title: Neuropsychological assessments for dementia research in the COVID-19 era: comparing remote and face-to-face testing

abstract:
ObjectivesWe explored whether adapting traditional neuropsychological tests for online administration against the backdrop of COVID-19 was feasible for people with diverse forms of dementia and healthy older controls. We compared face-to-face and remote settings to ascertain whether remote administration affected performance.

DesignWe used a longitudinal design for healthy older controls who completed face-to-face neuropsychological assessments between three and four years before taking part remotely. For patients, we used a cross-sectional design, contrasting a prospective remote cohort with a retrospective face-to-face cohort matched in age, education, and disease duration.

SettingRemote assessments were performed using video-conferencing and online testing platforms, with participants using a personal computer or tablet and situated in a quiet room in their own home. Face-to-face assessments were carried out in dedicated testing rooms in our research centre.

ParticipantsThe remote cohort comprised ten healthy older controls (also seen face-to-face 3-4 years previously) and 25 patients (n=8 Alzheimers disease (AD); n=3 behavioural variant frontotemporal dementia (bvFTD); n=4 semantic dementia (SD); n=5 progressive nonfluent aphasia (PNFA); n=5 logopenic aphasia (LPA)). The face-to-face patient cohort comprised 64 patients (n=25 AD; n=12 bvFTD; n=9 SD; n=12 PNFA; n=6 LPA).

Primary and secondary outcome measuresThe outcome measures comprised the strength of evidence under a Bayesian analytic framework for differences in performances between face-to-face and remote testing environments on a general neuropsychological (primary outcomes) and neurolingustic battery (secondary outcomes).

ResultsThere was evidence to suggest comparable performance across testing environments for all participant groups, for a range of neuropsychological tasks across both batteries.

ConclusionsOur findings suggest that remote delivery of neuropsychological tests for dementia research is feasible.

Strengths and limitations of this studyO_ST_ABSMethodological strengths of this study includeC_ST_ABSO_LIDiverse patient cohorts representing rare dementias with specific communication difficulties
C_LIO_LISampling of diverse and relevant neuropsychological domains
C_LIO_LIUse of Bayesian statistics to quantify the strength of evidence for the putative null hypothesis (no effect between remote and face-to-face testing)
C_LI

Limitations includeO_LIRelatively small cohort sizes
C_LIO_LILack of direct head-to-head comparisons of test environment in the same patients
C_LI


title: Islamic Perspective on Nursing and the Philosophy of Science

abstract: Although nursing theory developed in the modern Western scientific tradition has universal aspects, it is important to consider the different philosophies, beliefs and cultures of each different society to enrich the perspective and practice of nursing that is more sensitive to the patients background. As supported by the Transcultural Nursing Theory, in treating patients a nurse needs to pay attention to and respect the cultural preferences and beliefs of the patient. In this context, this article wants to contribute by describing the Islamic perspective on nursing in the context of nursing philosophy. Methods: This literature review uses articles published from 2018-2022 with source from databased ScienceDirect, Scopus, Sage Journals, EBSCO-Host, Springer Link, and ProQuest. The keywords used are Islamic, perspective, nursing, caring. Article selection follows "PRISMA" flow. Results: This systematic review have a total of 8 articles meet the criteria for analysis. This article has relevance both in Muslim-majority countries such as Indonesia, Malaysia and Middle Eastern countries, as well as countries where Muslims are a minority. We found 8 articles presents a number of opinions or research results that examine nursing issues and those related to it from an Islamic perspective. From a number of opinions and research findings studied, it can be concluded that although it can be said to offer universal core values, the Islamic perspective has fundamental differences with Western nursing philosophy or theory, especially in terms of the source of knowledge, the basic view of humans, and the importance of spirituality in nursing.

category: nursing


title: Phenotypic associations with the HMOX1 GT(n) promoter repeat in European populations

abstract: HO-1 is a key enzyme in the management of heme in humans. A GT(n) repeat length in the gene HMOX1, has previously been widely associated with a variety of phenotypes, including susceptibility and outcomes in diabetes, cancer, infections, and neonatal jaundice. However, studies are generally small and results inconsistent. In this study, we imputed the GT(n) repeat length in two European cohorts (UK Biobank, n = 463,005; and Avon Longitudinal Study of Parents and Children (ALSPAC n = 937), with the reliability of imputation tested in other cohorts (1000 Genomes, HGDP, and UK-PGP). Subsequently, we measured the relationship between repeat length and previously identified associations (diabetes, COPD, pneumonia and infection related mortality in UK Biobank; neonatal jaundice in ALSPAC) and performed a phenome-wide association study (PheWAS) in UK Biobank. Despite high quality imputation (correlation between true repeat length and imputed repeat length >0.9 in test cohorts), no clinical associations were identified in either the PheWAS or specific association studies. These findings were robust to definitions of repeat length and sensitivity analyses. Despite multiple smaller studies identifying associations across a variety of clinical settings; we could not replicate or identify any relevant phenotypic associations with the HMOX1 GT(n) repeat.

category: genetic and genomic medicine


title: A machine learning-based SNP-set analysis approach for identifying disease-associated susceptibility loci

abstract:
IntroductionIdentifying disease-associated susceptibility loci is one of the most pressing and crucial challenges in modeling complex diseases. Existing approaches to biomarker discovery are subject to several limitations including underpowered detection, neglect for variant interactions, and restrictive dependence on prior biological knowledge. Addressing these challenges necessitates more ingenious ways of approaching the "missing heritability" problem.

ObjectivesThis study aims to discover disease-associated susceptibility loci by augmenting previous genome-wide association study (GWAS) using the integration of random forest and cluster analysis.

MethodsThe proposed integrated framework is applied to a hepatitis B virus surface antigen (HBsAg) seroclearance GWAS data. Multiple cluster analyses were performed on (1) single nucleotide polymorphisms (SNPs) considered significant by GWAS and (2) SNPs with the highest feature importance scores obtained using random forest. The resulting SNP-sets from the cluster analyses were subsequently tested for trait-association.

ResultsThree susceptibility loci possibly associated with HBsAg seroclearance were identified: (1) SNP rs2399971, (2) gene LINC00578, and (3) locus 11p15. SNP rs2399971 is a biomarker reported in the literature to be significantly associated with HBsAg seroclearance in patients who had received antiviral treatment. The latter two loci are linked with diseases influenced by the presence of hepatitis B virus infection.

ConclusionThese findings demonstrate the potential of the proposed integrated framework in identifying disease-associated susceptibility loci. With further validation, results herein could aid in better understanding complex disease etiologies and provide inputs for a more advanced disease risk assessment for patients.


title: Updating mortality risk estimation in intensive care units from high-dimensional electronic health records with incomplete data

abstract:
ContextIntensive care units (ICU) are subject to a high mortality rate, currently addressed by the implementation of scores (SAPS II, SOFA, APACHE II) assessing the risk of in-hospital mortality from admission data. Their performances are satisfactory to predict death when complications occur early after admission; however, they may become irrelevant in the case of long hospital stays.

MethodsUsing the MIMIC-III database, we developed predictive models of short-term mortality in ICU from longitudinal data collected throughout patients stays of at least 48 hours. Several statistical learning approaches were compared, including deep neural networks and penalized regression. Missing data were handled using either complete case analysis or multiple imputation. Models performances were evaluated via repeated 5-fold cross-validation.

ResultsPredictions relying on longitudinal data were more accurate than those relying solely on admission data. Complete case analyses from 19 predictors showed good discrimination (area under the ROC curve [AUC] > 0.77 for several statistical learning approaches) to predict death between 12 and 24 hours onwards, while keeping only 25% of patients in the sample. Multiple imputation allowed to include 70 predictors and keep 95% of patients, with similar performances, hence allowing predictions in patients with incomplete data. Calibration was satisfactory for all models.

DiscussionThis proof of concept supports that automated analysis of electronic health records can be of great interest throughout patients stays, as a surveillance tool likely to detect lethal complications in ICU soon enough to take corrective measures. Though this framework relies on a large set of predictors, it is robust to data imputation and may be effective early after admission, as data is still scarce.

category: health informatics


title: Heterogeneity of Provider Preferences for HIV Care Coordination Program Features: Latent Class Analysis of a Discrete Choice Experiment

abstract:
BackgroundThe PROMISE study was launched in 2018 to assess revisions to an HIV care coordination program (CCP) designed to address gaps in care and treatment engagement among people living with HIV in New York City (NYC). We report on the heterogeneity of provider preferences regarding a revised CCP elicited from a discrete choice experiment (DCE).

MethodsFrom January to March 2020, 152 CCP providers in NYC completed a DCE with 4 program attributes: 1) help with adherence to antiretroviral therapy, 2) help with primary care appointments, 3) help with issues other than primary care, and 4) program visit location. Each attribute had 3-4 levels. Latent class analysis (LCA) was used to detect subgroups with differing attribute importance and part-worth utility patterns. Choice simulation was used to estimate providers endorsement of eight hypothetical CCPs.

ResultsLCA identified three subgroups. The two larger subgroups (n = 133) endorsed more intensive attribute levels, particularly clients receiving directly observed therapy, and home visits. The remaining smaller subgroup (n = 19) endorsed clients receiving medication reminders and meeting with clients at the program. Simulation showed that intensive medical case management programs had the highest degree of endorsement (62%).

ConclusionWhile our results indicate high endorsement among providers for intensive CCP features, overall, they also suggest the need for flexible service delivery options to meet the needs of the clients that these programs serve. Additional information sharing across and within agencies may be warranted to improve the fidelity with which the CCP is implemented.

category: hiv aids


title: Interest of seroprevalence surveys for the epidemiological surveillance of the SARS-CoV-2 pandemic in African populations: insights from the ARIACOV Project in Benin

abstract:
BackgroundMany SARS-CoV-2 seroprevalence surveys since the end of 2020 have disqualified the first misconception that Africa had been spared by the pandemic. Through the analysis of three SARS-CoV-2 seroprevalence surveys carried out in Benin as part of the ARIACOV project, we argue that the integration of epidemiological serosurveillance of the SARS-COV2 infection in the national surveillance package would be of great use to refine the understanding of the COVID-19 pandemic in Africa.

MethodsThree repeated cross-sectional surveys have been carried out in Benin, two in Cotonou, the economic capital in March and May 2021, and one in Natitingou, a semi-rural city in North in August 2021. The global and by age-groups weighted seroprevalences have been estimated and the risk factors of the infection by SARS-COV-2 have been assessed by using logistic regression.

ResultsIn Cotonou, a slight increase in overall age-standardized SARS-CoV-2 seroprevalence from 29.77% (95% CI: 23.12-37.41%) at the first survey to 34.86% (95% CI: 31.57-38.30%) at the second survey was observed. In Natitingou the global adjusted seroprevalence was 33.34% (95% CI: 27.75-39.44%), much higher than expected. Adults over 40 seemed to be more at risk than the youngest during the first survey in Cotonou but no longer in the second survey, showing the persistence of the SARS-COV-2 virus circulation outside the epidemic waves.

ConclusionsA routine serological surveillance on strategic sentinel sites and / or populations could constitute a cost / effective compromise to better anticipate the onset of new waves and define public health strategies.

category: infectious diseases


title: Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

abstract: Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas(R) SARS-CoV-2 assays, defined by a [≥]2 thermocycles delay in detection of the ORF1ab gene compared to the E gene. We demonstrate that pOGTF is 97% sensitive and 99% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may impact transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.


title: "Utilization of health insurance by patients with diabetes or hypertension in urban hospitals in Mbarara, Uganda"

abstract:
BackgroundDiabetes and hypertension are among the leading contributors to global mortality and require life-long medical care. However, many patients cannot access quality healthcare due to high out-of-pocket expenditures, thus health insurance would help provide relief. This paper examines factors associated with utilization of health insurance by patients with diabetes or hypertension at two urban hospitals in Mbarara, southwestern Uganda.

MethodsWe used a cross-sectional survey design to collect data from patients with diabetes or hypertension attending two hospitals located in Mbarara. Logistic regression models were used to examine associations between demographic factors, socio-economic factors and awareness of scheme existence and health insurance utilization.

ResultsWe enrolled 370 participants, 235 (63.5%) females and 135 (36.5%) males, with diabetes or hypertension. Patients who were not members of a microfinance scheme were 76% less likely to enrol in a health insurance scheme (OR = 0.34, 95% CI: 0.15 - 0.78, p = 0.011). Patients diagnosed with diabetes/hypertension 5 - 9 years ago were more likely to enrol in a health insurance scheme (OR = 2.99, 95% CI: 1.14 - 7.87, p = 0.026) compared to those diagnosed 0 - 4 years ago. Patients who were not aware of the existing schemes in their areas were 99% less likely to take up health insurance (OR = 0.01, 95% CI: 0.0 - 0.02, p < 0.001) compared to those who knew about health insurance schemes operating in the study area. Majority of respondents expressed willingness to join the proposed national health insurance scheme although concerns were raised about high premiums and misuse of funds which may negatively impact decisions to enrol.

ConclusionBelonging to a microfinance scheme positively influences enrolment by patients with diabetes or hypertension in a health insurance program. Although a small proportion is currently enrolled in health insurance, the vast majority expressed willingness to enrol in the proposed national health insurance scheme. Microfinance schemes could be used as an entry point for health insurance programs for patients in these settings.

category: cardiovascular medicine


title: Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation and gut microbiota composition in a twin study

abstract: NAD+ precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have failed to report positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twins from 22 BMI-discordant monozygotic pairs were supplemented with an escalating dose of NR (250-1000 mg/day) for 5 months (clinicaltrials.gov entry NCT03951285). NR improved blood and tissue NAD+ metabolism, muscle mitochondrial number, myoblast differentiation and gut microbiota composition independent of BMI. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD+ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.

category: endocrinology


title: Life stage-specific effects of genetic susceptibility to higher body size on body fat and lean mass: prospective cohort study

abstract:
Background/ObjectivesSeparate genetic variants are associated with larger body size in childhood and adulthood. Whether these variants predominantly influence adiposity, and whether these truly differ by life stage is unknown. We examined how genetic variants influence total body fat and total lean mass trajectories from childhood to young adulthood.

MethodsData were from the Avon Longitudinal Study of Parents and Children birth cohort. Sex-specific genetic risk scores (GRS) for childhood and adulthood body size were generated, and dual-energy X-ray absorptiometry scans were used to measure total body fat and lean mass 6 times between ages 9-25y. We used mutually-adjusted multilevel linear spline models to examine the independent sex-specific associations of childhood and adulthood body size GRSs with fat and lean mass trajectories from 9 -25y.

ResultsIn males, the childhood and adulthood GRS were associated with similar differences in fat mass from 9 to 18y; 8.3% (95% confidence interval (CI): 5.1,11.6)) and 7.5% (95% CI: 4.3,10.8) higher fat mass at 18y per standard deviation (SD) higher childhood and adulthood GRS respectively. At 25y, childhood GRS associations with fat mass attenuated while adulthood GRS associations remained similar to those at 18y for males. Among females, associations for the childhood GRS were almost two-fold stronger than the adulthood GRS from 9 to 18y: 10.5% (95% CI: 8.5, 12.4) higher fat mass at 9y per SD higher childhood GRS compared with 5.1% (95% CI 3.2, 6.9) per SD higher adulthood GRS. At 25y, associations of the childhood and adulthood GRS with fat mass were similar; 5.0% (95% CI: 2.5, 7.5) and 5.8% (95% CI: 3.3, 8.3) higher fat mass per SD higher childhood and adulthood GRS respectively: Lean mass effect sizes were much smaller.

ConclusionsGenetic variants for body size are more strongly associated with adiposity than lean mass from childhood to early adulthood; childhood variants are more strongly associated with adiposity in females until early adulthood whereas childhood and adulthood variants are similarly associated with adiposity across early life in males. Findings may inform selection of instruments for life stage-specific adiposity in future Mendelian randomization studies.

category: epidemiology


title: Incorporating Vaccination into Compartment Models for Infectious Diseases

abstract: The standard way of incorporating vaccination into a compartment model for an infectious disease is as a spontaneous transition process that applies to the entire susceptible class. The large degree of COVID-19 vaccine refusal and initial limitations of supply and distribution require reconsideration of this standard treatment. In this paper, we address these issues for models on endemic and epidemic time scales. On an endemic time scale, we partition the susceptible class into prevaccinated and unprotected subclasses and show that vaccine refusal has a significant impact on endemic behavior, particularly for diseases where immunity is short-lived. On an epidemic time scale, we develop a supply-limited Holling type 3 vaccination model and show that it is an excellent fit to vaccination data. We also extend the Holling model to a COVID-19 scenario in which the population is divided into two risk classes, with the high-risk class being prioritized for vaccination. For both cases with and without stratification by risk, we see significant differences in epidemiological outcomes between the Holling vaccination model and naive models. Finally, we use the new model to explore implications for public health policies in future pandemics.


title: Feasibility of an online antigen self-testing strategy for SARS-CoV-2 addressed to health care and education professionals in Catalonia (Spain). The TESTAT- COVID Project

abstract:
We aimed to implement a pilot intervention based on offering online COVID-19 selftest kits addressed to healthcare and education professionals in Spain during the peak of the 6th wave caused by Omicron variant. Kits were ordered online and sent by mail, participants answered an online acceptability/usability survey and uploaded the picture of results. 492 participants ordered a test, 304 uploaded the picture (61.8%). Eighteen positive cases were detected (5.9%). 92.2% were satisfied/very satisfied with the intervention; and 92.5% found performing the test easy/very easy. We demonstrated that implementing online COVID-19 self-testing in schools and healthcare settings in Spain is feasible.

Key findingsO_LIWe implemented a pilot intervention based on offering online COVID-19 selftest kits in Spain.
C_LIO_LIWe demonstrated the feasibility of the intervention during the peak of the 6th wave caused by Omicron variant.
C_LIO_LIThe intervention counted with high acceptability among healthcare and education professionals in Spain.
C_LIO_LIOur results may contribute to define screening strategies addressed to key populations, particularly during peaks of high community transmission of SARS-CoV-2.
C_LI


title: Multi-level analysis of adipose tissue reveals the relevance of perivascular subpopulations and an increased endothelial permeability in early-stage lipedema

abstract: Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on tissue level as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here we showed for the first time, that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.

category: pathology


title: The global effects of alcohol consumption on Gross Domestic Product in high- and low-income countries: a systematic review and meta-analysis

abstract:
Aims and objectivesThis study aims to measure the disease burden and the economic burden associated with alcohol consumption in both high- and low-income countries. To emphasise the necessity of making this issue a worldwide priority, the percentage of GDP attributable to alcohol-related costs will be stated.

DesignSystematic review and meta-analysis

Data sourcesA systematic search concerning health and social costs was conducted primarily through PubMed and subsequent citation chaining of appropriate systematic reviews. Other electronic databases such as Google Scholar was also freely searched.

Eligibility criteria for selecting studiesObservational studies examining alcohol-related harm, alcohol-related disease, and alcohol-related expenditure with all studies measuring alcohol-related harm using the alcohol-attributable fraction (AAF).

Results9 cross-sectional studies were obtained assessing the consequences of alcohol on the respective countrys economy with all studies utilising a prevalence-based approach. 5 studies were eligible for a meta-analysis in the statistically programming software, R. The pooled estimate of the economic burden of alcohol in 5 countries equated to be 0.01% of GDP. Though inconsistencies in cost estimations resulted in an underestimation, our results provide evidence to suggest that alcohol negatively affects both individuals and society. The available literature on the topic of the economic impact of alcohol is inadequate; especially when investigating concerns in poorer regions of the world.

ConclusionThough the current estimate of global GDP attributable to alcohol use is low, the evidence suggesting the global increase of alcohol consumption is paramount to avoid future calamities. Cooperative leadership from the World Health Organisation (WHO), International Monetary Fund, and the World Bank are requisite to control the harmful patterns of alcohol consumption seen across the globe.

STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThis is the first systematic review assessing the detrimental consequences of alcohol on economic health with the inclusion of both lower-middle income and high-income countries.
C_LIO_LIThis study provides a pooled estimate of the global estimate of the percentage of GDP attributable to alcohol related costs using statistical package, R which has not been done before.
C_LIO_LIThe obtainment of research conducted in low-income countries proved to be difficult, and as a result no low-middle income countries were used when calculating the pooled estimate. Therefore, the accuracy of the provided estimate was decreased.
C_LI

category: health economics


title: CLINICAL MANIFESTATIONS AND DIAGNOSIS OF CO-INFECTION OF COVID-19, TUBERCULOSIS AND OPPORTUNISTIC PULMONARY INFECTIONS IN LATE-STAGE HIV PATIENTS WITH IMMUNODEFICIENCY

abstract:
ObjectiveThe purpose of the study was to investigate the specific features of clinical manifestations and diagnosis of co-infection of COVID-19, tuberculosis and opportunistic pulmonary infections in late-stage HIV patients.

Design27 patients with co-infection of COVID-19, tuberculosis, opportunistic pulmonary infections and late-stage HIV infection with immunodeficiency without antiretroviral therapy (group 1) and 27 patients with equivalent parameters but without COVID-19 (group 2) were examined.

ResultsThe patients of the group 1 and group 2 are the persons with social maladjustment and substance addiction. All of them have concomitant viral hepatitis B/C, COPD, opportunistic pulmonary infections and similar clinical and radiological manifestations, which can only be differentiated with microbiological and molecular genetic studies. The patients with co-infection of COVID-19, tuberculosis and HIV pose a high risk of transmission of infection to healthy persons in view of non-adherence to examination and treatment.

ConclusionTo prevent the spread of infection among the healthy population, it is necessary to arrange in a mandatory manner an active and regular COVID-19 testing of all patients with tuberculosis/HIV co-infection, especially of late-stage HIV patients without antiretroviral therapy, in the tuberculosis care unit for HIV-infected persons at the tuberculosis dispensary.

SettingThere are few data on the specific features of clinical manifestations of co-infection of COVID-19, tuberculosis (TB) and opportunistic pulmonary infections (OPI) in late-stage HIV patients with immunodeficiency.

ObjectiveStudy purpose is to investigate the specific features of clinical manifestations and diagnosis of co-infection of COVID-19, TB and OPI in late-stage HIV patients with immunodeficiency.

DesignFifty-four (54) patients admitted for inpatient treatment at the TB Clinical Hospital N 3 named after Zakharyin were enrolled in this prospective study. The participants were assigned to two groups: group 1 (main) and group 2 (comparison group). Group 1 consisted of twenty-seven (27) aged 28-52 patients (18 men (66.7 {+/-} 9.1%) and 9 women (33.3 {+/-} 9.1%)) with known co-infection of COVID-19, sputum smear-positive for M. tuberculosis (MBT) pulmonary tuberculosis (PTB) and with late-stage HIV infection in progression phase without antiretroviral therapy (ART). Group 2 included 27 patients who were selected using the "copy-pair" method and were completely identical to the patients of the main group (with virtually the same age, sex, social parameters and clinical and laboratory indicators), but without diagnosis of COVID-19.


title: Mortality among healthcare workers in Indonesia during 18 months of COVID-19

abstract: The impact of SARS-CoV-2 infections upon Indonesian health care workers (HCWs) remains unclear, as mortality data specific to HCWs is not systematically collected or analyzed in this setting. This report describes findings from a systematic collation, abstraction and analysis of HCW fatalities during the first 18 months of COVID-19 in Indonesia. HCW who died during the period of March 2020 to July 2021 across Indonesia were identified on Pusara Digital, a community web-based digital cemetery database dedicated to HCW. We calculated mortality rates and death risk ratio among HCWs and the general population. Qualitative methods explored concerns regarding mortality among HCWs. The analysis suggests that at least 1,545 HCWs died during the study period. The death of males and females HCWs were almost equally distributed (51% vs. 49%). Most were medical doctors and specialists (535, 35%), nurses (428, 28%), and midwives (359, 23%). Deaths most frequently occurred in the age group of 40 to 59 years old with the median age of 50 years (IQR: 39-59). At least 322 (21%) deaths occurred with pre-existing conditions, including 45 who were pregnant. We estimated a minimal HCW mortality rate in Indonesia at 1.707 deaths per 1000 HCW during the first 18 months of COVID-19. Provincial HCW mortality rates ranged from 0.136 (West Sulawesi) to 5.32 HCW deaths per 1000 HCWs (East Java). HCW had a significantly higher mortality rate than the general population (RR = 4.92, 95% CI 4.67 - 5.17). The COVID-19 event in Indonesia resulted in the loss of many hundreds of HCWs, most of them being senior physicians, nurses, and midwives. The HCW death rates is 5-times higher than everyone else. The sheer sparseness of the workforce requires more protective steps and a national systematic surveillance of occupational mortality is urgently needed in this setting.

category: public and global health


title: Cross-sectional association of skeletal muscle mass and strength with dietary habits and physical activity among first-year university students in Japan: Results from KEIJI-U study

abstract:
BackgroundRecently, the high prevalence of young Japanese people who are underweight has received attention because of its potential impact on healthy life expectancy. Sarcopenia, defined as the presence of low muscle mass and function, is often observed in the underweight. However, few reports have described the prevalence and characteristics of sarcopenia in youth.

MethodsIn this cross-sectional study, we measured skeletal muscle mass using a multifrequency bioelectrical impedance analysis device and handgrip strength (HGS) and administered questionnaires on dietary habits and physical activity to 1,264 first-year university students aged 18-20 years (838 males and 426 females). Sarcopenia was diagnosed based on the presence of both low skeletal muscle mass (SMI) and weak HGS according to the Asian Working Group for Sarcopenia.

ResultsA total of 145 males (17.3%) and 69 females (16.2%) were diagnosed as underweight. Low SMI was diagnosed in 75 males (8.9%) and 18 females (4.2%), and weak HGS was diagnosed in 28 males (3.3%) and 10 females (2.3%). Then, sarcopenia was diagnosed in 8 males (1.0%) and 5 females (1.2%). There was a significantly higher prevalence of low SMI and/or weak HGS in underweight individuals compared with individuals in the other BMI ranges. The multivariate analyses indicated that SMI and HGS were significantly associated with BMI in both sexes. Furthermore, after adjusting for BMI, both SMI and HGS were significantly associated with physical activity in males, and SMI was significantly associated with energy intake and frequency of breakfast intake in females.

ConclusionsFirst-year university students showed a high incidence of being underweight with low SMI and/or weak HGS, but the prevalence of sarcopenia was low in both sexes. BMI, energy intake, frequency of breakfast intake, and physical activity were independently associated with skeletal muscle mass and strength in youth.


title: Preclinical interstitial lung disease in relatives of familial pulmonary fibrosis patients

abstract: Family history is amongst the strongest risk factors for interstitial lung disease (ILD), with emerging evidence for a shared genetic aetiology across ILD subtypes. Recruited families comprised at least two first-degree relatives who had been previously diagnosed with an ILD. All living cases and available unaffected first-degree relatives underwent a clinical examination for evidence of ILD. Preclinical ILD was diagnosed in 47.7% of first-degree relatives who had previously self-reported as unaffected. This study highlights the strong genetic predisposition in family members of ILD cases, and supports the call for routine screening of individuals with a family history of ILD.

category: respiratory medicine


title: Patient satisfaction in the use of non-pharmacological therapies in the management of postoperative pain: a study in a tertiary hospital, Ghana

abstract:
BackgroundNon-pharmacological therapies are the non-medicinal methods used in postoperative pain (POP) management by health care practitioners such as massage, positioning, breathing exercise, music therapy, and distraction. It has been discovered that therapies that are non-pharmacological for the relief of pain are effective with minimal side effects. Studies have also revealed that non-pharmacological interventions in the management of pain lessen or alter pain perception by decreasing intensity and intensifying the tolerance of pain. This study, therefore, seeks to determine how frequently non-pharmacological methods (NPMs) are used in the management of POP and the influence of these NPMs on patient satisfaction

MethodsThis study was a descriptive cross-sectional design. A quantitative approach was utilized with a structured questionnaire to obtain responses from patients from October to December 2019. The study was conducted in the female and male surgical wards of Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. 138 patients within the first 72 hours post-operative period who consented and fulfilled the inclusion criteria were enrolled in the study. A convenience sampling method was used to collect the data. Inferential and descriptive statistics were used in analyzing the data.

ResultsThe majority of the patients, 52.2% responded to using some form of (NPMs) for pain relief. The most widely used non-pharmacological method of pain relief was walking representing 79.2%, followed by relaxation 5 (6.8%), distraction 4 (5.6%), listening to music 3 (4.2%), deep breathing 2 (2.8%), and meditation 1 (1.4%). The male participants were observed to use more NPMs of pain relief as compared to the females. Most of the patients (51.4%) who used NPMs for their pain relief reported having their pain not relieved. A majority (90.6%) of the participants desired for more pain treatment. The type of surgery the patients underwent had a statistically significant negative correlation with the use of NPMs of pain relief (Spearman Correlation Coefficient = -0.233, p-value <0.05). A higher percentage (71%) of participants were highly satisfied with the overall pain treatment received.

ConclusionNon-pharmacological management of POP have been proven to be efficient, inexpensive, and have little or no side effect on patients. There should be continuous education on non-pharmacological management of POP to nurses and other healthcare professionals to help promote the efficiency of intervening in postoperative pain with these methods.


title: Smoking and socio-economic factors linked to acute exacerbations of COPD: analysis from an Asthma + Lung UK survey

abstract: Understanding the factors driving acute exacerbations of COPD is key to reducing their impact on human health and wellbeing. 5997 patients, mean 66 years, 64% female, completed an online survey between December 2020 and May 2021 about living with COPD developed by the charity Asthma+Lung UK. The 3731(62.2%) reporting frequent([≥]2/year) exacerbations were more likely to smoke (AOR 1.70, 95%CI 1.470-1.98), have lower annual household income ([≤]{pound}20,000, (AOR: 1.72, 1.36-2.17), live in a cold and damp home (AOR: 1.78, 1.50-2.11), and report previous occupational exposure to dust, fumes, and chemicals. Strategies to improve COPD outcomes must address issues of social justice.


title: Intraoperative calculus or hemorrhage in transurethral seminal vesiculoscopy as a risk factor for recurrent hemospermia

abstract: We summarized our experience regarding Transurethral Seminal Vesiculoscopy (TUSV) and analyzed both recurrence status and risk factors for recurrence. From January 2010 to December 2020, 48 patients with intractable hemospermia received successful TUSV at Taichung Invalids General Hospital. For the intraoperative findings, the five-year Disease-free Survival rates (DFS) were 74.1% in the no calculus group compared to 37.1% in the calculus group with a significant difference (log-rank p = 0.015), 75.0% in the no hemorrhage or no blood clot group compared to 43.2% in the hemorrhage or blood clot group with significant difference (log-rank p = 0.032). Univariate analysis showed intraoperative calculus (p = 0.040; HR: 2.94, 95% CI: 1.05-8.21) to be significantly associated with recurrence (p < 0.05). Patients with intractable hemospermia who were diagnosed with stones or blood clots found during TUSV experienced a higher rate of hemospermia recurrence.

category: urology


title: Abnormal synergies and associated reactions post-hemiparetic stroke reflect the neuroanatomy of brainstem motor pathways

abstract: Individuals with moderate-to-severe post-stroke hemiparesis have difficulty controlling proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called the flexion and extension synergies. Over the last three decades, we and others have quantitatively characterized these patterns and have provided evidence that they emerge because of an increased influence of diffusely-projecting brainstem motor pathways following stroke-induced damage to corticospinal and corticobulbar pathways. In our recent work that has focused on how they influence post-stroke hand function, we observed three notable aspects of synergy expression that we have never studied systematically: (1) paretic wrist and finger muscles were often activated maximally while individuals contracted muscles at a different joint, not during a maximal voluntary contraction of the wrist and finger muscles themselves; (2) there were differences in the magnitude of synergy expression when elicited via contraction of proximal muscles vs. distal muscles; (3) there was consistent movement resembling flexion or extension synergy patterns in the paretic limb during maximal efforts with the non-paretic limb (a phenomenon described clinically as an associated reaction), and the strength of these movement seemed to differ based on which muscles in the non-paretic limb were being activated. In the current study, we investigated the above behaviors systematically during maximal isometric contractions of shoulder, elbow and wrist/finger muscles, specifically focusing on differences between proximal vs. distal joints and flexor vs. extensor muscles. Our overall hypothesis is that the muscle-dependent nature of the behaviors we have observed is consistent with how the muscles are impacted by corticofugal damage and the upregulation of brainstem motor pathways that results. That is, we expected that our findings would reflect the fact that the greatest proportion of descending neural control comes from the corticospinal tract for distal muscles and from brainstem motor pathways for proximal muscles. We further expected that findings would reflect the fact that the reticulospinal tract, thought to underlie the flexion synergy, has bilateral effects in the upper limbs and favors facilitation of flexor muscles on the ipsilateral side. Supporting this hypothesis, we found that for some participants, joint torque and muscle activation generated during maximal voluntary contractions were lower than during maximal synergy-induced contractions. This was more prevalent and more severe in magnitude at the wrist and fingers than at the shoulder and elbow. We also found that synergy-driven contractions were strongest when elicited via proximal joints and weakest when elicited via distal joints. Finally, we found that associated reactions in the paretic wrist/finger flexors were stronger than those of other paretic muscles and were the only ones whose response depended on whether the contralateral contraction was at a proximal or distal joint. Our results provide indirect evidence for how an increased reliance on brainstem motor pathways post-stroke contributes to abnormal motor behaviors and demonstrate the need to examine whole-limb behavior when studying or seeking to rehabilitate the paretic upper limb.

category: rehabilitation medicine and physical therapy


title: A Solution to the Kermack and McKendrick Integro-Differential Equations

abstract:
In this manuscript, we derive a closed form solution to the full Kermack and McKendrick integro-differential equations (Kermack and McKendrick 1927) which we call the KMES. The KMES can be cast in the form of a step function response to the input of new infections; and that response is the time series of the total infections. We demonstrate the veracity of the KMES using independent data from the Covid 19 pandemic and derive many previously unknown and useful analytical expressions for diagnosing and managing an epidemic. These include new expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections.

Since the publication of Kermack and McKendricks seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions which are putatively derived from the integro-differential equations, to model epidemic dynamics. Implicit in the use of the SIR approximation are the beliefs that there is no closed form solution to the more complex integro-differential equations, that the approximation adequately reproduces the dynamics of the integro-differential equations, and that herd immunity always exists. However, as we explicate in this manuscript, the KMES demonstrates that the SIR models are not adequate representations of the integro-differential equations, and herd immunity is not guaranteed. Our conclusion is that the KMES obsoletes the need for the SIR approximations; and provides a new level of understanding of epidemic dynamics.


title: Detection of M. tuberculosis in the environment as a tool for identifying high-risk locations for tuberculosis transmission

abstract: Tuberculosis (TB) remains a leading cause of infectious mortality globally, yet most cases cannot be epidemiologically linked even with extensive contact investigations and whole genome sequencing. Consequently, there remain major gaps in our understanding of where and when M. tuberculosis (Mtb) exposures occur. We aimed to investigate whether Mtb can be detected in environments where TB patients were recently present, which could serve as a tool for characterizing exposure risk. We collected 389 environment surface (ES) swabs from two high TB burden prisons in Brazil, sampling 41 (n=340) cells occupied by individuals with active TB and 7 (n=49) cells from individuals without TB. In a subset of pooled swabs (n=6) and a swab from a cigarette lighter from the cell with active TB patients, we enriched Mtb DNA using RNA-bait hybrid capture assays and performed whole genome sequencing. In prison cells, Mtb DNA was detected in 55/340 (16%) of ES swabs from cells occupied by active TB patients and none (0/49) from cells in which no active TB patients were present. Mtb was detected in 13/16 (81%) prison cells occupied by the individuals with high/medium sputum Xpert Mtb load and 8/25 (32%) with low/very low sputum Mtb load (p=0.003). Seven hybrid capture samples had a median genomic coverage of 140X. rpoB mutations conferring high-level rifampin resistance were detected in 3/7 ES swabs. Mtb was frequently detectable in environments recently occupied by individuals with active TB. This approach could be applied in congregate environments to identify and characterize high-risk settings for Mtb exposure.


title: Therapeutic effects of different timing for PTCD and ERCP in obstructive severe acute biliary pancreatitis

abstract:
ObjectiveThis study compared the therapeutic effects of different timing for PTCD and ERCP in obstructive severe acute biliary pancreatitis.

MethodsWe evaluated the clinical data for 62 patients with obstructive severe acute biliary pancreatitis in Beijing Tiantan Hospital. The study was performed from July, 2013 to July, 2019. According to the treatment, patients were divided into three groups: conservative group (n=16), PTCD group (n=22) and ERCP group (n=24), and the PTCD and ERCP groups were divided into early (24-72 h) and delayed (>72 h) groups. Laboratory indices, recovery time of liver function, remission time of abdominal pain, hospitalization length, curability and complications were compared among groups.

ResultsThe average hospitalization length, time for abdominal pain relief and laboratory indices recovery were shorter (p <0.05) in early PTCD and ERCP groups than in the conservative group. Further, the average days of hospitalization in the ERCP group was shorter (p <0.05) than in the PTCD group. The complications were low in ERCP (33.33%) and PTCD (27.27%) groups, compared to the conservative group (62.50%).

ConclusionsFor patients who cannot determine the severity of biliary pancreatitis in the first place and exclude patients who have performed ERCP within 24 hours, ERCP is recommended for relieving obstruction of obstructive severe acute biliary pancreatitis within 24-72 hours, however, PTCD may be considered in patients failed to be cured by ERCP.

category: gastroenterology


title: Artificial Intelligence Enables Quantitative Assessment of Ulcerative Colitis Histology

abstract: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is characterized by a relapsing and remitting course. Appropriate assessment of disease activity is critical for adequate treatment decisions. In addition to endoscopic mucosal healing, histologic remission is emerging as a treatment target and a key factor in the evaluation of disease activity and therapeutic efficacy. However, there is no standardized definition of histologic remission, limiting the utility of histologic scoring, and manual pathologist evaluation is subject to intra-and inter-observer variability. Machine learning approaches are increasingly being developed to aid pathologists in accurate and reproducible scoring of histology, and can enable sensitive assessment of clinically relevant features. Here we report a proof-of-concept study using the PathAI platform to develop ML models for identification and quantification of UC histological features directly from hematoxylin and eosin (H&E)-stained whole slide images. Model-predicted histological features were used to quantify tissue area proportions and cell count proportions and densities, which correlated with disease severity and pathologist-assigned Nancy Histological Index (NHI) scores. Moreover, using multivariate analysis based on selected model-predicted histological features, we were able to accurately predict NHI scores, with a weighted kappa (k=0.93) and Spearman correlation ({rho}=0.93, p<0.001) when compared to manual pathologist consensus NHI scores. We were also able to predict histological remission, based on the resolution of active inflammation, with high accuracy of 0.94. These results demonstrate the accuracy of ML models in quantifying histologic features of UC and predicting NHI scores, and highlight the potential of this approach to enable standardized and robust assessment of histologic remission for improved evaluation of disease activity and prognosis.


title: Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects

abstract: Alterations in gray matter (GM) and monoamine oxidase A (MAO-A) distribution across the brain have been found in various neuropsychiatric conditions. MAO-A catalyzes the oxidative degradation of various monoamines and is thus implicated in neuroplastic processes that influence GM density (GMD) and microstructure (GMM) of the brain. Sex-specific differences in these patterns are well documented, however studying the long-term effects of certain sex steroids on the brain are limited due to hormonal fluctuations under naturalistic conditions. Due to the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy represent a valuable cohort to investigate such changes of GM and concomitant MAO-A density. Here, we investigated the effects of long-term gender-affirming hormone therapy over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men were recruited. All participants underwent two MRI scans in a longitudinal design. PET scans using [11C]harmine were performed before each MRI session in a subset of 35 individuals. Between baseline and follow-up imaging, transgender subjects underwent gender-affirming hormone therapy. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: pFWE+Bonferroni < 0.025). In terms of MAO-A distribution volume, no significant effects were found. The present results are indicative of a reliable influence of gender-affirming hormone therapy on GMD and GMM following an interregional pattern. Nevertheless, future studies with larger sample sizes are needed to further investigate the relationship between sex steroids, gray matter alterations and MAO-A density.

category: psychiatry and clinical psychology


title: Maternal depressive symptoms, neonatal white matter, and toddler social-emotional development

abstract: Maternal prenatal depression is associated with increased likelihood of neurodevelopmental and psychiatric conditions in offspring. The relationship between maternal depression and offspring outcome may be mediated by in-utero changes in brain development. Recent advances in magnetic resonance imaging (MRI) have enabled in vivo investigations of neonatal brains, minimising the effect of postnatal influences. The aim of this study was to examine associations between maternal prenatal depressive symptoms, infant white matter, and toddler behaviour. 413 mother-infant dyads enrolled in the developing Human Connectome Project. Mothers completed the Edinburgh Postnatal Depression Scale (median = 5, range = 0-28, n=52 scores [≥] 11). Infants (n=223 male) (median gestational age at birth=40 weeks, range 32.14-42.29) underwent MRI (median postmenstrual age at scan=41.29 weeks, range 36.57-44.71). Fixel-based fibre metrics (mean fibre density, fibre cross- section, and fibre density modulated by cross-section) were calculated from diffusion imaging data in the left and right uncinate fasciculi and cingulum bundle. For n=311, internalizing and externalizing behaviour, and social-emotional abilities were reported at a median corrected age of 18 months (range 17-24). Statistical analysis used multiple linear regression and mediation analysis with bootstrapping. Maternal depressive symptoms were positively associated with infant fibre density in the left (B =.0005, p=.003, q=.027) and right (B=.0006, p=.003, q=.027) uncinate fasciculus, with the left uncinate fasciculus, in turn, positively associated with social-emotional abilities in toddlerhood (B =105.70, p=.0007, q=.004). In a mediation analysis, higher maternal depressive symptoms predicted toddler social-emotional difficulties (B=.342, t(307)=3.003, p=.003), but this relationship was not mediated by fibre density in the left uncinate fasciculus (Sobel test p=.143, bootstrapped indirect effect=.035, SE=.02, 95%CI [-.01.08]). There was no evidence of an association between maternal depressive and cingulum fibre properties. These findings suggest that maternal perinatal depressive symptoms are associated with neonatal uncinate fasciculi microstructure, but not fibre bundle size, and toddler behaviour.


title: Adaptation and validation of a French version of the Vaccination Attitudes Examination (VAX) scale

abstract: Over the past decades, vaccination has proven to be largely beneficial to global health. Despite vaccine efficacy, the French population has been recently affected by more anti-vaccination attitudes and vaccine refusal, and it is therefore necessary to develop and validate tools to study this health issue. The Vaccination Attitudes Examination scale is a brief 12-item questionnaire targeting adults, that assesses general attitudes towards vaccination. The aims of the study were (1) to translate and adapt the original English version of the scale into French and (2) to test the psychometric properties of the scale in a French population-based sample of adults. We included 450 French speaking adults that completed the French Vaccination Attitudes Examination scale and other questionnaires in order to assess convergent and divergent validities. Exploratory and confirmatory factor analyses showed that the French version of the Vaccination Attitudes Examination scale replicated the factorial structure of the original scale. Moreover, it demonstrated high internal consistency, good convergent and divergent validities, and excellent temporal stability. Also, scores on the scale differentiated vaccinators from non-vaccinator respondents. Results on the scale provides us with insight into factors involved in vaccine hesitancy in France, therefore allowing French authorities and policy makers to address these specific concerns and by consequence improve vaccine acceptance rates in this country.


title: Understanding Definitions and Reporting of Deaths Attributed to COVID-19 in the UK - Evidence from FOI Requests

abstract:
Death is a widely used outcome to assess the severity of pandemics. Accuracy in assigning the cause of death is of vital importance to define the impact of the agent, monitor its evolution, and compare its threat with those of other agents. Throughout the COVID-19 pandemic, there has been widespread reporting of aggregate death data with little attention paid to the accuracy of the assignment of causation.

We aimed to analyse public authorities understanding of the assignment of cause of deaths during the SARS-CoV-2 pandemic in the UK by accessing Freedom of Information requests posed in three periods in 2020-21. By public authorities, we mean NHS Health Trusts, laboratories, and government agencies such as Public Health England and the Department of Health and Social Care. We searched WhatDoTheyKnow using the terms "covid and death". We excluded those requests to bodies that cannot provide an answer (e.g. Councils) and those dealing with the effects of vaccines.

We grouped questions into themes addressing the definitions and causes of death relevant to the pandemic. We looked at the responses to the questions of the definition of cause of death, the accuracy of the attribution, the role of other pre-existing pathologies and how these were reported and quantified.

We found 800 requests from over 90 individuals. There was no consistency in the definition of cause of death or contributory cause of death across national bodies and in different bodies within the same nation. Nursing home providers, as well as medical practitioners, can assign a cause of death according to the Care Quality Commission. Post-mortem examinations were uncommon, the ONS did not incorporate their results in the summary of deaths by cause during the pandemic period. The meaning of the words "test" or "swab" was never clarified by any of the respondents. In care homes in England 1,304 out of 17,264 COVID-19 (7.6%, range 0% to 63%) mentioned COVID-19 in the absence of contributory or other factors in the death certificate, making it impossible to ascertain a chain of causality. The inconsistencies already noted hinder the ascertainment of the role of each factor leading to death and the quantification of the importance of infection. Some responses indicate that SARS-CoV-2 negative individuals or those whose death was not caused by COVID-19 were classified as "COVID-19 deaths". We found 14 different ways of attributing the causes of death mentioned by respondents.

The overall lack of consistency has confused the public and likely led to erroneous conclusions. We are unable to separate the effects on deaths of SARS-CoV-2 from those of human interventions. A coherent process based on consistent definitions across the devolved nations is required. Furthermore, to enhance the accuracy of causation in pandemics a subset of deaths should be verified using autopsies with full medical documentation.


title: Multi-center evaluation of baseline neutrophil:lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in Idiopathic Pulmonary Fibrosis

abstract:
BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes for people with IPF.

MethodWe adopted a two-stage discovery and validation design using patients from the UCL partners (UCLp) cohort. For the discovery analysis, we included 71 patients from UCLH. In the validation analysis, we included 928 people with IPF, using real-life data from UCLH and 5 other UK centres. Data were collected from patients presenting over a 13-year period with a mean follow up time of 3.7 years.

FindingsIn the discovery analysis, we showed that values of NLR (<2.9 vs >/=2.9) were associated with increased risk of mortality (HR 2.04, 95% CI 1.09-3.81; p=0.025). In the validation cohort we confirmed this association of high NLR with mortality (HR 1.65, 95% CI 1.39-1.95; p<0{middle dot}0001) and showed incorporation of baseline NLR in a modified GAP-stage/index (GAP/index)-plus improved predictive ability

InterpretationWe have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines clinical GAP-staging. NLR may help ILD specialist centres prioritise at risk patients in a timely way, even in the absence of lung function.


title: Cognitive improvement after dual-task training in Parkinsons disease: a follow-up study

abstract: The reaction times of patients with Parkinsons disease (PD) in tests of simultaneous dual-task accuracy are dependent on the subjects cognitive ability. We now report that one week training on dual-task tests improved cognitive function. Forty-six PD patients were compared with 47 age matched healthy controls and 26 patients were followed for one year. Five dual-task tests consisting of a primary cognitive task to be performed simultaneously with a secondary motor task were repeated for five consecutive days. Testing was repeated after 6 and 12 months. Participants reaction times, including Hits and Misses, were quantified. Initial tests indicated slower reaction times in patients compared to controls, with fewer Hits and more Misses, especially in PD patients over 65 years of age. Training by daily repeated dual-task tests improved performance within 3 days (p < 0. 01 or p < 0.001), with no deterioration after 6 months. We conclude that dual-tasks are objective and sensitive tests for detecting early cognitive difficulties in PD, with improvements in both by repeated exposure to testing. A few days of testing produced cognitive improvement lasting many months. It is recommended that the use of simultaneous, dual-task testing is used to produce long-lasting improvement of cognitive function in PD patients.

category: neurology


title: Genetic risk score for intracranial aneurysms to predict aneurysmal subarachnoid hemorrhage and identify associations with patient characteristics

abstract:
BackgroundRupture of an intracranial aneurysm (IA) causes aneurysmal subarachnoid hemorrhage (ASAH). There is no accurate prediction model for IA or ASAH in the general population. Recent discoveries in genetic risk for IA may allow improved risk prediction.

MethodsWe constructed a genetic risk score including genetic association data for IA and 17 traits related to IA (a metaGRS) to predict ASAH incidence and IA presence. The metaGRS was trained in 1,161 IA cases and 407,392 controls in the UK Biobank and validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68,568 controls from the Nordic HUNT study. We further assessed association between genetic risk load and patient characteristics in a cohort of 5,560 IA patients.

ResultsThe hazard ratio for ASAH incidence was 1.34 (95% confidence interval = 1.20-1.51) per SD increase of metaGRS. Concordance index increased from 0.63 [0.59-0.67] to 0.65 [0.62-0.69] upon including the metaGRS on top of clinical risk factors. The odds ratio for prediction of IA presence was 1.09 [95% confidence interval: 1.01-1.18], but did not improve area under the curve. The metaGRS was statistically significantly associated with age at ASAH ({beta}=-4.82x10-3 per year [-6.49x10-3 to -3.14x10-3], P=1.82x10-8), and location at the internal carotid artery (OR=0.92 [0.86 to 0.98], P=0.0041).

ConclusionsThe metaGRS was predictive of ASAH incidence with modest added value over clinical risk factors. Genetic risk plays a role in clinical heterogeneity of IA. Additional studies are needed to identify the biological mechanisms underlying this heterogeneity.

KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSRecent advanced in the understanding of genetic risk for IA opened and opportunity for risk prediction by combining genetic and conventional risk factors.

What this study addsHere, we developed a genetic risk score based on genetic association information for IA and 17 related traits. This risk score improved prediction compared to a model including only conventional risk factors. Further, genetic risk was associated with age at ASAH and IA location.

How this study might affect research, practice, or policyThis study emphasizes the importance of combining conventional and genetic risk factors in prediction of IA. It provides a metric to develop an accurate risk assessment method including conventional and genetic risk factors.


title: Transcriptomic meta-analysis of non-Hodgkins B-cell lymphomas reveals reliance on pathways associated with the extracellular matrix

abstract: Approximately 450,000 cases of Non-Hodgkins lymphoma are diagnosed annually worldwide, resulting in [~]240,000 deaths. An augmented understanding of the common mechanisms of pathology among relatively large numbers of B-cell Non-Hodgkins Lymphoma (BCNHL) patients is sorely needed. We consequently performed a large transcriptomic meta-analysis of available BCNHL RNA-sequencing data from GEO, consisting of 322 relevant samples across ten distinct public studies, to find common underlying mechanisms across BCNHL subtypes. The study was limited to GEOs publicly available human B-cell RNA-sequencing datasets that met our criteria, and limitations may include lack of diversity in ethnicities and age groups. We found [~]10,400 significant differentially expressed genes (FDR-adjusted p-value < 0.05) and 33 significantly modulated pathways (Bonferroni-adjusted p-value < 0.05) when comparing lymphoma samples to non-diseased samples. Our findings include a significant class of proteoglycans not previously associated with lymphomas as well as significant modulation of extracellular matrix-associated proteins. Our drug prediction results yielded new candidates including ocriplasmin and collagenase. We also used a machine learning approach to identify the BCNHL biomarkers YES1, FERMT2, and FAM98B, novel biomarkers of high predictive fidelity. This meta-analysis validates existing knowledge while providing novel insights into the inner workings and mechanisms of B-cell lymphomas that could give rise to improved diagnostics and/or therapeutics. No external funding was used for this study.

category: oncology


title: Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

abstract:
BackgroundMental health diseases are a major component of morbidity and health care costs. Obesity and gut disorders are comorbid with mental health, with the gut microbiome hypothesized to play a key mechanistic role in linking them. Pharmacological and behavioral interventions are currently used to treat mental health disorders, but they have limited efficacy. Dietary and weight-loss interventions have been shown to provide different benefits. Still, there exists conflicting evidence regarding their effects which may be due to an individuals genetic or microbiome factors modulating the improvement of symptoms.

ObjectiveWe aimed to identify genetic and gut microbiome factors that explain the improvement in mental health after a dietary and lifestyle intervention for weight loss.

MethodsWe recruited 369 individuals participating in the Digbi Health personalized digital care program, for which we evaluated the association between 23 genetic scores, the abundance of 178 gut microbiome genera, and 42 gut-brain modules (pathways related to neuroactive metabolites produced by gut microbes) with the presence/absence of anxiety/depression or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight.

ResultsThe mean BMI and age of the study cohort were 34.6 and 48.7, respectively, and there was an overrepresentation of individuals with functional gastrointestinal disorders (84%). On average, the individuals lost 5.4% of body weight at the time of follow-up (mean of 88 days), and more than 95% reported improvement in at least one outcome. We found significant correlations between genetic scores with anxiety and depression at baseline, gut microbial functions with sleep problems at baseline, and genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Among the gut microbial functions identified, the abundance of butyrate synthesis genes was associated with less than average improvement in depression symptoms, the abundance of kynurenine synthesis genes was associated with less than average improvement in anxiety symptoms, and the abundance of genes able to synthesize and degrade neuroactive hormones like nitric oxide was associated with greater than average improvement in depression and insomnia symptoms. Among the genetic scores identified, anxiety or depression at baseline were associated with genetic scores for alcohol use disorder and major depressive disorder, and greater than average improvement in anxiety and depression symptoms was associated with an obstructive sleep apnea genetic score. Furthermore, a type 1 diabetes genetic score was associated with a greater than average improvement of insomnia symptoms, whereas a type 2 diabetes genetic score was associated with a less than average improvement of insomnia symptoms. We compared the relative ability of demographic, genetic, and microbiome factors to explain baseline and improvement in mental health and found that genetic and microbiome factors provide value above demographic variables alone. Medication and recreational drug use do not confound microbiome associations with mental health.

ConclusionsThe digital therapeutics care program significantly decreased body weight and concomitantly decreased self-reported mental health symptom intensity. Our results provide evidence that genetic and gut microbiome factors help explain interindividual differences in mental health improvement after dietary and lifestyle interventions for weight loss. Thus, individual genetic and gut microbiome factors provide a basis for designing and further personalizing dietary interventions to improve mental health.


title: Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination

abstract:
ImportanceOmicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification.

ObjectiveTo estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine.

DesignTest-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022.

SettingPopulation-based, province of Quebec, Canada

ParticipantsCommunity-dwelling [≥]12-year-olds tested for SARS-CoV-2.

ExposuresPrior laboratory-confirmed infection with/without mRNA vaccination.

OutcomesLaboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test-negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing-indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose.

ResultsWithout vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and <30% thereafter. The more severe the prior infection, the greater the risk reduction: 8% (95%CI:17-28), 43% (95%CI:37-49) and 68% (95%CI:51-80) for prior asymptomatic, symptomatic ambulatory or hospitalized infections. mRNA vaccine effectiveness against Omicron infection was consistently significantly higher among previously-infected vs. non-infected individuals at 65% (95%CI:63-67) vs. 20% (95%CI:16-24) for one-dose; 68% (95%CI:67-70) vs. 42% (95%CI:41-44) for two doses; and 83% (95%CI:81-84) vs. 73% (95%CI:72-73) for three doses.

Infection-induced protection against Omicron hospitalization was 81% (95%CI: 66-89) increasing to 86% (95%CI:77-99) with one, 94% (95%CI:91-96) with two and 97%(95%CI:94-99) with three mRNA vaccine doses. Two-dose effectiveness against hospitalization among previously-infected individuals did not wane across 11 months and did not significantly differ from three-dose effectiveness despite longer follow-up (median 158 and 27 days, respectively).

Conclusions and relevancePrior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals.


title: Clinical Features and Outcomes of COVID-19 at a Teaching Hospital in Kingston, Jamaica

abstract:
ObjectiveWe examined the demographic, clinical characteristics and indicators of poor outcomes among hospitalized adults with COVID-19 at the University Hospital of the West Indies, Jamaica.

MethodsA retrospective medical record review between March 10 and December 31, 2020 analyzed data for 362 participants.

ResultsThere were 218 males (mean age 59.5 years) and 144 females (mean age 55.7 years). Hypertension, diabetes mellitus, cardiovascular disease, obesity and chronic kidney disease were the most common comorbidities. Cough, shortness of breath, fever and malaise were the most common presenting complaints. Fifty-one percent of patients were moderately to severely ill on admission; 11% were critically ill; 18% were admitted to the Intensive Care Unit (ICU). Death occurred in 62 (17%) patients (95% CI 13.6-21.4%). Among obese participants, there were increased odds of developing respiratory failure (OR 5.2, p < 0.001), acute kidney injury (OR 4.7, p < 0.001), sepsis (OR 2.9, p =0.013) and the need for ICU care (OR 3.7, p < 0.001). Factors independently associated with increased odds of death were age (OR 1.03 per year, p = 0.013) and obesity (OR 2.26, p = 0.017). Mortality also correlated significantly with D-dimer > 1000 ng/ml (OR 2.78; p = 0.03), serum albumin < 40 g/L (OR 3.54; p = 0.03) and serum LDH > 485 U/L OR 1.92, p = 0.11).

ConclusionsTargeted interventions among these high-risk patient subgroups may reduce in-patient morbidity and mortality.


title: Similar performances but markedly different triaging thresholds in three CAD4TB versions risk systematic errors in TB screening programs

abstract: Tuberculosis (TB) screening programs may apply computer-aided diagnostic (CAD) tools on chest radiographs to select people for microbiological sputum examination using a pre-selected triaging threshold. CAD software-updates are frequently introduced and it is unknown whether their use requires adjustment of triaging thresholds. In a community-based screening program in South Africa, we compared the scores between the three recent CAD4TB versions (v5, v6, and v7) and assessed their performance to identify microbiologically-confirmed TB. The performance of all versions was similar (v5: AUC 0.78, v6: AUC 0.79, v7: AUC 0.80; p-values>0.05), but along a 0-100 point scale, each had markedly different score distributions and optimal triaging thresholds (v5: 40, v6: 47, v7: 20). This has the potential to cause confusion within TB screening programs as these tools are increasingly adopted and new versions released. Independent guidance for adapting CAD triaging thresholds for frequently released software updates is needed.


title: Differences in epidemiology of enteropathogens in children pre- and post-rotavirus vaccine introduction in Kilifi, coastal Kenya

abstract:
BackgroundIn July 2014, Kenya introduced the Rotarix(R) vaccine into its national immunization program. The impact of this vaccination programme on the local epidemiology of enteropathogens is unclear.

MethodsThe TaqMan Array Card (TAC) was used for screening for 28 different enteropathogens in 718 stools from children less than 13 years of age who presented with diarrhea and were admitted to Kilifi County Hospital, coastal Kenya, in 2013 (before vaccine introduction) and in 2016-2018 (after vaccine introduction). The differences between pre- and post-Rotarix(R) vaccination periods were examined using univariate and multivariable logistic regressions.

ResultsIn 665 specimens (92.6%), one or more enteropathogens were detected, while in 323 specimens (48.6%), three or more enteropathogens were detected. There was a significant increase in the proportion of samples containing enteroaggregative Escherichia coli (35.7% vs 45.3%, p=0.014), cytomegalovirus (4.2% vs 9.9%, p=0.008), Vibrio cholerae (0.0% vs 2.3%, p=0.019), Strongyloides species (0.8% vs 3.6%, p=0.048) and Dientamoeba fragilis (2.1% vs 7.8%, p=0.004) post-vaccine introduction. Sapovirus detection decreased significantly (7.6% vs 4.0%, p=0.030) post-vaccine introduction. The proportion of samples that tested positive for rotavirus group A did not statistically differ between the pre- and post-vaccine periods (27.4% vs. 23.5%, p=0.253).

ConclusionsIn this setting, the burden of childhood enteropathogen infection was high both pre- and post-rotavirus vaccination introduction, with some specific changes in the burden of enteropathogens in hospitalized children after rotavirus vaccination introduction.


title: Iron status and risk of sepsis: a Mendelian randomisation analysis.

abstract:
ObjectiveTo evaluate the association between four iron biomarkers and sepsis.

DesignAn observational cohort and two sample Mendelian randomisation (MR) study.

SettingThe UK Biobank prospective cohort study (for the observational cohort and for MR outcomes), the FinnGEN cohort study (replication of MR outcomes) and three large genome wide association studies (GWAS, for iron exposures).

Participants453,169 participants enrolled in UK Biobank, 356,000 participants enrolled in FinnGen and between 131,471 - 246,139 participants enrolled across the three iron biomarker GWAS.

ExposuresIn the observational cohort, iron status was determined using ferritin levels recorded in general practice data. In the MR analyses, four iron biomarkers were used: serum iron, serum ferritin, the total iron binding capacity (TIBC), and transferrin saturation (TSAT).

Main outcome measuresHospital admission with an ICD-10 coded sepsis diagnosis.

ResultsIn the observational cohort, the odds of sepsis increased as ferritin levels increased, with odds ratios of >1 once ferritin was more than >160 ug/L, within the normal accepted reference range for ferritin. Extremely low ferritin (<40ug/L) was also associated with increased odds of sepsis.

In inverse-variance-weighted mendelian randomisation analyses, increases in all iron biomarkers were associated with increasing odds of sepsis (OR 1.10 for each SD increase in TSAT; 95% CI 1.03 to 1.17) with similar results for serum iron (OR 1.07; 95% CI 0.98 to 1.16), and ferritin (OR 1.09; 95% CI 0.99 to 1.2), with the opposite result for TIBC (OR 0.92; 95% CI 0.86 to 0.99). Effect estimates were slightly larger in those with iron deficiency or anaemia.

Results were similar in the replication cohort (FinnGen) and were robust to sensitivity analyses of Mendelian randomisation.

ConclusionsIncreasing measures of iron and related biomarkers are associated with increased risk of sepsis in a healthy adult volunteer cohort. MR analyses suggest this association is causal. Clinicians and policymakers should be aware of this potential risk when manipulating iron levels.


title: Leveraging infectious disease models to interpret randomized controlled trials: controlling enteric pathogen transmission through water, sanitation, and hygiene interventions

abstract:
Randomized controlled trials (RCTs), which evaluate hypotheses in specific contexts, are often considered the gold standard of evidence for infectious disease interventions, but their results cannot immediately generalize to other contexts. Mechanistic models are one approach to generalizing findings between contexts, but infectious disease transmission models are not immediately suited for analyzing RCTs, since they often rely on time-series surveillance data that is rarely collected by RCTs. We developed a modeling framework to explain the main outcome of an infectious disease RCT--relative risk--and applied it to a water, sanitation, and hygiene (WASH) RCT. This model can generalize the RCT results to other contexts and conditions. We developed this compartmental modeling framework to account for key WASH RCT factors: i) transmission across multiple environmental pathways, ii) multiple interventions applied individually and in combination, iii) adherence to interventions or preexisting conditions, and iv) the impact of individuals not enrolled in the study. We employed a hybrid sampling-importance resampling and estimation framework to obtain posterior estimates of mechanistic parameters and their uncertainties and illustrated our model using WASH Benefits Bangladesh RCT data (n=17,187). Our model reproduced reported diarrheal prevalence in this RCT. The baseline estimate of the basic reproduction number [R]0 for the control arm (1.15, 95% CI: 1.09, 1.27) corresponded to an endemic prevalence of 13% (95% CI: 9-21%) in the absence of intervention or preexisting WASH conditions. No single pathway was likely able to sustain transmission: pathway-specific [R]0s for water, fomites, and all other pathways were 0.49 (95% CI: 0.07, 0.99), 0.26 (95% CI: 0.04, 0.57), and 0.40 (95% CI: 0.02, 0.88), respectively. An infectious disease modeling approach to evaluating RCTs can complement RCT analysis by providing a rigorous framework for generating data-driven hypotheses that explain trial findings, particularly unexpected null results, opening up existing data to deeper epidemiological understanding.

Author summaryA randomized controlled trial (RCT) testing an intervention to reduce infectious disease transmission can provide high-quality scientific evidence about the impact of that intervention in a specific context, but the results are often difficult to generalize to other policy-relevant contexts and conditions. Infectious disease transmission models can be used to explore what might happen to disease dynamics under different conditions, but the standard use of these models is to fit to longitudinal, surveillance data, which is rarely collected by RCTs. We developed a framework to fit an infectious disease model to steady-state diarrheal prevalence data in water, sanitation, and hygiene RCTs, explicitly accounting for completeness, coverage, and compliance. Although this framework is developed with water, sanitation, and hygiene interventions for enteropathogens in mind, it could be extended to other disease contexts. By leveraging existing large-scale RCT data sets, it will be possible to better understand the underlying disease epidemiology and investigate the likely outcomes of policy-relevant scenarios. Ultimately, this work can be incorporated into decision making for public health policy and programs.


title: Genome-wide analysis of binge-eating disorder identifies the first three risk loci and implicates iron metabolism

abstract: Binge-eating disorder (BED) is the most common eating disorder yet its genetic architecture remains largely unknown. Studying BED is challenging because it is often comorbid with obesity, a common and highly polygenic trait, and it is underdiagnosed in biobank datasets. To address this limitation, we apply a supervised machine learning approach to estimate the probability of each individual having BED based on electronic medical records from the Million Veteran Program. We perform a genome-wide association study on individuals of African (n = 77,574) and European (n = 285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE, MCHR2 and LRP11 genes, which are reproducible across three independent cohorts. We identify genetic association between BED and several neuropsychiatric traits and implicate iron metabolism in the pathophysiology of BED. Overall, our findings provide insights into the genetics underlying BED and suggest directions for future translational research.


title: PCR Testing in the UK During the SARS-CoV-2 Pandemic - Evidence from FOI Requests

abstract:
Polymerase Chain Reaction ("PCR") tests have been used to identify cases of COVID-19 during the course of the pandemic. Notably, PCR alone cannot differentiate between the presence of whole viruses (which can be transmitted and infect individuals) and small fragments of genetic material that are not infectious. A feature of PCR known as the cycle threshold (Ct) can be used to discriminate between these states, but the relationship between Ct and infectiousness is still poorly understood.

This well-known limitation of the test compromises the identification of cases and their trends, and consequently those measures to interrupt transmission (such as isolation) that are undertaken on the basis of reliably identifying infectious individuals.

Here, we interrogate the public authorities understanding of PCR testing for SARS-CoV-2 in the UK by accessing Freedom of Information requests submitted in 2020-21.We searched WhatDoTheyKnow and found 300 FOI requests, from over 150 individuals. We grouped their questions into four themes addressing the number of tests in use, the reporting of cycle thresholds ( Ct), the Ct values themselves, and the accuracy of tests.

The number of validated tests in use in the UK is currently not clear: In FOI responses, Public Health England (PHE) report it may be "80" or "85". However, European regulations suggest there could be over 400 different CE marked tests available on the market and available for use. Laboratories have a statutory duty to report positive cases to PHE, but they do not have to advise which tests they are using nor submit Ct values. Only two FOI responses provided answers on Ct values, indicating that in a set time span, 24-38% of the Ct values were over 30. The most common FOI asked if there was a cycle threshold for positivity. In those that responded, the Ct for a positive result varied from 30 to 45. We found limited information on the technical accuracy of the tests. Several responses stated there is no  static,  specific or  standard cycle threshold.

The current system requires significant changes to ensure it offers accurate diagnostic data to enable effective clinical management of SARS-CoV-2. PCR is an important and powerful tool, but its systematic misuse and misreporting risk undermining its usefulness and credibility.


title: Occupational differences in SARS-CoV-2 infection: Analysis of the UK ONS Coronavirus (COVID-19) Infection Survey

abstract:
BackgroundConsiderable concern remains about how occupational SARS-CoV-2 risk has evolved during the COVID-19 pandemic. We aimed to ascertain which occupations had the greatest risk of SARS-CoV-2 infection and explore how relative differences varied over the pandemic.

MethodsAnalysis of cohort data from the UK Office of National Statistics Coronavirus (COVID-19) Infection Survey from April 2020 to November 2021. This survey is designed to be representative of the UK population and uses regular PCR testing. Cox and multilevel logistic regression to compare SARS-CoV-2 infection between occupational/sector groups, overall and by four time periods with interactions, adjusted for age, sex, ethnicity, deprivation, region, household size, urban/rural neighbourhood and current health conditions.

ResultsBased on 3,910,311 observations from 312,304 working age adults, elevated risks of infection can be seen overall for social care (HR 1.14; 95% CI 1.04 to 1.24), education (HR 1.31; 95% CI 1.23 to 1.39), bus and coach drivers (1.43; 95% CI 1.03 to 1.97) and police and protective services (HR 1.45; 95% CI 1.29 to 1.62) when compared to non-essential workers. By time period, relative differences were more pronounced early in the pandemic. For healthcare elevated odds in the early waves switched to a reduction in the later stages. Education saw raises after the initial lockdown and this has persisted. Adjustment for covariates made very little difference to effect estimates.

ConclusionsElevated risks among healthcare workers have diminished over time but education workers have had persistently higher risks. Long-term mitigation measures in certain workplaces may be warranted.

What is already known on this topicSome occupational groups have observed increased rates of disease and mortality relating to COVID-19.

What this study addsRelative differences between occupational groups have varied during different stages of the COVID-19 pandemic with risks for healthcare workers diminishing over time and workers in the education sector seeing persistent elevated risks.

How this study might affect research, practice or policyIncreased long term mitigation such as ventilation should be considered in sectors with a persistent elevated risk. It is important for workplace policy to be responsive to evolving pandemic risks.

category: occupational and environmental health


title: Medical text prediction and suggestion using generative pre-trained transformer models with dental medical notes

abstract:
BackgroundGenerative pre-trained transformer (GPT) models are one of the latest large pre-trained natural language processing (NLP) models, which enables model training with limited datasets, and reduces dependency on large datasets which are scarce and costly to establish and maintain. There is a rising interest to explore the use of GPT models in healthcare.

ObjectiveWe investigate the performance of GPT-2 and GPT-Neo models for medical text prediction using 374,787 free-text dental notes.

MethodsWe fine-tune pre-trained GPT-2 and GPT-Neo models for next word prediction on a dataset of over 374,000 manually written sections of dental clinical notes. Each model was trained on 80% of the dataset, validated on 10%, and tested on the remaining 10%. We report model performance in terms of next word prediction accuracy and loss. Additionally, we analyze the performance of the models on different types of prediction tokens for categories. We annotate each token in 100 randomly sampled notes by category (e.g. Names, Abbreviations, Clinical Terms, Punctuation, etc.) and compare the performance of each model by token category.

ResultsModels present acceptable accuracy scores (GPT-2: 76%, GPT-Neo: 53%), and the GPT-2 model also performs better in manual evaluations, especially for names, abbreviations, and punctuation. The results suggest that pre-trained models have the potential to assist medical charting in the future. We share the lessons learned, insights, and suggestions for future implementations.

ConclusionThe results suggest that pre-trained models have the potential to assist medical charting in the future. Our study presented one of the first implementations of the GPT model used with medical notes.

category: health informatics


title: HematoNet: Expert Level Classification of Bone Marrow Cytology Morphology in Hematological Malignancy with Deep Learning

abstract: There have been few efforts made to automate the cytomorphological categorization of bone marrow cells. For bone marrow cell categorization, deep-learning algorithms have been limited to a small number of samples or disease classifications. In this paper, we proposed a pipeline to classify the bone marrow cells despite these limitations. Data augmentation was used throughout the data to resolve any class imbalances. Then, random transformations such as rotating between 0{degrees} to 90{degrees}, zooming in/out, flipping horizontally and/or vertically, and translating were performed. The model used in the pipeline was a CoAtNet and that was compared with two baseline models, EfficientNetV2 and ResNext50. We then analyzed the CoAtNet model using SmoothGrad and Grad-CAM, two recently developed algorithms that have been shown to meet the fundamental requirements for explainability methods. After evaluating all three models performance for each of the distinct morphological classes, the proposed CoAtNet model was able to outperform the EfficientNetV2 and ResNext50 models due to its attention network property that increased the learning curve for the algorithm which was represented using a precision-recall curve.


title: Trends in diabetes incidence and associated risk factors among people living with HIV in the current treatment era, 2008-2018

abstract: People with HIV (PWH) have an increased risk for diabetes mellitus. Our objectives were to characterize the prevalence and incidence of diabetes in a cohort of people with HIV (PWH), and to evaluate both traditional and HIV-specific risk factors contributing to incident diabetes diagnoses. We conducted a retrospective study of a Southeastern US academic HIV clinic. All PWH age > 18 years of age who attended at least two clinic visits between 2008 and 2018 were evaluated to assess time to diabetes incidence. Laboratory, demographic, clinical, medication and diagnoses data were extracted from the Clinic EMR. Diabetes was defined when at least two of the following three criteria were met: (1) laboratory data consistent with a diagnosis as defined by the ADA SOC (Hgb A1C [≥] 6.5% and/or 2 glucose results >200 mg/dl (at least 30 days apart)), (2) diagnosis of diabetes in the EMR, or (3) exposure to diabetes medication. Time to Diabetes incidence was computed from the entire clinic population for each study year. Univariate Cox proportional hazard models were developed to evaluate associations between each baseline factor and time to DM. Multivariable Cox proportional hazard regression models with time-dependent covariates were created to evaluate the independent association between significant parameters from univariate analyses and time to incident DM. From 4113 PWH included in the analysis, we identified 252 incident cases of diabetes. In multivariable analysis, BMI classification, liver disease, steroid exposure, and use of Integrase Inhibitors were associated with incident diabetes. Additional associated factors included lower CD4 cell counts, duration of HIV infection, exposure to non-statin lipid lowering therapy, and dyslipidemia. Incident diabetes rates are increasing at an alarming rate among PWH. Diabetes prevalence increased from 8.8% in 2008 to 14% in 2018. Both traditional and HIV-related risk factors, particularly body weight, steroid exposure, and use of Integrase Inhibitors, were associated with incident diabetes. Notably, several of the risk factors identified are modifiable and should be targeted for intervention.

category: hiv aids


title: Design and validation of HIV peptide pools for detection of HIV-specific CD4+ and CD8+ T cells

abstract: Reagents to monitor T cell responses to the entire HIV genome, based on well characterized epitopes, are missing. Evaluation of HIV-specific T cell responses is of importance to study natural infection, and therapeutic and vaccine interventions. Experimentally derived CD4+ and CD8+ HIV epitopes from the HIV molecular immunology database were developed into Class I and Class II HIV megapools (MPs). We assessed HIV responses in persons with HIV pre combined antiretroviral therapy (cART) (n=17) and post-cART (n=18) and compared these responses to 15 controls without HIV (matched by sex, age, and ethnicity). Using the Activation Induced Marker (AIM) assay, we quantified HIV-specific total CD4+, memory CD4+, circulating T follicular helper, total CD8+ and memory CD8+ T cells. We also compared the Class I and Class II HIV MPs to commercially available HIV gag peptide pools. Overall, HIV Class II MP detected HIV-specific CD4+ T cells in 21/35 (60%) HIV positive samples and 0/15 HIV negative samples. HIV Class I MP detected an HIV-specific CD8+ T cells in 17/35 (48.6%) HIV positive samples and 0/15 HIV negative samples. Our innovative HIV MPs are reflective of the entire HIV genome, and its performance is comparable to other commercially available peptide pools. Here, we detected HIV-specific CD4+ and CD8+ T cell responses in people on and off cART, but not in people without HIV.


title: Brief: Implementation of a Novel Clinic/Community Partnership Addressing Food Insecurity Among Adults with HIV in the Southern United States

abstract: Food insecurity is highly prevalent among people with HIV. Traditional calorie-rich, nutrient poor food assistance programs may improve food security but increase risk for other chronic diseases. This case study describes the process evaluation of a novel clinic/community partnership to provide nutritionally adequate, tailored food assistance to adults with HIV in Alabama. Methods used include semi-structured interviews with program staff at Birmingham AIDS Outreach and the University of Alabama at Birminghams 1917 HIV/AIDS Clinic, and analysis of descriptive characteristics of individuals enrolled in the food program for a minimum of one year between 2017-2019. The new program served 1,311 patients and enabled more than 300 previously lost-to-follow-up patients to re-engage in HIV care. The program implementation reviewed here can serve as a roadmap to develop clinic/community partnerships focused on a variety of health outcomes and quality of life among food insecure patients.