estimated to be 1.28. Considering only two exposed cases as the initial cases in the model, the cumulative number of exposed cases was estimated to be 15,252,372 individuals since the beginning of the outbreak. The prediction of the short-term future trends of COVID-19 cases with different scenarios showed that another peak of the pandemic cases occurs in the next weeks. By immediate lockdown implementation the number of active infected cases was estimated to be 397,585.

ConclusionDifferent scenarios of short-term prediction of the future trends of COVID-19 cases indicated that immediate strict social distancing policies need to be implemented to prevent a tremendous burden of the fourth major wave of COVID-19 infections on the health care system of Iran.


abstract: The purpose of this study was to examine the association between loneliness and psychological distress during the COVID-19 pandemic in Japan. We conducted a cross-sectional, online study from 22 to 26 December 2020. A total of 27,036 participants, all employed at the time of the survey, were included in the analysis. Participants were asked if they felt loneliness in a single-item question. The Kessler 6 (K6) was used to assess psychological distress defined as K6 scores of 5 or higher, and 13 or higher. The odds ratios (ORs) of psychological distress associated with loneliness were estimated using a multilevel logistic model nested in the prefecture of residence, with adjustment for age, sex, marital status, equivalent income, educational level, smoking, alcohol consumption, job type, number of workplace employees, and cumulative incidence rate of COVID-19 in the prefecture. Communication with friends, acquaintances, and family was strongly associated with psychological distress, so we adjusted for these factors and eating meals alone. Results showed a significant association between loneliness and psychological distress (OR = 36.62, 95%CI = 32.95-40.69). Lack of friends to talk to, lack of acquaintances to ask for help, and lack of people to communicate with through social networking sites were all strongly associated with psychological distress, as were family time and solitary eating. Even after adjusting for these factors, loneliness was still strongly associated with psychological distress (OR = 29.36, 95%CI = 26.44-32.98). The association between loneliness during the COVID-19 pandemic and psychological distress indicates the need for intervention.

category: psychiatry and clinical psychology


title: Family Planning Performance in 113 Countries Using a New Composite Performance Index

abstract: In this paper we measure family planning performance in 113 countries of the world using a composite performance index that takes into account both the met demand for family planning and the composition of the met demand. The composite performance index used in the present paper is an improvement over the existing approaches of measuring family planning performance. The analysis reveals that family planning performance varies widely across countries and it remains either poor or very poor in more than 40 per cent countries. There is no country where the performance is very high. Moreover, there are many countries where the family planning performance appears to have deteriorated over time. There are only a few countries where family planning performance has improved in recent years. The analysis calls for increased investment in family planning to meet the target set under the Sustainable Development Goals.

category: sexual and reproductive health


title: A Phase II study to evaluate the safety and efficacy of prasinezumab in early Parkinson's disease (PASADENA): rationale, design and baseline data

abstract:
BackgroundCurrently available treatments for Parkinsons disease (PD) do not slow clinical progression nor target alpha-synuclein, the main pathology associated with the disease.

ObjectiveThe study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. The study rationale, design, and baseline characteristics of enrolled subjects are presented here.

MethodsThe PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1500 mg or 4500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis [≤]2 years; having bradykinesia plus one other cardinal sign of PD (e.g. resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naive or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinsons Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naive and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations.

ResultsOf the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. The mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society - Unified Parkinsons Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naive PASADENA cohorts (MDS-UPDRS Total score [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naive and 36.4% on MAO-B inhibitor) also showed a similar severity in MDS-UPDRS scores (e.g. MDS-UPDRS Total score [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naive).

ConclusionsThe PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.

Trial RegistrationNCT03100149

category: neurology


title: Adipose tissue distribution from body MRI is associated with cross-sectional and longitudinal brain age in adults

abstract: There is an intimate body-brain connection in ageing, and obesity is a key risk factor for poor cardiometabolic health and neurodegenerative conditions. Although research has demonstrated deleterious effects of obesity on brain structure and function, the majority of studies have used conventional measures such as waist-to-hip ratio, waist circumference, and body mass index. While sensitive to gross features of body composition, such global anthropomorphic features fail to describe regional differences in body fat distribution and composition, and to determine visceral adiposity, which is related to a range of metabolic conditions. In this mixed cross-sectional and longitudinal design (interval mean and standard deviation = 19.7 {+/-} 0.5 months), including 790 healthy individuals (mean (range) age = 46.7 (18-94) years, 53% women), we investigated cross-sectional body magnetic resonance imaging (MRI, n = 286) measures of adipose tissue distribution in relation to longitudinal brain structure using MRI-based morphometry and diffusion tensor imaging (DTI). We estimated tissue-specific brain age at two time points and performed Bayesian multilevel modelling to investigate the associations between adipose measures at follow-up and brain age gap (BAG) at baseline and follow-up. We also tested for interactions between BAG and both time and age on each adipose measure. The results showed credible associations between T1-based BAG and liver fat, muscle fat infiltration (MFI), and weight-to-muscle ratio (WMR), indicating older-appearing brains in people with higher measures of adipose tissue. Longitudinal evidence supported interaction effects between time and MFI and WMR on T1-based BAG, indicating accelerated ageing over the course of the study period in people with higher measures of adipose tissue. The results show that specific measures of fat distribution are associated with brain ageing and that different compartments of adipose tissue may be differentially linked with increased brain ageing, with potential to identify key processes involved in age-related transdiagnostic disease processes.


title: Impacts of COVID-19 on sick leave

abstract:
AimTo explore sick leave after COVID-19, by comparing doctor-certified sick leave for up to 6 months after testing for SARS-CoV-2 across employees who tested positive and negative.

MethodsIn all persons (20-70 year of age) with an employment contract, who were tested for the SARS-CoV-2 in Norway from March 1st to November 1st 2020 (N=740 182 with mean [SD] age 39 [13] years, 44% men), we used a difference-in-difference design to contrast doctor-certified sick leave before and after testing, across employees with negative test and positive test by age and sex groups.

ResultsSick leave for those testing positive (N=11 414) remained elevated for up to 2 months after testing when compared to those testing negative (N= 728 768), for men and women aged 20-44 and for men aged 45-70 years (relative increase in sick-leave [~]344-415%, (Ball strata=0.079, 95% CI=0.076, 0.082). The increase in sick leave was prolonged for women aged 45-70 years only, persisting for up to 4 months after testing positive (relative increase = 35%, B=0.010, 95% CI=0.004-0.035).

ConclusionSick leave following COVID-19 is elevated for up to two to four months after initial infection, thereafter not elevated compared with employees who tested negative for COVID-19. Women aged 45-70 years tend to have a larger impact of COVID-19 on their work ability than men and younger women.

category: occupational and environmental health


title: Multicenter evaluation of a fully automated high-throughput SARS-CoV-2 antigen immunoassay

abstract:
IntroductionMolecular testing for SARS-CoV-2 continues to suffer from delays and shortages. Antigen tests have recently emerged as a viable alternative to detect patients with high viral loads, associated with elevated risk of transmission. While rapid lateral flow tests greatly improved accessibility of SARS-CoV-2 detection in critical areas, their manual nature limits scalability and suitability for large-scale testing schemes. The Elecsys(R) SARS-CoV-2 Antigen assay allows antigen immunoassays to be carried out on fully automated high-throughput serology platforms.

MethodsA total of 3139 nasopharyngeal and oropharyngeal swabs were collected at 3 different testing sites in Germany. Swab samples were pre-characterized by RT-qPCR and consecutively subjected to the antigen immunoassay on either the cobas e 411 or cobas e 801 analyzers.

ResultsOf the tested respiratory samples, 392 were PCR positive for SARS-CoV-2 RNA. Median concentration was 2.95x104 (interquartile range [IQR] 5.1x102-3.5x106) copies/mL. Overall sensitivity and specificity of the antigen immunoassay were 60.2% (95% confidence interval [CI] 55.2-65.1) and 99.9% (95% CI 99.6-100), respectively. A 93.7% (95% CI 89.7-96.5) sensitivity was achieved at a viral RNA concentration [≥]104 copies/mL ([~]cycle threshold (Ct) value<29.9).

ConclusionThe Elecsys SARS-CoV-2 Antigen assay reliably detected patient samples with viral loads of 10,000 copies/mL and higher. It thus represents a viable high-throughput alternative for screening of patients, or in situations where PCR testing is not readily available.

Key Summary PointsO_ST_ABSWhy carry out this study?C_ST_ABSO_LIThe SARS-CoV-2 pandemic has led to a surge in demand for reliable, mass diagnostic tests worldwide.
C_LIO_LIA thorough clinical evaluation of a fully automated high-throughput Elecsys(R) SARS-CoV-2 Antigen assay on a total of 3139 clinical samples pre-characterized by quantitative RT-PCR was carried out.
C_LI

What was learned from the study?O_LIThe assay demonstrated excellent specificity (99.9%) and good relative sensitivity, with an overall sensitivity of 60.2% and a sensitivity of 93.7% for samples containing [≥]104 viral RNA copies/mL.
C_LIO_LIThe Elecsys SARS-CoV-2 Antigen assay is a viable high-throughput, automated alternative to manual lateral-flow antigen tests.
C_LI

category: infectious diseases


title: Visually-biased perception in cochlear implant users: a study of the McGurk and sound-induced flash illusions

abstract: The reduction in spectral resolution by cochlear implants oftentimes requires complementary visual speech cues to aid in understanding. Despite substantial clinical characterization of auditory-only speech outcome measures, relatively little is known about the audiovisual integrative abilities that most cochlear implant (CI) users rely on for daily speech comprehension. In this study, we tested audiovisual integration in 63 CI users and 69 normal-hearing (NH) controls using the McGurk and sound-induced flash illusions. This study is the largest to-date measuring the McGurk effect in this population and the first to test the sound-induced flash illusion. When presented with conflicting audiovisual speech stimuli (i.e., the phoneme "ba" dubbed onto the viseme "ga"), we found that 55 CI users (87%) reported a fused percept of "da" or "tha" on at least one trial. However, overall, we found that CI users experienced the McGurk effect less often than controls--a result that was concordant with results with the sound-induced flash illusion where the pairing of a single circle flashing on the screen with multiple beeps resulted in fewer illusory flashes for CI users. While illusion perception in these two tasks appears to be uncorrelated among CI users, we identified a negative correlation in the NH group. Because neither illusion appears to provide further explanation of variability in CI outcome measures, further research is needed to determine how these findings relate to CI users speech understanding, particularly in ecological listening conditions that are naturally multisensory.

category: otolaryngology


title: Effective connectivity during faces processing in major depression: Distinguishing markers of pathology, risk, and resilience

abstract:
BackgroundAberrant brain connectivity during emotional processing, especially within the fronto-limbic pathway, is one of the hallmarks of major depressive disorder (MDD). However, a lack of systematic approaches in previous studies made it difficult to determine whether a specific alteration in brain connectivity reflects a cause, correlate, or effect of the disorder. The current study aimed to investigate neural mechanisms that correspond to disease, risk and resilience in major depression during implicit processing of emotion cues.

MethodsForty-eight patients with MDD, 49 first-degree relatives of patients with MDD and 103 healthy controls performed a face-matching task during functional magnetic resonance imaging. We used dynamic causal modelling to estimate task-dependent effective connectivity at the subject level. Parametric empirical Bayes was then performed to quantify group differences in effective connectivity.

ResultsDepressive pathology was associated with decreased effective connectivity from the left amygdala and left dorsolateral prefrontal cortex to the right fusiform gyrus, whereas familial risk for depression corresponded to decreased connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus. Resilience for depression was related to increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex.

ConclusionsOur results suggest that the depressive state alters top-down control of higher visual regions during the processing of emotional faces, whereas increased connectivity within the cognitive control network promotes resilience to depression.


title: Acceptability of human papillomavirus (HPV) self-sampling among never- and under-screened Indigenous and other minority women: a randomised three-arm community trial in Aotearoa New Zealand

abstract:
BackgroundInternationally, self-sampling for human papillomavirus (HPV) has been shown to increase participation in cervical-cancer screening. In Aotearoa New Zealand, there are long-standing ethnic inequalities in cervical-cancer screening, incidence, and mortality; particularly for indigenous M[a]ori women, as well as Pacific, and Asian women.

MethodsWe invited never- and markedly under-screened ([≥]5 years overdue) 30-69-year-old M[a]ori, Pacific, and Asian women to participate in an open-label, three-arm, community-based, randomised controlled trial, with a nested sub-study. We aimed to assess whether two specific invitation methods for self-sampling improved screening participation over usual care among the least medically served populations. Women were individually randomised 3:3:1 to: clinic-based self-sampling (CLINIC - invited to take a self-sample at their usual general practice); home-based self-sampling (HOME - mailed a kit and invited to take a self- sample at home); and usual care (USUAL - invited to attend a clinic for collection of a standard cytology sample). Neither participants nor research staff could be blinded to the intervention. In a subset of general practices, women who did not participate within three months of invitation were opportunistically invited to take a self-sample, either next time they attended a clinic or by mail.

FindingsWe randomised 3,553 women: 1,574 to CLINIC, 1,467 to HOME, and 512 to USUAL. Participation was highest in HOME (14.6% among M[a]ori, 8.8% among Pacific, and 18.5% among Asian) with CLINIC (7.0%, 5.3% and 6.9%, respectively) and USUAL (2.0%, 1.7% and 4.5%, respectively) being lower. In fully adjusted models, participation was statistically significantly more likely in HOME than USUAL: M[a]ori OR=9.7, (95%CI 3.0-31.5); Pacific OR=6.0 (1.8-19.5); and Asian OR=5.1 (2.4-10.9). There were no adverse outcomes reported. After three months, 2,780 non-responding women were invited to participate in a non-randomised, opportunistic, follow-on substudy. After 6 months,192 (6.9%) additional women had taken a self-sample.

InterpretationUsing recruitment methods that mimic usual practice, we provide critical evidence that self-sampling increases screening among the groups of women (never and under-screened) who experience the most barriers in Aotearoa New Zealand, although the absolute level of participation through this population approach was modest. Follow-up for most women was routine but a small proportion required intensive support.

Trial registrationANZCTR Identifier: ACTRN12618000367246 (date registered 12/3/2018) https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371741&isReview=true;UTN:U1111-1189-0531

FundingHealth Research Council of New Zealand (HRC 16/405)

Protocolhttp://publichealth.massey.ac.nz/assets/Uploads/Study-protocol-V2.1Self-sampling-for-HPV-screening-a-community-trial.pdf

category: public and global health


title: How to tie dangerous surgical knots - easily. Can we avoid this?

abstract:
ObjectiveSecure knots are essential. Previous publications have concentrated on security of different knot types, but could individual technique be important?

Determine whether the technique of formation of each layer of a surgical knot is important to the security of the knot formed.

Design studyProspective analysis of technique on knot security

Materials and methodsSenior and resident surgeons, and medical students, tied knots with three techniques, using four study materials, 2/0 polyglactin 910 (vicryl), 3/0 polydioxanone (PDS), 4/0 poliglecaprone 25 (monocryl) and 1 nylon (Ethilon); a standard flat reef knot (FRK), knots tied under tension (TK), and knots laid without appropriate hand crossing (NHCK). Each knot technique was performed reproducibly, and security determined by distraction with increasing force, till each material broke, or the knot separated completely.

Results20% of flat reef knots (FRK) tied with all suture materials slipped; all knots tied with the other two techniques, with all materials, slipped, TK (100%) and NHCK (100%). The quantitative degree of slip, was significantly less for FRK (mean 6.3% 95%CI 2.2-10.4%) than for TK (mean 312% 95%CI 280.0-344.0%) and NHCK (mean 113.0% 95%CI 94.3-131.0%).

The mean lengths of suture in loops held within knots, tied under tension (TK mean 17.0mm 95%CI 16.3-17.7mm), and tied without appropriate hand crossing (NHCK mean 16.3mm 95%CI 15.9-16.7mm) were significantly lower than for flat reef knots (FRK mean 25.1mm 95%CI 24.2-26.0mm). The first two types of knot may have tightened more than anticipated, in comparison to flat reef knots, with potential undue tissue tension.

ConclusionMeticulous technique of knot tying, is essential for secure knots, appropriate tissue tension, and the security of anastomoses and haemostasis effected.

Strengths and limitationsThe study design was simple, with equal numbers of knots tied for each technique, and for each material.

Only a small number of participants tied knots, limiting any assessment to the effect of the knot tying technique. No inference could be drawn regarding the effect of seniority of participant.

A relatively small number of knots were tied with each of the materials limiting more detailed assessment of the effect of the suture material and size on knot security, or whether material and size had any significant influence.

category: medical education


title: Objective quantitation of EGFR protein levels using Quantitative Dot Blot (QDB) method for prognosis of gastric cancer patients

abstract:
BackgroundOne causing factor underlying failures of several clinical trials of anti-EGFR therapies is the lack of effective method to select patients overexpressing EGFR protein. Quantitative Dot Blot method (QDB) is proposed here to measure EGFR protein levels objectively and quantitatively. Its feasibility was evaluated for prognosis of overall survival (OS) of gastric cancer patients.

MethodsFormalin Fixed Paraffin Embedded (FFPE) slices of 2x5 m from gastric and Lung cancer specimens were used to extract total tissue lysate for QDB measurement. Absolutely quantitated EGFR protein levels were used for Kaplan-Meier Overall Survival (OS) analysis of gastric cancer patients.

ResultsEGFR protein levels ranged from 0 to 772 pmole/g (n=246) for gastric, and from 0 to 2695 pmole/g (n=81) for lung cancer patients. Poor correlation was observed between quantitated EGFR levels and immunohistochemistry (IHC) scores with r=0.018, p=0.786 from Spearmans correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric patients only through absolute quantitation, with HR at 2.29 (95%CI:1.23-4.26, p=0.0089) from multivariate cox regression OS analysis. A cutoff of 207.7 pmole/g was proposed to stratify gastric cancer patients, with 5-year survival probability at 37% for those whose EGFR levels were above the cutoff, and at 64% those below the cutoff based on Kaplan-Meier OS analysis. p=0.0057 from Log Rank test.

ConclusionA QDB-based assay was developed for both gastric and Lung cancer specimens to measure EGFR protein levels absolutely, quantitatively and objectively. This assay should facilitate clinical trials aiming to evaluate anti-EGFR therapies retrospectively and prospectively.

category: oncology


title: Analysis across Taiwan Biobank, Biobank Japan and UK Biobank identifies hundreds of novel loci for 36 quantitative traits

abstract: Genome-wide association studies (GWAS) have identified tens of thousands of genetic loci associated with human complex traits and diseases1,2. However, the majority of GWAS were conducted in individuals of European ancestry3. Failure to capture global genetic diversity has limited biological discovery and impeded equitable delivery of genomic knowledge to diverse populations4. Here we report findings from 102,900 individuals across 36 human quantitative traits in the Taiwan Biobank (TWB), a major biobank effort that broadens the population diversity of genetic studies in East Asia (EAS). We identified 979 novel genetic loci, pinpointed novel causal variants through fine-mapping, compared the genetic architecture across TWB, Biobank Japan (BBJ)5-7 and UK Biobank (UKBB)8,9, and evaluated the utility of cross-phenotype, cross-population polygenic risk scores (PRS) in disease risk prediction. These results demonstrated the potential to advance genomic discovery through increasing and diversifying GWAS populations, and provided insights into the common genetic background for human complex traits in East Asian populations.

category: genetic and genomic medicine


title: Performance of vaccination with CoronaVac in a cohort of healthcare workers (HCW) - preliminary report

abstract:
BackgroundCoronaVac, a vaccine containing inactivated SARS-CoV-2, demonstrated efficacy of 50.39% 14 days or more after the 2nd dose.

The objective of this study is to report the occurrence of symptomatic COVID-19 in a cohort of HCW vaccinated with CoronaVac and to estimate its effectiveness.

MethodsCoronaVac was given to HCWs inHospital das Clinicas on 18-21 January, 2021 (epi week 3) (22,402 HCWs), and on 14-16 February, 2021 (epi week 7) (21,652 HCWs). Weekly cases of symptomatic COVID-19 were evaluated. Using the period from 2020 epi week 24 through 2021 epi week 2 (before vaccination), a Poisson regression was fit to model the HCWs with COVID-19 of the hospital, and the officially reported cases in the city of Sao Paulo. The predicted numbers of cases among HCWs for 2021 epi weeks 3-12 were then compared to the observed numbers of cases (after vaccination). Effectiveness was estimated for weeks 9-12 (2 to 5 weeks after the 2nd dose). 142 samples after vaccination were evaluated for SARS-CoV-2 variants of concern.

ResultsSince the 1st dose there were 380 HCW diagnosed with COVID-19. On visual analysis, the number of cases of COVID-19 in the city increased sharply in 2021. The number of cases among the HCW did not follow. The estimated effectiveness 2 and 3 weeks after 2nd dose was 50.7% and 51.8%, respectively, and increased over the next 2 weeks. 67/142 samples (47%) were variants of concern, mostly P1 (57).

ConclusionCoronavac is effective in preventing COVID-19.


title: Making Words Count with Computerised Identification of Hypertrophic Cardiomyopathy Patients

abstract:
BackgroundThe traditional outpatient model in hypertrophic cardiomyopathy (HCM) is under pressure. Population health management based on an accurate patient record provides an efficient, cost-effective alternative.

MethodsTo improve the accuracy of the HCM patient list in a single hospital, we developed a rule-based information extraction natural language processing (NLP) framework. The framework employed ontological expansion of vocabulary and exclusion-first annotation, and received training by an  expert in the loop. The output stratified patients with atrial fibrillation (AF) and heart failure (HF), those without active cardiology care and likely screened individuals.

ResultsThe algorithm was validated against multiple data sources, including manual validation, for HCM, AF and HF and family history of the disease. Overall precision and recall were 0.854 and 0.865 respectively. The pipeline found 25,356 documents featuring HCM-related terms belonging to 11,083 patients. Excluding scanned documents resulted in 17,178 letters from 3,120 patients. Subsequent categorisation identified 1,753 real cases, of whom 357 had AF and 205 had HF. There were 696 likely screened individuals. Adjusting for 304 false-negative patients, the total HCM cohort was 2,045 patients. 214 were not under a cardiologist. NLP uncovered 709 patients who were absent in the registry or hospital disease codes.

ConclusionThis novel NLP framework generated a hospital-wide record of patients with HCM and defined various cohorts, including the small set of HCM patients lacking current cardiology input. Existing data sources inadequately described this population, spotlighting NLPs essential role for clinical teams planning to move to a population health management model of care.

category: cardiovascular medicine


title: Deep Neural Survival Networks for Cardiovascular Risk Prediction: The Multi-Ethnic Study of Atherosclerosis (MESA)

abstract:
BackgroundThere is growing interest in utilizing machine learning techniques for routine atherosclerotic cardiovascular disease (ASCVD) risk prediction. We investigated whether novel deep learning survival models can augment ASCVD risk prediction over existing statistical and machine learning approaches.

Methods6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed over 16 years to assess incidence of all-cause mortality (mortality) or a composite of major adverse events (MAE). Features were evaluated within the categories of traditional risk factors, inflammatory biomarkers, and imaging markers. Data was split into an internal training/testing (four centers) and external validation (two centers). Both machine learning (COXPH, RSF, and lSVM) and deep learning (nMTLR and DeepSurv) models were evaluated.

ResultsIn comparison to the COXPH model, DeepSurv significantly improved ASCVD risk prediction for MAE (AUC: 0.82 vs. 0.79, P[≤]0.001) and mortality (AUC: 0.86 vs. 0.80, P[≤]0.001) with traditional risk factors alone. Implementing non-categorical NRI, we noted a 65% increase in correct reclassification compared to the COXPH model for both MAE and mortality (P[≤]0.05). Assessing the relative risk of participants, DeepSurv was the only learning algorithm to develop a significantly improved risk score criteria, which outcompeted COXPH for both MAE (4.07 vs. 2.66, P[≤]0.001) and mortality (6.28 vs. 4.67, P=0.014). The addition of inflammatory or imaging biomarkers to traditional risk factors showed minimal/no significant improvement in model prediction.

ConclusionDeepSurv can leverage simple office-based clinical features alone to accurately predict ASCVD risk and cardiovascular outcomes, without the need for additional features, such as inflammatory and imaging biomarkers.


title: Facemask usage during the COVID-19 pandemic among people with primary ciliary dyskinesia: a participatory project

abstract:
BackgroundFacemasks help prevent transmission of SARS-CoV-2 and are particularly important for people with chronic respiratory disease such as primary ciliary dyskinesia (PCD). We studied the usage of facemasks and its consequences among people with PCD in an international context.

MethodsWe used data from COVID-PCD, an international observational cohort study which collects longitudinal data from people with PCD during the COVID-19 pandemic via weekly online questionnaires. An online questionnaire investigating use of facemasks was posted in October 2020. It asked about frequency of facemask usage in different public places, problems experienced with use of facemasks, affordability of masks, and beliefs regarding their effectiveness.

Results282 participants (50%) completed the questionnaire. Participants came from 27 different countries; median age was 32 years (interquartile range 17-48), and 63% were female. Almost all wore a facemask whenever they left their house. In addition, many avoided public places altogether. For example, 159 (57%) did not use public transport at all, 108 (39%) always wore a facemask in public transport, 4 (1%) sometimes, and 7 (3%) never. 81% agreed with the statement that facemasks protect the person who wears the mask, and 91% agreed that facemasks protect others. One third reported that it was uncomfortable to wear a mask because of their runny nose, 31% because of cough, and 22% because of difficulty breathing. Participants less often wore facemasks in public when there was no national requirement. Only two persons had a personal exemption from wearing a facemask prescribed by a physician.

ConclusionsThis international study found that people with PCD carefully shield themselves, and most wear facemasks everywhere in public. People who did not wear facemasks in public came from countries without a national facemask requirement. National policies mandating facemask use in public are important for universal use to protect high-risk populations from SARS-CoV-2 infections.

category: epidemiology


title: Association between comorbidities and death from COVID-19 in different age groups

abstract:
BackgroundThis new COVID-19 pandemic challenges health systems around the world; therefore, it is extremely important to determine which patients with COVID-19 can evolve to more severe outcomes. Accordingly, we decided to assess the role that comorbidities play in death from COVID-19.

MethodsTwo age groups (<60 and [≥] 60 years) were defined for analysis. Decision trees were made to identify which comorbidities had the highest fatality rate (FR). Multiple logistic regressions were performed to measure the association between comorbidities and death.

ResultsA significant difference was found between the FR of <60 group and [≥] 60 group. The most frequent comorbidity were cardiac diseases and diabetes. The combination of comorbidities with the highest FR was diabetes with kidney disease. Combinations of more than two comorbidities presented higher FR. The comorbidities had higher Odd ratios in the younger group than in the older group.

ConclusionsComorbidities seem to play a greater role in death from COVID-19 in the younger group, while in the> 60 group; age seems to be the most important factor. We assigned a score to the comorbidities and their combinations for both age groups to help the health personnel make decisions.


title: Quarantine, relaxation and mutation explaining the CoViD-19 epidemic in Sao Paulo State (Brazil)

abstract:
BackgroundThe continuous SARS-CoV-2 transmission in several countries could contribute to the mutations appearance. The circulation of more virulent variants may increase the number of severe CoViD-19 needing hospital care and fatalities hugely.

MethodsThe partial quarantine in Sao Paulo State and further relaxation associated with the mutations are explained by a mathematical model based on the CoViD-19 natural history encompassing the age-dependent fatality. The model parameters were fitted considering the observed data from Sao Paulo State.

ResultsThe partial quarantine was explained by the less virulent SARS-CoV-2 transmission, but the relaxation alone could not explain the epidemic observed in Sao Paulo State. However, more virulent variants plus the transmission among isolated individuals explained the increased CoViD-19 fatalities.

ConclusionsThe model described the CoViD-19 epidemic in Sao Paulo State by considering the partial quarantine, relaxation and mutations. The model provided a potential epidemiological scenario in the absence of mass vaccination.


title: Breakpoint modelling of temporal associations between non-pharmaceutical interventions and the incidence of symptomatic COVID-19 in the Republic of Ireland

abstract:
BackgroundTo constrain propagation and mitigate the burden of COVID-19, most countries initiated and continue to implement several non-pharmaceutical interventions (NPIs), including national and regional lockdowns. In the Republic of Ireland, the first national lockdown was decreed on 23rd of March 2020, followed by a succession of restriction increases and decreases (phases) over the the following year. To date, the effects of these interventions remain unclear, and particularly within differing population subsets. The current study sought to assess the impact of individual NPI phases on COVID-19 transmission patterns within delineated population subgroups in the Republic of Ireland.

Methods and FindingsConfirmed, anonymised COVID-19 cases occurring between the 29th of February 2020 and 30th November 2020 (n= 72,654) were obtained. Segmented modelling via breakpoint regression with multiple turning points was employed to identify structural breaks across sub-populations, including primary/secondary infections, age deciles, urban/commuter/rural areas, patients with underlying health conditions, and socio-demographic profiles. These were subsequently compared with initiation dates of eight overarching NPI phases.

Five distinct breakpoints were identified. The first breakpoint, associated with a decrease in the daily COVID-19 incidence, was reported within 14 days of the first set of restrictions in mid-March 2020 for most population sub-groups. Results suggest that moderately strict NCIs were more effective than the strictest Phase 5 (National Lockdown). Divergences were observed across population sub-groups; lagged response times were observed among populations >80 years, residents of rural/ commuter regions, and cases associated with a below-median deprivation score.

ConclusionsStudy findings suggest that many NPIs have been successful in decreasing COVID-19 incidence rates, however the strictest Phase 5 NPI was not. Moreover, NPIs were not equally successful across all sub-populations, with differing response times noted. Mitigation strategies and interventions may need to be increasingly bespoke, based on sub-population profiles and required responses.


title: Covid-19: Early evening curfews are not effective and may backfire

abstract:
BackgroundDuring the COVID-19 pandemic, some countries have introduced early evening curfews. Several studies try measure the effectiveness of such measures across different countries, but clear identification of effects is elusive.

ObjectiveWe examined the impact of an early evening curfew on mobility by studying a shift in curfews from 9pm to 6pm in Greece.

Data and MethodsWe took advantage of a natural experiment in Greece, where curfews shifted from 9pm to 6pm in one Region, but not in another. We followed a difference-in-differences econometric approach, where we compared trends in mobility in groceries and pharmacies as well as residential spaces before and after the introduction of the 6pm curfew, in the two regions.

ResultsThe relative difference in the time spent in groceries and pharmacies between the two regions before and after the intervention, is statistically insignificant [coeff: -9.95; 95%CI -44.358 to 24.458]. The relative increase in time spent at residential spaces after the 6pm curfew was only 4.625 percentage points [coeff: 4.625; 95%CI 1.412 to 7.838].

ConclusionsWe found that the 6pm instead of 9pm curfew in Athens led to a 4.63 percentage point relative increase in time spent at home and had no effect on time spent in groceries and pharmacies. Considering that this was a result of a 18.75% reduction in hours where people were allowed to leave home, it seems that the early evening curfew led to more crowding in indoor spaces - which may facilitate the spread of disease. Interventions should be based on a thorough analysis of human behaviour, that anticipates substitution of activities.


title: Do people reduce compliance with COVID-19 guidelines following vaccination? A longitudinal analysis of matched UK adults

abstract:
IntroductionCOVID-19 vaccines do not confer immediate immunity and vaccinated individuals may still be at risk of transmitting the virus. Governments have not exempted vaccinated individuals from behavioural measures to reduce the spread of COVID-19, such as practicing social distancing. However, vaccinated individuals may have reduced compliance with these measures, given lower perceived risks.

MethodsWe used monthly panel data from October 2020 - March 2021 in the UK COVID-19 Social Study to assess changes in compliance following vaccination. Compliance was measured with two items on compliance with guidelines in general and compliance with social distancing. We used matching to create comparable groups of individuals by month of vaccination (January, February, or not vaccinated by February) and fixed effects regression to estimate changes in compliance over the study period.

ResultsCompliance increased between October 2020 - March 2021, regardless of vaccination status or month of vaccination. There was no clear evidence that vaccinated individuals decreased compliance relative to those who were not yet vaccinated.

ConclusionThere was little evidence that sample members vaccinated in January or February reduced compliance after receiving vaccination for COVID-19. Continued monitoring is required as younger individuals receive the vaccine, lockdown restrictions are lifted and individuals receive second doses of the vaccine.


title: Trajectories of compliance with COVID-19 related guidelines: longitudinal analyses of 50,000 UK adults

abstract:
BackgroundGovernments have implemented a range of measure to tackle COVID-19, primarily focusing on changing citizens behaviours in order to lower transmission of the virus. Some policymakers have expressed concern that citizens would not maintain high levels of compliance with these behaviours over the pandemic and would instead exhibit so-called "behavioural fatigue". While the concept has been criticized, there have been few tests of behavioural fatigue using data from the COVID-19 pandemic, and none that have tracked individuals compliance trajectories.

MethodsWe used longitudinal data on self-reported compliance from 50,851 adults in the COVID-19 Social Study collected across two waves of the pandemic in the UK (01 April 2020 - 22 February 2021). We modelled typical compliance trajectories using latent growth curve analysis (LGCA) and tested for behavioural fatigue by attempting to identify a set of participants whose compliance decreased substantially over the study period.

ResultsWe selected a four-class LGCA solution. Most individuals maintained high levels of compliance over the pandemic and reported similar levels of compliance across the first and second waves. Approximately one in seven participants had decreasing levels of compliance across the pandemic, reporting noticeably lower levels of compliance in the second wave, a pattern compatible with behavioural fatigue. Individuals with declining compliance levels differed from those with consistently high compliance on multiple characteristics, including (young) age, better physical health, lower empathy and conscientiousness and greater general willingness to take risks.

ConclusionWhile a minority, not all individuals have maintained high compliance across the pandemic. Decreasing compliance is related to several psychological traits. The results suggest that targeting of behaviour change messages later in the pandemic may be needed to increase compliance.


title: Seroepidemiology among Employees of New York City Health and Hospitals during the First Wave of the SARS-CoV-2 Epidemic

abstract:
ObjectiveEstimate the seroprevalence of SARS-CoV-2 antibodies among New York City Health + Hospitals healthcare workers, and identify demographic and occupational factors associated with SARS-CoV-2 antibodies among healthcare workers.

MethodsThis was an observational, cross-sectional study using data from SARS-CoV-2 serological tests accompanied by a demographic and occupational survey administered to healthcare workers. Participants were employed by New York City Health + Hospitals (NYC H+H) and either completed serologic testing at NYC H+H between April 30 and June 30, 2020, or completed SARS-CoV-2 antibody testing outside of NYC H+H and were able to self-report results.

ResultsSeven hundred twenty-seven survey respondents were included in analysis. Participants had a mean age of 46 years (SD= 12.19) and 543 (75%) were women. Two hundred fourteen (29%) participants tested positive or reported testing positive for the presence of SARS-CoV-2 antibodies (IgG+). Characteristics associated with positive SARS-CoV-2 serostatus were Black race (25% IgG+ vs. 15% IgG-, p=0.001), having someone in the household with COVID symptoms (49% IgG+ vs. 21% IgG-, p<0.001), or having a confirmed COVID-19 case in the household (25% IgG+ vs 5% IgG-, p<0.001). Characteristics associated with negative SARS-CoV-2 serostatus included working on a COVID patient floor (27% IgG+ vs. 36% IgG-, p=0.02), working in the ICU (20% IgG+ vs. 28% IgG-, p=0.03), or having close contact with a patient with COVID-19 (51% IgG+ vs. 62% IgG-, p=0.03).

ConclusionsResults underscore the significance of community factors and inequities might have on SARS-CoV-2 exposure for healthcare workers.

What is already known about this subject?Healthcare workers are at risk of occupational transmission of SARS-CoV-2, and the risk of infection varies by demographic characteristics and work location.

What are the new findings?Healthcare worker race and household contacts were significantly associated with SARS-CoV-2 seropositivity, while working on a COVID patient floor or ICU was associated with seronegativity.

How might this impact on policy or clinical practice in the foreseeable future?Results underscore the significance of community factors and inequities on healthcare worker exposure to SARS-CoV-2, and the need to address these inequities at the community level where healthcare workers live.


title: Use of Modeling to Inform Decision-Making During the COVID-19 Pandemic: A Qualitative Study

abstract:
BackgroundThe COVID-19 Pandemic has popularized computer-based decision-support models as a tool for decision-makers to manage their organizations. It is unclear how decision-makers have considered these models to inform COVID-19-related decisions.

MethodsWe interviewed decision-makers from North Carolina across diverse organizational backgrounds to assess major decision-making processes during COVID-19, including the use of modeling as an input to inform decision-making.

ResultsInterviewees were aware of models during COVID-19, with some depending upon multiple models. Models were used to compare trends in disease spread across localities, allocate scarce resources, and track disease spread within small geographic areas. Decision-makers desired models to project disease spread within subpopulations and estimate where local outbreaks could occur as well as estimate the outcomes of social distancing policies, including consequences beyond typical health-related outcomes. Challenges to the use of modeling included doubts that models could reflect nuances of human behavior, concerns about the quality of data used in models, and the limited amount of modeling at the local level.

ConclusionsThroughout COVID-19, decision-makers perceived modeling as valuable for understanding disease spread within their communities and to inform organization decisions, yet there were variations in organizations ability and willingness to use models for these purposes.

category: health policy


title: Efficacy of a nasal spray containing Iota-Carrageenan in the prophylaxis of COVID-19 in hospital personnel dedicated to patients care with COVID-19 disease. A pragmatic multicenter, randomized, double-blind, placebo-controlled trial (CARR-COV-02)

abstract:
BackgroundIota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In vitro, I-C inhibits SARS-CoV-2 infection in cell culture.

MethodsThis is a pragmatic multicenter, randomized, double-blind, placebo-controlled trial assessing the use of a nasal spray containing I-C in the prophylaxis of COVID-19 in hospital personnel dedicated to care of COVID-19 patients.

Clinically healthy physicians, nurses, kinesiologists and others medical providers were assigned in a 1:1 ratio to receive four daily doses of I-C spray or placebo for 21 days.

The primary end point was clinical COVID-19, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 21 days. The trial is registered at ClinicalTrials.gov (NCT04521322).

FindingsA total of 394 individuals were randomly assigned to receive I-C or placebo. Both treatment groups had similar baseline characteristics.

The incidence of COVID19 was significantly lower in the I-C group compared to placebo (1{middle dot}0% vs 5{middle dot}0%) (Odds Ratio 0{middle dot}19 (95% confidence interval 0{middle dot}05 to 0{middle dot}77; p= 0{middle dot}03). Workday loss in placebo group compared to I-Cc were 1.6% days / person (95% ci, 1.0 to 2.2); p <0.0001

There were no differences in the incidence of adverse events across the two groups (17{middle dot}3% in the I-C group and 15{middle dot}2% in the placebo group, p= 0{middle dot}5).

InterpretationI-C showed significant efficacy in preventing SARS-Cov-2 infection in hospital personnel dedicated to care patients with COVID-19 disease.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for research articles published up to February 14, 2021, with no language restrictions, using the terms "SARS-CoV-2" or "COVID-19", "prevention", "clinical trial", and "prophylaxis". Except for studies on vaccines we only found three peer-reviewed publications available on the efficacy of Hydroxycholoquine to prevent COVID-19 disease in individuals at risk of exposure. Hydroxychloroquine did not prevent COVID-19 used as pre or postexposure prophylaxis. We also did not find results from clinical trials on the efficacy of carrageenan in the prevention or treatment of cOVID-19.

Added value of this studyWe report the clinical efficacy of a nasal spray with Iota-Carrageenan for the prevention of COVID-19 disease in a randomised, double-blind, placebo-controlled, multicentre study in Republica Argentina, including 394 participants.

Implications of all the available evidenceA simple intervention such as the administration of a nasal spray with Iota-Carrageenan, in addition to hand hygiene, use of personal protective equipment and social distancing, could provide additional protection until vaccines can be administered to the majority of the population.


title: Protocol for the COG-UK hospital onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in United Kingdom NHS hospitals

abstract:
IntroductionNosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a significant cause of mortality in National Health Service (NHS) hospitals during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the impact of rapid whole genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, to inform infection prevention and control (IPC) practice within NHS hospital settings.

Methods and analysisCOG-UK HOCI (COG-UK Consortium Hospital-Onset COVID-19 Infections study) is a multicentre, prospective, interventional, superiority study. Eligible patients must be admitted to hospital with first confirmed SARS-CoV-2 PCR positive test result >48h from time of admission, where COVID-19 diagnosis was not suspected upon admission. The projected sample size for 14 participating sites covering all study phases over winter-spring 2020/2021 in the United Kingdom is 2,380 patients. The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab) and within 5-10 days in a second phase (mimicking central lab use), comparing the viral genome from an eligible study participant with others within and outside the hospital site. The primary outcomes are the incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study and analysis, underpinned by iterative programme theory of the sequence report. Health economic analysis will be conducted to determine cost-benefit of the intervention, and whether this leads to economic advantages within the NHS setting.

Ethics and disseminationThe protocol has been approved by the National Research Ethics Service Committee (Cambridge South 20/EE/0118). This manuscript is based on version 5.0 of the protocol. The study findings will be disseminated through peer-reviewed publications.

Study Registration numberISRCTN50212645

Strengths and limitations of this studyO_LIThe COG-UK HOCI study harnesses the infrastructure of the UKs existing national COVID-19 genome sequencing platform to evaluate the specific benefit of sequencing to hospital infection control.
C_LIO_LIThe evaluation is thought to be the first interventional study globally to assess effectiveness of genomic sequencing for infection control in an unbiased patient selection in secondary care settings.
C_LIO_LIA range of institutional settings will participate, from specialist NHS-embedded or academic centres experienced in using pathogen genomics to district general hospitals.
C_LIO_LIThe findings are likely to have wider applicability in future decisions to utilise genome sequencing for infection control of other pathogens (such as influenza, respiratory syncytial virus, norovirus, clostridium difficile and antimicrobial resistant pathogens) in secondary care settings.
C_LIO_LIThe study has been awarded UK NIHR Urgent Public Health status, ensuring prioritised access to NIHR Clinical Research Network (CRN) research staff to recruit patients.
C_LIO_LIThe study does not have a randomised controlled design due to the logistics of managing this against diverse standard practice.
C_LI


title: A distinct metabolic profile associated with a fatal outcome in COVID-19 patients during early epidemic in Italy

abstract: Leveraging the unique biological resource based upon the initial COVID-19 patients in Policlinico di Milano (Italy), our study provides the first metabolic profile associated with a fatal outcome. The identification of potential predictive biomarkers offers a vital opportunity to employ metabolomics in a clinical setting as diagnostic tool of disease prognosis upon hospital admission.


title: Central obesity, smoking habit and hypertension are associated with a blunted serological response to COVID-19 mRNA vaccine

abstract:
AimsTo explore variables associated with the serological response following COVID-19 mRNA vaccine.

MethodsHealthcare workers adhering to the vaccination campaign against COVID-19 were enrolled in January-February 2021. All subjects underwent two COVID-19 mRNA vaccine inoculations (Pfizer/BioNTech) separated by three weeks. Blood samples were collected before the first and 1-4 weeks after the second inoculation. Clinical history, demographics, and vaccine side effects were recorded. Baseline anthropometric parameters were measured, and body composition was performed through dual-energy-X-ray absorptiometry.

ResultsEighty-six patients were enrolled. Those with central obesity had lower antibody (Ab) titers compared with those with no central obesity [1426(1436)vs1971(1819), p=0.04]; smokers had a blunted response compared to non-smokers [1099(1350)vs1921(1375), p=0.007], as well as hypertensive vs normotensive [650{+/-}1192vs1911(1364), p=0.001] and dyslipidemic compared to those with normal serum lipids [534(972)vs 1872(1406), p=0.005]. Multivariate analysis showed that higher waist circumference, smoking, hypertension and longer time elapsed since second vaccine inoculation were associated with lower Ab titers, independent of BMI, age and gender. The association between waist circumference and Ab titers was lost when controlling for body fat, suggesting that visceral accumulation may explain this result.

ConclusionsIt is currently impossible to determine whether lower SARS CoV-2 Abs lead to higher likelihood of developing COVID-19. However, neutralizing abs correlate with protection against several viruses including SARS-CoV-2, and the finding that central obesity, hypertension and smoking are associated with a blunted response warrants further attention. Our findings must lead to a vigilant approach, as these subjects could benefit from earlier vaccine boosters or different vaccine schedules.

category: endocrinology


title: Disparities in SARS-CoV-2 Vaccination-to-Infection Risk, Massachusetts 2020-2021

abstract:
BackgroundEffective vaccine-based containment strategies for SARS-CoV-2 require equitable coverage of communities at greatest risk of infection. We sought to examine the alignment of vaccination and SARS-CoV-2 risk in Massachusetts to inform public health response.

MethodsWe aggregated cumulative SARS-CoV-2 testing and vaccination data from the Massachusetts Department of Public Health and the Boston Public Health Commission from January 29, 2020 to April 9, 2021. We used two approaches to assess vaccination equity: vaccination-to-infection risk (VIR) ratio and Lorenz curves. The VIR ratio was calculated for each community as the quotient of the number of fully vaccinated individuals divided by the cumulative number of confirmed SARS-CoV-2 infections. Lorenz curves were used to describe vaccination relative to COVID-19 burden. A multivariable Poisson model was used to assess predictors of VIR ratio.

ResultsA total of 607,120 (8.9%) SARS-CoV-2 infections were confirmed in Massachusetts residents and 1,485,266 (21.8%) residents were fully vaccinated. Communities with increased socioeconomic vulnerability had lower VIR ratios indicating less equitable vaccination relative to infection risk. In multivariable analysis, decreased vaccination relative to infection risk was independently associated with increasing socioeconomic vulnerability (aRR 0.82 per quartile increase, 95% CI 0.77 to 0.87) and with greater than 20% of the community identified as Black and/or Latinx (aRR 0.67, 95% CI 0.56 to 0.81). Improved community vaccine delivery was associated with higher community proportion of residents aged 65 or older (aRR 1.23 per 5% increase in proportion, 95% CI 1.15 to 1.31). Lorenz curves indicated considerable inequity (Gini 0.46 between communities). An estimated 330,000 full vaccination courses would need to be diverted to under-vaccinated communities to achieve equity.

ConclusionIn conclusion, disparities in vaccine delivery highlight ongoing inequities in our approach to COVID-19 and imperil efforts to control the pandemic.


title: Ornithine Decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of  Helicobacter pylori  CagA serostatus

abstract: The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI: 2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 x 10-3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the risk allele, C, at rs2302615.

category: gastroenterology


title: Distorted TCR repertoires define multisystem inflammatory syndrome in children

abstract: While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with severe (n=12) or mild (n=8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n=8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of severely ill children are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines severity of disease in children.

category: allergy and immunology


title: Strong anti-viral responses in pediatric COVID-19 patients in South Brazil

abstract: Epidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Childrens T cell responses differed from adults in that their CD8+ TNF+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.


title: Treatment of Early Hypertension among Persons Living with HIV in Haiti: protocol for a randomized controlled trial

abstract:
BackgroundPeople living with HIV (PLWH) are at increased risk of cardiovascular disease (CVD) and death, with greater burdens of both HIV and CVD in lower-middle income countries. Treating prehypertension in PLWH may reduce progression to hypertension, CVD risk and potentially mortality. However, no trial has evaluated earlier blood pressure treatment for PLWH. We propose a randomized controlled trial to assess the feasibility, benefits, and risks of initiating antihypertensive treatment among PLWH with prehypertension, comparing prehypertension treatment to standard of care following current WHO guidelines.

MethodsA total of 250 adults 18-65 years and living with HIV (PLWH) with viral suppression in the past 12 months, who have prehypertension will be randomized to prehypertension treatment versus standard of care. Prehypertension is defined as having a systolic blood pressure (SBP) 120-139 mmHg or diastolic blood pressure (DBP) 80-89 mmHg. In the prehypertension treatment arm, participants will initiate amlodipine 5 mg daily immediately. In the standard of care arm, participants will initiate amlodipine only if they develop hypertension defined as SBP [≥] 140 mmHg or DBP [≥] 90 mmHg. The primary outcome is the difference in mean change of SBP from enrollment to 12 months. Secondary outcomes include feasibility, acceptability, adverse effects, HIV viral suppression, and medication adherence. Qualitative in-depth interviews with providers and participants will explore attitudes about initiating amlodipine, satisfaction, perceived CVD risk, and implementation challenges.

DiscussionPLWH have a higher CVD risk and may benefit from a lower BP threshold for initiation of antihypertensive treatment.

Trial registrationClinicaltrials.gov registration number NCT04692467, registration date December 15, 2020, protocol ID 20-03021735.


title: Preparations of Dutch emergency departments for the COVID-19 pandemic: a questionnaire-based study

abstract:
BackgroundThe onset of the COVID-19 pandemic was characterized by rapidly increasing patient volumes, which necessitated a swift emergency department (ED) overhaul. Challenges mainly concerned surge capacity, frontline staff protection and the segregation of patients with suspected COVID-19. To date, only few studies have assessed nation-wide ED preparedness for the COVID-19 pandemic. This study aimed to form an overview of preparations that were taken in Dutch EDs during the initial phase of this public health crisis.

MethodsThis study was designed as a nation-wide, cross-sectional, questionnaire-based study among Dutch hospital organizations with [≥]1 ED. The questionnaire was conducted between the first and the second wave of the COVID-19 pandemic in the Netherlands and contained close-ended and open-ended questions on changes in ED infrastructure, ED workforce adaptions and the role of emergency physicians (EPs) in the hospitals crisis organization.

ResultsOverall response rate was 79.5%. All EDs had made preparations in anticipation of a possible COVID-19 surge. Treatment capacity was expanded in 69.7% of EDs, with a median increase of 49% (IQR 32.5-72.7%). COVID-19 suspected patients were segregated from non-COVID-19 patients in 86.4% of EDs. Non-COVID-19 patients were more often assessed at alternative locations than patients with suspected COVID-19 infection. In 81.8% of EDs the workforce was expanded, which mainly concerned expansion of nursing staff. A formal role of EPs in the hospitals crisis organization was reported by 93.9% of EP staffed hospital organizations.

ConclusionAll Dutch EDs made preparations for COVID-19 in a short time span and with many uncertainties. Preparations predominantly concerned expansion of treatment capacity and segregation of COVID-19 ED care. EPs had a prominent role, both in direct patient COVID-19 ED care and in the hospitals crisis organizations. Although it is vital for EDs to be able to dynamically adapt to community needs, variability of pandemic ED preparedness was high.

category: emergency medicine


title: A very simple model to account for the rapid rise of the British variant of SARS-CoV-2 in several countries and the world

abstract:
Since its first detection in the UK in September 2020, a highly contagious version of the coronavirus, called the British variant or B.1.1.7 SARS-CoV-2 virus lineage, is rapidly spreading across several countries and becoming the dominant strain in the outbreak.

Here it is shown that a very simple evolutionary model, when including the latest available data from March 2021, can fit the observed change in frequency of B.1.1.7 for several countries, regions of countries and the whole world with a single parameter which is almost universal.


title: Evaluating the impact of keeping indoor dining closed on COVID-19 rates among large US cities: a quasi-experimental design

abstract:
ObjectiveIndoor dining is one of the potential key drivers of COVID-19 transmission. We leverage the heterogeneity in state government preemption of city indoor dining closures, to estimate the impact of keeping indoor dining closed on COVID-19 incidence.

MethodsWe obtained case rates and city/state re-opening dates from March to October 2020 in 11 U.S. cities. We categorized cities as (treatment) cities that were allowed by the state to reopen but kept indoor dining closed; and (comparison) cities that would have kept indoor dining closed but were preempted by their state and had to reopen indoor dining.

ResultsKeeping indoor dining closed was associated with a 43% (IRR=0.57, 95% CI 0.46 to 0.69) decline in COVID-19 incidence over 4-weeks compared with cities that reopened indoor dining. These results were consistent after testing alternative modeling strategies.

ConclusionsKeeping indoor dining closed contributes to reductions in COVID-19 spread.

Policy ImplicationsEvidence of the relationship between indoor dining and COVID-19 incidence can inform state and local decisions to restrict indoor dining as a tailored strategy to reduce COVID-19 incidence.


title: Clumpiness: Modeling the Impact of Social Dynamics on COVID-19 Spread

abstract: We present an agent based simulation model configured for exploring the dynamics of disease spread in the context of agents that group together through homophily, the principle of "like attracts like". To study the properties of this model, we introduce two novel social network inter-connectivity measures, "clumpiness" and "hoprank," that are the same basic concept defined at global and local levels, respectively. The measures may be computed from samples of readily available demographic data, and are useful for measuring probabilistic packet transmission through social networks. In three studies we apply clumpiness to measure the effects, on COVID-19 transmission, caused by social networks of both homophilic physical proximity and homophilic information replication. The particular characteristic we are interested in about disease transmission is herd immunity, the percentage of a population that has to be immune in order to prevent infection from spreading to those who are not. Two studies demonstrate innovations measuring herd immunity levels and predicting future outbreak locations, procedures relevant to epidemiological control policy. In the first study, we look at how homophilic physical proximity networks form natural bubbles that act as frictive surfaces that affect the speed of transmission of packets and influence herd immunity levels. In the second study, we test clumpiness in homophilic proximity social networks as a predictor of future infection outbreaks at the level of individual schools, restaurants, and workplaces. Our third study demonstrates that protective social bubbles form naturally from homophilic information replication networks, and enhance the natural bubbles that come from the homophilic physical proximity networks. Accurate description of this information environment lays the foundation for epidemiological messaging policy formation.


title: Study protocol for a cross-sectional study on knowledge, attitude, and practice towards thalassemia among Indonesian youth.

abstract:
IntroductionThalassemia is an inherited hemoglobinopathy with high prevalence and incidence in Indonesia. It leads to health, psychosocial, and economic burdens that affect patients, caregivers, and the country. As treatments for thalassemia in Indonesia remain expensive, not readily available, or associated with poor compliance, thalassemia prevention through screening programs is highly recommended to reduce the number of new cases. It is best to target thalassemia prevention and education to youth, but baseline data regarding their knowledge, attitude, and practice must first be assessed to measure their current awareness level as well as behavioral patterns regarding thalassemia. Currently, there has been limited research on public perception towards thalassemia in Indonesia.

Methods and analysisThis observational, cross-sectional study will recruit at least 500 participants between the age of 15 - 24 across all provinces in Indonesia. This is the first nationwide thalassemia study that explores knowledge, attitude, and practice among Indonesian youth (15 - 24 years old) - including thalassemia major patients, carriers, unaffected individuals, and individuals with unknown carrier status. A questionnaire will be disseminated online through social media. The questionnaire will consist of 28 questions to assess knowledge, attitude, and practice from the general population and 38 questions to assess knowledge, attitude, and practice specifically from thalassemia major patients. Questions about whether thalassemia is perceived as a curse, role of consanguinity on the mode of inheritance, and willingness to undergo screening are incorporated to specifically suit Indonesian sociocultural settings.

Ethics and disseminationThis study has been approved by the Ethical Committee of Faculty of Medicine, Universitas Indonesia, and Cipto Mangunkusumo Hospital. Informed consent will be obtained from all participants before completing the online questionnaire. Results will be published in a relevant journal and scientific meetings as well as shared with local stakeholders and policymakers.

Study registrationThis study has been registered at ClinicalTrials.gov (NCT04706585).

ARTICLE SUMMARYO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIFirst nationwide knowledge, attitude, and practice study on Indonesian youth that provides baseline data for thalassemia major patients, carriers, unaffected individuals, and individuals with unknown carrier status.
C_LIO_LIIncorporation of knowledge, attitude, and practice questions that are specific to Indonesian cultural settings, which include perception of thalassemia as a curse and impact of consanguinity on inheritance of thalassemia.
C_LIO_LIOnline dissemination of the survey via social media allows us to reach a large number of Indonesian youth from all backgrounds who are located in all 34 provinces of Indonesia
C_LIO_LIThe use of online self-administered questionnaire for data collection may discourage those with poor Internet connection, particularly in remote areas, from participating.
C_LIO_LILack of background data on public perception towards thalassemia in Indonesia means that some assumptions from expert opinions and educated guesses have to be made when developing the questionnaire.
C_LI

category: pediatrics


title: Just Say No to Postmortem Drug Dose Calculations

abstract: It has long been known that forensic and clinical toxicologists should not determine the dose of a drug administered based on postmortem blood drug concentrations but to date there has been limited information as to how unreliable these dose calculations can be. Using amitriptyline as a model drug this study used the empirically determined pharmacokinetic variables for amitriptyline from clinical studies and clinical, overdose (where the individual survived) and death (ascribed to amitriptyline toxicity) case studies in which the dose of drug administered or taken was known. Using these data, standard pharmacokinetic equations and general error propagation it was possible to estimate the accuracy of the consumed dose of amitriptyline compared to the actual dose consumed. As was expected in postmortem cases, depending on the pharmacokinetic equation used, the accuracy (mean +128 to +2347 %) and precision (SD {+/-} 383 to 3698%) were too large to allow reliable estimation of the dose of drug taken or administered prior to death based on postmortem blood drug concentrations. This work again reinforces that dose calculations from postmortem blood drug concentrations should not be carried out.

category: pharmacology and therapeutics


title: COMplex mental health PAThways (COMPAT) Study: a mixed methods study to inform an evidence-based service delivery model for people with complex needs: Study protocol

abstract:
BackgroundMental health services for adults, as they are currently configured, have been designed to provide predominantly community-based interventions. It has long been recognised that some patients have such significant clinical and/or risk needs that those needs cannot be adequately met within standard service delivery models, resulting in a pressing need to consider the best models for this group of people. This paper shares a protocol for a mixed methods study that aims to understand: the profile and history of service users described as having complex needs; the decision-making processes by clinicians that lead to complex needs categorisation; service users and carers experience of service use; and, associated economic impact. This protocol describes a comprehensive evaluation that aims to inform an evidence-based service delivery model for people with complex needs.

MethodsWe will use a mixed methods design, combining quantitative and qualitative methods using in-depth descriptive and inferential analysis of patient records, written medical notes and in-depth interviews with service users, carers, and clinicians. The study will include five components: (1) a quantitative description and analysis of the demographic clinical characteristics of the patient group; (2) an economic evaluation of alternative patient pathways; (3) semi-structured interviews about service user and carer experiences; (4) using data from components 1-3 to co-produce vignettes jointly with relevant stakeholders involved in the care of service users with complex mental health needs; and, (5) semi-structured interviews about clinical decision-making by clinicians in relation to this patient group, using the vignettes as example case studies.

DiscussionThe studys key outcomes will be to: examine the resource use and cost-impact associated with alternative care pathways to the NHS and other sectors of the economy (including social care); explore patient health and non-health outcomes associated with alternative care pathways; and, gain an understanding of a complex service user group and how treatment decisions are made to inform consistent and person-centred future service delivery.

category: psychiatry and clinical psychology


title: Real-time PCR assay for detection and differentiation of Coccidioides immitis and Coccidioides posadasii from culture and clinical specimens

abstract: Coccidioidomycosis (Valley Fever) is a pulmonary and systemic fungal disease with increasing incidence and expanding endemic areas. The differentiation of etiologic agents Coccidioides immitis and C. posadasii remains problematic in the clinical laboratories as conventional PCR and satellite typing schemes are not facile. Therefore, we developed Cy5- and FAM-labeled TaqMan-probes for duplex real-time PCR assay for rapid differentiation of C. immitis and C. posadasii from culture and clinical specimens. The RRA2 gene encoding proline-rich antigen 2, specific for Coccidioides genus, was the source for the first set of primers and probe. Coccidioides immitis contig 2.2 (GenBank: AAEC02000002.1) was used to design the second set of primers and probe. The second primers/probe did not amplify the corresponding C. posadasii DNA, because of an 86-bp deletion in the contig. The assay was highly sensitive with limit of detection of 0.1 pg gDNA/PCR reaction, which was equivalent to approximately ten genome copies of C. immitis or C. posadasii. The assay was highly specific with no cross-reactivity to the wide range of fungal and bacterial pathogens. Retrospective analysis of fungal isolates and primary specimens submitted from 1995 to 2020 confirmed 129 isolates and three primary specimens as C. posadasii and 23 isolates as C. immitis from human coccidioidomycosis cases, while all eight primary samples from two animals were confirmed as C. posadasii. A preliminary analysis of cerebrospinal fluid (CSF) and pleural fluid samples showed positive correlation between serology tests and real-time PCR for two of the 15 samples. The Coccidioides spp. duplex real-time PCR will allow rapid differentiation of C. immitis and C. posadasii from clinical specimens and further augment the surveillance of coccidioidomycosis.


title: The impact of COVID-19 upon the delivery of exercise services within cystic fibrosis clinics in the United Kingdom

abstract: The COVID-19 pandemic has resulted in unprecedent change to clinical practice. As the impact upon delivery of exercise services for people with cystic fibrosis (CF) in the UK was unknown, this was characterised via a national survey. In total, 31 CF centres participated. Principal findings included a significant reduction in exercise testing, and widespread adaptation to deliver exercise training using telehealth methods. Promisingly, 71% stated that they would continue to use virtual methods of engaging patients in future practice. This does, however, highlight a need to develop sustainable and more standardised telehealth services further to manage patients moving forwards.

category: respiratory medicine


title: Specific heterozygous frameshift variants in hnRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy

abstract: RNA-binding proteins (RBPs) are essential for post-transcriptional regulation and processing of RNAs. Pathogenic missense variants in RBPs underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, inclusion body myopathy, distal myopathy, and Pagets disease of the bone. Here, we present ten independent families with a severe, progressive, early-onset muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD), caused by heterozygous frameshift variants in the prion-like domain of hnRNPA2B1. We found that in contrast with the previously reported missense variants, the frameshift hnRNPA2B1 variants do not promote, but rather decelerate the fibrillization of the protein. Importantly, the frameshift variants harbor altered nuclear-localization sequences and exhibit reduced affinity for the nuclear-import receptor, Karyopherin-{beta}2, which promotes their cytoplasmic accumulation in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with hnRNPA2B1 to include a severe, early-onset disease reminiscent of OPMD, caused by a distinct class of frameshift variants that alter its nucleocytoplasmic transport dynamics.


title: Seroprevalence of anti-SARS-CoV-2 antibodies among school and daycare children and personnel: Protocol for a cohort study in Montreal, Canada

abstract:
BackgroundFurther evidence is needed to understand the contribution of schools and daycares to the spread of COVID-19 in the context of diverse transmission dynamics and continually evolving public health interventions. The Enfants et COVID-19: Etude de seroprevalence (EnCORE) study will estimate the seroprevalence and seroconversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among school and daycare children and personnel. In addition, the study will examine associations between seroprevalence and socio-demographic characteristics and reported COVID-19 symptoms and tests, and investigates changes in health, lifestyle and well-being outcomes.

MethodsThis study includes children and personnel from 62 schools and daycares in four neighbourhoods in Montreal, Canada. All children age 2-17 years attending one of the participating schools or daycares and their parents are invited to participate, as well as a sample of personnel members. Participants respond to brief questionnaires and provide blood samples, collected via dried blood spot (DBS), at baseline (October 2020-March 2021) and follow-up (May-June 2021). Questionnaires include socio-demographic and household characteristics, reported COVID-19 symptoms and tests, potential COVID-19 risk factors and prevention efforts, and health and lifestyle information. Logistic regression using generalized estimating equations will be used to estimate seroprevalence and seroconversion, accounting for school-level clustering.

DiscussionThe results of the EnCORE study will contribute to our knowledge about SARS-CoV-2 transmission in schools and daycares, which is critical for decisions regarding school attendance and the management of school outbreaks through the remainder of this school year and beyond.


title: Comorbidity Risk Factors Contributing to COVID-19 Related Deaths in Florida, March 1, 2020-January 16, 2021

abstract:
ObjectivesTo assess the association of specific comorbid conditions to COVID-19 deaths in Florida among decedents 16 to 64 years of age.

MethodsThis report uses Florida vital statistics death data over the period of March 1, 2020 through January 16, 2021, to estimate the effects of comorbid conditions on COVID-19 mortality for decedents 16 to 64 years of age. All cases of COVID-19 death occurring in Florida, regardless of resident status, were evaluated. The comorbidities, or contributing causes of death, identified in this report include Down syndrome, asthma, diabetes, pulmonary fibrosis, obesity, dementia, immunodeficiency, kidney disease, chronic obstructive pulmonary disease, hypertension, heart disease, and chronic liver disease and cirrhosis. The study uses a binary logistic regression to examine the relationship between COVID-19 and non-COVID-19 death and contributing causes of death based on information in the death record. Odds ratios were calculated as a residual of the logistic regression.

ResultsAmong COVID-19 deaths, Down syndrome was 15.26 times more likely to be a contributing cause of death compared to non-COVID-19 deaths followed by asthma (OR 7.74), diabetes (OR 6.11), pulmonary fibrosis (OR 5.13), obesity (OR 4.66), dementia (OR 4.51), immunodeficiency (OR 2.49), and kidney disease (OR 2.13). Chronic liver disease and cirrhosis (OR 0.95) and cancer (OR 0.79) had lower odds of being a contributing cause of death.

ConclusionsHeart disease, chronic liver disease and cirrhosis, and cancer were not risk factors for death from COVID-19 among decedents. Additional studies are needed to elucidate associations between race/ethnicity, socioeconomic status, and behavioral factors.

category: infectious diseases


title: #AstraZeneca vaccine disinformation on Twitter

abstract:
We analyzed 50,080 tweets about # AstraZeneca in English from 2021. We found that the news most common in the frequently retweeted tweets abound in negative information, and in many cases come from media sources well-known for disinformation. Also, we found that RT, a Russian state-sponsored news website, as well as Al Arabiya, a Saudi-owned news website, are frequently retweeted with information about the vaccine. Our analysis identified large coordination networks involved in political astroturfing and vaccine diplomacy in South Asia but also vaccine advocacy networks associated with European Commission employees. Our results show that Twitter discourse about # AstraZeneca is filled with disinformation and bad press, and may be distributed not only organically by anti-vaxxer activists, but also systematically by professional sources.

HighlightsO_LIMost commonly retweeted media news links abound in negative information
C_LIO_LIWell established disinformation media sources are retweeted more
C_LIO_LIState coordinated networks are active in # AstraZeneca astroturfing
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category: health informatics


title: Randomized, Comparative, Clinical Trial to Evaluate Efficacy and Safety of PNB001 in Moderate COVID-19 Patients

abstract:
ABSTARCTO_ST_ABSObjectiveC_ST_ABSTo evaluate the efficacy and safety of PNB001 a CCK-A agonist and CCK-B antagonist, a new chemical entity with anti-inflammatory and immune stimulation properties, along with Standard of Care (SOC) in patients with moderate COVID-19 infection.

DesignMulti-center, randomized, parallel group, comparative, open label study.

SettingTwo tertiary-care hospitals in India.

ParticipantsPatients with laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) within 2 days of randomization, having pneumonia with no signs of severe disease (severe disease means SpO2[≤]94% on room air), and any two of the following signs or symptoms suggestive of COVID-19: fever, cough, dyspnea, or hypoxia.

InterventionsPatients were randomized 1:1 to receive PNB001 at an oral dose of 100 mg three times daily for 14 days with Standard of Care (PNB001+SOC) or only SOC.

Main outcome measuresThe primary endpoints were mean change in the 8-point WHO Ordinal Scale score from baseline by Day 14 and mortality rate by Day 28. The key secondary endpoints were percentage of patients showing change in clinical status using the ordinal scale, improvement in inflammatory segments in X-ray chest, reduction of days of hospitalization, duration of supplemental oxygen use, days to negative PCR for COVID-19 and change in inflammation markers Interlukin-6 (IL6) and C-reactive protein (CRP) from baseline by Day 14.

ResultsA total of 40 (20 in PNB 001+SOC arm and 20 in SOC arm) patients were randomized and received treatment. The primary endpoint showed significant clinical improvement from baseline to Day 14 with PNB001+SOC (0.22 Vs 1.12; P=0.0421). One patient in PNB001+SOC arm and two patients in SOC arm died (1 Vs 2; HR: 2.0 [95%CI=0.18, 22.05]; P=0.5637) by Day 28. At the end of the treatment by Day 14, more patients achieved zero ordinal scale in PNB001+SOC arm (17 Vs 12; P=0.0766). In the PNB001+SOC arm, change in mean chest X-ray score showed significant improvement (2.05 Vs 1.16; P=0.0321), and more patients quickly showed complete improvement (10 Vs 7; HR: 1.48 [95%CI=0.64, 3.44]; P=0.4309). In the PNB001+SOC arm, patients needed shorter duration of hospitalization in days (9.45 Vs 9.80) and more patients attained earlier discharge from the hospital (19 Vs 15; P=0.0486) with respect to days. The mean duration of supplemental oxygen requirement in days was shorter (5.45 Vs 7.10) and complete withdrawal from supplemental oxygen was more frequent with PNB001+SOC compared to SOC by Day 14 (17 Vs 13; P=0.1441). All patients in both the arms had negative PCR by the end of the study (18 Vs 17; P=0.6265) by similar time (7.6 Vs 7.0). Exploratory analysis done for IL-6, CRP, Neutrophil-Lymphocyte-Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Erythrocyte Sedimentation Rate (ESR) showed statistically significant reduction by Day 14 demonstrating PNB001s anti-inflammatory and immunomodulatory properties. Lymphocyte and neutrophil counts also improved by Day 14. 11 adverse events (AE) in 8 patients were observed with PNB001+SOC compared to 13 AEs in 10 patients with SOC; none of the AEs in PNB001+SOC arm were related to PNB001. The most common AE were tachycardia and acute respiratory distress syndrome; there were isolated cases of hepatic enzyme elevation and hyperglycemia. Overall, safety profile was similar between PNB001+SOC and SOC arms.

ConclusionsPNB001 with standard of care showed significant clinical improvement in moderate COVID-19 patients when compared to standard of care and was well tolerated by moderate COVID-19 patients.

Trial RegistrationCTRI/2020/10/028423


title: Multiplex Fragment Analysis Identifies SARS-CoV-2 Variants

abstract: The rapid spread of SARS-CoV-2 Variants of Concern (VOC) necessitates systematic efforts for epidemiological surveillance. The current method for identifying variants is viral whole genome sequencing (WGS). Broad clinical adoption of sequencing is limited by costly equipment, bioinformatics support, technical expertise, and time for implementation. Here we describe a scalable, multiplex, non-sequencing-based capillary electrophoresis assay to affordably screen for SARS-CoV-2 VOC.


title: Association between physical-activity trajectories and cognitive decline in adults 50 years of age or older

abstract:
ObjectivesTo investigate the associations of physical-activity trajectories with the level of cognitive performance and its decline in adults 50 years of age or older.

MethodsWe studied 38729 individuals (63 {+/-} 9 years; 57% women) enrolled in the Survey of Health, Ageing and Retirement in Europe (SHARE). Physical activity was self-reported and cognitive performance was assessed based on immediate recall, verbal fluency, and delayed recall. Physical-activity trajectories were estimated using growth mixture modelling and linear mixed effects models were used to investigate the associations between the trajectories and cognitive performance.

ResultsThe models identified two physical-activity trajectories of physical activity: constantly-high physical activity (N=27634: 71%) and decreasing physical activity (N=11095; 29%). Results showed that participants in the decreasing physical-activity group exhibited a lower level of cognitive performance compared to the high physical-activity group (immediate recall: {beta}=0.94; 95% confidence interval [CI]=0.92 to 0.95; verbal fluency: {beta}=0.98; 95% CI=0.97 to 0.98; delayed recall: {beta}=0.95; 95% CI=0.94 to 0.97). Moreover, compared with participants in the constantly-high physical-activity group, participants in the decreasing physical-activity group showed a steeper decline in all cognitive measures (immediate recall: {beta}=-0.04; 95% CI=-0.05 to -0.04; verbal fluency: {beta}=-0.22; 95% CI=-0.24 to -0.21; delayed recall: {beta}=-0.04; 95% CI=-0.05 to -0.04).

ConclusionsPhysical-activity trajectories are associated with the level and evolution of cognitive performance in adults over 50 years. Specifically, our findings suggest that a decline in physical activity over multiple years is associated with a lower level and a steeper decline in cognitive performance.


title: The CADM2 gene and behavior: A phenome-wide scan in UK-Biobank

abstract: This phenome-wide association study examined SNP and gene-based associations of the CADM2 gene with 242 psycho-behavioral traits (N=12,211-453,349). We found significant associations with 51 traits, many more than for other genes. We replicated previously reported associations with substance use, risk-taking, and health behavior, and uncovered novel associations with sleep and dietary traits. Accordingly, CADM2 is involved in many psycho-behavioral traits, suggesting a common denominator in their biology.


title: Human Leukocyte Antigen-C and Haplotypes: Associations with Resistance and Susceptibility to HIV-1 Infection among Serodiscordant Couples in Nigeria

abstract:
INTRODUCTIONThe Human Leucocyte Antigen (HLA) class-1 is known to play a significant role in mediating resistance or susceptibility to HIV infection in the clinical course of AIDS. Recent studies have identified HLA-C as a key molecule that affects HIV disease progression. However, the role of HLA class 1 in heterosexual HIV-1 susceptibility or resistance in serodiscordant couples is not known in Nigeria. Therefore, this study evaluated the association between HLA-C susceptibility and resistance in HIV-1 transmission amongst heterosexual serodiscordant couples in Nigeria.

METHODSA total of 271 serodiscordant, concordant HIV positive and negative couples who gave informed consent were enrolled into this study. Extracted genomic DNA was sequenced for high resolution HLA-C class 1 genotypes using allele-specific primers (on exons 2 and 3) for HLA-C sequencing and typing.

RESULTSThe highest frequency distribution of high-resolution HLA-C alleles observed in the HIV positive subjects were: HLA-C*040101 178 (35.0%) followed by C*0701 124 (24.9%) compared with HIV negative subjects: C*040101 108(39.0%) followed by C*0701 64(24.7%). Alleles C*070201 (OR = 4.19, P<0.05) and C*0804 (OR = 3, P<0.045) were found to be independently associated with HIV-1 susceptibility in the cohort of serodiscordant couples. HLA-C*0802 (OR=0.5. P<0.005) and C*0304 (OR=0.34. P<0.002) were significantly associated with HIV-1 resistance to HIV-1 infection among the cohort.

CONCLUSIONThe result has contributed to the importance of how host HLA-C genetic factors can influence HIV-1 disease susceptibility (HLA-C*070201; C*0804) and resistance (HLA-C*0802; C*0304) in serodiscordant couples. This information may contribute to the development of future effective HIV vaccine in Nigeria.

category: hiv aids