title: Type 2 Diabetes and Risk of Early-Onset Colorectal Cancer

abstract:
ObjectiveEarly-onset colorectal cancer (CRC) is increasing in many developed countries. Type 2 diabetes mellitus has increased substantially in younger adults; however, its role in early-onset CRC remains unidentified.

DesignWe conducted a claims-based nested case-control study using IBM(R) MarketScan(R) Commercial Database (2006-2015). Incident early-onset CRC diagnosed at ages 18-49 were identified by ICD-9-CM diagnosis code, and the first coded diagnostic pathology date was assigned as the index date. Controls were frequency matched with cases. Type 2 diabetes, stratified by severity, was identified through ICD-9-CM using the Klabunde algorithm. Multivariate logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (Cls).

ResultsA total of 6001 early-onset CRC and 52104 controls were included. Type 2 diabetes was associated with an increased risk of early-onset CRC (5.0% in cases vs. 3.7% in controls; OR 1.24; 95% CI 1.09 to 1.41). The positive association was more pronounced for uncontrolled (OR 1.37; 95% CI 1.12 to 1.67) or complicated (OR 1.59; 95% CI 1.08-2.35) type 2 diabetes compared to controlled diabetes (OR 1.13; 95% CI 0.94 to 1.36). The positive association was driven by proximal (OR 1.35; 95% CI 1.03 to 1.77) and distal (OR 1.67; 95% CI 1.30 to 2.15) colon cancer but not rectal cancer.

ConclusionsIndividuals with type 2 diabetes have a higher risk of early-onset CRC, with stronger associations for uncontrolled/complicated diabetes. The rising prevalence of type 2 diabetes among younger adults in the US may partially contribute to the increasing incidence of early-onset CRC.

category: gastroenterology


title: Autoimmune profiling suggests paraneoplastic etiology in pediatric ROHHAD

abstract: ROHHAD (Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation) is a rare, yet severe pediatric disorder resulting in hypothalamic dysfunction and frequent sudden death. Genetic and other investigations have failed to identify an etiology or diagnostic test. Frequent co-occurrence of neuroblastic tumors (NTs) and cerebrospinal fluid inflammation point to an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Here, we screened antibodies from a curated cohort of ROHHAD patients (n=9) and controls (n=150) using a programmable phage display of the human peptidome (PhIP-Seq). Our ROHHAD cohort exhibited frequent association with NTs (8/9) and features consistent with autoimmune etiology. Autoantibodies to Zinc finger and SCAN domain-containing protein 1 (ZSCAN1) were discovered and orthogonally validated in 7 of 9 ROHHAD patients, all of whom had NTs, and shown to be absent in non-ROHHAD pediatric patients with NTs. Notably, human ZSCAN1 expression was confirmed in ROHHAD tumor and healthy human hypothalamus. Our results support the notion that tumor-associated ROHHAD is a pediatric PNS, potentially initiated by an immune response to peripheral NT. ZSCAN1 autoantibodies may aid in an accurate diagnosis of ROHHAD, thus providing a means toward early detection and treatment. Lastly, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches in addition to the classical rodent-based approaches for detecting novel PNS subtypes.

category: pediatrics


title: The Relative Importance of Mindfulness Facets in Chronic Pain: Relations to the General Negative Affect, Depression, Anxiety, and Obsessive-Compulsive Symptoms

abstract:
ObjectivesThis study had three objectives: first, to investigate the relative importance of the five mindfulness facets to negative affect (NA) among patients with chronic musculoskeletal pain; second, to test the hypothesis that observing is associated with lower NA only if occurs in an accepting manner; and third, to investigate the relation between mindfulness and obsessive-compulsive symptoms (OCS).

MethodsOne hundred and nineteen patients with chronic musculoskeletal pain filled the Five-Facets Mindfulness Questionnaire (FFMQ), the Depression, Anxiety, Stress Scale (DASS), and the Obsessive- compulsive Inventory-Revised (OCI-R). A latent variable was constructed to represent NA. Multiple regression analysis was conducted, and several indices of relative importance were calculated.

ResultsExcept for Observing, all mindfulness facets had significant bivariate and unique relation with NA. Acting with Awareness was the most important predictor, followed by Nonjudging and Describing. The contribution of Nonreactivity was small. Regarding the second objective, the Observing x Nonjudging and Observing x Nonreactivity interactions were not significant. Finally, the five facets of mindfulness explained about one-half of the variance in obsession and one-fifth of the variance in compulsion. After excluding the shared variance between obsession and compulsion, mindfulness was only related to obsession.

ConclusionsExcept for Observing, all mindfulness facets seem to have unique contributions to psychological symptoms; among them, Acting with Awareness seems most important. Current evidence is inconsistent in supporting the moderating role of acceptance in the influence of observing. Finally, in the context of OCS, it seems that mindfulness is more related to obsession than compulsion.

category: psychiatry and clinical psychology


title: The Relative Importance of Mindfulness Facets and Their Interactions: Relations to Psychological Symptoms in Chronic Pain


title: Early Epidemiological Evidence of Public Health Value of WA Notify, a Smartphone-based Exposure Notification Tool: Modeling COVID-19 Cases Averted in Washington State

abstract:
BackgroundSecure and anonymous smartphone-based exposure notification tools are recently developed public health interventions that aim to reduce COVID-19 transmission and supplement traditional public health suriveillance. We assessed the impact of Washington States exposure notification tool, WA Notify, in mitigating the spread of COVID-19 during its first four months of implementation.

MethodsDue to the constraints of privacy-preservation, aggregate metrics and disparate data sources were utilized to estimate the number of COVID-19 cases averted based on a modelling approach adapted from Wymant et al (2021) using the following parameters: number of notifications generated; the probability that a notified individual goes on to become a case; expected fraction of transmissions preventable by strict quarantine after notification; actual adherence to quarantine; and expected size of the full transmission chain if a contact had not been notified.

ResultsThe model was run on a range of secondary attack rates (5.1%-13.706%) and quarantine effectiveness (53% and 64%). Assuming a 12.085% secondary attack rate and 53% quarantine effectiveness, the model shows that 5,500 cases (central 95% range of sensitivity analyses 2,800-8,200) were averted statewide during the first four months of its implementation. Based on an estimated COVID-19 case fatality of 1.4%, WA Notify saved 40-115 lives during the study period.

ConclusionsThese findings demonstrate the value of exposure notification tools as a novel public health intervention to mitigate the spread of COVID-19 in the U.S. As new variants emerge and non-essential travel bans are lifted, exposure notification tools may continue to play a valuable role in limiting the spread of COVID-19.

category: public and global health


title: Sociodemographic factors associated with Public knowledge of dementia in a Cuban population

abstract:
ObjectivesTo explore knowledge and beliefs among a cross-section of the Cuban adult population with regard to dementia risk factors and to determine the demographic variables related with it.

Study designA cross-sectional survey was carried out on 1004 Cubans.

MethodsThe survey measured the importance placed on dementia, risk reduction knowledge and the actions to prevent it. Logistic regression was undertaken to identify variables associated with knowledge.

ResultsMost respondents (47.5%) believe that dementia risk reduction should start before age of 40. Cognitive stimulation and physical activities were selected with major frequency. Being older than 48 years, having previous contact with dementia and university education increases the probability of having healthy lifestyles.

ConclusionsThe exploration of demographic variables allows the prediction of likelihood to know about or have positive beliefs in relation to dementia. They should be contemplated into strategies for dementia prevention in Cuban population.


title: Self-reported adaptability among postgraduate dental learners and their instructors: accelerated change induced by COVID-19

abstract:
It is forecasted that the skills and competencies necessary for post-pandemic success in higher education need to be founded upon adaptability, coping, and Self-regulated Learning (SRL). It is worth investigating how stakeholders perceived their adaptability and coping with the accelerated change accompanying COVID-19. Accordingly, the purpose of this study was to assess the self-reported adaptability of postgraduate dental learners and their instructors in the context of abrupt transition to distance learning induced by the pandemic.

This study utilized a convergent mixed methods study design. The qualitative and quantitative data were concurrently collected from instructors and learners. The datasets were analyzed independently, and the generated information was integrated using a joint model analysis.

The percentage of average of self-reported adaptability of both groups was 81.15%. The instructors, with a mean of satisfaction of 17.94 ({+/-}1.76), rated their adaptability significantly higher than the learners, with a mean of satisfaction of 15.66 ({+/-}2.77) (p=0.002). The thematic analysis resulted in two interrelated themes: Self and Environment. Within the Self theme, three subthemes surfaced: Cognitions, Emotions, Behaviors. As for the Environment theme, it encapsulated two subthemes: Enablers and Impediments.

The stakeholders perceived themselves to have adapted well to the transition, and SRL appeared as a cornerstone in the adaptation to the accelerated change (accompanying COVID-19). There appeared to be an interplay between the cognitions, emotions, and behaviors on the level of the self as part of the adaptation process. Also, building upon existent models of SRL, this study uncovered that the stakeholders considered the environment to play a crucial role in their adaptation process. This highlights the importance of developing a climate that remains, despite external pressures, conducive to attaining learning and teaching goals. It is also crucial for university-level mental health promotion activities to proactively foster, among learners and instructors, adaptability, building  academic resilience.

category: medical education


title: Caregiver Perspectives of Pre-Transplant Evaluation in Children

abstract: Pre-transplant evaluation is mandated by Centers for Medicare and Medicaid Services, but there is wide institutional variation in implementation, and the family experience of the process is incompletely understood. Current literature largely focuses on adult transplant recipients. This qualitative study begins to fill the knowledge gap about family experience of the pre-transplant evaluation for children through interviews with caregivers at a large pediatric transplant center. Prominent themes heard from caregivers include (1) the pre-transplant evaluation is overwhelming and emotional, (2) prior experiences and background knowledge frame the evaluation experience, and (3) frustration with communication among teams is common. These findings are relevant to efforts by transplant centers to optimize information delivery, minimize concrete barriers, and address healthcare systems issues.

category: nephrology


title: Socioeconomic Status, Biological Aging, and Memory in a Diverse National Sample of Older US Men and Women

abstract:
ImportanceExposure to socioeconomic disadvantage is associated with rapid cognitive aging. Biological aging, the progressive loss of system integrity that occurs as we age is proposed as a modifiable process mediating this health inequality.

ObjectiveTo test the hypothesis that socioeconomic disparities in cognitive aging in older adults is explained by accelerated biological aging.

DesignObservational cohort study.

SettingU.S. Health and Retirement Study DNA-methylation sub-study.

ParticipantsN=3,648 (49% male) adults aged 50-100 (M=70, SD=10) with DNA methylation data.

ExposuresSocioeconomic status (SES) was measured from years of education and household wealth. The extent and pace of biological aging were quantified using three DNA-methylation measures: PhenoAge, GrimAge, and DunedinPoAm.

Main Outcomes and MeasuresCognitive aging was measured from repeated longitudinal assessments of immediate and delayed word recall. Latent growth curve modeling estimated participants level of memory performance and rate of decline over 2-11 follow-up assessments spanning 2-20 years. Models were estimated to assess whether the relationship between SES and memory trajectories was mediated by biological aging.

ResultsOlder adults with lower SES had lower memory performance, faster decline and exhibited accelerated biological aging (SES {beta}=.33, 99% CI[.30-.36], biological-aging measure effect size associations ranged from .08 to .20). Accelerated biological aging was associated with decreased memory performance and faster memory decline (effect-size range .03 to .18). Higher SES was associated with slower biological aging for White and Black men and women, but not Latinx participants. The relationship between biological aging measures and memory was weaker for Black and Latinx participants compared with White people. In mediation analysis, biological aging accounted for 3-9% of the SES-memory gradient in White participants. There was no evidence of mediation in Black or Latinx participants.

Conclusions and RelevanceAmong a national sample of older adults, DNA-methylation measures of biological aging were associated with memory trajectories in White, but not Black or Latinx older adults. These results challenge the assumption that DNA-methylation biomarkers of aging that were developed in primarily White people can quantify aging processes affecting cognition in Black and Latinx older adults.

category: neurology


title: Biallelic and de novo variants in ATP6V0A1 cause progressive myoclonus epilepsy and developmental and epileptic encephalopathy

abstract: The vacuolar H+-ATPase is a large multi-subunit proton pump, composed of an integral membrane V0 domain, involved in proton translocation, and a peripheral V1 domain, catalysing ATP hydrolysis. This complex is widely distributed on the membrane of various subcellular organelles, such as endosomes and lysosomes, and plays a critical role in cellular processes ranging from autophagy to protein trafficking and endocytosis. Variants in ATP6V0A1, the brain-enriched isoform in the V0 domain, have been recently associated with developmental delay and epilepsy in four individuals. Here we identified 17 individuals from 14 unrelated families with both with new and previously characterised variants in this gene, representing the largest cohort to date. Five affected subjects with biallelic variants in this gene presented with a phenotype of early-onset progressive myoclonus epilepsy with ataxia, while 12 individuals carried de novo missense variants and showed severe developmental and epileptic encephalopathy. The R740Q mutation, which alone accounts for almost 50% of the mutations identified among our cases, leads to failure of lysosomal hydrolysis by directly impairing acidification of the endolysosomal compartment, causing autophagic dysfunction and severe developmental defect in C. elegans. Altogether, our findings further expand the neurological phenotype associated with variants in this gene and provide a direct link with endolysosomal acidification in the pathophysiology of ATP6V0A1-related conditions.


title: Prevalence of laboratory-related musculoskeletal disorders among biomedical scientists

abstract:
BackgroundLaboratory-related musculoskeletal disorders (LMSDs) are injuries resulted from working in the laboratory. Biomedical scientists (BMSs) play an important role in any health care system. However, they are at high risk of exposure to LMSDs. This study aimed to estimate the prevalence and the associated risk factors of LMSDs among this group of healthcare professionals.

MethodsA cross-sectional survey (Nordic musculoskeletal) was used to estimate the prevalence of LMSDs among BMSs. Data were analyzed using Statistical Package for Social Science software version 25. Chi-square was performed to find the significant association between LMSDs and different risk factors.

ResultsThe study included 83 BMSs. Females represented 63.9% and 36.1% were in the age group of 35-44. The overall prevalence of LMSDs was 77.1%. The most prevalent LMSDs were neck, shoulders, and lower back with 50.6%, 49.4%, and 43.4%, respectively. Neck complaints and upper back complaints were found statistically significant with the female gender. Shoulders complaints were associated with pipetting and microscopy. Lower back complaints were associated with pipetting and heavy work at home. A total of 65.57% of BMSs had irregular symptoms of LMSDs, 54.10% experienced moderate pain due to these symptoms, and 44.26% had symptoms that persisted from hours to days.

ConclusionThe study found that the prevalence of LMSDs among BMSs was high. Good knowledge, attitude, practice, and training of ergonomics may minimize the prevalence of LMSDs among BMSs.

category: occupational and environmental health


title: Genome-wide gene-air pollution interaction analysis of lung function in 300,000 individuals

abstract:
Impaired lung function is predictive of mortality and is a key component in the diagnosis of chronic obstructive pulmonary disease. Lung function has a strong genetic component but is also affected by environmental factors such as increased exposure to air pollution. How genetic factors and air pollution interact to affect lung function is however less understood.

We conducted a genome-wide gene-air pollution interaction analysis of spirometry measures with three measures of air pollution at home address: particulate matter (PM2.5 & PM10) and nitrogen dioxide (NO2), in approximately 300,000 unrelated European individuals from UK Biobank. We explored air pollution interactions with previously identified lung function signals and determined their combined interaction effect using a polygenic risk score (PRS).

We identified seven genome-wide interaction signals (P < 5 x 10-8), and a further ten suggestive interaction signals (P < 5 x 10-7). We found statistical evidence of interaction with PM2.5 for previous lung function signal, rs10841302, near AEBP2, suggesting increased susceptibility of FEV1/FVC to PM2.5, as copies of the G allele increased (interaction beta: -0.073 percentage points, 95%CI: -0.105, -0.041). There was no observed interaction between air pollutants and the weighted genetic risk score.

We carried out the largest genome-wide gene-air pollution interaction study of lung function and identified effects of clinically relevant size and significance. We observed up to 440ml lower lung function for certain genotypes associated with mean levels of outdoor air pollution at baseline, which is approximately equivalent to nine years of normal loss of lung function.


title: Anti-spike protein receptor-binding domain IgG levels after COVID-19 infection or vaccination against SARS-CoV-2 in a seroprevalence study

abstract:
PurposeIn a country-wide seroprevalence study of COVID-19 in Estonia we aimed to determine the seroprevalence and the dynamics of IgG against SARS-CoV-2 after vaccination or positive PCR-test.

MethodsLeftover blood samples were selected between February 8 to March 25, 2021, by SYNLAB Estonia from all counties and age groups (0-9, 10-19, 20-59, 60-69, 70-79, 80-100 years) proportionally to the whole Estonian population and tested for IgG against SARS-CoV-2 spike protein receptor-binding domain (anti-S-RBD IgG) using Abbott SARS-CoV-2 IgG II Quant assay. Antibody levels after positive PCR-test or vaccination were described by nonlinear model.

ResultsA total of 2517 samples were tested. Overall seroprevalence (95% CI) was 20.1% (18.5-21.7%), similar in all age groups. If all individuals vaccinated with the first dose at least 14 days before antibody measurement were assumed to be seronegative, the overall seroprevalence was 15.8% (14.4-17.3%), 4-fold larger than the proportion of confirmed COVID-19 cases. According to nonlinear models, age increased anti-S-RBD IgG production after positive PCR-test but decreased after vaccination. The peak of anti-S-RBD IgG in a 52-year-old (median age of PCR-positive and/or vaccinated individuals) was significantly higher after vaccination compared with positive PCR-test (22082 (12897...26875) vs 6732 (2321...8243) AU/mL), but half-life was similar (26.5 (6.9...46.1) vs 38.3 (8.2...68.5) days).

ConclusionOne year after the start of COVID-19 pandemic the actual prevalence of infection is still underestimated compared with confirmed COVID-19 cases, underlining the importance of seroepidemiological studies. Older individuals have lower anti-S-RBD IgG level after vaccination, but similar decline rate to younger.

category: infectious diseases


title: Highly sensitive scent-detection of COVID-19 patients in vivo by trained dogs

abstract: Timely and accurate diagnostics are essential to fight the COVID-19 pandemic, but no test satisfies both conditions. Dogs can scent-identify the unique odors of the volatile organic compounds generated during infection by interrogating specimens or, ideally, the body of a patient. After training 6 dogs to detect SARS-CoV-2 in human respiratory secretions (in vitro scent-detection), we retrained 5 of them to diagnose the infection by scenting the patient directly (in vivo scent-detection). Then, efficacy trials were designed to compare the diagnostic performance of the dogs against that of the rRT-PCR in 848 human subjects: 269 hospitalized patients (COVID-19 prevalence 30.1%), 259 hospital staff (prevalence 2.7%), and 320 government employees (prevalence 1.25%). The limit of detection in vitro was lower than 10-12 copies ssRNA/mL. In vivo, all dogs detected 92 COVID-19 patients present among the 848 study subjects. Detection was immediate, and independent of prevalence, time post-exposure, or presence of symptoms, with 95.2% accuracy and high sensitivity (95.9%; 95% C.I. 93.6-97.4), specificity (95.1%; 94.4-95.8), positive predictive value (69.7%; 65.9-73.2), and negative predictive value (99.5%; 99.2-99.7). To determine real-life performance, we waited 75 days to carry out an effectiveness assay among the riders of the Metro System of Medellin, deploying the human-canine teams without previous training or announcement. Three dogs (one of each breed) scent-interrogated 550 citizens who volunteered for simultaneous canine and rRT-PCR testing. Negative predictive value remained at 99.0% (95% C.I. 98.3-99.4), but positive predictive value dropped to 28.2% (95% C.I. 21.1-36.7). Canine scent-detection in vivo is a highly accurate screening test for COVID-19, and it detects more than 99% of infected individuals independently of the key variables. However, real-life conditions increased substantially the number of false positives, indicating the necessity of training a threshold for the limit of detection to discriminate environmental odoriferous contamination from infection.


title: The efficacy and safety of monoclonal antibody treatments against COVID-19: A systematic review and meta-analysis of randomized clinical trials

abstract:
ObjectivesThe use of monoclonal antibody for COVID-19 showed conflicting results in prior studies and its efficacy remains unclear. We aimed to comprehensively determine the efficacy and safety profile of monoclonal antibodies in COVID-19 patients.

MethodsSixteen RCTs were analyzed using RevMan 5.4 to measure the pooled estimates of risk ratios (RRs) and standardized mean differences (SMDs) with 95% CIs.

ResultsThe pooled effect of monoclonal antibodies demonstrated mortality risk reduction (RR=0.89 (95%CI 0.82-0.96), I2=13%, fixed-effect). Individually, tocilizumab reduced mortality risk in severe to critical disease (RR=0.90 (95%CI 0.83-0.97), I2=12%, fixed-effect)) and lowered mechanical ventilation requirements (RR=0.76 (95%CI 0.62-0.94), I2=42%, random-effects). Moreover, it facilitated hospital discharge (RR=1.07 (95%CI 1.00-1.14), I2=60%, random-effects). Meanwhile, bamlanivimab-etesevimab and REGN-COV2 decrease viral load ((SMD=-0.33 (95%CI -0.59 to -0.08); (SMD=-3.39 (95%CI -3.82 to -2.97)). Interestingly, monoclonal antibodies did not improve hospital discharge at day 28-30 (RR=1.05 (95%CI 0.99-1.12), I2=71%, random-effects) and they displayed similar safety profile with placebo/standard therapy (RR=1.04 (95%CI 0.76-1.43), I2=54%, random-effects).

ConclusionTocilizumab improved hospital discharge and reduced mortality as well as the need for mechanical ventilation, while bamlanivimab-etesevimab and REGN-COV2 reduced viral load in mild to moderate outpatients. In general, monoclonal antibodies are safe and should be considered in severe to critical COVID-19 patients.

RegistrationPROSPERO (CRD42021235112)


title: SARS-CoV-2 Seroprevalence Among Firefighters in Los Angeles, California

abstract:
ObjectiveWe estimate the seroprevalence of SARS-CoV-2 antibodies among firefighters in the Los Angeles, California fire department in October 2020 and compare demographic and contextual factors for seropositivity.

MethodsWe conducted a serologic survey of firefighters in Los Angeles, California, USA, in October 2020. Individuals were classified as seropositive for SARS-CoV-2 if they tested positive for immunoglobulin G, immunoglobulin M, or both. We compared demographic and contextual factors for seropositivity.

ResultsOf 713 participants, 8.9% tested positive for SARS-CoV-2 antibodies. Seropositivity was not associated with gender, age, or race/ethnicity. Furthermore, firefighters who worked in zip codes with lower income or higher share of minority population did not have higher rates of SARS-CoV-2 infection. Seropositivity was highest among firefighters who reported working in the vicinity of Los Angeles International Airport, which had a known outbreak in July 2020.

ConclusionsSeroprevalence among firefighters was no higher than seroprevalence in the general population, suggesting that workplace safety protocols, such as access to PPE and testing, can mitigate increased risk of infection at work. Workplace safety protocols for firefighters also eliminated differences in disease burden by geography and race/ethnicity observed in the general population.


title: The Effect of Pandemic Prevalence on the Reported Efficacy of SARS-CoV-2 Vaccine Candidates: A Systematic Review and Meta-analysis

abstract:
ImportanceThe efficacy of SARS-CoV-2 vaccine candidates reported in Phase 3 trials varies from [~]45% to [~]95%. It is important to explain the reasons for this heterogeneity.

ObjectiveTo test the hypothesis that the efficacy of SARS-CoV-2 vaccine candidates falls with increasing prevalence of the COVID-19 pandemic.

Data SourcesClinicalTrials.gov, WHO, McGill and LSHTM trackers of COVID-19 candidate vaccines, peer reviewed publications, and press releases were searched until March 31st, 2021.

Study SelectionAll RCTs reporting efficacy outcomes from Phase 3 trials till March 31st, 2021 were included. Of the 11 vaccine candidates that had started their Phase 3 trials by November 1, 2020. Phase 3 efficacy outcomes were available for 8 vaccine candidates. (PROSPERO CRD42021243121).

Data Extraction and SynthesisBoth authors independently extracted the data required from identified sources, using PRISMA guidelines. The analysis included all RCTs reported in peer reviewed publications and publicly available sources. A random effects model with restricted maximum likelihood estimator was used to summarize the treatment effects. Cochrane Risk of Bias Assessment Tool was used to assess risk of bias. Certainty of evidence was assessed using the GRADE tool.

Main Outcomes and MeasuresSARS-CoV-2 infections per protocol in vaccine and placebo groups, risk ratio, prevalence of the COVID-19 infection rate in the populations where the Phase 3 trials were conducted.

Results8 vaccine candidates had reported efficacy data from a total of 20 independent Phase 3 trials, representing a total of 221,968 subjects, 453 infections across the vaccinated groups and 1,554 infections across the placebo groups. The overall estimate of the risk-ratio is 0.24 (95% CI, 0.17-0.34, p < 0.01), with an I2 statistic of 88.73%. The meta-regression analysis with pandemic prevalence as the moderator explains almost half the variance in risk ratios across trials (R2=49.06%, p<0.01).

Conclusion and RelevancePandemic prevalence explains almost half of the between-trial variance in reported efficacies. Efficacy of SARS-CoV-2 vaccine candidates declines as the pandemic prevalence increases.

Key PointsO_ST_ABSQuestionC_ST_ABSDoes the prevalence of the COVID-19 pandemic explain the heterogeneity in efficacies reported across Phase 3 trials of SARS-CoV-2 vaccine candidates?

FindingsAlmost 50% of the variance in efficacies reported across Phase 3 trials can be explained by differences in COVID-19 infection rate prevailing across trials. Efficacy of evaluated SARS-CoV-2 vaccine candidates falls significantly with increasing prevalence of the COVID-19 pandemic across trial sites.

MeaningEfficacy of SARS-CoV-2 vaccine candidates needs to be interpreted in conjunction with the prevalence of the COVID-19 pandemic. Adjustment for location-level prevalence analysis would provide better insights into the efficacy results of Phase 3 trials.


title: Factors influencing plasma galectin-3 concentrations in catheter-bearing hospitalized patients

abstract:
IntroductionCatheters are an integral part of modern medicine although their use is not without complications. Catheter-related infection triggers a strong inflammatory reaction and has been associated with high morbidity, mortality, and healthcare costs. The clinical diagnosis of catheter-related infection is made difficult by non-specific symptoms. Investigating the alterations in biochemical parameters related to infectious and inflammatory processes in these patients constitute an active line of research. The aim of this study was to investigate factors influencing the plasma concentration of galectin-3 in catheter-bearing patients and to explore its potential usefulness as an index for catheter-related infections.

MethodsCirculating concentrations of galectin-3, chemokine (C-C) motif ligand 2, procalcitonin and C-reactive protein were measured in 110 patients with a central venous catheter, 165 patients with a urinary catheter, and 72 control subjects.

ResultsCatheter-bearing patients had significantly higher concentrations of galectin-3 and the other markers than the control group. We identified chronic kidney disease as an independent determinant of plasma galectin-3 concentrations in patients with a central catheter, and serum creatinine concentration, cardiovascular disease and the number of days the catheter was indwelling as determinants in urinary catheter patients. We also found that measuring galectin-3 in urinary catheter patients with a catheter-related infection was more accurate for diagnosis than the other parameters. At galectin-3 = 15 ng/mL, sensitivity was 90%.

ConclusionWe conclude that measurement of galectin-3 concentration may be useful for assessing the inflammatory status of catheter-bearing patients and may contribute to the diagnosis of catheter-related infection in those with a urinary catheter.


title: SARS-CoV-2 variants of concern dominate in Lahore, Pakistan in April 2021

abstract:
BackgroundThe SARS-CoV-2 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Indian sub-continent. Pakistan has one of the world  s largest population, of over 200 million people and is experiencing a severe third wave of infections caused by SARS-CoV-2 that begun in March 2021.In Pakistan, during third wave until now only 12 SARS-CoV-2 genomes have been collected and among these 9 are from Islamabad. This highlights the need for more genome sequencing to allow surveillance of variants in circulation. In fact more genomes are available among travellers with a travel history from Pakistan, than from within the country itself.

MethodsFor a better understanding of the circulating variants in Lahore and surrounding areas with a combined population of 11.1 million, within a week of April 2021, 102 samples were sequenced. The samples were randomly collected from 2 hospitals with a diagnostic polymerase chain reaction (PCR) cutoff value of less than 25 cycles.

ResultsAnalysis of the lineages shows that B.1.1.7 (first identified in the UK, Alpha variant) dominates, accounting for 97.9% (97/99) of cases, with B.1.351 (first identified in South Africa, Beta variant) accounting for 2.0% (2/99) of cases. No other lineages were observed.

DiscussionIn depth analysis of the B.1.1.7 lineages indicates multiple separate introductions and subsequent establishment within the region. Eight samples were identical to genomes observed in Europe (7 UK, 1 Switzerland), indicating recent transmission. Genomes of other samples show evidence that these have evolved, indicating sustained transmission over a period of time either within Pakistan or other countries with low density genome sequencing. Vaccines remain effective against B.1.1.7, however the low level of B.1.351 against which some vaccines are less effective demonstrates the requirement for continued prospective genomic surveillance.


title: The effect of pre-anaesthetic assessment clinic: a systematic review of randomised and non-randomised prospective controlled studies

abstract:
ObjectivesThe aim of this systematic review was to examine the effectiveness of pre-anaesthetic assessment clinics (PACs) implemented to improve quality and patient safety in perioperative care.

DesignSystematic review.

Data sourcesThe electronic databases CINAHL Plus with Full Text (EBSCOhost), Medline, and Embase (OvidSP) were systematically searched from 1st April, 1996 to 4th February, 2021.

Eligibility criteriaThe main inclusion criterion was that the study, using empirical quantitative methods, addressed the effectiveness of PACs.

Data extraction and synthesisTitles, abstracts, and full texts were screened in duplicate by two authors. Risk of bias assessment, using the Joanna Briggs Institute critical appraisal checklist for quasi-experimental studies, and data extraction were performed by one author and checked by the other author. Results were synthesised narratively owing to the heterogeneity of the included studies.

ResultsSeven prospective controlled studies were conducted. Most studies had a high risk of bias. Three studies reported a significant reduction in the length of the hospital stay, and two studies reported a significant reduction in cancellation of surgery for medical reasons when patients were seen in the PAC. In addition, the included studies presented mixed results regarding anxiety in patients.

ConclusionThis systematic review demonstrated a reduction in the length of hospital stay and cancellation of surgery when the patients had been assessed in the PAC. There is a need for high-quality prospective studies to gain a deeper understanding of the effectiveness of PACs.

PROSPERO registration numberCRD42019137724

ARTICLE SUMMARYO_ST_ABSStrengths and Limitations of this studyC_ST_ABSO_LIOnly prospective studies were included in this systematic review.
C_LIO_LIThe systematic review was conducted in accordance with international guidelines.
C_LIO_LIOnly seven studies were identified, highlighting the need for further research on pre-anaesthetic assessment clinics.
C_LIO_LIOverall, the quality of the included studies was low, and the current practice possesses limited evidence base.
C_LI

category: anesthesia


title: Estimating Time-Dependent Disease Transmission Intensity using Reported Data: An Application to Ebola and Selected Public Health Problems

abstract: Obtaining reasonable estimates for transmission rates from observed data is a challenge when using mathematical models to study the dynamics of "infectious" diseases, like Ebola. Most models assume the transmission rate of a contagion does not vary over time. However, these rates do vary during an epidemic due to environmental conditions, social behaviors, and public-health interventions deployed to control the disease. Therefore, obtaining time-dependent rates can aid in understanding the progression of disease through a population. We derive an analytical expression using a standard SIR-type mathematical model to compute time-dependent transmission rate estimates for an epidemic in terms of either incidence or prevalence type available data. We illustrate applicability of our method by applying data on various public health problems, including infectious diseases (Ebola, SARS, and Leishmaniasis) and social issues (obesity and alcohol drinking) to compute transmission rates over time. We show that transmission rate estimates can have a large variation over time, depending on the type of available data and other epidemiological parameters. Time-dependent estimation of transmission rates captures the dynamics of the problem and can be utilized to understand disease progression through population accurately. Alternatively, constant estimations may provide unacceptable results that could have major public health consequences.

category: epidemiology


title: Ecological Analysis of the Temporal Trends in the Association of Social Vulnerability and Race/Ethnicity with County-Level COVID-19 Incidence and Outcomes in the United States

abstract:
BackgroundThe COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the U.S. initially, but the temporal trends during the year-long pandemic remain unknown.

ObjectiveWe examined the temporal association between the county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the U.S. in the year starting in March 2020.

MethodsCounties (n=3091) with [≥] 50 COVID-19 cases by March 6th, 2021 were included in the study. Associations between SVI (and its subcomponents) and county level racial composition with the incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time varying associations between weekly number of cases/deaths and SVI or racial composition. Data was adjusted for percentage of population aged [≥]65 years, state level testing rate, comorbidities using the average Hierarchical Condition Category (HCC) score, and environmental factors including average fine particulate matter (PM2.5), temperature and precipitation.

ResultsHigher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio [IRR] per-10 percentile increase:1.02, (95% CI 1.02, 1.03, p<0.001), and death per capita (1.04, (95% CI 1.04, 1.05, p<0.001). SVI became an independent predictor of incidence starting from March 2020, but this association became weak or insignificant by the winter, a period that coincided with a sharp increase in infection rates and mortality, and when counties with higher proportion of White residents were disproportionately represented ("third wave"). By Spring of 2021, SVI was again a predictor of COVID-19 outcomes. Counties with greater proportion of Black residents also observed similar temporal trends COVID-19-related adverse outcomes. Counties with greater proportion of Hispanic residents had worse outcomes throughout the duration of the analysis.

ConclusionExcept for the winter "third wave" when majority White communities had the highest incidence of cases, counties with greater social vulnerability and proportionately higher minority populations, experienced worse COVID-19 outcomes.

Article Summary/Strengths & LimitationsO_LIExamined full 12 months of county-level data in the US delineating the temporal trends in the association between social vulnerability index and COVID-19 outcomes
C_LIO_LIInvestigated COVID-19 outcomes in predominantly Black and Hispanic communities in comparison to White communities in the US
C_LIO_LIAnalysis is ecological, descriptive, and on the county-level rather than on an individual level
C_LIO_LIAnalysis adjusted for confounders including county level age [≥] 65, comorbidities, and environmental factors
C_LIO_LIAnalysis limited to the US
C_LI


title: Introduction and transmission of SARS-CoV-2 B.1.1.7 in Denmark

abstract: In early 2021, the SARS-CoV-2 lineage B.1.1.7 became dominant across large parts of the world. In Denmark, comprehensive and real-time test, contact-tracing, and sequencing efforts were applied to sustain epidemic control. Here, we use these data to investigate the transmissibility, introduction, and onward transmission of B.1.1.7 in Denmark. In a period with stable restrictions, we estimated an increased B.1.1.7 transmissibility of 58% (95% CI: [56%,60%]) relative to other lineages. Epidemiological and phylogenetic analyses revealed that 37% of B.1.1.7 cases were related to the initial introduction in November 2020. Continuous introductions contributed substantially to case numbers, highlighting the benefit of balanced travel restrictions and self-isolation procedures coupled with comprehensive surveillance efforts, to sustain epidemic control in the face of emerging variants.


title: Gut Bacterial Microbiome Profiles Associated with Colorectal Cancer Risk: A Systematic Review and Meta-Analysis

abstract:
ObjectiveRecent studies have shown a potential link between gut microbiome and colorectal cancer (CRC). Initially, a wide array of research into this topic was discovered from the past decade, illustrating a keen interest in the potential causal relationship between the gut microbiome and CRC. However, the cancer research community is lacking a summarised systematic review of this kind which aims to explore the evidence linking the human gut microbiome to risk of CRC.

DesignThis systematic review was carried out with two independent reviewers assessing the database outcomes from Medline and EMBASE during May 2020. A meta-analysis was undertaken studying the link between Helicobacter pylori and CRC; processed through Stata.

Results31 papers were included in the systematic review, followed by 12 for the meta-analysis. From these papers, Fusobacterium and Bacteroides were reported most frequently as enriched in CRC versus control. The meta-analysis showed an Odds Ratio of 1.49 (95% CI 1.19 - 1.86), including a total of 20,001 events. This meta-analysis concluded that H. pylori infection significantly increases the risk of CRC, albeit with evidence of publication bias.

ConclusionsBacteria have been discovered to increase the risk of CRC, however a definitive causal relationship cannot be concluded or excluded using case-control studies. To fully understand the potential link of the bacteria listed, alterations in research design and execution are required. The assessment found a need for a large-scale cohort study conducted over a significant period of time to thoroughly evaluate the potential relationship between gut microbiome and CRC risk.

O_TEXTBOXSignificance of studyWhat is already known on this subject?

[tpltrtarr]Roughly 10% of all cancer deaths in the UK are attributed to colorectal cancer (CRC), with CRC being the third most common cancer worldwide.
[tpltrtarr]The risk of developing CRC has been closely linked to the composition of the gut microbiome
[tpltrtarr]H. pylori is a known causative agent of gastric cancer

What are the new findings?

[tpltrtarr]To the best of the researchers knowledge, this is the first systematic review of this type conducted into this topic, investigating the genera/species of bacteria in the human gut microbiome and the risk of CRC.
[tpltrtarr]This systematic review found a strong association between Fusobacterium and Bacteroides, amongst other species, and CRC.
[tpltrtarr]The meta-analysis found a significant link between H. pylori infection and increased risk of CRC.

How might this impact on clinical practice in the foreseeable future?

[tpltrtarr]This systematic review provides potentially actionable evidence in the personalised management of patients to reduce their risk of CRC.
[tpltrtarr]This review has highlighted the need for a large population prospective cohort study, with standardised sampling methods.
[tpltrtarr]The meta-analysis reinforces the importance of H. pylori testing and eradication in those deemed at high risk of CRC

C_TEXTBOX


title: A Systematic Review and Meta-Analysis of the Mental Health Symptoms during the Covid-19 Pandemic in Southeast Asia

abstract:
AimsThe Covid-19 pandemic has had a substantial impact on the mental health of the general public and high-risk groups worldwide. Due to its proximity and close links to China, Southeast Asia was one of the first regions to be affected by the outbreak. The aim of this systematic review was to evaluate the prevalence of anxiety, depression and insomnia in the general adult population and healthcare workers (HCWs) in Southeast Asia during the course of the first year of the pandemic.

MethodsSeveral literature databases were systemically searched for articles published up to February 2021 and two reviewers independently evaluated all relevant studies using pre-determined criteria. The prevalence rates of mental health symptoms were calculated using a random-effect meta-analysis model.

ResultsIn total, 32 samples from 25 studies with 20,352 participants were included. Anxiety was assessed in all 25 studies and depression in 15 studies with pooled prevalence rates of 22% and 16% respectively. Only two studies assessed insomnia, which was estimated at 19%. The prevalence of anxiety and depression was similar amongst frontline HCWs (18%), general HCWs (17%), and students (20%) whilst being noticeably higher in the general population (27%).

ConclusionsThis is the first systematic review to investigate the mental health impact of the Covid-19 pandemic in Southeast Asia. A considerable proportion of the general population and HCWs reported mild to moderate symptoms of anxiety and depression; the pooled prevalence rater, however, remain significantly lower than those reported in other areas such as China and Europe.


title: ''Time does not heal all wounds'': Sexual victimisation is associated with depression, anxiety and PTSD in old age

abstract:
BackgroundSexual violence (SV) has an important impact on mental health. Childhood sexual abuse is linked to internalising disorders in later life. In older adults, SV occurs more often than previously believed. Moreover, health care workers lack the skills to address SV in later life. Studies researching the mental health impact of lifetime SV, i.e. SV during childhood, adulthood and old age, are lacking.

MethodsBetween July 2019 and March 2020, 513 older adults living in Belgium participated in structured face-to-face-interviews. Selection occurred via a cluster random probability sampling with a random walk finding approach. Depression, anxiety and posttraumatic stress syndrome (PTSD) were measured using validated scales. Participants were asked about suicide attempts and self-harm during their lifetime and in the past 12-months. SV was measured using behaviourally specific questions based on a broad SV definition.

ResultsRates for depression, anxiety and PTSD were 27%, 26% and 6% respectively, 2% had attempted suicide, 1% reported self-harm in the past 12-months. Over 44% experienced lifetime SV, 8% in the past 12-months. Lifetime SV was linked to depression (p =.001), anxiety (p =.001), and PTSD in participants with a chronic illness/disability (p = .002) or no/lower education (p <.001). We found no link between lifetime SV and suicide attempts or self-harm in the past 12-months.

ConclusionsLifetime SV is linked to mental health problems in late life. Tailored mental health care for older SV victims is necessary. Therefore, capacity building of professionals, and development of clinical guidelines and care procedures are important.


title: Prediction of severe COVID-19 cases requiring intensive care in Osaka, Japan

abstract:
BackgroundTo avoid exhaustion of medical resources by COVID-19 care, policy-makers must predict care needs, specifically estimating the proportion of severe cases likely to require intensive care. In Osaka prefecture, Japan, the number of these severe cases exceeded the capacity of ICU units prepared for COVID-19 from mid-April, 2021.

ObjectiveThis study used a statistical model to elucidate dynamics of severe cases in Osaka and validated the model through prospective testing.

MethodsThe study extended from April 3, 2020 through April 26, 2021 in Osaka prefecture, Japan prefecture. We regressed the number of severe cases on the number of severe cases the day prior and the newly onset patients of more than 21 days prior.

ResultsWe selected the number of severe cases the day prior and the number of newly onset patients on 21 and 28 days prior as explanatory variables for explaining the number of severe cases based on the adjusted determinant coefficient. The adjusted coefficient of determination was greater than 0.995 and indicated good fit. Prospective out of sample three-week prediction forecast the peak date precisely, but the level was not t.

Discussion and ConclusionA reason for the gap in the prospective prediction might be the emergence of variant strains.


title: Effects of immunosuppressive therapy reduction and early post-infection graft function in kidney transplant recipients with COVID-19

abstract:
BackgroundKidney transplant recipients with COVID-19 are at high risk of poor outcome because of comorbidities and immunosuppression. The effects of immunosuppressive therapy reduction are unclear in patients with COVID-19.

MethodsWe conducted a retrospective study on 45 consecutive kidney transplant recipients followed at the University Hospital of Modena who tested positive for COVID-19 by RT-PCR analysis.

ResultsThe median age of patients was 56.1 (interquartile range, [IQR] 47.3-61.1) years with a predominance of male (64.4%). Kidney transplantation vintage was 10.1 (2.7-16) years, and more than half of patients (55.6%) was on triple immunosuppressive therapy. Early reduction of immunosuppression occurred in 62.8% of patients and included antimetabolite (88.8%) and calcineurin inhibitor withdrawal (22.2%).

Of the 45 patients, 88.9% became symptomatic and 40% required hospitalization. Overall mortality was 17.8%. There were no differences in outcomes between full- and reduced-dose immunosuppressive therapy at the end of follow-up. One hospitalized patient experienced irreversible graft failure. There were no differences in serum creatinine level and proteinuria in non-hospitalized patients with COVID-19. Admitted patients had better kidney function after dismission (P=0.019). Risk factors for death were age (odds ratio [OR]: 1.19; 95%CI: 1.01-1.39), and duration of kidney transplant (OR: 1.17; 95%CI: 1.01-1.35). One kidney transplant recipient experienced symptomatic COVID-19 reinfection after primary infection and anti-SARS-CoV-2 mRNA vaccine.

ConclusionsDespite the reduction of immunosuppression, COVID-19 affected survival of kidney transplant recipients with COVID-19. Age and duration of kidney transplant were independent predictors of death in COVID-19. Early kidney function was favorable in most survivors after COVID-19.


title: Prospective comparison of Bayesian and frequentist adaptive clinical trials : The SHADOW - SHINE project

abstract:
ImportanceBayesian adaptive trial design has the potential to create more efficient clinical trials. However, one of the barriers to the uptake of Bayesian adaptive designs for confirmatory trials is limited experience with how they may perform compared to a frequentist design.

ObjectiveCompare the performance of a Bayesian and a frequentist adaptive clinical trial design.

DesignProspective observational study comparing two trial designs using individual patient level data from a completed stroke trial, including the timing and order of enrollments and outcome ascertainment. The implemented frequentist design had group sequential boundaries for efficacy and futility interim analyses when 90-days post-randomization was met for 500, 700, 900, and 1,100 patients. The Bayesian alternative utilized predictive probability of trial success to govern early termination for efficacy and futility with a first interim analysis at 500 randomized patients, and subsequent interims after every 100 randomizations.

SettingMulti-center, acute stroke study conducted within a National Institutes of Health neurological emergencies clinical trials network.

ParticipantsPatient level data from 1,151 patients randomized in a clinical trial comparing intensive insulin therapy to standard in acute stroke patients with hyperglycemia.

Main Outcome(s) and Measure(s)Sample size at end of study. This was defined as the sample size at which each of the studies stopped accrual of patients.

ResultsAs conducted, the frequentist design passed the futility boundary after 936 participants were randomized. Using the same sequence and timing of randomization and outcome data, the Bayesian alternative crossed the futility boundary about 3 months earlier after 800 participants were randomized.

Conclusions and RelevanceBoth trial designs stopped for futility prior to reaching the planned maximum sample size. In both cases, the clinical community and patients would benefit from learning the answer to the trials primary question earlier. The common feature across the two designs was frequent interim analyses to stop early for efficacy or for futility. Differences between how this was implemented between the two trials resulted in the differences in early stopping.

Trial RegistrationThe SHINE trial was registered and results are reported on clinicaltrials.gov under identifier: NCT01369069


title: Low frequency interictal EEG biomarker for localizing seizures

abstract:
ObjectiveWe want to identify seizure onset zone (SOZ) from interictal EEG biomarkers. We hypothesize that a combination of interictal EEG biomarkers, including a novel low frequency marker, can predict mesial temporal involvement and can assist in prognosis related to surgical resections.

MethodsInterictal direct current wide bandwidth invasive EEG recordings from 83 patients implanted with 5,111 electrodes were retrospectively studied. Logistic regression was used to classify electrodes and patient outcomes. A feed-forward neural network was implemented to understand putative mechanisms.

ResultsInterictal infraslow frequency EEG activity was decreased for SOZ electrodes while faster frequencies such as delta (2-4 Hz) and beta-gamma (20-50 Hz) activity were increased. These spectral changes comprised a novel interictal EEG biomarker that was significantly increased for mesial temporal SOZ electrodes compared to non-SOZ electrodes. Interictal EEG biomarkers correctly classified mesial temporal SOZ electrodes with a specificity of 87% and positive predictive value of 80%. These interictal EEG biomarkers also correctly classified patient outcomes after surgical resection with a specificity of 91% and positive predictive value of 87%.

InterpretationInterictal infraslow EEG activity is decreased near the SOZ while higher frequency power is increased, suggesting distinct underlying physiologic mechanisms. Decreased interictal infraslow activity may reflect the loss of neural inhibition. Narrowband interictal EEG power bands provide information about the SOZ and can help predict mesial temporal involvement in seizure onset. Together with interictal epileptiform discharges and high frequency oscillations, these interictal biomarkers may provide prognostic information prior to surgical resection.


title: Ambient air pollution and COVID-19 in National Capital Territory of Delhi, India: a time-series evidence

abstract:
ObjectivesThis study aimed to explore the short-term health effects of ambient air pollutants PM2.5, PM10, SO2, NO2, O3, and CO on COVID-19 daily new cases and COVID-19 daily new deaths.

Study designA time-series design used in this study. Data were obtained from 1 April 2020 to 31 December 2020 in the National Capital Territory (NCT) of Delhi, India.

MethodsThe generalized additive models (GAMs) were applied to explore the associations of six air pollutants with COVID-19 daily new cases and COVID-19 daily new deaths. We also conducted sensitivity analysis using the population mobility variable in terms of lockdowns.

ResultsThe GAMs revealed statistically significant associations of ambient air pollutants with COVID-19 daily new cases and COVID-19 daily new deaths. Besides, in sensitivity analysis after controlling for the population mobility, these associations became more prominent.

ConclusionsThese findings suggest that governments need to give greater considerations to regions with higher concentrations of PM2.5, PM10, SO2, NO2, O3, and CO, since these areas may experience a more serious COVID-19 pandemic or, in general, any respiratory disease.


title: When to be vaccinated? What to consider? Modelling decision-making and time preference for COVID-19 vaccine through a conjoint experiment approach

abstract:
How do citizens choose COVID-19 vaccines, and when do they wish to be vaccinated? A choice-based conjoint experiment was fielded in Hong Kong to examine factors that shape citizens preference toward COVID-19 vaccines and their time preference to be vaccinated, which is overlooked in extant literature. Results suggest people are most concerned about vaccines efficacy and severe side-effects, and that cash incentives are not useful in enhancing vaccine appeal. The majority of respondents show low intention for immediate vaccination, and many of them want to delay their vaccination. Further analysis shows that their time preference is shaped more by respondent characteristics than vaccine attributes. In particular, confidence in the vaccine, trust in government, and working in high-risk professions are associated with earlier timing for vaccine uptake. Meanwhile, forced COVID testing would delay vaccination. The findings offer a novel view in understanding how people decide whether and when to receive new vaccines, which have pivotal implications for a head start of any mass vaccination programs.

HighlightsO_LIPeople are most concerned about vaccines efficacy and severe side-effects when choosing COVID-19 vaccines
C_LIO_LICash incentives are not useful in enhancing vaccines appeal
C_LIO_LITime preference of vaccination is shaped more by respondent characteristics than vaccine attributes
C_LIO_LIForced COVID testing might delay vaccination decision
C_LI

category: health policy


title: Law, Criminalisation and HIV in the World: Have countries that criminalise achieved more or less successful AIDS pandemic response?

abstract:
How does the use of criminal law affect disease-fighting efforts, particularly in a pandemic? This longstanding question for governments around the world is felt acutely in the context of the COVID-19 and HIV pandemics. Many countries have laws and policies that criminalise behaviours, making same-sex relationships, illicit drug use, and sex work illegal. Meanwhile, some countries have enshrined gender- and rights-protective institutions in law. Under the global AIDS strategy of the last five years, national AIDS response efforts in countries have focused on reaching people living with HIV with testing and antiretroviral treatment to suppress the HIV virus, preventing mortality and HIV transmission. At the end of this 5-year push, this article provides an ecological analysis of whether those countries with criminalising legal environments achieved more or less success. In countries where same-sex relationships were fully criminalised, the portion of people living with HIV who knew their status was 11% lower and viral suppression rates were 8% lower. Under sex-work criminalization, the rate of people living with HIV who knew their status was 10% lower and viral suppression 6% lower. Drug use criminalisation was associated with 14% lower knowledge of status and viral. On the other hand in countries with laws advancing non-discrimination, human rights institutions, and gender-based violence response, HIV services indicators were significantly better. This ecological evidence on the relationships between the legal environment and successful HIV response provides support for a strategy that includes a focus on law reform to achieve goals missed in 2020.

Summary BoxO_LICountries around the world, across economic and geographic boundaries, have taken different approaches to the application of criminal law to same-sex sex, sex work, and drug use--with most taking a partially or fully criminalising legal approach in one or more of these areas.
C_LIO_LIIn tackling the AIDS pandemic, globally agreed goals for 2020 focused on ensuring most people living with HIV were aware of their HIV status and had suppressed the HIV virus through effective antiretroviral treatment.
C_LIO_LIThe AIDS response in countries that criminalised was less successful than those that did not--achieving significantly lower levels of HIV status knowledge and HIV viral suppression.
C_LIO_LICountries with clear laws advancing non-discrimination, human rights institutions, and gender-based violence response had better knowledge of HIV status and viral suppression rates.
C_LIO_LIThis analysis suggests a new global AIDS strategy that includes a focus on law reform may hold promise in achieving goals that were missed in 2020.
C_LI

category: hiv aids


title: Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness

abstract:
ObjectiveStudies have demonstrated a potential link between low vitamin D levels and both an increased risk of infection with SARS-CoV-2 and poorer clinical outcomes but have not established temporality. This retrospective study examined if, and to what degree, a relationship exists between pre-infection serum vitamin D levels and disease severity and mortality of SARS-CoV-19.

Design and patientsThe records of individuals admitted between April 7th, 2020 and February 4th, 2021 to the Galilee Medical Center (GMC) in Nahariya, Israel with positive polymerase chain reaction (PCR) tests for SARS-CoV-2 were searched for vitamin D (VitD) levels measured 14 to 730 days prior to the positive PCR test.

MeasurementsPatients admitted to GMC with COVID-19 were categorized according to disease severity and VitD level. Association between pre-infection VitD levels and COVID-19 severity was ascertained utilizing a multivariate regression analysis.

ResultsOf 1176 patients admitted, 253 had VitD levels prior to COVID-19 infection. Compared with mildly or moderately diseased patients, those with severe or critical COVID-19 disease were more likely to have pre-infection vitamin D deficiency of less than 20 ng/mL (OR=14.30, 95%, 4.01-50.9; p < .001); be older (OR=1.039 for each year, 95% CI for OR, 1.017-1.061; p< .01), and have diabetes (OR=2.031, 95% CI for OR, 1.04-3.36; p= 0.038). Vitamin D deficiency was associated with higher rates of mortality (p<0.001) and comorbidities including COPD (p=0.006), diabetes (p=0.026), and hypertension (p=0.016).

ConclusionsAmong hospitalized COVID-19 patients, pre-infection deficiency of vitamin D was associated with increased disease severity and mortality.


title: Factors associated with excess all-cause mortality in the first wave of COVID-19 pandemic in the UK: a time-series analysis using the Clinical Practice Research Datalink

abstract:
ObjectivesExcess mortality captures the total effect of the COVID-19 pandemic on mortality and is not affected by mis-specification of cause of death. We aimed to describe how health and demographic factors have been associated with excess mortality during the pandemic.

DesignTime-series analysis.

SettingUK primary care data from practices contributing to the Clinical Practice Research Datalink on July 31st 2020.

ParticipantsWe constructed a time-series dataset including 9,635,613 adults ([≥]40 years old) who were actively registered at the general practice during the study period.

Main outcome measuresWe extracted weekly numbers of deaths between March 2015 and July 2020, stratified by individual-level factors. Excess mortality during wave 1 of the UK pandemic (5th March to 27th May 2020) compared to pre-pandemic was estimated using seasonally adjusted negative binomial regression models. Relative rates of death for a range of factors were estimated before and during wave 1 by including interaction terms.

ResultsAll-cause mortality increased by 43% (95% CI 40%-47%) during wave 1 compared with pre-pandemic. Changes to the relative rate of death associated with most socio-demographic and clinical characteristics were small during wave 1 compared with pre-pandemic. However, the mortality rate associated with dementia markedly increased (RR for dementia vs no dementia pre-pandemic: 3.5, 95% CI 3.4-3.5; RR during wave 1: 5.1, 4.87-5.28); a similar pattern was seen for learning disabilities (RR pre-pandemic: 3.6, 3.4-3.5; during wave 1: 4.8, 4.4-5.3), for Black or South Asian ethnicity compared to white, and for London compared to other regions.

ConclusionsThe first UK COVID-19 wave appeared to amplify baseline mortality risk by a relatively constant factor for most population subgroups. However disproportionate increases in mortality were seen for those with dementia, learning disabilities, non-white ethnicity, or living in London.

Summary boxO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIAll-cause mortality during the COVID-19 pandemic was higher than in previous years; this excess mortality was particularly pronounced among elderly people, males, people of non-white ethnicity, people of lower socio-economic status and people living in care-homes.
C_LIO_LISeveral other papers have studied a wider range of factors associated with mortality due to COVID-19 using cause-of-death data.
C_LIO_LIThere is little evidence on how all-cause mortality has changed in people with comorbidities.
C_LI

What this study addsO_LIOur study shows that during Wave 1 of the pandemic all cause death rates increased by a similar proportional degree for almost all population subgroups regardless of their health or socio-demographic circumstances; the exceptions were those with a diagnosis of dementia or learning disabilities and those of non-white ethnicity or living in London.
C_LIO_LIThis suggests that COVID-19 has dialled up the risk of death by a similar proportional degree for everyone except those exposed to a higher risk of infection.
C_LI


title: Early epidemiological signatures of novel SARS-CoV-2 variants: establishment of B.1.617.2 in England

abstract:
The rapid emergence of SARS-CoV-2 mutants with new phenotypic properties is a critical challenge to the control of the ongoing pandemic. B.1.1.7 was monitored in the UK through routine testing and S-gene target failures (SGTF), comprising over 90% of cases by March 2021. Now, the reverse is occurring: SGTF cases are being replaced by an S-gene positive variant, which we associate with B.1.617.2. Evidence from the characteristics of S-gene positive cases demonstrates that, following importation, B.1.617.2 is transmitted locally, growing at a rate higher than B.1.1.7 and a doubling time between 5-14 days. S-gene positive cases should be prioritised for sequencing and aggressive control in any countries in which this variant is newly detected.

One-Sentence SummaryThe B.1.617.2 variant of SARS-CoV-2 is replacing B.1.1.7 and emerging as the dominant variant in England, evidenced by sustained local transmission.


title: Spatial prediction of air pollution levels using a hierarchical Bayesian spatiotemporal model in Catalonia, Spain

abstract:
Our objective in this work was to present a hierarchical Bayesian spatiotemporal model that allowed us to make spatial predictions of air pollution levels in an effective way and with very few computational costs.

We specified a hierarchical spatiotemporal model, using the Stochastic Partial Differential Equations of the integrated nested Laplace approximations approximation. This approach allowed us to spatially predict, in the territory of Catalonia (Spain), the levels of the four pollutants for which there is the most evidence of an adverse health effect.

Our model allowed us to make fairly accurate spatial predictions of both long- term and short-term exposure to air pollutants, with a low computational cost. The only requirements of the method we propose are the minimum number of stations distributed throughout the territory where the predictions are to be made, and that the spatial and temporal dimensions are either independent or separable.

HighlightsWe show a hierarchical Bayesian spatiotemporal model.

Our model provides predictions of both long-term and short-term exposure.

The computational cost is low.

The model only needs a minimum number of stations being distributed throughout the territory.

The other requirement of our model is that the spatial and temporal dimensions are either independent or separable.

Graphical abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/21258419v1_ufig1.gif" ALT="Figure 1">
View larger version (24K):
org.highwire.dtl.DTLVardef@16781dorg.highwire.dtl.DTLVardef@127f583org.highwire.dtl.DTLVardef@67712dorg.highwire.dtl.DTLVardef@13778f4_HPS_FORMAT_FIGEXP  M_FIG C_FIG Software and Data availabilityWe used open data with free access using these sources. Air pollutants

Departament de Territori i Sostenibilitat, Generalitat de Catalunya [Available at: https://analisi.transparenciacatalunya.cat/en/Medi-Ambient/Qualitat-de-l-aire-als-punts-de-mesurament-autom-t/tasf-thgu, last accessed on March 14, 2021].

Meteorological variables

METEOCAT, Generalitat de Catalunya. Meteorological data from XEMA [Available at: https://analisi.transparenciacatalunya.cat/en/Medi-Ambient/Dades-meteorol-giques-de-la-XEMA/nzvn-apee, last accessed on March 14, 2021].

AEMET. AEMET Open Data [in Spanish] [Available at: http://www.aemet.es/es/datos_abiertos/AEMET_OpenData, last accessed on March 14, 2021].

Digitized cartography of the ABS

Departament de Salut. Cartography [Available at: https://salutweb.gencat.cat/ca/el_departament/estadistiques_sanitaries/cartografia/, accessed on March 14, 2021].

Code will be available at www.researchprojects.es


title: Immunogenicity of the ChAdOx1 nCoV-19 and the BBV152 Vaccines in Patients with Autoimmune Rheumatic Diseases

abstract:
IntroductionThere is limited information on the effectiveness of COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD).

Methods136 consecutive patients with rheumatic diseases who never had a diagnosis of COVID-19 previously, and had completed vaccination with either the ChAdOx1 or BBV152 vaccines were recruited. Their IgG antibody titres to the Spike protein were estimated 1 month after the second dose.

Results102 patients had AIRD while the 34 had non-AIRD. Lesser patients with AIRD (92/102) had positive antibodies titres than ones with non-AIRD(33/34) [p<0.001]. Amongst patients who received the ChAdOX1 vaccine, the AIRD group had lower antibody titres. Although the AIRD patients receiving BBV152 had similarly lower titres numerically, this did not attain statistical significance probably due to lesser numbers. Comparing the two vaccines, 114(95%) of those who received ChAdOx1 (n=120) and 11(68.7%) of those who received BBV152(n=16) had detectable antibodies [p=0.004]. Antibody titres also were higher in ChAdOx1 recipients when compared to BBV152.

To validate the findings, we estimated antibody titres in 30 healthy people each who had received either vaccine. All 30 who had received ChAdOX1 and only 23/30 of those who had received BBV152 had positive antibodies (p=0.011).

ConclusionIn this preliminary analysis, patients with AIRD had lower seroconversion rates as well as lower antibody titres as compared to patients with non-AIRD. Also,the humoral immunogenicity of the BBV152 vaccine appears to be less than that of the ChAdOX1 vaccine. Validation using larger numbers and testing of cellular immunity is urgently required.

category: rheumatology


title: Revealing public opinion towards COVID-19 vaccines using Twitter data in the United States: a spatiotemporal perspective

abstract:
BackgroundThe COVID-19 pandemic has imposed a large, initially uncontrollable, public health crisis both in the US and across the world, with experts looking to vaccines as the ultimate mechanism of defense. The development and deployment of COVID-19 vaccines have been rapidly advancing via global efforts. Hence, it is crucial for governments, public health officials, and policy makers to understand public attitudes and opinions towards vaccines, such that effective interventions and educational campaigns can be designed to promote vaccine acceptance.

ObjectiveThe aim of this study is to investigate public opinion and perception on COVID-19 vaccines by investigating the spatiotemporal trends of their sentiment and emotion towards vaccines, as well as how such trends relate to popular topics on Twitter in the US.

MethodsWe collected over 300,000 geotagged tweets in the US from March 1, 2020 to February 28, 2021. We examined the spatiotemporal patterns of public sentiment and emotion over time at both national and state scales and identified three phases along the pandemic timeline with the significant changes of public sentiment and emotion, further linking to eleven key events and major topics as the potential drivers to induce such changes via cloud mapping of keywords and topic modelling.

ResultsAn increasing trend of positive sentiment in parallel with the decrease of negative sentiment are generally observed in most states, reflecting the rising confidence and anticipation of the public towards vaccines. The overall tendency of the eight types of emotion implies the trustiness and anticipation of the public to vaccination, accompanied by the mixture of fear, sadness and anger. Critical social/international events and/or the announcements of political leaders and authorities may have potential impacts on the public opinion on vaccines. These factors, along with important topics and manual reading of popular posts on eleven key events, help identify underlying themes and validate insights from the analysis.

ConclusionsThe analyses of near real-time social media big data benefit public health authorities by enabling them to monitor public attitudes and opinions towards vaccine-related information in a geo-aware manner, address the concerns of vaccine skeptics and promote the confidence of individuals within a certain region or community, towards vaccines.

category: health informatics


title: Long-COVID following mild SARS CoV-2 infection: characteristic T cell alterations and response to antihistamines

abstract:
BackgroundLong-COVID is characterised by the emergence of multiple debilitating symptoms following SARS CoV2 infection. Its aetiology is unclear, and it often follows a mild acute illness. Anecdotal reports of gradual clinical responses to histamine receptor antagonists (HRA) suggest a histamine-dependent mechanism distinct from anaphylaxis. Histamine is a paracrine regulator of T-cells: although T-cell perturbations are reported in acute COVID-19, the T-cell landscape in recovered patients and its relationship to long-COVID remains under-explored.

ObjectiveTo survey T-cell populations in patients recovered from mild COVID-19, comparing those with long-COVID and asymptomatic individuals, and to analyse these data in light of symptoms and response to HRA.

DesignProspective observational cohort study.

SettingSingle-site outpatient clinic

Participants65 (87 to 408 days post mild COVID-19). None had sought treatment for acute COVID-19. 16 recovered uneventfully (asymptomatic group), 49 presented with long-COVID (symptomatic group), of whom 25 received HRA.

MeasurementsStructured long-COVID symptom questionnaire; quantification of T-cell subsets using a standard diagnostic assay.

ResultsHRA significantly reduced mean symptom burden. T-cell profiles distinguished asymptomatic and long-COVID groups, but did not predict response to HRA. Long-COVID patients had reduced CD4+ and CD8+ effector memory (EM) cells and increased PD-1 expression on central memory (CM) cells. Asymptomatic controls had reduced CD8+ EM cells and increased CD28 expression on CM cells.

ConclusionHRA reduce long-COVID symptoms. T-cell perturbations persist for up to 400 days following mild acute COVID-19 irrespective of long-COVID symptoms.

LimitationsPreliminary, single health system study.

Primary Funding SourcePhilanthropic donations from The Dominvs Group and Sir Peter Wood


title: Outcomes of SARS-CoV-2 Infection in Patients with Chronic Liver Disease and Cirrhosis: a N3C Study

abstract:
Background and AimsIn patients with chronic liver diseases (CLD) with or without cirrhosis, existing data on the risk of adverse outcomes with SARS-CoV-2 infection have been mixed or have limited generalizability. We used the National COVID Cohort Collaborative (N3C) Data Enclave, a harmonized electronic health record (EHR) dataset of 5.9 million nationally-representative, diverse, and gender-balanced patients, to describe outcomes in patients with CLD and cirrhosis with SARS-CoV-2.

MethodsWe identified all chronic liver diseases patients with and without cirrhosis who had SARS-CoV-2 testing documented in the N3C Data Enclave as of data release date 5/15/2021. The primary outcome was 30-day all-cause mortality. Survival analysis methods were used to estimate cumulative incidences of death, hospitalization, and mechanical ventilation, and to calculate the associations of SARS-CoV-2 infection, presence of cirrhosis, and demographic and clinical factors to 30-day mortality.

ResultsWe isolated 217,143 patients with CLD: 129,097 (59%) without cirrhosis and SARS-CoV-2 negative, 25,844 (12%) without cirrhosis and SARS-CoV-2 positive, 54,065 (25%) with cirrhosis and SARS-CoV-2 negative, and 8,137 (4%) with cirrhosis and SARS-CoV-2 positive. Among CLD patients without cirrhosis, 30-day all-cause mortality rates were 0.4% in SARS-CoV-2 negative patients and 1.8% in positive patients. Among CLD patients with cirrhosis, 30-day all-cause mortality rates were 4.0% in SARS-CoV-2 negative patients and 9.7% in positive patients.

Compared to those who tested SARS-CoV-2 negative, SARS-CoV-2 positivity was associated with more than two-fold (aHR 2.43, 95% CI 2.23-2.64) hazard of death at 30 days among patients with cirrhosis. Compared to patients without cirrhosis, the presence of cirrhosis was associated with a three-fold (aHR 3.39, 95% CI 2.96-3.89) hazard of death at 30 days among patients who tested SARS-CoV-2 positive. Age (aHR 1.03 per year, 95% CI 1.03-1.04) was associated with death at 30 days among patients with cirrhosis who were SARS-CoV-2 positive.

ConclusionsIn this study of nearly 220,000 CLD patients, we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.43-times mortality hazard, and the presence of cirrhosis among CLD patients infected with SARS-CoV-2 were associated with 3.39-times mortality hazard. Compared to previous studies, our use of a nationally-representative, diverse, and gender-balanced dataset enables wide generalizability of these findings.


title: Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorder

abstract: Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N=684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p=1.03x10-3; R2=1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p=0.01; R2=0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p=6.84x10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p=8.44x10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p=3.78x10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.


title: Disrupted Ca2+ homeostasis and immunodeficiency in patients with functional Inositol 1,4,5-trisphosphate receptor subtype 3 defects

abstract: Calcium signaling is essential for lymphocyte activation, with genetic disruptions resulting in severe immunodeficiency. The inositol 1,4,5-trisphosphate receptor (IP3R), formed from homo- or hetero-tetramers of the IP3R isoforms 1-3, amplifies lymphocyte signaling by releasing Ca2+ from ER stores into the cytosol following antigen-stimulation. While knockout of all 3 IP3R isoforms results in immunodeficiency in mice, the seeming redundancy of subunits was thought to explain the absence of IP3R mutation as a cause of human immunodeficiency. Here, we identify compound heterozygous variants in ITPR3 in two unrelated Caucasian patients presenting with combined immunodeficiency, in one case requiring hematopoietic stem cell transplantation. We observed disrupted Calcium homeostasis in patient-derived fibroblasts and immune cells, with abnormal proliferation and activation responses following B and T cell receptor stimulation. Reconstitution of IP3R knockout cell lines identified the variants as functional hypomorphs with reduced discrimination between homeostatic and induced states, validating a link between genotype and phenotype. These results demonstrate a functional linkage between defective ER Ca2+ channels and immunodeficiency, and identify IP3Rs as diagnostic targets for patients with specific inborn errors of immunity.

category: allergy and immunology


title: Drug Repurposing of potential drug targets for treatment of COVID-19

abstract: Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic--COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR<0.05, log2FC>1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.


title: Knowledge, attitude and practice towards antibiotic use and resistance among the veterinarians in Bangladesh

abstract:
BackgroundThe emergence of antimicrobial resistance is growing human and animal health concern around the world. When a number of studies have emphasized the Knowledge, Attitude and Practice (KAP) regarding antibiotic use and resistance in humans, little attention has been paid to the veterinary sector. The aim of this study was to understand the KAP towards antibiotic use and resistance among the veterinarians in Bangladesh.

MethodsA cross-sectional online based questionnaire survey was conducted from August to September 2020 among the registered veterinary practitioners. A self-administered Google form questionnaire consists of 45 questions on knowledge, attitude and practice regarding antibiotic use and resistance were used.

ResultsA total of 208 registered veterinarians participated in this study. 85.1% of the participants were male and 54.8% of the participants had a Masters degree. Around 52% of the veterinarians were poultry practitioners. All respondents were familiar with antimicrobials. The participants (91.4%) knew that antibiotics can not cure viral infections while 97.6% believed that frequent antibiotic prescription rendered them less effective. Participants claimed that only they are eligible to prescribe drugs for the treatment of animals and around 80% disagreed with adding antibiotics with feed/water as a growth promoter in livestock. Of the total participants, 87% believed that a local antimicrobial guideline would be more effective than an international one. However, gaps in practices were highlighted in our study, suggesting training deficiencies.

ConclusionThe present study for the first time conducted in Bangladesh dictates the future interventions like academic courses, workshops, and seminars on antibiotic usage and resistance are needed to ameliorate the knowledge, behavior and practice of veterinarians with regards to the rational use of antibiotics.


title: Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)

abstract:
BackgroundDefinitive antiviral treatment is not available for COVID-19 infection except remdesivir that even with many doubts. Various combination antivirals have been tried.

MethodsA single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in COVID-19. Enrolled patients in severe category were randomized into three groups: A: standard treatment, B: hydroxychloroquine+ribavirin+standard treatment, or C: lopinavir+ritonavir+ribavirin+standard treatment; while non-severe category into two groups: A: standard treatment or B: hydroxychloroquine+ribavirin. Combination antivirals was given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report.

ResultsTotal 111 patients randomized: 24, 23, and 24 in severe category A, B, and C respectively, and 20 in each non-severe group. Two patients receiving ribavirin experienced drug induced liver injury and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups respectively showed symptomatic recovery compared to 93.3% and 86.7% in A and B groups respectively in the non-severe category at 72hrs (P>0.05).

ConclusionsThe results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19. However, results do indicate the benefit of non-standard interventional combination therapy in severe disease. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.


title: Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

abstract:
BackgroundAspirin has been proposed as a treatment for COVID-19 on the basis of its antithrombotic properties.

MethodsIn this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150mg aspirin once daily until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).

FindingsBetween 01 November 2020 and 21 March 2021, 7351 patients were randomly allocated to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) patients allocated to aspirin and 1299 (17%) patients allocated to usual care died within 28 days (rate ratio 0{middle dot}96; 95% confidence interval [CI] 0{middle dot}89-1{middle dot}04; p=0{middle dot}35). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 vs. 9 days) and a higher proportion were discharged from hospital alive within 28 days (75% vs. 74%; rate ratio 1{middle dot}06; 95% CI 1{middle dot}02-1{middle dot}10; p=0{middle dot}0062). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0{middle dot}96; 95% CI 0{middle dot}90-1{middle dot}03; p=0{middle dot}23). Aspirin use was associated with an absolute reduction in thrombotic events of 0.6% (SE 0.4%) and an absolute increase in major bleeding events of 0.6% (SE 0.2%).

InterpretationIn patients hospitalised with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death but was associated with a small increase in the rate of being discharged alive within 28 days.

FundingUK Research and Innovation (Medical Research Council), National Institute of Health Research (Grant ref: MC_PC_19056), and the Wellcome Trust (Grant Ref: 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator.


title: Interventions to treat post-traumatic disorder (PTSD) in vulnerably housed populations and trauma-informed care: A scoping review

abstract:
ObjectivesThe goals of this study are to identify and analyse interventions that aim to treat Post Traumatic Stress Disorder (PTSD) and complex PTSD in individuals who are vulnerably housed and to describe how these treatments have been delivered using trauma-informed care.

DesignScoping review

Search strategyWe searched electronic databases including MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, Web of Science, and PTSDpubs for published literature up to March 2020 for any studies that examined the treatment of PTSD in adults who were vulnerably housed. Websites of relevant organizations and other grey literature sources were searched to supplement the electronic database search. The characteristics and effect of the interventions were analyzed. We also explored how the interventions were delivered and the elements of trauma-informed care that were described.

Results26 studies were included. We identified four types of interventions: (1) trauma focused psychotherapies; (2) non-trauma psychotherapies; (3) housing interventions; and (4) pharmacotherapies. The trauma-informed interventions were small case series and the non-trauma focused therapies included four randomized controlled trials, were generally ineffective. Of the ten studies which described trauma-informed care the most commonly named elements were physical and emotional safety, the experience of feeling heard and understood, and flexibility of choice. The literature also commented on the difficulty of providing care to this population including lack of private space to deliver therapy; the co-occurrence of substance use; and barriers to follow-up including limited length of stay in different shelters and high staff turnover.

ConclusionsThis scoping review identified a lack of high-quality trials to address PTSD in the vulnerably housed. There is a need to conduct well designed trials that take into account the unique setting of this population and which describe those elements of trauma-informed care that are most important and necessary.

Strengths and limitations of this studyO_LIFirst review of how trauma-informed care is being operationalized in the treatment of PTSD for the vulnerably housed.
C_LIO_LIProvides a clear picture emphasizing the need to consistently utilize a trauma-informed care approach for PTSD treatment in the vulnerably housed.
C_LIO_LILargely homogenous populations (primarily women and US Veterans) included in studies, may not be representative of broader population.
C_LIO_LIOften no mention of ethnic or cultural factors to consider when providing treatment.
C_LIO_LIMany of the studies available were of low methodological quality.
C_LI


title: Interventions to treat post-traumatic stress disorder (PTSD) in vulnerably housed populations and trauma-informed care: A scoping review


title: A Meta-Analysis of Mental Health among Latino Adults: Elucidating Disparities from Differences

abstract: Latinos continue to experience disparities in access to treatment for mental health, and these appear to be worsening with time. This meta-analysis identified and compared studies (N=20): (1) Across Latino origin groups, (2) Across immigration-related characteristics, and (3) with non-Latino groups. For the first comparison, results consistently showed Puerto Ricans had the highest rate of utilization compared to their Mexican, Cuban, Central American, and Other counterparts. For the second comparison, U.S-born Latinos had higher utilization and mental health costs for services, as well as higher rate of depression/anxiety symptomatology compared to their immigrant counterparts. For the third comparison, results were not as consistent but trended towards lower/less rates by Latinos compared to non-Latino whites. More research is needed on the different Latino groups and across the acculturation spectrum if we are to understand disparities from differences in risk and service use among this heterogeneous group.


title: Prevalence of dysphagia in patients with multiple sclerosis; a systematic review and meta-analysis

abstract:
ObjectivesDysphagia is a major comorbidity observed in patients with multiple sclerosis, yet different prevalence rates are reported for it. Therefore, we have designed this systematic review to estimate the pooled prevalence of dysphagia in patients with MS.

MethodWe searched PubMed, Scopus, EMBASE, Web of Science, and gray literature including references from the identified studies, reviews studies, and conference abstracts which were published up to February 2021. Articles that were relevant to our topic and could provide information regarding the prevalence of dysphagia among MS patients were included; however, articles with self-report screening strategies were excluded.

ResultsThe literature search found 1993 articles. After eliminating duplicates, 1272 articles remained. Sixteen abstract conference papers were included for final analysis. A total of 10846 MS cases and 4913 MS patients with dysphagia included in the analysis. The pooled prevalence of dysphagia in the included studies was 45.3% (95% CI: [40.7%-50%])

ConclusionThe results of this systematic review shows that the prevalence of dysphagia in MS patients is 45% which is greatly higher compared to the general population.