title: No magic bullet: limiting in-school transmission in the face of variable SARS-CoV-2 viral loads

abstract: In the face of a long-running pandemic, understanding the drivers of ongoing SARS-CoV-2 transmission is crucial for the rational management of COVID-19 disease burden. Keeping schools open has emerged as a vital societal imperative during the pandemic, but in-school transmission of SARS-CoV-2 can contribute to further prolonging the pandemic. In this context, the role of schools in driving SARS-CoV-2 transmission acquires critical importance. Here we model in-school transmission from first principles to investigate the effectiveness of layered mitigation strategies on limiting in-school spread. We examine the effect of masks and air quality (ventilation, filtration and ionizers) on steady-state viral load in classrooms, as well as on the number of particles inhaled by an uninfected person. The effectiveness of these measures in limiting viral transmission is assessed for variants with different levels of mean viral load (Wuhan, Delta, Omicron). Our results suggest that a layered mitigation strategy can be used effectively to limit in-school transmission, with certain limitations. First, poorly designed strategies (insufficient ventilation, no masks, staying open under high levels of community transmission) will permit in-school spread even if some level of mitigation is ostensibly present. Second, for viral variants that are sufficiently contagious, it may be difficult to construct any set of interventions capable of blocking transmission once an infected individual is present, underscoring the importance of other measures. Our findings provide several practical recommendations: the use of a layered mitigation strategy that is designed to limit transmission, with other measures such as frequent surveillance testing and smaller class sizes (such as by offering remote schooling options to those who prefer it) as needed.

category: public and global health


title: Attitudes and Experiences Surrounding Female Genital Mutilation/Cutting in the United States: A Scoping Review

abstract: In recent decades, growing migration to the United States from countries where female genital mutilation/cutting (FGM/C) is widely practiced has caused a rise in the number of women and girls in the United States who could have potentially experienced FGM/C. A scoping review was conducted to identify research and gaps in literature about FGM/C-related attitudes and experiences among individuals from FGM/C-practicing countries living in the United States. This scoping review identified 40 articles meeting inclusion criteria. The findings of this review suggest that both women and men from FGM/C-practicing countries living in the United States generally oppose FGM/C, and that women with FGM/C have significant physical and mental health needs and have found US healthcare providers to lack understanding of FGM/C. Future research can improve measurement of FGM/C by applying a health equity lens and taking into account the sociocultural influences on FGM/C-related attitudes and experiences.


title: Can electroencephalography (EEG) identify ADHD subtypes? A systematic review.

abstract: Attention Deficit/Hyperactivity Disorder (ADHD) has been associated with atypical patterns of neural activity measured by electroencephalography (EEG). However, the identification of EEG diagnostic biomarkers has been complicated by the disorders heterogeneity. The objective of this review was to synthesize the literature investigating EEG variation in patients diagnosed with ADHD, addressing the following questions: 1) Are the diagnostic ADHD subtypes associated with different EEG characteristics? 2) Are EEG measures correlated with ADHD traits and/or symptom severity? and 3) Do classification techniques using EEG measures reveal different clinical presentations of ADHD? Outcomes highlight the potential for electrophysiological measures to provide meaningful insights into the heterogeneity of ADHD, although direct translation of EEG biomarkers for diagnostic purposes is not yet supported. Key measures that show promise for the discrimination of existing ADHD subtypes and symptomatology include: resting state and task-related modulation of alpha, beta and theta power, and the event-related N2 and P3 components. Prescriptions are discussed for future studies that may help to bridge the gap between research and clinical application.

category: neurology


title: Identification of carcinogenesis and tumor progression processes in pancreatic ductal adenocarcinoma using high-throughput proteomics

abstract:
Pancreatic adenocarcinoma (PDAC) is an aggressive disease with an overall 5 year-survival rate of just 5%. A better understanding of both the carcinogenesis processes and the mechanisms of progression of PDAC disease is mandatory. Proteomics offers complementary information to genomics, measuring the direct effectors of the biological processes.

From a cohort of 110 PDAC patients treated with surgery and adjuvant therapy, 52 patients, of which primary tumor and normal tissue, preneoplastic lesions (PanIN), and/or lymph node metastases were available, were selected for the study. Proteins were extracted from small punches obtained from formalin fixed, paraffin embedded tissue, and analyzed by LC-MS/MS using a data-independent acquisition approach. Protein expression data was analyzed using probabilistic graphical models, allowing functional characterization. Functional node activities were calculated as the mean of expression of those proteins related to the main function of each node. Comparisons between groups were done using linear mixed models.

First, analyzing the tumor tissue, three proteomics subtypes were defined: T1 (32% of patients) presented higher activity of adhesion and complement activation nodes, T2 (34%) had higher mitochondrial and metabolic node activity, and T3 (34%) had higher nucleoplasm node activity. Second, relevant biological processes related to carcinogenesis and tumor progression were studied in each subtype. We found differences between T1 PanIN and primary tumors in adhesion, translation, mitochondria and pancreatic secretion nodes, suggesting an involvement of these processes in tumor development. Differences between tumors and lymph nodes, related to tumor progression, were identified in nucleoplasm, translation, adhesion, extracellular matrix, and complement activation nodes. Mitochondria and metabolism nodes had differential activity between T2 normal tissue, PanIN and tumors, and also between tumors and lymph nodes. T3 analyses point out that nucleoplasm, metabolism and mitochondria, and extracellular matrix nodes could be involved in T3 tumors carcinogenesis. Interestingly, identified processes were different between the three proteomics subtypes suggesting that the motor of the disease is characteristic of each subtype. Additionally, these proteomics subtypes were validated into the PDAC TCGA cohort.

In this study, three PDAC proteomics subtypes were defined, an adhesion-related subtype (T1), a metabolic-related subtype (T2), and a nucleoplasm subtype (T3). We also suggest several biological processes involved in tumor development and progression exclusive of each proteomics subtype. These biological processes could be relevant as a guide to select candidates for future tailored therapeutics treatments in PDAC. Proteomics data are available via ProteomeXchange with identifier PXD032076.

category: oncology


title: Rigorous benchmarking of T cell receptor repertoire profiling methods for cancer RNA sequencing

abstract: The ability to identify and track T cell receptor (TCR) sequences from patient samples is becoming central to the field of cancer research and immunotherapy. Tracking genetically engineered T cells expressing TCRs that target specific tumor antigens is important to determine the persistence of these cells and quantify tumor responses. The available high-throughput method to profile T cell receptor repertoires is generally referred to as TCR sequencing (TCR-Seq). However, the available TCR-Seq data is limited compared to RNA sequencing (RNA-Seq). In this paper, we have benchmarked the ability of RNA-Seq-based methods to profile TCR repertoires by examining 19 bulk RNA-Seq samples across four cancer cohorts including both T cell rich and poor tissue types. We have performed a comprehensive evaluation of the existing RNA-Seq-based repertoire profiling methods using targeted TCR-Seq as the gold standard. We also highlighted scenarios under which the RNA-Seq approach is suitable and can provide comparable accuracy to the TCR-Seq approach. Our results show that RNA-Seq-based methods are able to effectively capture the clonotypes and estimate the diversity of TCR repertoires, as well as to provide relative frequencies of clonotypes in T cell rich tissues and monoclonal repertoires. However, RNA-Seq-based TCR profiling methods have limited power in T cell poor tissues, especially in polyclonal repertoires of T cell poor tissues. The results of our benchmarking provide an additional appealing argument to incorporate the RNA-Seq into immune repertoire screening of cancer patients as it offers broader knowledge into the transcriptomic changes that exceed the limited information provided by TCR-Seq.


title: Genetically personalised organ-specific metabolic models in health and disease

abstract: Understanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage human genome-scale metabolic networks to define how genetic variants affect biochemical reaction fluxes across major human tissues, including skeletal muscle, adipose, liver, brain and heart. As proof of concept, we build personalised organ-specific metabolic flux models for 524,615 individuals of the INTERVAL and UK Biobank cohorts and perform a fluxome-wide association study (FWAS) to identify 4,411 associations between personalised flux values and the concentration of metabolites in blood. Furthermore, we apply FWAS to identify 97 metabolic fluxes associated with the risk of developing coronary artery disease, many of which are linked to processes previously described to play in role in the disease. Our work demonstrates that genetically personalised metabolic models can elucidate the downstream effects of genetic variants on biochemical reactions involved in common human diseases.

category: genetic and genomic medicine


title: DraculR: A web based application for in silico haemolysis detection in high throughput small RNA sequencing data

abstract:
MotivationThe search for novel microRNA (miRNA) biomarkers in plasma is hampered by haemolysis, the lysis and subsequent release of red blood cell (RBC) contents, including miRNAs, into surrounding fluid. The biomarker potential of miRNAs comes in part from their multi-compartment origin, and the long-lived nature of miRNA transcripts in plasma, giving researchers a functional window for tissues that are otherwise difficult or disadvantageous to sample. The inclusion of RBC derived miRNA transcripts in downstream analysis introduces a source of error that is difficult to identify post hoc and may lead to spurious results. Where access to a physical specimen is not possible, our tool will provide an in silico approach to haemolysis prediction.

ResultsWe present DraculR, an interactive Shiny/R application that enables a user to upload microRNA expression data from short read sequencing of human plasma as a raw read counts table and interactively calculate a metric that indicates the degree of haemolysis contamination.

Availability and implementationDraculR and its tutorial are freely available from (https://mxhp75.shinyapps.io/shinyVamp/). Code is available from (https://github.com/mxhp75/shinyVamp.git).


title: A cystic fibrosis lung disease modifier locus harbors tandem repeats associated with gene expression

abstract: Variable number of tandem repeats (VNTRs) are major source of genetic variation in human. However due to their repetitive nature and large size, it is challenging to genotype them by short-read sequencing. Therefore, there is limited understanding of how they contribute to complex traits such as cystic fibrosis (CF) lung function. Genome-wide association study (GWAS) of CF lung disease identified two independent signals near SLC9A3 displaying a high density of VNTRs and CpG islands. Here, we used long-read (PacBio) phased sequence (N=58) to identify the boundaries and lengths of 49 common (frequency >2%) VNTRs in the region. Subsequently, associations of the VNTRs with gene expression were investigated in CF nasal epithelia using RNA sequencing (N=46). Two VNTRs tagged by the two GWAS signals and overlapping CpG islands were independently associated with SLC9A3 expression in CF nasal epithelia. The two VNTRs together explained 24% of SLC9A3 gene expression variation. One of them was also associated with TPPP expression. We then showed that the VNTR lengths can be estimated with good accuracy in short-read sequence in a subset of individuals with data on both long (PacBio) and short-read (10X Genomics) technologies (N=52). VNTR lengths were then estimated in the Genotype-Tissue Expression project (GTEx) and their association with gene expression was investigated. Both VNTRs were associated with SLC9A3 expression in multiple non-CF GTEx tissues including lung. The results confirm that VNTRs can explain substantial variation in gene expression and be responsible for GWAS signals, and highlight the critical role of long-read sequencing.


title: Using Genomic data to Investigate the Anti-Depressive Effects of Statins

abstract: Cholesterol-lowering statins, which are widely prescribed for treating and preventing cardiovascular diseases, have previously been reported to show anti-depressive properties. However, there is conflicting evidence on the association of statins with depression, and the molecular mechanisms that govern their potential anti-depressive effects remain largely veiled. We evaluated the anti-depressive activities of statins using a combined approach of transcriptomic signature matching and genetic association analysis. We interrogated pre-compiled Connectivity Map (CMap) perturbational gene expression signatures and found that compounds with highly similar signatures to statins (average connectivity score > 90) were enriched for antidepressants (p < 1E-05). Genes perturbed in the same direction by both statins and antidepressants were significantly enriched for various immune pathways, while genes perturbed in the opposite direction were enriched for lipid metabolism pathways. Using publicly available expression quantitative trait loci (eQTL) and genome-wide association summary data, we performed Mendelian randomisation analysis to infer association of genetically predicted statin target inhibition with various depression, immune and disease traits. Genetically proxied HMGCR inhibition was significantly associated with extensive changes in immune cell traits, particularly platelet-related indices, and while we observed no genetic association between HMGCR expression and depression risk (p = 0.21), we found nominal association with depression-related worrying symptoms (p = 0.042). Our analyses provide genomic evidence for the association between statins and extensive alterations in immune-related processes, which have been linked to depression. Our findings carry clinical relevance, both for treating the increasing prevalence of individuals with comorbid cardiovascular diseases and depression, and for exploring the potential of repurposing statins for modulating depression symptoms.


title: Detection of mosaic chromosomal alterations in children with severe developmental disorders recruited to the DDD study

abstract:
PurposeStructural mosaicism has been previously implicated in developmental disorders. We aim to identify rare mosaic chromosomal alterations (MCAs) in probands with severe undiagnosed developmental disorders.

MethodsWe identified MCAs in SNP array data from 12,530 probands in the Deciphering Developmental Disorders (DDD) study using MoChA.

ResultsWe found 61 MCAs in 57 probands, many of these were tissue specific. In 23/26 (88.5%) cases for which the MCA was detected in saliva where blood was also available for analysis, the MCA could not be detected in blood. The MCAs included 20 polysomies, comprising either one arm of a chromosome or a whole chromosome, for which we were able to show the timing of the error (25% mitosis, 40% meiosis I, 35% meiosis II). Only 2/57 (3.5%) of the probands in whom we found MCAs had another likely genetic diagnosis identified by whole exome sequencing, despite an overall diagnostic yield of [~]40% across the cohort.

ConclusionOur results show that identification of MCAs provides candidate diagnoses for previously undiagnosed patients with developmental disorders, potentially explaining [~]0.45% of cases in the DDD study. Nearly 90% of these MCAs would have remained undetected by analysing DNA from blood and no other tissue.


title: A Wide-bandwidth Nanocomposite-Sensor Integrated Smart Mask for Tracking Multi-phase Respiratory Activities for COVID-19 Endemic

abstract: A global sentiment in early 2022 is that the COVID-19 virus could become endemic just like common cold flu viruses soon. The most optimistic view is that, with minimal precautions, such as vaccination, boosters and optional masking, life for most people will proceed as normal soon. However, as warned by A. Katzourakis of Oxford University recently [1], we must set aside lazy optimism, and must be realistic about the likely levels of death, disability and sickness that will be brought on by a  COVID-19 endemic. Moreover, the world must also consider that continual circulation of the virus could give rise to new variants such as the new BA.2 variant (a subvariant of Omicron) continues to spread across the US and parts of Europe. Data from the CDC is already showing that BA.2 has been tripling in prevalence every two weeks [2]. Hence, globally, we must use available and proven weapons to continue to fight the COVID-19 viruses, i.e., effective vaccines, antiviral medications, diagnostic tests and stop an airborne virus transmission through social distancing, and mask wearing. For this work, we have demonstrated a smart mask with an optimally-coupled ultra-thin flexible soundwave sensors for tracking, classifying, and recognizing different respiratory activities, including breathing, speaking, and two-/tri-phase coughing; the masks functionality can also be augmented in the future to monitor other human physiological signals. Although researchers have integrated sensors into masks to detect respiratory activities in the past, they only based on measuring temperature and air flow during coughing, i.e., counting only the number of coughs. However, coughing is a process consisting of several phases, including an explosion of the air with glottal opening producing some noise-like waveform, a decrease of airflow to decrease sound amplitude, and a voiced stage which is the interruption of the air flow due to the closure of glottal and periodical vibration of partly glottis, which is not always present. Therefore, sensors used for cough detection should not be only sensitive to subtle air pressure but also the high-frequency vibrations, i.e., a pressure sensor that needs to be responsive to a wide input amplitude and bandwidth range, in order to detect air flows between hundreds of hertz from breath, and acoustic signals from voice that could reach [~] 8000 Hz. Respiratory activities data from thirty-one (31) human subjects were collected. Machine learning methods such as Support Vector Machines and Convolutional Neural Networks were used to classify the collected sensor data from the smart mask, which show an overall macro-recall of about 93.88% for the three respiratory sounds among all 31 subjects. For individual subjects, the 31 human subjects have the average macro-recall of 95.23% (ranging from 90% to 100%) for these 3 respiratory activities. Our work bridges the technological gap between ultra-lightweight but high-frequency response sensor material fabrication, signal transduction and conditioning, and applying machining learning algorithms to demonstrate a reliable wearable device for potential applications in continual healthy monitoring of subjects with cough symptoms during the eventual COVID-19 endemic. The monitoring and analysis of cough sound should be highly beneficial for human health management. These health monitoring data could then be shared with doctors via cloud storage and transmission technique to help disease diagnosis more effectively. Also, communication barriers caused by wearing masks can be alleviated by combining with the speech recognition techniques. In general, this research helps to advance the wearable device technology for tracking respiratory activities, similar to an Apple Watch or a Fitbit smartwatch in tracking physical and physiological activities.

category: health informatics


title: The responsiveness of health service provider and quality of services when provided at three selected urban primary health care sites in Dhaka city, Bangladesh: a cross-sectional study

abstract:
1IntroductionResponsiveness of Health Service Provider (HSP) and quality of services when provided resembles basic professional and social duties of HSP towards their clients. Because of poor responsiveness and quality of services when provided, clients lose their trust towards HSP. These factors are very important to improve relationship between HSP and clients, clients satisfaction, quality of care and finally increase utilization of Urban Primary Health Care Centre services (UPHC).

ObjectivesThis study was done to determine the responsiveness of health service provider and quality of services when provided at selected UPHCs in Dhaka city.

MethodologyA cross sectional quantitative study was conducted in three UPHCs in Dhaka city from November to December 2017. 257 exit interviews were conducted by systematic random sampling for responsiveness and quality of services when provided. 49 observations of client-provider interactions were conducted using Responsiveness of Physician (ROP) scale. For exit interview, dichotomous variable was used. Descriptive analysis was done using Stata v 12.1.

FindingsMajority (90%) of HSP listen carefully, explained about the diseases, facilitated about follow-up, and client understood information clearly. More than 70% of the clients found the providers approach were friendly though only 37% had social talk with the clients. 41% of the clients reported that the providers shared emergency contact number. Around 67% of clients were not asked allergic history and in 47% case consent was not taken before procedure. Being urban area, for more than 39% clients services were not given similar in terms of social status like gender, ethnicity, economic and social status.

For tangible items like gloves (80%) and thermometer (55%) were mostly missing in all UPHCs. 88% of the HSP were reliable, 93% assured the client and 91% showed empathy in all facilities. Clients were mostly satisfied with doctors behaviour and dissatisfied about the long waiting time (average 37 minutes) in all UPHCs.

ConclusionThis study has highlighted some important gaps in responsiveness of HSP which translate into the quality of care being provided to clients seeking care from UPHC. Friendliness of HSP should be increased and services should be provided with respect.

category: health systems and quality improvement


title: Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV: a nationwide prospective cohort study in the Netherlands

abstract:
BackgroundVaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown.

Methods and FindingsA prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines in adult PLWH, without prior COVID-19, compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response and reactogenicity.

Between February-September 2021, 1154 PLWH (median age 53 [IQR 44-60], 86% male) and 440 controls (median age 43 [IQR 33-53], 29% male) were included. 884 PLWH received BNT162b2, 100 mRNA-1273, 150 ChAdOx1-S, and 20 Ad26.COV2.S. 99% were on antiretroviral therapy, 98% virally suppressed, and the median CD4+T-cell count was 710 cells/{micro}L [IQR 520-913]. 247 controls received mRNA-1273, 94 BNT162b2, 26 ChAdOx1-S and 73 Ad26.COV2.S. After mRNA vaccination, geometric mean concentration was 1418 BAU/mL in PLWH (95%CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV-status remained associated with a decreased response (0.607, 95%CI 0.508-0.725). In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+T-cell counts 250-500 cells/{micro}L (2.845, 95%CI 1.876-4.314) or >500 cells/{micro}L (2.936, 95%CI 1.961-4.394), whilst a viral load >50 copies/mL was associated with a reduced response (0.454, 95%CI 0.286-0.720). Increased IFN-{gamma}, CD4+, and CD8+T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation induced marker assays, comparable to controls. Reactogenicity was generally mild without vaccine-related SAE.

ConclusionAfter vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH. To reach and maintain the same serological responses and vaccine efficacy as HIV-negative controls, additional vaccinations are probably required.

category: hiv aids


title: A 21L/BA.2-21K/BA.1 MixOmicron SARS-CoV-2 hybrid undetected by qPCR that screen for variant in routine diagnosis

abstract: Among the multiple SARS-CoV-2 variants identified since summer 2020, several have co-circulated, creating opportunities for coinfections and potentially genetic recombinations that are common in coronaviruses. Viral recombinants are indeed beginning to be reported more frequently. Here, we describe a new SARS-CoV-2 recombinant genome that is mostly that of a Omicron 21L/BA.2 variant but with a 3 tip originating from a Omicron 21K/BA.1 variant. Two such genomes were obtained in our institute from adults sampled in February 2022 in university hospitals of Marseille, southern France, by next-generation sequencing carried out with the Illumina or Nanopore technologies. The recombination site was located between nucleotides 26,858-27,382. In the two genomic assemblies, mean sequencing depth at mutation-harboring positions was 271 and 1,362 reads and mean prevalence of the majoritary nucleotide was 99.3{+/-}2.2% and 98.8{+/-}1.6%, respectively. Phylogeny generated trees with slightly different topologies according to whether genomes were depleted or not of the 3 tip. This 3 terminal end brought in the Omicron 21L/BA.2 genome a short transposable element of 41 nucleotides named S2m that is present in most SARS-CoV-2 except a few variants among which the Omicron 21L/BA.2 variant and may be involved in virulence. Importantly, this recombinant is not detected by currently used qPCR that screen for variants in routine diagnosis. The present observation emphasizes the need to survey closely the genetic pathways of SARS-CoV-2 variability by whole genome sequencing, and it could contribute to gain a better understanding of factors that lead to observed differences between epidemic potentials of the different variants.

category: infectious diseases


title: Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): a single blind, randomized, non-inferiority trial

abstract:
1BackgroundThe use of fractional dose regimens of COVID-19 vaccines has the potential to accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) have suggested that a fractional dose induces comparable antibody responses to the full, licensed dose in people below 55 years old. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine.

MethodsREDU-VAC is a participant-blinded, randomised, phase 4, multicentre, non-inferiority study investigating safety, reactogenicity and immunogenicity of BNT162b2. Adults aged between 18 and 55 years, without uncontrolled co-morbidities, either previously infected or infection naive, were eligible and recruited at five sites across Belgium. Participants were randomly assigned to receive 20{micro}g/20{micro}g (fractional dose) or 30{micro}g/30{micro}g (full dose) of BNT162b2, administered intra-muscularly at a three-week interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and the full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was greater than 0.67. The primary analysis was done on the per-protocol population, including infection naive participants only.

FindingsBetween April 19 and April 23, 2021, 145 participants were enrolled in the study and randomized, of whom 141 were vaccinated and reached the primary endpoint. Participants were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of SARS-CoV-2 anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540-0.944). No serious adverse events occurred.

ConclusionsWhile non-inferiority of the reduced dose regimen was not demonstrated, the SARS-CoV-2 anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials. The trial is registered at ClinicalTrials.gov (NCT04852861).


title: Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage

abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes govern this remain unknown.

In this study, we investigated the landscape of cardiac tissues collected at rapid autopsy from SARS-CoV-2, pH1N1, and control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by {gamma}-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of Interferon-stimulated genes (ISGs), in particular interferon and complement pathways, when compared with COVID-19 patients.

These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.


title: Global Reports of Myocarditis Following COVID-19 Vaccination: A Systematic Review and Meta-Analysis

abstract: In December 2020, the FDA granted emergency approval to Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) COVID-19 vaccines. There have been recent media reports of myocarditis after receiving COVID-19 vaccines, particularly the messenger RNA (mRNA) vaccines, causing public concern. This review summarizes information from published case series and case reports, with a strong emphasis on reporting patient and disease characteristics, investigation, and clinical outcome, to provide a comprehensive picture of the condition. Forty studies, including 147 cases, participated in this systematic review. The median age was 28.9 years; 93.9% were male and 6.1% were female. 72.1% of patients received the Pfizer-BioNTech (BNT162b2) vaccine, 24.5% of patients received the Moderna COVID-19 Vaccine (mRNA-1273), and the rest of the 3.3% received other types of vaccines. Furthermore, most myocarditis cases (87.1%) occurred after the second vaccine dose, after a median time interval of 3.3 days. The most frequently reported symptoms were chest pain, myalgia/body aches and fever. Troponin levels were consistently elevated in 98.6%. The admission ECG was abnormal in 88.5% of cases, and the left LVEF was lower than 50% in 26.5% of cases. The vast majority of patients (93.2%) resolved symptoms and recovered, and only 3 patients died. These findings may help public health policy to consider myocarditis in the context of the benefits of COVID-19 vaccination as well as to assess the cardiac condition before the choice of vaccine, which is offered to male adults. In addition, it must be carefully weighed against the very substantial benefit of vaccination.

category: cardiovascular medicine


title: Impact of spatiotemporal heterogeneity in COVID-19 disease surveillance on epidemiological parameters and case growth rates

abstract: SARS-CoV-2 case data are primary sources for estimating epidemiological parameters and for modelling the dynamics of outbreaks. Understanding biases within case based data sources used in epidemiological analyses are important as they can detract from the value of these rich datasets. This raises questions of how variations in surveillance can affect the estimation of epidemiological parameters such as the case growth rates. We use standardised line list data of COVID-19 from Argentina, Brazil, Mexico and Colombia to estimate delay distributions of symptom-onset-to-confirmation, -hospitalisation and -death as well as hospitalisation-to-death at high spatial resolutions and throughout time. Using these estimates, we model the biases introduced by the delay from symptom-onset-to-confirmation on national and state level case growth rates (rt) using an adaptation of the Richardson-Lucy deconvolution algorithm. We find significant heterogeneities in the estimation of delay distributions through time and space with delay difference of up to 19 days between epochs at the state level. Further, we find that by changing the spatial scale, estimates of case growth rate can vary by up to 0.13 d-1. Lastly, we find that states with a high variance and/or mean delay in symptom-onset-to-diagnosis also have the largest difference between the rt estimated from raw and deconvolved case counts at the state level. We highlight the importance of high-resolution case based data in understanding biases in disease reporting and how these biases can be avoided by adjusting case numbers based on empirical delay distributions. Code and openly accessible data to reproduce analyses presented here are available.

category: epidemiology


title: Strain-stream model of epidemic spread in application to COVID-19

abstract:
The recently developed model of the epidemic spread of two virus stains in a closed population is generalized for situation typical for the couple of strains delta and omicron, when there is high probability for omicron infection enough soon after recovering from delta infection. This model can be considered as some kind of weave of SIR and SIS models for the case of competition of two strains of the same virus having different contagiousness in a population.

PACS number(s)02.50.-r, 05.60.-k, 82.39.-k, 87.19.Xx


title: A Bayesian hierarchical framework to integrate dietary exposure and biomarker measurements into aetiological models

abstract: In nutritional epidemiology, self-reported assessments of dietary exposure are prone to measurement errors, which is responsible for bias in the association between dietary factors and risk of disease. In this study, self-reported dietary assessments were complemented by biomarkers of dietary intake. Dietary and serum measurements of folate and vitamin-B6 from two nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC) study were integrated in a Bayesian model to explore the measurement error structure of the data, and relate dietary exposures to risk of site-specific cancer. A Bayesian hierarchical model was developed, which included: 1) an exposure model, to define the distribution of unknown true exposure (X); 2) a measurement model, to relate observed assessments, in turn, dietary questionnaires (Q), 24-hour recalls (R) and biomarkers (M) to X measurements; 3) a disease model, to estimate exposures/cancer relationships. The marginal posterior distribution of model parameters was obtained from the joint posterior distribution, using Markov Chain Monte Carlo (MCMC) sampling techniques in JAGS. The study included 554 and 882 case/control pairs for kidney and lung cancer, respectively. In the measurement error component, the error correlation between Q measurements of vitamin-B6 and folate was estimated to be equal to 0.82 (95% CI: 0.76, 0.87). After adjustment for age, center, sex, BMI and smoking status, the kidney cancer odds ratios (OR) were 0.55 (0.16, 1.31) and 1.07 (0.33, 3.44) for one standard deviation increase of vitamin-B6 and folate, respectively. For lung cancer ORs were 0.85 (0.27, 2.42) for vitamin-B6 and 0.55 (0.14, 1.39) for folate. Bayesian models offer powerful solutions to handle complex data structures. After accounting for the role of measurement error, folate and vitamin-B6 were not associated to the risk of kidney and lung cancer.


title: Reducing societal impacts of SARS-CoV-2 interventions through subnational implementation

abstract: To curb the initial spread of SARS-CoV-2, many countries relied on nation-wide implementation of non-pharmaceutical interventions, at a high socio-economic cost. Using the first COVID-19 wave in the Netherlands as a case in point, we address how subnational implementations might have achieved similar levels of epidemiological control with fewer societal consequences; e.g., parts of the country could have stayed open for longer. To this end, we develop a high-resolution analysis framework reflecting a demographically stratified population with a spatially explicit, dynamic, individual contact pattern-based epidemiology, exploiting mobility trends extracted from mobile phone signals and Google mobility. The framework is exportable to other countries and settings, and may be used to develop policies on subnational approach as a better strategic choice for controlling future epidemics.


title: Predicting the time course of replacements of SARS-CoV-2 variants using relative reproduction numbers

abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved since its introduction to the human population in 2019. Natural selection selects variants with higher effective reproduction numbers, increasing the overall transmissibility of the circulating viruses. In order to establish effective control measures for a new variant, it is crucial to know its transmissibility and replacement time course in early phases of the variant replacement. In this paper, we conduct retrospective prediction tests of the variant replacement from Alpha to Delta in England. Our method firstly estimated the relative reproduction number, the ratio of the reproduction number of a variant to that of another, from partial observations up to a given time point. Secondly, the replacement time course after the time point was predicted based on the estimates of relative reproduction number. Thirdly, the estimated relative reproduction number and the predicted time course were evaluated by being compared to those estimated using the entire observations. We found that it is possible to estimate the relative reproduction number of Delta with respect to Alpha when the frequency of Delta was more than or equal to 0.25. Using these relative reproduction numbers, predictions targeting on 1st June 2021, the date when the frequency of Delta reached 0.90, had maximum absolute prediction errors of 0.015 for frequencies of Delta and 0.067 for the average relative reproduction number of circulating viruses with respect to Alpha. These results suggest that our method allows us to predict the time course of variant replacement in future from partial datasets observed in early phases of variant replacement.


title: Changing characteristics over time of individuals receiving COVID-19 vaccines in Denmark: A population-based descriptive study of vaccine uptake

abstract:
AimsThe Danish authorities implemented a differential rollout of the COVID-19 vaccines where individuals at high risk of COVID-19 were prioritized. We describe the temporal uptake of COVID-19 vaccines and changing characteristics of vaccine recipients in Denmark.

MethodsUsing the Danish national health care registries, we identified all Danish residents [≥]5 years of age who received at least one dose of a COVID-19 vaccine from December 27th, 2020, to January 29th, 2022. We charted the daily number of newly vaccinated individuals and the cumulative vaccine coverage over time, stratified by vaccine type, age groups, and vaccination priority groups. In addition, we described characteristics of vaccine recipients during 2-months-intervals and in vaccination priority groups.

ResultsBy January 29th, 2022, 86%, 84% and 63% of Danish residents [≥]5 years had received a first, second, and third dose, respectively, of a COVID-19 vaccine, most commonly the BNT162b2 vaccine (84% of vaccinated individuals). Vaccine uptake ranged from 48% in 5-11-year-olds up to 98% in 65-74-year-olds. Individuals vaccinated before June 2021 were older (median age 61-70 years vs. 10-35 years in later periods) and had more comorbidities such as hypertension (22-28% vs. 0.77-2.8% in later periods), chronic lung disease (9.4-15% vs. 3.7-4.6% in later periods), and diabetes (9.3-12% vs. 0.91-2.4% in later periods).

ConclusionsThe uptake of the COVID-19 vaccines is high in Denmark. We document substantial changes over time in characteristics of vaccine recipients which should be considered when designing and interpreting studies on the effectiveness and safety of COVID-19 vaccines.


title: Ethnic inequalities in multiple long-term health conditions in the United Kingdom: a systematic review and narrative synthesis

abstract: Indicative evidence suggests that minoritised ethnic groups have higher risk of developing multiple long-term conditions (MLTCs), and do so earlier than the white majority population. While there is evidence on ethnicity and single conditions and comorbidities, no review has attempted to look across these from a MLTCs perspective. As such, we currently have an incomplete understanding of the extent of ethnic inequalities in the prevalence of MLTCs. In this systematic review we aimed to 1) describe the literature that provides evidence of ethnicity and prevalence of MLTCs amongst people living in the UK, and 2) summarise the prevalence estimates of MLTCs across ethnic groups. We registered the protocol on PROSPERO (CRD42020218061). Between October and December 2020, we searched ASSIA, Cochrane Library, EMBASE, MEDLINE, PsycINFO, PubMed, ScienceDirect, Scopus, Web of Science, OpenGrey, and reference lists of key studies/reviews. The main outcome was prevalence estimates for MLTCs for at least one minoritised ethnic group, compared to the majority white population. We included studies conducted in the UK reporting on ethnicity and prevalence of MLTCs. To summarise the prevalence estimates of MLTCs across ethnic groups we included only studies of MLTCs that provided estimates adjusted at least for age. Two reviewers screened and extracted data from a random sample of studies (10%). Data were synthesised using narrative synthesis. Of the 7949 studies identified, 84 met criteria for inclusion. Of these, seven contributed to the evidence of ethnic inequalities in MLTCs. Five of the seven studies point to higher prevalence of MLTCs in at least one minoritised ethnic group compared to their white counterparts. Because the number/types of health conditions varied between studies and some ethnic populations were aggregated, the findings may not accurately reflect the true level of inequality. Thus, our conclusions can only be tentative. Future research should consider key explanatory factors, including those at the macrolevel (e.g. racism, discrimination), as they may play a role in the development of MLTCs in different ethnic groups.


title: Size of societal volunteering predicts COVID-19 mortality

abstract:
IntroductionDifferent countries responded differently to the COVID-19 pandemic in terms of timing and stringency of measures, and in types of policies adopted. Typically, policy makers tried to balance the capacity of healthcare systems to take care of the ill (as determined by ICU capacity, availability of nurses, etc.), with safeguarding economic output (preventing total lockdown of the labor force, etc.). Later on, also a broader array of considerations such as impact on schooling or the need for social contact were taken into account to varying degrees.

The broad and relatively fast availability of data on healthcare and economic capacity, together with the political estimate that these were the most critical determinants for maintaining societal structure and compliance with the measures taken, in many countries prioritized decision-making. What received far less attention, in part due to the difficulty of obtaining reliable data in a timely manner, was the opposite question: to what extent do societal structures - besides healthcare and economic systems - contribute to a countrys resilience during catastrophes such as the pandemic? While it is commonly understood that the impact of a pandemic goes beyond its death count, perhaps the death count itself is impacted by the way societies are structured.

One example of such societal structure is the contribution of volunteers during the COVID-19 response. Volunteers may contribute to well-functioning societies in different ways, both through practical actions (e.g. knitting face masks) as by strengthening societal cohesion (e.g. encouraging fellow citizens to comply with measures). This paper quantifies the association between COVID-19 mortality and the size of societal volunteering, using the unique context of the COVID-19 crisis with its intensity, sudden onset and global spread.


title: Efficacy of a multiple-component and multifactorial personalized fall prevention program in community-dwelling older adults at moderate-to-high fall risk: The PRE.C.I.S.A. Randomized Controlled Trial

abstract:
BackgroundThe fall risk in the elderly is a major public health issue due to the immediate injury-related consequences and the risk of associated long-term disability. However, the delivery of effective interventions for fall prevention in usual clinical practice still represents a challenge.

AimTo evaluate the efficacy of a multiple-component intervention combined with a multifactorial personalized intervention in reducing fall rates in community-dwelling older adults at moderate-to-high fall risk compared to usual care.

DesignRandomized Controlled Trial (unique identifier NCT03592420, clinicaltrials.gov).

SettingOutpatients in two Italian centers.

Population403 community-dwelling older adults at moderate-to-high fall risk, including subjects with Parkinsons Disease and stroke.

MethodsSubjects were randomized to the intervention (n=203) or the control group (n=200). A multiple-component and multifactorial personalized interventions were administered to the experimental intervention group. Participants allocated to the control group received usual care and recommendations to minimize the fall risk factors. In addition, each participant was given a diary to record falls and was followed for 12 months with monthly telephone contacts. The primary endpoint was represented by the total number of falls in each group over 12 months. The secondary endpoints were other fall-related indicators (fall rate of subjects with one or more falls, fall rate associated with hospitalization, fall severity, fall probability, and time to the first fall) recorded at the 12-month follow-up. Besides, several clinical scales were used to assess baseline (T1) and 3-month follow-up (T3) functioning.

ResultsA total of 690 falls were reported at 12-month follow-up, 337 (48.8%) in the intervention group and 353 (51.2%) in the control group with 1.66 ({+/-} 3.5) and 1.77 ({+/-} 3.2) mean falls per subject, respectively. The number of subjects with at least one fall was 236 (58.6%), with 119 (58.6%) and 117 falls (58.5%) in the intervention and control groups, respectively. No statistically significant differences were observed between groups regarding the number of falls, the fall probability, and the time to the first fall at 12-month follow-up. Furthermore, according to the subgroup analysis, no significant differences were reported between subgroups (i.e., the four etiological class categories of interest for the study). Finally, considering the two groups at pre-test (T1) and post-test (T3) evaluations, a statistically significant difference was found only for the Fullerton Advanced Balance Scale (p=0.006) and the Mini-BESTest (p=0.004) in favor of the intervention group.

ConclusionsThe proposed intervention was ineffective in reducing the number of falls, the fall probability, and the time to the first fall at 12-month follow-up in community-dwelling older adults at moderate-to-high fall risk. However, a lower number of falls, lower fall rates in multiple fallers, a lower mean number of falls per participant, and a lower rate of fall-related severe injuries were recorded for the intervention group, although not significant. Finally, a significant improvement for two balance-related indicators was recorded in the intervention group between pre and post-test evaluations. Future studies are needed to explore different effects of combined multiple-component and personalized multifactorial interventions to reduce falls and subsequent consequences. Future studies should also be planned with the clear aim of overcoming the limitations highlighted in the PRE.C.I.S.A. study.

category: rehabilitation medicine and physical therapy


title: Evaluation of cold pain tolerance in patients with fibromyalgia and opioid use by survival analysis

abstract:
PurposeCold pain tolerance is traditionally measured using the cold pressor test (CPT), a clinical pain research method in which participants immerse an extremity (i.e., hand or foot) into cold water for as long as tolerable. Prior research studies have investigated cold pain tolerance in patients with chronic pain, yet few have used survival analysis, which allows for proper handling of data censoring and therefore, the optimal statistical method for CPT data analysis. The goal of the present study was to use survival analysis to evaluate cold pain tolerance in patients with fibromyalgia. Furthermore, we aimed to model relationships between psychological and clinical variables as well as opioid medication use and cold pain tolerance.

Patients and MethodsA total of 85 patients with fibromyalgia (42 who were taking opioids) and 47 healthy pain-free controls were involved in two studies that provided CPT and questionnaire data. Survival analysis using Cox regression models evaluated group effects (patients vs. controls) and effects of psychological, clinical, and medication factors on cold pain tolerance.

ResultsPatients with fibromyalgia, as compared to healthy controls, exhibited significantly lower CPT survival (HR = 2.17, 95% CI: [1.42, 3.31], p = 0.00035). Cox regression models indicated that the psychological and clinical measures included did not strongly mediate this relationship (p > 0.05). When comparing across patient cohorts (Study 1 vs. Study 2), results were consistent across non-opioid-taking patient and healthy control groups, while differences in CPT survival were observed across the groups of patients taking opioid pain medications.

ConclusionReduced cold pain tolerance in patients with fibromyalgia is identified by survival analysis, an optimal method for time-to-event pain measures. While our selected psychological and clinical measures do not appear to be significantly associated with cold pain tolerance, opioid medication use may impart greater cold pain tolerance among some patients.

category: pain medicine


title: A Sex-Specific Genome-Wide Association Study of Depression Phenotypes in UK Biobank

abstract:
BackgroundThere are marked sex differences in the prevalence, phenotypic presentation and treatment response for major depression. While genome-wide association studies (GWAS) adjust for sex differences, to date no studies seek to identify sex-specific markers and pathways. In this study we performed a sex-stratified genome-wide association analysis for broad depression.

MethodsA genome-wide association study for broad depression was performed in the UK Biobank total participants (N=274,141), including only non-related participants, as well as separately in males (N=127,867) and females (N=146,274). Bioinformatics analyses were performed to characterize common and sex-specific markers and associated processes/pathways.

ResultsWe identified 11 loci passing genome level significance (P < 5* 10-8) in females and one in males. In both males and females, genetic correlations were significant between the broad depression GWA and other psychopathologies, however, correlations with educational attainment and metabolic features including body fat, waist circumference, waist-to-hip ratio and triglycerides were significant only in females. Gene-based analysis showed 147 genes significantly associated with broad depression in the total sample, 64 in the females and 53 in males. Gene-based analysis revealed "Regulation of Gene Expression" as a common biological process, but suggested sex-specific molecular mechanisms. Finally, sex-specific PRSs for broad depression outperformed total and the opposite sex PRSs in the prediction of broad MDD.

ConclusionsThese findings provide evidence for sex-dependent genetic pathways for clinical depression as well as for health conditions comorbid with depression.


title: Novel discoveries and enhanced genomic prediction from modelling genetic risk of cancer age-at-onset

abstract: Genome-wide association studies seek to attribute disease risk to DNA regions and facilitate subject-specific prediction and patient stratification. For later-life disease, inference from case-control studies is hampered by the uncertainty that control group subjects might later be diagnosed. Time-to-event analysis treats controls as right-censored, making no additional assumptions about future disease occurrence and representing a more sound conceptual alternative for more accurate inference. Here, using data on 11 common cancers from the UK and Estonian Biobank studies, we provide empirical evidence that discovery and genomic prediction are greatly improved by analysing age-at-diagnosis, compared to a case-control model of association. We replicate previous findings from large-scale case-control studies and find an additional 59 previously unreported independent genomic regions, out of which 16 replicated in independent data (an increase of 18% and 6% over current findings). Our novel discoveries provide new insights into underlying cancer pathways, and our model yields a better understanding of the polygenicity and genetic architecture of the 11 tumours. We find that heritable germline genetic variation plays a vital role in cancer occurrence, with risk attributable to many thousands of underlying genomic regions. Finally, we show that Bayesian modelling strategies utilising time-to-event data increase prediction accuracy. As sample size increases, incorporating time-to-event data should be commonplace, improving case-control studies by using richer information about the disease process.


title: Comparison of procedures performed and costs between an outsourced dental health plan with fee-for-service payment and an evidence-based, in-house dental health service with salaried professionals.

abstract:
It was evaluated a dental care services provided to almost 4,000 users (employees and their families) of a company (Moinhos de Vento Hospital, Brazil). The analysis was divided into two periods of time: from January 2000 to December 2002, during which time the dental care provided to employees (and families) was outsourced to a dental plan which operates with an accredited network, and from March 2003 to June 2005, when the dental care was provided by an in-house dental care service with preventive and evidence-based dentistry guidelines. Economic data were collected, as well as the type and number of procedures performed.

ConclusionsAn in-house service with evidence-based clinical protocols, as compared with an accredited network, decreased costs and also increased the number of procedures done, changed the profile of care for a less invasive dentistry and one more geared toward the causes of diseases, while still preserving the customers satisfaction.

category: health economics


title: The Application of Data Science Techniques and Algorithms in Women Health Research

abstract:
ObjectiveEvaluate and map data science methods employed to solve health conditions of women, examine the problems tackled and the effectiveness.

Research MethodText analytics, science mapping, and descriptive evaluation of data science methods utilized in women-related health research.

Findings(i). The trends in scholarships using data science methods indicate gaps between women and men relating to health burden and access to health. (ii). The coronavirus (SARS-CoV-2) outbreak and the ongoing COVID-19 pandemic tend to widen the identified health gaps, increasing the disease burden for women, while reducing access to health. There are noticeable additional health burdens on pregnant women and those with several health conditions (breast cancer, gynecologic oncology, cardiovascular disease, and more). (iii). Over 95% of studies using data science methods (artificial intelligence, machine learning, novel algorithms, predictive, big data, visual analytics, clinical decision support systems, or a combination of the methods) indicate significant effectiveness. (iv). Mapping of the scientific literature to authors, sources, and countries show an upward trend; 997 (16%), 113 (1.33%), and 57 (2.63%) per article, respectively. About 95% of research utilizing data science methods in womens health studies occurred within the last four (4) years.

ConclusionsThe application of data science methods in tackling different health problems of women is effective and growing, and capable of easing the burden of health in women. The ongoing COVID-19 pandemic tends to compound the health burden for women more than men. Policymakers must do more to improve access to health for women.


title: Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19

abstract: Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using in vitro microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs immediately resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.

category: hematology


title: Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial

abstract:
BackgroundThe antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in hospitalised patients with COVID-19, with indication of oxygen and/or ventilator support. Following prior publication of preliminary results, here we present the final results after completion of data monitoring.

MethodsIn this European multicentre, open-label, parallel-group, randomised, controlled trial (DisCoVeRy, NCT04315948; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care (SoC) alone or in combination with remdesivir, lopinavir/ritonavir, lopinavir/ritonavir and IFN-{beta}-1a, or hydroxychloroquine. Adult patients hospitalised with COVID-19 were eligible if they had clinical evidence of hypoxemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzyme, severe chronic kidney disease, any contra-indication to one of the studied treatments or their use in the 29 days before randomization, or use of ribavirin, as well as pregnancy or breast-feeding. Here, we report results for remdesivir + SoC versus SoC alone. Remdesivir was administered as 200 mg infusion on day 1, followed by once daily infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. Treatment assignation was performed via web-based block randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population.

FindingsBetween March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 843 participants were included for the evaluation of remdesivir (control, n=423; remdesivir, n=420).

At day 15, the distribution of the WHO ordinal scale was as follow in the remdesivir and control groups, respectively: Not hospitalized, no limitations on activities: 62/420 (14.8%) and 72/423 (17.0%); Not hospitalized, limitation on activities: 126/420 (30%) and 135/423 (31.9%); Hospitalized, not requiring supplemental oxygen: 56/420 (13.3%) and 31/423 (7.3%); Hospitalized, requiring supplemental oxygen: 75/420 (17.9%) and 65/423 (15.4%); Hospitalized, on non-invasive ventilation or high flow oxygen devices: 16/420 (3.8%) and 16/423 (3.8%); Hospitalized, on invasive mechanical ventilation or ECMO: 64/420 (15.2%) and 80/423 (18.9%); Death: 21/420 (5%) and 24/423 (5.7%). The difference between treatment groups was not statistically significant (OR for remdesivir, 1.02, 95% CI, 0.62 to 1.70, P=0.93). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups (remdesivir, n=147/410, 35.9%, versus control, n=138/423, 32.6%, p=0.29).

InterpretationRemdesivir use for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15.

FundingEuropean Union Commission, French Ministry of Health, DIM One Health Ile-de-France, REACTing, Fonds Erasme-COVID-ULB; Belgian Health Care Knowledge Centre (KCE), AGMT gGmbH, FEDER "European Regional Development Fund", Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Remdesivir was provided free of charge by Gilead.


title: Effectiveness of Typhoid Conjugate Vaccine in Zimbabwe used in response to an outbreak among children and young adults: a matched case control study

abstract:
BackgroundZimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare.

MethodsA matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls.

FindingsOf 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls.

The adjusted VE against confirmed TF was 75% (95%CI: 1-94, p=0.049) compared to facility controls, and 84% (95%CI: 57-94, p<0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26-77, p=0.153) compared to facility controls, and 67% (95%CI: 35-83, p=0.002) compared to community controls six months to 45 years old.

InterpretationThis study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.


title: Mapping brain endophenotypes associated with idiopathic pulmonary fibrosis genetic risk

abstract:
BackgroundIdiopathic pulmonary fibrosis (IPF) is a serious disease of the lung parenchyma. It has a known polygenetic risk, with at least seventeen regions of the genome implicated to date. Growing evidence suggests linked multimorbidity of IPF with neurodegenerative or affective disorders. However, no study so far has explicitly explored links between IPF, associated genetic risk profiles, and specific brain features.

MethodsWe exploited imaging and genetic data from more than 32,000 participants available through the UK Biobank population-level resource to explore links between IPF genetic risk and imaging-derived brain endophenotypes. We performed a brain-wide imaging-genetics association study between the 17 known loci of IPF genetic risk and 1,248 multi-modal imaging-derived features, which characterise brain structure and function.

FindingsWe identified strong associations between cortical thickness and white matter microstructure and IPF risk loci in chromosomes 17 (17q21.31) and 8 (DEPTOR). Through co-localisation analysis, we confirmed that the associated neuroimaging features and IPF share a single causal variant at the chromosome 8 locus. Exploratory post-hoc analysis suggested that forced vital capacity may act as a partial mediator in the association between the DEPTOR variant and white matter microstructure, but not between the DEPTOR risk variant and cortical thinning in the anterior cingulate.

InterpretationOur results reveal for the first time associations between IPF genetic risk and differences in brain structure, for both cortex and white matter. Differences in tissue-specific imaging signatures suggest distinct underlying mechanisms with focal cortical thinning in regions with known high DEPTOR expression unrelated to lung function, and more widespread microstructural white matter changes consistent with hypoxia or neuroinflammation with potential mediation by lung function.

FundingThis study was supported by the NIHR-funded Nottingham Biomedical Research Centre and the UK Medical Research Council.

O_TEXTBOXResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSIdiopathic pulmonary fibrosis (IPF) is a condition in which the lungs become scarred (fibrosed). Although IPF primarily affects the lungs, co-occurrence of impaired brain function, such as cognitive decline, increased risk of neurodegenerative disorders, cerebrovascular accidents, depression, and anxiety have been reported. The nature of this association is unclear and no post-mortem or in-vivo investigations have been performed to explore this directly. At the genetic level, 17 regions of the genome have been found to drive the genetic risk for IPF.

Added value of this studyUsing previously identified IPF genetic variants and neuroimaging-derived features from 32,431 participants available through the UK Biobank, we performed the first brain-wide association study for IPF risk variants. We identified brain endophenotypic associations for two IPF risk associated genetic variants, one in chromosome 17 and one in chromosome 8. In particular, increased IPF genetic risk, conferred by a variant near to the DEPTOR gene on chromosome 8, was associated with focal cingulate cortical thinning and more widespread changes in white matter microstructure. The cortical association signature was observed in regions with known DEPTOR expression while the subcortical findings may be mediated by forced vital capacity (measure of impaired lung function), hinting to distinct direct (cingulate) and indirect (subcortical) brain effects of DEPTOR risk alleles.

Implication of all the available evidenceThe reported brain-wide IPF risk association patterns reveal two plausible mechanisms that may explain the known association of IPF and brain disorders: (i) direct and focal, thought to be related to paralimbic mTOR dysregulation and (ii) indirect and widespread, in keeping with secondary effects from impaired lung function such as hypoxia. Taken together, these data support the hypothesis that genetic risk profiles may explain some of the observed comorbidity of IPF and brain disorders.

C_TEXTBOX


title: Identification of Global DNA Methylation Signatures in Patients of High Altitude Induced Venous Thrombo-Embolism (HA-VTE)

abstract:
BackgroundPathophysiology of venous thrombo-embolism (VTE) depends upon several acquired, inherited and environmental risk factors, including high altitude (HA) exposure. The present study aims to gain insights into pathophysiological mechanism(s) of high altitude induced VTE (HA-VTE) by studying global methylation signatures.

MethodologyBlood samples were collected from Indian Army volunteers divided into four study groups; sea level control (SLC), sea level VTE patients (SL-VTE), high altitude control (HAC) and high altitude VTE patients (HA-VTE). Methylation patterns were studied using whole genome bisulfate sequencing. Differentially methylated genes and pathways were identified by comparing percentage methylation.

ResultsHighest DM was observed in SL-VTE (1162 gene) compared to SLC where in hyper methylation was predominant (62.9%) compared to hypo methylation (37.05%). A reverse trend was observed in HA-VTE, where hypo methylation (61.69%) was predominant over hyper methylation (38.30%) in a total of 296 DM genes. Differential hypomethylation of genes involved in cell adhesion/platelet activity (CADM1, PTPRK, PDGFA) and immune response (CXCL12, IL4, IRF4, NLRP1) was observed in HA-VTE whereas genes encoding transcription factors (GSC, RPSKA1), trans membrane receptor (NOTCH2) and growth factor (TGFB2) were hypermethylated in comparison to SL-VTE. Methylation pattern of HA-VTE compared to HAC showed hypomethylation in genes involved in oxidative phosphorylation (CPOX), immune response and stress response (NDRG1), while those involved in signaling mechanisms (KALRN), neurotransmitter release (TMPRSS2) and transcription factor (ELF1) were hyper-methylated.

ConclusionsOur study for the first time reveals genome wide methylation pattern in HA-VTE group where in differential hypo methylation in cell adhesion and inflammation genes was observed.


title: Workload Indicators of Staffing Need (WISN) Method for Midwives Planning and Estimation at Asrade Zewude Memorial Primary Hospital, North west Ethiopia

abstract:
BackgroundWork force is a crucial component of health services delivery system. Ethiopia faces health workforce challenges with regard to evidence based health work force planning. First the health worker to population ratio was used and later standard staffing schedule for each health facility level was used. Both of these methods did not address the issue of evidence based workload variation between the same levels of facilities at different locations within a country. A workload indicator of staffing need method (WISN) addresses these variations. Therefore this study was assumed for recommendation on use of WISN for health facilities based on WISN results of midwives at Asrade Zewude memorial Hospital.

MethodsCross sectional study using WISN model was used to determine the gaps or excess and workload pressure in midwives at Asrade Zewude Memorial primary hospital, North West Ethiopia.

ResultsThe finding showed that there was five working days with 1030 hrs actual working time per year for midwives. This working time was spent on health service activities (58.4%), additional activities (36.6%) and support activities (5%). WISN calculation showed that a shortage of five midwives with WISN ratio of 0.8 at Asrade Zewude Memorial primary hospital North West Ethiopia.

ConclusionMidwives at the study area were doing their routine work with 20% under staffed by covering the additional five midwives position. With this working condition, it may be hard to achieve universal health coverage goals of the facility. Therefore the hospital should institutionalize WISN method to objectively employ midwifery professionals.

category: health policy


title: Human Papillomavirus (HPV) self-testing among un- and under-screened Maori, Pasifika, and Asian women in Aotearoa New Zealand: a preference survey among responders and interviews with clinical-trial non-responders

abstract:
AimM[a]ori, Pasifika, and Asian women are less likely to attend cervical screening and M[a]ori and Pasifika women are more likely to be diagnosed with later-stage cervical cancer than other women in Aotearoa New Zealand. This study - with under-screened women taking part in a randomised controlled trial comparing self-testing and standard screening - explored the acceptability of an HPV self-test kit and the preferred method for receiving it.

MethodsM[a]ori, Pasifika, and Asian women (N=376) completed a postal questionnaire. Twenty-six women who had not accepted the trial invitation were interviewed to understand their reasons for non-participation.

ResultsMost women found the self-test kit easy and convenient to use and reported that they did not find it painful, uncomfortable, or embarrassing. This was reflected in the preference for a self-test over a future smear test on the same grounds. Most women preferred to receive the kit by mail and take the test themselves, rather than having it done by a doctor or nurse. There was a range of preferences relating to how to return the kit. Phone calls with non-responders revealed that, although most had received the test kit, the reasons for not choosing to be involved included not wanting to, being too busy, or forgetting.

ConclusionsHPV self-testing was acceptable for M[a]ori, Pasifika, and Asian women in Aotearoa New Zealand. HPV self-testing has considerable potential to reduce the inequities in the current screening programme and should be made available with appropriate delivery options as soon as possible.


title: Engagement of health workers and peer educators from the National Adolescent Health Programme-Rashtriya Kishor Swasthya Karyakram during the COVID-19 pandemic: findings from a situational analysis

abstract:
BackgroundTo understand the impact of COVID-19 on implementation of the peer education programme of the National Adolescent Health Programme-Rashtriya Kishor Swasthya Karyakram; repurposing of the RKSK health workers and Peer Educators (PE) in COVID-19 response activities and; adolescents' health and development issues.

MethodsVirtual in-depth interviews were conducted with stakeholders (n=31) (aged 15 to 54) engaged in the implementation of the peer education programme at state, district, block, and village levels in Madhya Pradesh and Maharashtra (India). These interviews were thematically coded and analysed to address the research objectives.

ResultsDespite most peer education programme activities being stopped, delayed, or disrupted during the pandemic and subsequent lockdown, some communication networks previously established, helped facilitate public health communication regarding COVID-19 and RKSK, between health workers, peer educators, and adolescents. There was significant repurposing of RKSK health workers and Peer Educators role towards COVID-19 response-related activities. Peer educators, with support from health workers, were involved in disseminating COVID-19 information, maintaining migrant and quarantine records, conducting household surveys for finding COVID-19 active cases and providing essential items (grocery, sanitary napkins, etc.) to communities and adolescents.

ConclusionPeer Educators with support from community health workers are able to play a crucial role in meeting the needs of the communities during a pandemic. There is a need to further engage, involve and build the skills of Peer Educators to support the health system. PEs can be encouraged by granting more visibility and incorporating their role more formally by paying them within the public health system in India.


title: Ensuring a successful transition from Pap to HPV-based primary screening in Canada: a study protocol to investigate the psychosocial correlates of women's screening intentions

abstract:
IntroductionThe Human Papillomavirus (HPV) test has emerged as a significant improvement over cytology for primary cervical cancer screening. In Canada, provinces and territories are moving towards implementing HPV testing in cervical cancer screening programs. While an abundance of research exists on the benefits of HPV-based screening, there is a dearth of research examining womens understanding of HPV testing. In other countries, failure to adequately address womens concerns about changes has disrupted implementation of HPV-based screening. This study protocol describes a multi-step approach to develop psychometrically valid measures and to investigate psychosocial correlates of womens intentions to participate in HPV-based cervical cancer screening.

Materials and MethodsWe conducted a web-based survey of Canadian women to assess the acceptability and feasibility of a questionnaire, including validation of scales examining: cervical cancer knowledge, HPV testing knowledge, HPV testing attitudes and beliefs, and HPV test self-sampling attitudes and beliefs. Preferences for cervical cancer screening were assessed using Best-Worst Scaling methodology.

A second web-based survey will be administered to a national sample of Canadian women in June-July of 2022 using the validated scales. Differences in the knowledge, attitudes, beliefs, and preferences of women who are currently either underscreened or adequately screened for cervical cancer will be examined through bivariate analyses. Multinomial logistic regression will be used to estimate the associations between psychosocial and sociodemographic factors and intentions to screen using HPV-based screening.

Study Impact and DisseminationFindings will provide direction for Canadian public health authorities to align guidelines to address womens concerns and optimize acceptability and uptake of HPV-based primary screening. Validated scales can be used by other researchers to improve and standardize measurement of psychosocial factors impacting HPV test acceptability. Study results will be disseminated through peer-reviewed journal articles, conference presentations, and direct communication with researchers, clinicians, policymakers, media, and specialty organizations.


title: Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: a retrospective cohort study

abstract:
BackgroundThe aim of the study was to assess inflammatory markers and clinical outcomes in adult patients admitted to hospital with mild-to-moderate COVID-19 and treated with targeted immunosuppressive therapy using anti-IL-17A (netakimab), anti-IL-6R (tocilizumab), or JAK1/JAK2 inhibitor (baricitinib) or with standard-of-care (SOC) therapy.

MethodsThe retrospective, observational cohort study included 154 adults hospitalized between February and August, 2020 with RT-PCR-confirmed SARS-CoV-2 with National Early Warning Score2 (NEWS2) < 7 and C-reactive protein (CRP) levels [≤] 140 mg/L on the day of the start of the therapy or observation. Patients were divided into the following groups: I) 4 mg baricitinib, 1 or 2 times a day for an average of 5 days (n = 38); II) 120 mg netakimab, one dose (n = 48); III) 400 mg tocilizumab, one dose (n = 34), IV) SOC: hydroxychloroquine, antiviral, antibacterial, anticoagulant, and dexamethasone (n = 34).

FindingsCRP levels significantly decreased after 72 h in the tocilizumab (p = 1 x 10-5) and netakimab (p = 8 x 10-4) groups and remained low after 120 h. The effect was stronger with tocilizumab compared to other groups (p = 0.028). A significant decrease in lactate dehydrogenase (LDH) levels was observed 72 h after netakimab therapy (p = 0.029). NEWS2 scores significantly improved 72 h after tocilizumab (p = 6.8 x 10-5) and netakimab (p = 0.01) therapy, and 120 h after the start of tocilizumab (p = 8.6 x 10-5), netakimab (p = 0.001), or baricitinib (p = 4.6 x 10-4) therapy, but not in the SOC group. Blood neutrophil counts (p = 6.4 x 10-4) and neutrophil-to-lymphocyte ratios (p = 0.006) significantly increased 72 h after netakimab therapy and remained high after 120 h. The percentage of patients discharged 5-7 days after the start of therapy was higher in the tocilizumab (44.1%) and netakimab (41.7%) groups than in the baricitinib (31.6%) and SOC (23.5%) groups. Compared to SOC (3/34, 8.8%), mortality was lower in netakimab (0/48, 0%, RR=0.1 (95% CI: 0.0054 to 1.91)), tocilizumab (0/34, 0%, RR=0.14 (95% CI: 0.0077 to 2.67)), and baricitinib (1/38, 2.6%, RR=0.3 (95% CI: 0.033 to 2.73)) groups.

InterpretationIn hospitalized patients with mild-to-moderate COVID-19, anti-IL-17A or anti-IL-6R therapy were superior or comparable to the JAK1/JAK2 inhibitor, and all three were superior to SOC. Whereas previous studies did not demonstrate significant benefit of anti-IL-17A therapy for severe COVID-19, our data suggest that such therapy could be a rational choice for mild-to-moderate disease, considering the generally high safety profile of IL-17A blockers. The significant increase in blood neutrophil counts in the netakimab group may reflect efflux of neutrophils from inflamed tissues. We therefore hypothesize that neutrophil count and neutrophil-to-lymphocyte ratio could serve as markers of therapeutic efficiency for IL-17A-blocking antibodies in the context of active inflammation.

category: allergy and immunology


title: Patterns of antibiotic cross-resistance by bacterial sample source: a retrospective cohort study

abstract:
BackgroundAntimicrobial resistance is a major healthcare burden, exasperated when it extends to multiple drugs. While cross-resistance across multiple drugs is well-studied experimentally, it is not the case in clinical settings, and especially not while considering confounding. In addition, bacteria from different sample sources may have undergone different evolutionary trajectories, therefore examining cross-resistance across sources is desirable.

MethodsWe employed additive Bayesian network (ABN) modelling to examine antibiotic cross-resistance in five major bacterial species, obtained from different sources (urine, wound, blood, and sputum) in a clinical setting, collected in a large hospital in Israel over a 4-year period. ABN modelling allowed for examination of the relationship between resistance to different drugs while controlling for major confounding variables.

FindingsPatterns of cross-resistance differ across sample sources. Importantly, even when positive cross-resistance exists between two antibiotics in different sample sources, its magnitude may vary substantially.

InterpretationOur results highlight the importance of considering sample sources when assessing likelihood of antibiotic cross-resistance and determining antibiotic treatment regimens and policies.

category: pharmacology and therapeutics


title: Evidence for feasibility of mobile health and social media-based interventions for early psychosis and clinical high risk

abstract:
BackgroundDigital technology, the internet and social media are increasingly investigated as a promising means for monitoring symptoms and delivering mental health treatment. These apps and interventions have demonstrated preliminary acceptability and feasibility, but previous reports suggests that access to technology may still be limited among individuals with psychotic disorders relative to the general population.

ObjectiveWe evaluated and compared access and use of technology and social media in young adults with psychotic disorders (PD), clinical risk for psychosis (CR), and psychosis-free youths (PF).

MethodsParticipants were recruited through a coordinated specialty care clinic dedicated towards early psychosis as well as ongoing studies. We surveyed 21 PD, 23 CR, and 15 PF participants regarding access to technology and use of social media, specifically Facebook and Twitter. Statistical analyses were conducted in R. Categorical variables were compared among groups Fishers exact test, continuous variables were compared using one-way ANOVA, and multiple linear regressions were used to evaluate for covariates.

ResultsAccess to technology and social media were similar among PD, CR and PF. Individuals with PD, but not CR, were less likely to post at a weekly or higher frequency compared to psychosis-free individuals. We found that decreased active social media posting was unique to psychotic disorders and did not occur with other psychiatric diagnoses or demographic variables. Additionally, variation in age, sex, Caucasian vs. non-Caucasian race did not affect posting frequency.

ConclusionsFor young people with psychosis spectrum disorders, there appears to be no "technology gap" limiting the implementation of digital and mobile health interventions. Active posting to social media was reduced for individuals with psychosis, which may be related to negative symptoms or impairment in social functioning.

category: psychiatry and clinical psychology


title: Behaviour change interventions improve maternal and child nutrition in sub-Saharan Africa: a systematic review

abstract:
BackgroundEvidence that nutrition-specific and nutrition-sensitive interventions can improve maternal and child nutrition status in sub-Saharan Africa is inconclusive. Using behaviour change theory and techniques in intervention design may increase effectiveness and make outcomes more predictable. This systematic review aimed to determine whether interventions that included behaviour change functions were effective.

MethodsSix databases were searched systematically, using MeSH and free-text terms, for articles describing nutrition-specific and nutrition-sensitive behaviour change interventions published in English until January 2022. Titles, abstracts and full-text papers were double-screened. Data extraction and quality assessments followed Centre for Reviews and Dissemination guidelines. Behaviour change functions of interventions were mapped onto the COM-B model and Behaviour Change Wheel. PROSPERO registered (135054).

FindingsThe search yielded 1149 articles: 71 articles met inclusion criteria, ranging from low (n=30) to high (n=11) risk of bias. Many that applied behaviour change theory, communication or counselling resulted in significant improvements in infant stunting and wasting, household dietary intake and maternal psychosocial measures. Interventions with >2 behaviour change functions (including persuasion, incentivisation, environmental restructuring) were the most effective.

InterpretationWe recommend incorporating behaviour change functions in nutrition interventions to improve maternal and child outcomes, specifically drawing on the Behaviour Change Wheel, COM-B model. To enhance the designs of these interventions, and ultimately improve the nutritional and psychosocial outcomes for mothers and infants in sub-Saharan Africa, collaborations are recommended between behaviour change and nutrition experts, intervention designers, policy makers and commissioners to fund and roll-out multicomponent behaviour change interventions.

category: nutrition


title: Breast and Cervical Cancer Screening Rates in Student-Run Free Clinics: A Systematic Review

abstract:
ObjectiveTo assess rates of breast and cervical cancer screening at student-run free clinics to better understand challenges and strategies for advancing quality and accessibility of womens health screening at student-run free clinics.

Data sourcesWe performed a systematic search of Ovid MEDLINE, PubMed, Web of Science, and Google Scholar databases from database inception to 2020 using keywords related to student-run clinics, breast cancer screening, and cervical cancer screening.

Study eligibility criteriaWe included all English-language publications describing screening rates of breast and/or cervical cancer at student-run free clinics within the United States. Five authors screened abstracts and reviewed full texts for inclusion.

Study appraisal and synthesis methodsTwo reviewers extracted data independently for each publication using a structured data extraction table. Disagreements were resolved by group consensus. Two reviewers then assessed for risk of bias for each text using a modified Agency for Healthcare Research and Quality checklist for cross-sectional and prevalence studies. Results were synthesized qualitatively due to study heterogeneity.

ResultsOf 3634 references identified, 12 references met study inclusion criteria. The proportion of patients up-to-date on breast cancer screening per guidelines ranged from 45% to 94%. The proportion of patients up-to-date on cervical cancer screening per guidelines ranged from 40% to 88%.

ConclusionStudent-run free clinics can match breast and cervical cancer screening rates amongst uninsured populations nationally, though more work is required to bridge the gap in care that exists for the underinsured and uninsured.

category: obstetrics and gynecology


title: The impact of COVID-19 pandemic on influenza surveillance: a systematic review and meta-analysis

abstract: Influenza activity was reported to be below the seasonal levels during the COVID-19 pandemic globally. However, during the SARS-CoV-2 outbreak, the routine real-time surveillance of influenza like illness (ILI) and acute respiratory infection (ARI) was adversely affected due to the changes in priorities, economic constraints, repurposing of hospitals for COVID care and closure of outpatient services. A systematic review and meta-analysis were carried out to assess the pooled proportion of symptomatic cases tested for influenza virus before the COVID-19 pandemic in 2019 and during the pandemic in 2020/2021. The study was designed based on PRISMA guidelines and the meta-analysis was performed to synthesise the pooled proportion of patients sampled for influenza surveillance before the COVID-19 pandemic in 2019 and during the pandemic in 2020/21 with 95% confidence interval (CI). The overall pooled proportion of symptomatic cases undergone influenza surveillance before and during the pandemic was 2.38% (95% CI 2.08%-2.67%) and 4.18% (95% CI 3.8%-4.52%) respectively. However, the pooled proportion of samples tested for influenza before the pandemic was 0.69% (95% CI 0.45-0.92%) and during the pandemic was 0.48% (95% CI 0.28-0.68%) when studies from Canada were excluded. The meta-analysis concludes that globally there was a decline in influenza surveillance during the COVID-19 pandemic except in Canada.


title: Interpretation of non-responders to SARS-CoV-2 vaccines using WHO International Standard

abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with more than 485 millions infected. Questions about non-responders to SARS-CoV-2 vaccines remain unaddressed. Here, we report data from people after administering the complete dose of SARS-CoV-2 vaccines using the World Health Organization International Standard for anti-SARS-CoV-2 immunoglobulin. Our study showed that immune cells such as CD4 cells, CD8 cells, and B cells and anti-spike immunoglobulin G levels were significantly reduced in the elderly. There were 7.5% non-responders among the 18-59 yr group and 11.7% in the [≥]60 yr group. A titer of anti-SARS-CoV-2 spike immunoglobulin G is blew 50 BAU/mL to be considered as non-responders at intervals of 30 to 90 days after the last vaccine dose. Booster vaccination may be recommended for non-responders to reduce the disease severity and mortality.


title: Changes in Apolipoprotein A1 and B, Glucose Metabolism, and Skeletal Muscle Mass in Peripheral Artery Disease after Endovascular Treatment: A Pilot Study

abstract: Peripheral artery disease impairs walking and physical activity, resulting in further loss of skeletal muscle. However, peripheral artery disease can be treated with endovascular treatment. The thigh muscle has been shown to correlate with systemic skeletal muscle volume. We assessed the changes in the metabolism of apolipoproteins A1 and B, blood glucose, and thigh muscle mass after endovascular treatment in above-the-knee peripheral artery disease where vessels supply the thigh muscle. Mid-thigh muscle volume was measured with computed tomography before and at 6 months after endovascular treatment. Apolipoproteins A1 and B, fasting blood glucose, post-load (75 g oral glucose tolerance test) 2 h-blood glucose, and glycated hemoglobin A1c (HbA1c) levels were measured concomitantly. The relationships between changes in apolipoproteins A1, apolipoproteins B, blood glucose, post-oral glucose tolerance test 2 h-blood glucose, Rutherford classification, and gain or loss of thigh muscle were investigated. Thigh muscle mass did not correlate with changes in apolipoproteins A1, B, fasting glucose, post-oral glucose tolerance test 2 h-blood glucose, HbA1c, and Rutherford classification. Among patients with muscle gain post-endovascular treatment, apolipoproteins A1 increased significantly, while apolipoproteins B levels were similar. Post-oral glucose tolerance test 2 h-blood glucose levels decreased. Preferable metabolic changes were observed in patients with skeletal muscle gain contrasted with muscle loss.


title: Recurrent aphthous stomatitis affects quality of life

abstract: Recurrent aphthous stomatitis are recurrent oral ulcers that can affect important daily activities, such as oral hygiene and eating. In this prospective case-control study (n=62), we show that, during ulcer episodes, patients report a poorer quality of life compared to ulcer-free periods, and that this impact is positively associated with the number and size of lesions. Our results suggest that, if intervened locally, general relief of the condition could be achieved.

category: dentistry and oral medicine


title: Modeling and Global Sensitivity Analysis of Strategies to Mitigate Covid-19 Transmission on a Structured College Campus

abstract: In response to the COVID-19 pandemic, many higher educational institutions moved their courses on-line in hopes of slowing disease spread. The advent of multiple highly-effective vaccines offers the promise of a return to "normal" in-person operations, but it is not clear if - or for how long - campuses should employ non-pharmaceutical interventions such as requiring masks or capping the size of in-person courses. In this study, we develop and fine-tune a model of COVID-19 spread to UC Merceds student and faculty population. We perform a global sensitivity analysis to consider how both pharmaceutical and non-pharmaceutical interventions impact disease spread. Our work reveals that vaccines alone may not be sufficient to eradicate disease dynamics and that significant contact with an infected surrounding community will maintain cases on-campus. Our work provides a foundation for higher-education planning allowing campuses to balance the benefits of in-person instruction with the ability to quarantine/isolate infected individuals.