title: Effectiveness of lower limb rehabilitation protocol using mobile health on quality of life, functional strength and functional capacity among knee osteoarthritis patients who were overweight and obese: A randomized controlled trial

abstract:
ObjectiveThis study aimed to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) using mobile health (mHealth) on quality of life (QoL), functional strength, and functional capacity among knee OA patients who were overweight and obese.

Materials and MethodsIn the current trial, 114 patients were recruited and randomized into either the rehabilitation group with mobile health (RGw-mHealth) receiving reminders by using mHealth to carry on the strengthening exercises of LLRP and instructions of daily care (IDC), the rehabilitation group without mobile health (RGwo-mHealth) following the strengthening exercises of LLRP and instructions of daily care (IDC) and control group (CG) only following the IDC for duration of 12-weeks. The reminders for using mHealth were provided two times a day for three days a week. Primary outcome measures were QoL assessed by the Western Ontario and McMaster Universities Osteoarthritis Index summary score, and functional strength by Five-Repetition Sit-To-Stand Test. Secondary outcome measure was functional capacity assessed by the Gait Speed Test. The assessments of QoL, functional strength, and functional capacity were taken at baseline and posttest after 12-weeks of intervention.

ResultsAfter 12 weeks of intervention, patients in all three groups had statistically significant improvement in QoL within groups (p < 0.05). Furthermore, patients in the RGw-mHealth and RGwo-mHealth had statistically significant improvement in functional strength and walking gait speed within groups (p < 0.05). The pairwise between-group comparisons (Bonferroni post hoc test) of the mean changes in QoL, functional strength, and functional capacity at posttest assessments revealed that patients in the RGw-mHealth had statistically significant greater mean change in QoL, functional strength and functional capacity relative to both the RGwo-mHealth and CG (p < 0.001).

ConclusionImprovement in QoL, functional strength, and functional capacity was larger among patients in the RGw-mHealth compared with the RGwo-mHealth or CG.

TRIAL REGISTRATIONChinese Clinical Trial Registry: ChiCTR1900028600

Date of registration: 28-12-2019

Registration Status: Prospective

URL: http://www.chictr.org.cn


title: Cellular and humoral immunity to SARS-CoV-2 infection in multiple sclerosis patients on ocrelizumab and other disease-modifying therapies: a multi-ethnic observational study

abstract:
ObjectiveTo determine the impact of MS disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to SARS-CoV-2 infection.

MethodsMS patients aged 18-60 were evaluated for anti-nucleocapsid and anti-Spike RBD antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture ELISA; and IL-2 and IFN{gamma} ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity.

ResultsBetween 1/6/2021 and 7/21/2021, 389 MS patients were recruited (mean age 40.3 years; 74% female; 62% non-White). Most common DMTs were ocrelizumab (OCR) - 40%; natalizumab - 17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. 177 patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, 47 - asymptomatic. Antibody responses were markedly attenuated in OCR compared to other groups (p[≤] 0001). T-cell responses (IFN{gamma} were decreased in S1P (p=0.03), increased in natalizumab (p<0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r=0.45, p=0.0002) and non-OCR (r=0.64, p<0.0001). Immune responses did not differ by race/ethnicity. COVID-19 clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized.

InterpretationDMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and non-disabled group of MS patients.

category: neurology


title: Altered plasma, urine, and tissue profiles of sulfatides and sphingomyelins in patients with renal cell carcinoma

abstract: Renal cell carcinoma (RCC) represents the most common type of kidney cancer and, despite the progress of surgical and medical management, is associated with high mortality. In this study, we demonstrate that RCC-related processes change body fluids sphingolipid concentrations, which may be used to monitor tumor presence using non-invasive lipid-based blood and urine tests. We investigate 674 plasma, urine, and tissue samples from 369 RCC patients and controls. For the first time, we show the significant concentration changes of low abundant sulfatides in plasma and urine of RCC patients. Elevated concentrations of lactosylsulfatides, decreased concentrations of sphingomyelins with long saturated N-fatty acyls and sulfatides with hydroxylated fatty acyls are the crucial alternations in RCC. These changes are stage-dependent and are more emphasized in late-stage RCC. Similar trends in body fluids and tissues indicate that RCC widely influences lipid metabolism and highlights the potential of lipidomic profiling for cancer detection.

category: oncology


title: Mycobacterium avium complex (MAC) genomics and transmission in a London hospital

abstract:
Non-tuberculous mycobacteria (NTM) are ubiquitous environmental microorganisms and opportunistic pathogens in individuals with pre-existing lung conditions such as cystic fibrosis (CF) and non-CF bronchiectasis (BX). Whilst recent studies of Mycobacterium abscessus have identified transmission within single CF centres as well as nationally and globally, transmission of other NTM species is less well studied. We sequenced 996 Mycobacterium avium complex (MAC) isolates from CF and non-CF patients at the Royal Brompton Hospital (RBH), London. Genomic analysis was used to analyse local transmission. Epidemiological links were identified from patient records. These and previously published genomes were used to characterise global population structures. Analysis of the three predominant MAC species identified putative transmission clusters that contained patients with CF, BX and other lung conditions, although few epidemiological links could be identified. For M. avium, lineages were largely limited to single countries, whilst for M. chimaera, global transmission clusters previously associated with heater cooler units (HCUs) were found. However, the immediate ancestor of the lineage causing the major HCU-associated outbreak was a lineage already circulating in patients with pre-existing lung conditions. CF and non-CF patients shared transmission chains even in the presence of CF patient-focussed hospital control measures, although the lack of epidemiological links suggested that most transmission is indirect and may involve environmental intermediates or else asymptomatic carriage in the wider population. The major HCU-associated M. chimaera lineage being derived from an already circulating lineage, suggests that HCUs, while being responsible for a major global transmission event, are not the sole vector nor the ultimate source of this wider patient-infecting lineage. Future studies should include sampling of environmental reservoirs and potential asymptomatic carriers.

Author summaryWhilst recent studies in Mycobacterium abscessus have identified transmission within single CF centres as well as nationally and globally, the transmission dynamics between CF and non-CF patients has not yet been comprehensively examined in the Mycobacterium avium complex (MAC). We believe this is the first study to use a well-sampled longitudinal isolate dataset, that includes both CF and non-CF patients from a single hospital setting, to investigate transmission of MAC species. We identified transmission clusters in the three predominant MAC species circulating in the hospital and showed that these included both CF and non-CF patients. We then incorporated isolates from previous studies to examine the global population structure of MAC species and showed that for M. avium there were UK-specific lineages circulating amongst patients, whilst for M. chimaera we could identify global lineages associated with HCUs. For the first time, we also show that the predominant HCU-associate lineage is likely derived from already circulating lineages associated with patients with respiratory diseases. Our study shows the value of integrating whole genome sequencing with epidemiological data to perform high-resolution molecular analyses to characterise MAC populations and identify transmission clusters. Knowledge of putative transmission networks can improve responses to outbreaks and inform targeted infection control and clinical practice.

category: infectious diseases


title: A Novel Scoring System for Early Assessment of the Risk of the COVID-19-associated Mortality in Hospitalized Patients: COVID-19 BURDEN

abstract:
BackgroundCorona Virus Disease 2019 (COVID-19) presentation resembles common flu or can be more severe; it can result in hospitalization with significant morbidity and/or mortality. We made an attempt to develop a predictive model and a scoring system to improve the diagnostic efficiency for COVID-19 mortality via analysis of clinical features and laboratory data on admission.

MethodsWe retrospectively enrolled 480 consecutive adult patients, aged 21-95, who were admitted to Faghihi Teaching Hospital. Clinical and laboratory features were extracted from the medical records and analyzed using multiple logistic regression analysis.

ResultsA novel mortality risk score (COVID-19 BURDEN) was calculated, incorporating risk factors from this cohort. CRP (> 73.1 mg/L), O2 saturation variation (greater than 90%, 84-90%, and less than 84%), increased PT (>16.2s), diastolic blood pressure ([≤]75 mmHg), BUN (>23 mg/dL), and raised LDH (>731 U/L) are the features comprising the scoring system. The patients are triaged to the groups of low- (score <4) and high-risk (score [≥] 4) groups. The area under the curve, sensitivity, and specificity for predicting non-response to medical therapy with scores of [≥] 4 were 0.831, 78.12%, and 70.95%, respectively.

ConclusionUsing this scoring system in COVID-19 patients, the severity of the disease will be determined in the early stages of the disease, which will help to reduce hospital care costs and improve its quality and outcome.


title: Improved evaluation of left ventricular hypertrophy using the spatial QRS-T angle by electrocardiography

abstract:
BackgroundConventional electrocardiographic (ECG) signs of left ventricular hypertrophy (LVH) lack sensitivity. The aim was to identify LVH based on an abnormal spatial peaks QRS-T angle, and evaluate its diagnostic and prognostic performance compared to that of conventional ECG criteria for LVH.

MethodsThis was an observational study with four cohorts, all with a QRS duration <120 ms: (1) Healthy volunteers to define normality (n=921), (2) Separate healthy volunteers to compare test specificity (n=461), (3) Patients with at least moderate LVH by cardiac imaging (Imaging-LVH) to compare test sensitivity (n=225), and (4) Patients referred for cardiovascular magnetic resonance imaging to evaluate the combined outcome of hospitalization for heart failure or all-cause death (Clinical-Consecutive, n=783).

ResultsAn abnormal spatial peaks QRS-T angle was defined as exceeding the upper limit of normal, which was found to be [≥] 40{degrees} for females and [≥] 55{degrees} for males. In healthy volunteers, the specificity of the QRS-T angle to detect LVH was 96% (females) and 98% (males). In Imaging-LVH, the QRS-T angle had a higher sensitivity to detect LVH than conventional ECG criteria (93-97% vs 13-56%, p<0.001 for all). In Clinical-Consecutive, of those who did not have any LVH, 238/556 (43%) had an abnormal QRS-T angle, suggesting it can occur even without LVH. There was an association with outcomes in univariable analysis for the QRS-T angle, Cornell voltage, QRS duration, and Cornell product (hazard ratios 1.68-2.5, p<0.01 for all) that persisted in multivariable analysis only for the QRS-T angle and QRS duration (p<0.001 for both).

ConclusionsAn increased QRS-T angle rarely occurred in healthy volunteers, was a mainstay of moderate or greater LVH, was common in clinical patients without LVH but with cardiac co-morbidities, and associated with outcomes. Thus, an increased QRS-T angle identifies left ventricular electrical remodeling that can occur in the absence of LVH detected by imaging. The improved diagnostic and independent prognostic performance for the QRS-T angle suggests that it should be investigated when ECGs are evaluated.

category: cardiovascular medicine


title: COVID-19 impact on Socio-economic and Health Interventions: A Gaps and Peaks analysis using Clustering Approach

abstract: A quantifiable model to describe the peaks and gaps during the several waves of COVID-19 is generated and applied to the progression of 120 countries. The number of waves encountered and how many more to be encountered is a question which is currently explored by all the scientific communities. In the same quest, an attempt has been made to quantitatively model the peaks and the gaps within them which have been encountered by 120 most affected countries from February 2020 - December 2021. These 120 countries were ranked based on the number of confirmed cases and deaths recorded during this period. This study further cluster these countries based on socio-economic and health interventions to find an association with three dependent features of COVID-19 i.e. number of confirmed cases, deaths and death-infectivity rate. The findings in this study suggests that, every wave had multiple peaks within them and as the number of peaks increased, predicting their growth rate or decline rate turns to be extremely difficult. However, considering the clusters which share the common features even with diverse countries, there is some possibility to predict what might be coming next. This study involves exhaustive analysis of reliable data which are available in open access and marks an important aspect to the COVID-19 research communities.

category: epidemiology


title: SARS-CoV-2 risk taxation model and validation based on large scale Dutch test-events

abstract: In response to the outbreak of SARS-CoV-2 many governments decided in 2020 to impose lockdowns on societies. Although the package of measures which constitute such lockdowns differs between countries, it is a general rule that contacts between people, and especially in large groups of people, are avoided or prohibited. The main reasoning behind these measures is preventing that healthcare systems become overloaded. As of 2021 vaccines against SARS-CoV-are available, but these do not guarantee 100% risk reduction and it will take a while for the world to reach a sufficient immune status. This raises the question whether and under which conditions events like theater shows, conferences, professional sports events, concerts and festivals can be organized. The current paper presents a COVID-19 Risk taxation method for (large scale) events. This method can be applied to events to define an alternative package of measures replacing generic social distancing.


title: Quantifying behavior change during the first year of the COVID-19 pandemic in the United States

abstract:
BackgroundDuring the first year of the COVID-19 pandemic, the most effective way to reduce transmission and to protect oneself was to reduce contact with others. However, it is unclear how behavior changed, despite numerous surveys about peoples attitudes and actions during the pandemic and public health efforts to influence behavior.

MethodsWe used two sources of data to quantify changes in behavior at the county level during the first year of the pandemic in the United States: aggregated mobile device (smartphone) location data to approximate the fraction of people staying at home each day and digital invitation data to capture the number and size of social gatherings.

ResultsBetween mid-March to early April 2020, the number of events fell and the fraction of devices staying at home peaked, independently of when states issued emergency orders or stay-at-home recommendations. Activity began to recover in May or June, with later rebounds in counties that suffered an early spring wave of reported COVID-19 cases. Counties with high incidence in the summer had more events, higher mobility, and less stringent state-level COVID-related restrictions the month before than counties with low incidence. Counties with high incidence in early fall stayed at home less and had less stringent state-level COVID-related restrictions in October, when cases began to rise in some parts of the US. During the early months of the pandemic, the number of events was inversely correlated with the fraction of devices staying at home, but after the fall of 2020 mobility appeared to stay constant as the number of events fell. Greater changes in behavior were observed in counties where a larger fraction voted for Biden in the 2020 US Presidential election. The number of people invited per event dropped gradually throughout the first year of the pandemic.

ConclusionsThe mobility and events datasets uncovered different kinds of behavioral responses to the pandemic. Our results indicate that people did in fact change their behavior in ways that likely reduced COVID exposure and transmission, though the degree of change appeared to be affected by political views. Though the mobility data captured the initial massive behavior changes in the first months of the pandemic, the digital invitation data, presented here for the first time, continued to show large changes in behavior later in the first year of the pandemic.


title: Scabies epidemiology in health care centers for refugees and asylum seekers in Greece

abstract:
BackgroundScabies is a global health concern disproportionally affecting vulnerable population such as refugees and asylum seekers. Greece is a main geographical point of entry in Europe for refugees, but epidemiological data on scabies in this population is scarce. We aimed to evaluate the epidemiology of scabies, including trends over the study period.

Methodology/Principal findingsData were collected from June, 2016 to July, 2020, using the surveillance system of the Greek National Public Health Organization. Staff at health centers for refugees/asylum seekers compiled daily reports on scabies and other infectious diseases. Observed proportional morbidity for scabies was calculated using consultations for scabies as a proportion of total consultations.

There were a total of 13118 scabies cases over the study period. Scabies was the third most frequently observed infectious disease in refugees/asylum seekers population after respiratory infections and gastroenteritis without blood in the stool. The scabies monthly observed proportional morbidity varied between 0.3% (August 2017) to 5.6% (January 2020). Several outbreaks were documented during the study period. An increasing number of cases was observed from October 2019 until the end of the study period, with a peak of 1663 cases in January 2020, related to an outbreak at one center. Spearman correlation test between the number of reported scabies cases and time confirmed an increasing trend ({rho}=0.67).

Conclusions/SignificanceScabies is one of the most frequently reported infectious diseases by health care workers in refugee/asylum seekers centers in Greece. Consultations for scabies increased over time and there were several outbreaks. The current surveillance system effectively detects new cases in an early stage. Public health interventions, including mass drug administration, should be considered to reduce the burden of scabies in refugee/migrant populations.

Author summaryScabies is a skin disease caused by ectoparasitic mite Sarcoptes scabiei var. hominis. A person infected by scabies manifests symptoms like itching and skin rash, while the most complicated forms of the infection can lead to bacterial infections and sepsis. Scabies is a global health concern and as of 2017, it is officially included in the portfolio of conditions prioritized by the Department of Neglected Tropical Diseases, according to the World Health Organization. Furthermore, scabies can disproportionally affect vulnerable population, such as refugees and asylum seekers. Greece is one of the main points of entry in Europe for refugees. However, the prevalence of scabies amongst refugees in Greece has not been thoroughly investigated. In this study, we utilized data weekly reported within the epidemiological surveillance in refugees/asylum seekers centers of the Greek National Public Health Organization, in order to obtain a clear overview of scabies epidemiology and identify any trends over time. Our findings confirmed the high prevalence of scabies among refugees and identified a clear trend of significant increase over time. Further public health interventions, like mass drug administration could help restrain the dissemination of the disease and lower its burden among refugees.

category: public and global health


title: Germline predisposition to pediatric Ewing sarcoma is uniquely characterized by inherited pathogenic variants in DNA damage repair genes

abstract: More knowledge is needed around the role and importance of specific genes in germline predisposition to Ewing sarcoma to inform biological investigation and clinical practice. In this study, we evaluated the enrichment of pathogenic germline variants in Ewing sarcoma relative to other pediatric sarcoma subtypes, as well as patterns of inheritance of these variants. We carried out an ancestry-matched case-control analysis to screen for enrichment of pathogenic germline variants in 141 established cancer predisposition genes in 1138 individuals with pediatric sarcoma diagnoses (222 Ewing sarcoma cases) relative to identically processed cancer-free controls. Findings in Ewing sarcoma were validated with an additional cohort of 425 individuals, and 301 Ewing sarcoma parent-proband trios were analyzed for inheritance patterns of identified pathogenic variants. A distinct pattern of pathogenic germline variants was seen in Ewing sarcoma relative to other sarcoma subtypes. FANCC was the only gene with an enrichment signal for heterozygous pathogenic variants in the discovery Ewing sarcoma cohort (OR 14.4, 95% CI 3.5 - 51.2, p = 0.002, FDR = 0.28). This enrichment in FANCC heterozygous pathogenic variants was seen again in the Ewing sarcoma validation cohort (OR 5.1, 95% CI 1.2 - 18.5, p = 0.03, single hypothesis), representing a broader importance of genes involved in DNA damage repair, which were also nominally enriched in Ewing sarcoma cases. Pathogenic variants in DNA damage repair genes were acquired through autosomal inheritance. Our study provides new insight into germline risk factors contributing to Ewing sarcoma pathogenesis.

category: genetic and genomic medicine


title: Two viruses competition in the SIR model of epidemic spread: application to COVID-19

abstract:
The SIR model of the epidemic spread is used for consideration the problem of the competition of two viruses having different contagiousness. It is shown how the more contagious strain replaces over time the less contagious one. In particular the results can be applied to the current situation when the omicron strain appeared in population affected by the delta strain.

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


title: General anxiety and depression are associated with the physical activity and social interaction levels: Study in Argentinean university students during the COVID-19 outbreak

abstract:
BackgroundDue to the coronavirus disease 2019 (COVID-19), the planet is going through a historical time of exceptional concern and uncertainty, which impacts peoples mental health. Here, we explored the levels of depression and Generalized Anxiety Disorder (GAD) and their relation with the degree of physical activity and social interaction during the pandemic.

MethodsWe performed a structured survey containing the PHQ-9 and GAD-7 tests to evaluate depressive symptoms and GAD levels. We also asked about weekly physical activity and the level of social interaction. We surveyed two groups of University students in the Buenos Aires Metropolitan Area: an internal group from the Instituto Tecnologico de Buenos Aires (ITBA), and an external group of students from multiple universities. The survey was conducted in late October/early-November 2020, after a peak of contagions. Some of the participants were surveyed again in January 2021, during academic holidays and after a valley of contagion, for longitudinal analysis

ResultsOur data show that men and women of both groups exhibited a significant positive linear correlation between depression and GAD levels. Moreover, low levels of depression and anxiety were associated with performing physical activity for more than two days a week and to longer periods of social interaction. Finally, the second survey revealed a decrease of the symptoms.

ConclusionsOur results suggest that performing regular physical activity and avoiding long periods of social isolation gave benefits to mental health. We suggest that public policies could consider protecting these behaviors under health and safety standards.

category: psychiatry and clinical psychology


title: Household secondary attack rates of SARS-CoV-2 by variant and vaccination status: an updated systematic review and meta-analysis

abstract:
We previously reported a household secondary attack rate (SAR) for SARS-CoV-2 of 18.9% through June 17, 2021. To examine how emerging variants and increased vaccination have affected transmission rates, we searched PubMed from June 18, 2021, through January 7, 2022. Meta-analyses used generalized linear mixed models to obtain SAR estimates and 95%CI, disaggregated by several covariates. SARs were used to estimate vaccine effectiveness based on the transmission probability for susceptibility (VES,p), infectiousness (VEI,p), and total vaccine effectiveness (VET,p). Household SAR for 27 studies with midpoints in 2021 was 35.8% (95%CI, 30.6%-41.3%), compared to 15.7% (95%CI, 13.3%-18.4%) for 62 studies with midpoints through April 2020. Household SARs were 38.0% (95%CI, 36.0%-40.0%), 30.8% (95%CI, 23.5%-39.3%), and 22.5% (95%CI, 18.6%-26.8%) for Alpha, Delta, and Beta, respectively. VEI,p, VES,p, and VET,p were 56.6% (95%CI, 28.7%-73.6%), 70.3% (95%CI, 59.3%-78.4%), and 86.8% (95%CI, 76.7%-92.5%) for full vaccination, and 27.5% (95%CI, -6.4%-50.7%), 43.9% (95%CI, 21.8%-59.7%), and 59.9% (95%CI, 34.4%-75.5%) for partial vaccination, respectively. Household contacts exposed to Alpha or Delta are at increased risk of infection compared to the original wild-type strain. Vaccination reduced susceptibility to infection and transmission to others.

SummaryHousehold secondary attack rates (SARs) were higher for Alpha and Delta variants than previous estimates. SARs were higher to unvaccinated contacts than to partially or fully vaccinated contacts and were higher from unvaccinated index cases than from fully vaccinated index cases.


title: Cardiopulmonary imaging utilization and findings among hospitalized COVID-19 patients in Latin America (From RIMAC: Registry IMAging Cardiopulmonary among hospitalized COVID-19 patients in LATAM)

abstract:
ObjectivesTo describe the use and findings of cardiopulmonary imaging - chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS)) and/or cardiac magnetic resonance imaging (cMRI) - in COVID-19-associated hospitalizations in Latin America (LATAM)

BackgroundThe SARS-Cov-2 is one of the largest and most active threats to healthcare in living memory. There is an information gap on imaging services resources (ISR) used and their findings during the pandemic in LATAM.

MethodsThis was a multicenter, prospective, observational study of COVID-19 inpatients conducted from March to December 2020 from 12 high-complexity centers in nine LATAM countries. Adults (> 18 yrs) with at least one imaging modality performed, followed from admission until discharge and/or in-hospital death, were included.

ResultsWe studied 1435 hospitalized patients (64% males) with a median age of 58 years classified into three regions: 262 from Mexico (Mx), 428 from Central America and Caribbean (CAC), and 745 from South America (SAm). More frequent comorbidities were overweight/obesity (61%), hypertension (45%), and diabetes (27%). During hospitalization, 58% were admitted to ICU. The in-hospital mortality was 28% (95%CI 25-30) highest in Mx (37%).

The most frequent cardiopulmonary imaging performed were cCT (61%)-more frequent in Mx and SAm-, and cX-ray (46%) -significantly used in CAC-. The cEcho was carried out in 18%, similarly among regions, and LUS in 7%, more frequently in Mx. The cMRI was performed in only one patient in the cohort. Abnormal findings on the cX-ray were related to peripheral (63%) or basal infiltrates (52%), and in cCT with ground glass infiltrates (89%). Both were more commonly in Mx. In LUS, interstitial syndrome (56%) was the most related abnormal finding, predominantly in Mx and CAC.

ConclusionsThe use and findings of cardiopulmonary imaging in LATAM varied between regions and may have been influenced by clinical needs, the personnel protection measures and/or hospitalization location.

Condensed AbstractThe SARS-Cov-2 is one of the largest and most active threats to healthcare in living memory. There is limited information on imaging services resources (ISR) used and their findings during the pandemic in LATAM.

To our knowledge, RIMAC aimed the first international, multicenter study at registering the use and findings of cardiopulmonary imaging modalities performed for the diagnosis, prognosis, and treatment of patients hospitalized for infection with SARS-CoV-2 in Latin America. We studied their demographic parameters, comorbidities, in-hospital events, laboratory results, and treatments focusing on their impact in clinical complications.

category: radiology and imaging


title: Machine Learning Prediction of Progression in FEV1 in the COPDGene Study

abstract:
BackgroundThe heterogeneous nature of COPD complicates the identification of the predictors of disease progression and consequently the development of effective therapies. We aimed to improve the prediction of disease progression in COPD by using machine learning and incorporating a rich dataset of phenotypic features.

MethodsWe included 4,496 smokers with available data from their enrollment and 5-year follow-up visits in the Genetic Epidemiology of COPD (COPDGene) study. We constructed supervised random forest models to predict 5-year progression in FEV1 from 46 baseline demographic, clinical, physiologic, and imaging features. Using cross-validation, we randomly partitioned participants into training and testing samples. We also validated the results in the COPDGene 10-year follow-up visit.

ResultsPredicting the change in FEV1 over time is more challenging than simply predicting the future absolute FEV1 level. Nevertheless, the area under the ROC curves for the prediction of subjects in the top quartile of observed disease progression was 0.70 in the 10-year follow-up data. The model performance accuracy was best for GOLD1-2 subjects and it was harder to achieve accurate prediction in advanced stages of the disease. Predictive variables differed in their relative importance as well as for the predictions by GOLD grade.

ConclusionThis state-of-the art approach along with deep phenotyping predicts FEV1 progression with reasonable accuracy. There is significant room for improvement in future models. This prediction model facilitates the identification of smokers at increased risk for rapid disease progression. Such findings may be useful in the selection of patient populations for targeted clinical trials.

category: respiratory medicine


title: Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases

abstract:
Proteome-wide Mendelian randomization (MR) shows value in prioritizing drug targets in Europeans, but limited data has made identification of causal proteins in other ancestries challenging. Here we present a multi-ancestry proteome-wide MR analysis pipeline based on cross-population data from the Global Biobank Meta-analysis Initiative (GBMI). We estimated the causal effects of 1,545 proteins on eight complex diseases in up to 32,658 individuals of African ancestries and 1.22 million individuals of European ancestries. We identified 45 and seven protein-disease pairs with MR and genetic colocalization evidence in the two ancestries respectively. 15 protein-disease pairs showed evidence of differential effects between males and females. A multi-ancestry MR comparison identified two protein-disease pairs with MR evidence of an effect in both ancestries, seven pairs with European-specific effects and seven with African-specific effects. Integrating these MR signals with observational and clinical trial evidence, we were able to evaluate the efficacy of one existing drug, identify seven drug repurposing opportunities and predict seven novel effects of proteins on diseases. Our results highlight the value of proteome-wide MR in informing the generalisability of drug targets across ancestries and illustrate the value of multi-cohort and biobank meta-analysis of genetic data for drug development.

Graphical abstract

O_FIG O_LINKSMALLFIG WIDTH=150 HEIGHT=200 SRC="FIGDIR/small/21268473v1_ufig1.gif" ALT="Figure 1">
View larger version (58K):
org.highwire.dtl.DTLVardef@120cdforg.highwire.dtl.DTLVardef@10b2d8aorg.highwire.dtl.DTLVardef@dae897org.highwire.dtl.DTLVardef@1dc2c9d_HPS_FORMAT_FIGEXP  M_FIG C_FIG Notation: genome-wide association study (GWAS); Mendelian randomization (MR); primary open-angle glaucoma (POAG); idiopathic pulmonary fibrosis (IPF); chronic obstructive pulmonary disease (COPD); heart failure (HF), venous thromboembolism (VTE). European ancestry (EUR); African ancestry (AFR)*For the seven protein-disease associations, one association passed FDR threshold of 0.05 in proteome-wide MR, six additional associations passed FDR of 0.05 in the multi-ancestry comparison analysis.

HighlightsO_LIA multi-ancestry proteome-wide Mendelian randomization (MR) analysis of 1,545 proteins on eight diseases in more than 1.26 million individuals from a disease GWAS meta-analysis of 19 biobanks.
C_LIO_LIWe find evidence for putative causal effects in 45 protein-disease pairs in European ancestry and seven protein-disease pairs in African ancestry, with 15 pairs showing sex specific effects.
C_LIO_LIWe identify evidence of causality for two protein-disease pairs that are common to both African and European ancestries, seven pairs with European-specific effects and seven pairs with African-specific effects.
C_LIO_LITriangulating with clinical trial and observational evidence prioritizes seven new targets, seven drug repurposing opportunities and one existing drug target that generalise to African ancestry.
C_LI


title: Analytic sensitivity of the Abbott BinaxNOW lateral flow immunochromatographic assay for the SARS-CoV-2 Omicron variant

abstract: The emergence of the SARS-CoV-2 Omicron variant has motivated a re-evaluation of the test characteristics for lateral flow immunochromatographic assays (LFIAs), commonly referred to as rapid antigen tests. To address this need, we evaluated the analytic sensitivity of one of the most widely used LFIAs in the US market, the Abbott BinaxNOW COVID-19 Ag At-Home Card using 32 samples of Omicron and 30 samples of the Delta variant. Samples were chosen to intentionally over-represent the range of viral loads where differences are most likely to appear. We found no changes in the analytic sensitivity of the BinaxNOW assay by variant even after controlling for variation in cycle threshold values in the two populations. Similar to prior studies, the sensitivity of the assay is highly dependent on the amount of virus present in the sample. While the analytic sensitivity of the BinaxNOW LFIA remains intact versus the Omicron variant, its clinical sensitivity is influenced by the interaction between viral replication, the dynamics of tissue tropism and the timing of sampling. Further research is necessary to optimally adapt current testing strategies to robustly detect early infection by the Omicron variant to prevent transmission.


title: Clinical outcomes among patients infected with Omicron (B.1.1.529) SARS-CoV-2 variant in southern California

abstract: The Omicron (B.1.1.529) variant of SARS-CoV-2 rapidly achieved global dissemination following its emergence in southern Africa in November, 2021.1,2 Epidemiologic surveillance in multiple settings has revealed changes in COVID-19 case-to-hospitalization and case-to-mortality ratios following Omicron variant emergence.3-7 However, interpretation of these changes is difficult due to potential differences in immunity among cases with Omicron or Delta (B.1.617.2) variant SARS-CoV-2 infections, as well as possible longer-term changes in testing and other healthcare practices.8 Here we report clinical outcomes and characteristics of 228,594 cases with Omicron variant infections and 42,515 cases with Delta variant infections within the Kaiser Permanente Southern California healthcare system, who were followed longitudinally from an initial outpatient test during a period of mixed circulation of the Omicron and Delta variants. Adjusted hazard ratios of progression to symptomatic hospital admission, intensive care unit admission, mechanical ventilation, and death were 0.62 (95% confidence interval: 0.54-0.72), 0.59 (0.51-0.69), 0.45 (0.26-0.78), and 0.36 (0.18-0.74), and 0.21 (0.10-0.42) respectively, for cases with Omicron versus Delta variant infections. These differences in risk of severe clinical endpoints were most pronounced among individuals who had not received any vaccination against COVID-19, owing to partial vaccine protection against severe disease associated with both Omicron and Delta variant infections. Among hospitalized symptomatic cases, average duration of hospital stay was 70.7% (64.4-76.0%) shorter among patients with Omicron as compared to Delta variant infections. These findings demonstrate that the Omicron SARS-CoV-2 variant is associated with substantially severity of illness in comparison to the Delta variant.


title: Prune intake ameliorates chronic constipation symptoms and causes little discomfort from diarrhea and loose stools: A randomized placebo-controlled trial

abstract:
AimLittle data is available regarding the effectiveness of natural foods in treating chronic constipation. We aimed to identify whether prune ameliorates chronic constipation and can be used safely for a relatively long time.

MethodsIn this double-blind, randomized, placebo-controlled trial, 84 subjects with chronic constipation, presenting more than 6 months before and persisting for more than 3 months, were randomized to prune (n=42) or placebo (n=42) intake for 8 weeks. We assessed daily Bristol stool form scale (BSFS) scores and stool frequencies and administered the gastrointestinal symptom rating scale (GSRS) questionnaire, as primary outcomes for constipation improvement.

ResultsThe prune group showed significantly decreased rates of hard stool (BSFS1 or 2) and increased rates of normal stool (BSFS 3 or 4) after 1 week, which were more evident after 7 weeks between the two groups. Prune significantly increased stool frequency immediately after 1 week. Furthermore, GSRS of hard stools, flatulence, and incomplete evacuation significantly improved after 4-8 weeks of prune intake, of which constipation and hard stools were significantly reduced compared to the placebo group. In contrast, prune intake did not cause diarrhea, loose stools, or urgent need for defecation during 8 weeks evaluated by GSRS score. We found no abnormal laboratory tests of liver function, renal function, inflammation, or urinalysis after prune intake.

ConclusionsDaily prune intake ameliorates chronic constipation, improving quality of life, and causes few diarrhea-related symptoms or side effects. Our results emphasize a new, useful, and easy strategy for chronic constipation. (UMIN ID:000041384)

category: gastroenterology


title: Estimating the cost of antibiotic use on future collateral resistance: a retrospective comparison of cefuroxime versus cefazolin and amoxicillin/clavulanate

abstract:
BackgroundQuantitative estimates of collateral resistance induced by antibiotic use are scarce. This study compared the effects of treatment with amoxicillin/clavulanate or cefazolin, compared to cefuroxime, on future resistance to ceftazidime among hospitalized patients.

MethodsA retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016-2019 was conducted. Patients were restricted to those treated with either amoxicillin/clavulanate, cefazolin, or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. A 1:1 matching was performed for each patient in the amoxicillin/clavulanate and cefazolin groups, to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and g-formula (standardization) were used to estimate the odds ratio (OR), risk difference (RD), and number needed to harm (NNH).

ResultsCefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin: the marginal OR was 1.76)95%CI 1.16-2.83) compared to amoxicillin/clavulanate, and 1.98 (95%CI 1.41-2.8) compared to cefazolin; The RD was 0.118 (95%CI 0.031-0.215) compared to amoxicillin/clavulanate, and 0.131 (95%CI 0.058-0.197) compared to cefazolin. We also estimated the NNH: replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime-resistance in one more patient for every 8.5 (95% CI 4.66-32.14) or 7.6 (95% CI 5.1-17.3) patients re-hospitalized in the following year.

ConclusionsOur results indicate that treatment with amoxicillin/clavulanate or cefazolin is preferable to cefuroxime, in terms of future collateral resistance. The results presented here are a first step towards quantitative estimations of the ecological damage caused by different antibiotics.

Key pointsWe performed a retrospective study estimating collateral resistance of treatment with cefuroxime relative to amoxicillin/clavulanate or cefazolin. Application of novel analytical methods allowed us to estimate the number needed to harm and hence ecological damage of the different treatments.


title: Geospatial modeling of pre-intervention prevalence of Onchocerca volvulus infection in Ethiopia as an aid to onchocerciasis elimination

abstract:
BackgroundOnchocerciasis is a neglected tropical and filarial disease transmitted by the bites of blackflies, causing blindness and severe skin lesions. The change in focus for onchocerciasis management from control to elimination requires thorough mapping of pre-control endemicity to identify areas requiring interventions and to monitor progress. Onchocerca volvulus infection prevalence in sub-Saharan Africa is spatially continuous and heterogeneous, and highly endemic areas may contribute to transmission in areas of low endemicity or vice-versa. Ethiopia is one such onchocerciasis-endemic country with heterogeneous O. volvulus infection prevalence, and many districts are still unmapped despite their potential for O. volvulus infection transmission.

Methodology/Principle findingsA Bayesian geostatistical model was fitted for retrospective pre-intervention nodule prevalence data collected from 916 unique sites and 35,077 people across Ethiopia. We used multiple environmental, socio-demographic, and climate variables to estimate the pre-intervention prevalence of O. volvulus infection across Ethiopia and to explore their relationship with prevalence. Prevalence was high in southern and northwestern Ethiopia and low in Ethiopias central and eastern parts. Distance to the nearest river (-0.015, 95% BCI: -0.025 - -0.005), precipitation seasonality (-0.017, 95% BCI: -0.032 - -0.001), and flow accumulation (-0.042, 95% BCI: -0.07 - -0.019) were negatively associated with O. volvulus infection prevalence, while soil moisture (0.0216, 95% BCI: 0.014 - 0.03) was positively associated.

Conclusions/SignificanceInfection distribution was correlated with habitat suitability for vector breeding and associated biting behavior. The modeled pre-intervention prevalence can be used as a guide for determining priority for intervention in regions of Ethiopia that are currently unmapped, most of which have comparatively low infection prevalence.

Authors summaryAreas with unknown onchocerciasis endemicity may pose a threat to the goal of eliminating transmission: they may re-introduce onchocerciasis to areas where interventions have been successful. Additionally, because the vectors (and thus Onchocerca volvulus transmission) have specific ecological requirements for growth and development, changes in these ecological factors due to human activities (deforestation, modification of river flows by dam construction, climate change) might change patterns of parasite transmission and endemicity. To estimate the impact of these environmental changes, we must first identify ecological factors that determine transmission and prevalence. We have employed Bayesian geostatistical modeling to create a nationwide O. volvulus infection prevalence map for Ethiopia based on pre-intervention nodule prevalence and have explored the effect of environmental variables on O. volvulus infection prevalence. We have also identified areas that need additional data to increase the prediction accuracy of the map. We found that hydrological variables such as distance to the nearest river, precipitation seasonality, soil moisture, and flow accumulation are associated significantly with O. volvulus infection prevalence. We show that the pre-intervention prevalence can be estimated based on the ecological data and that predicted prevalence can be used as a guide to prioritize pre-intervention mapping.


title: Factors influencing the motivation of maternal health workers in conflict setting of Mogadishu, Somalia.

abstract:
BackgroundMotivated health workers play an important role in delivering high-quality maternal health services, especially in low-income countries where maternal mortality rates are high, and shortages of human resource for health is prevalent. The aim of this study is to investigate maternal health workers motivation in three tertiary hospitals in Mogadishu Somalia.

MethodTo investigate health worker motivation in Somalia, we used a semi-structured questionnaire that was validated and widely used in Sub-Saharan Africa. Data were collected from 220 health workers across three tertiary hospitals in Mogadishu between February and April 2020. Health worker motivation was measured using seven constructs: general motivation, burnout, job satisfaction, intrinsic job satisfaction, organizational commitment, conscientiousness, timeliness and attendance. A multivariate regression analysis was performed to determine the predictors of health worker motivation.

ResultsThe study found that male health workers have a higher work motivation, with a mean score of 92.75 (SD 21.31) versus 90.43 (SD 21.61) in women. A significant correlation was found between health workers motivation and being an assistant, nurse, physician, pediatric-assistant, midwife, supervisor and pharmacist. Unexpectedly, the gynecologists and midwives were the least motivated groups among the different professions, with mean scores of 83.63, (SD: 27.41) and 86.95 (SD: 21.08), respectively. Of the aforementioned seven motivation constructs, the highest mean motivation scores (from 1-5) were observed in conscientiousness and intrinsic job satisfaction.

ConclusionThe results highlight the importance of targeted interventions that increase female health workers motivation, particularly gynecologists and midwives in Somalia. This can be done by providing non-financial incentives, in addition to encouraging their participation in the decision-making process. Further research is needed to investigate the effect of a lack of motivation among gynecologists and midwives on maternal health in Somalia.


title: The Psychosocial Benefits of Sport Participation During COVID-19 Are Only Partially Explained by Increased Physical Activity

abstract: The purpose of this study was to determine whether physical activity (PA) increases were responsible for the improvements in mental health and quality of life (QOL) seen among adolescents who returned to sport during the COVID-19 pandemic.Adolescent athletes were asked to complete a survey in October 2020 regarding demographic information, whether they had returned to sport participation (no [DNP], yes [PLY]), school instruction type (virtual, in-person, hybrid), anxiety, depression, QOL, and PA. Anxiety, depression, QOL and PA were compared between PLY and DNP using least squares means from linear models adjusted for age, gender, and instruction type. Mediation analysis assessed whether the relationship between sport status and anxiety, depression, and QOL was mediated by PA. 171 athletes had returned to play, while 388 had not. PLY athletes had significantly lower anxiety (3.6{+/-}0.4 v 8.2{+/-}0.6, p<0.001) and depression (4.2{+/-}0.4 v 7.3{+/-}0.6, p<0.001), and significantly higher QOL (88.1{+/-}1.0 v 80.2{+/-}1.4, p<0.001) and PA (24.0{+/-}0.5 v 16.3{+/-}0.7, p<0.001). PA explained a significant, but relatively small portion of the difference in depression (22.1%, p=0.02) and QOL (16.0%, p=0.048) between PLY and DNP athletes, but did not explain the difference in anxiety (6.6%, p=0.20). Increased PA is only responsible for a small portion of the improvements in depression and QOL among athletes who returned to sports and unrelated to improvements in anxiety. This suggests that the majority of the mental health benefits of sport participation for adolescents during the COVID-19 pandemic are independent of, and in addition to, the benefits of increased PA.

category: sports medicine


title: Prevalence and determinants of persistent symptoms after infection with SARS-CoV-2: Protocol for an observational cohort study (LongCOVID-study)

abstract:
BackgroundA substantial proportion of individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) report persisting symptoms weeks and months following acute infection. Estimates on prevalence vary due to differences in study designs, populations, heterogeneity of symptoms and the way symptoms are measured. Common symptoms include fatigue, cognitive impairment and dyspnea. However, knowledge regarding the nature and risk factors for developing persisting symptoms is still limited. Hence in this study we aim to determine the prevalence, severity, risk factors and impact on quality of life of persisting symptoms in the first year following acute SARS-CoV-2 infection.

MethodsThe LongCOVID-study is both a prospective and retrospective cohort study with a one year follow up. Participants aged 5 years and above with self-reported positive or negative tests for SARS-CoV-2 will be included in the study. The primary outcome is the prevalence and severity of persistent symptoms in participants that tested positive for SARS-CoV-2 compared to controls. Symptom severity will be assessed for fatigue using the Checklist Individual Strength (CIS subscale fatigue severity), pain (Rand-36/SF-36 subscale bodily pain), dyspnea (Medical Research Council (mMRC)) and cognitive impairment using the Cognitive Failure Questionnaire (CFQ). Secondary outcomes include loss of health-related quality of life (HRQoL) and risk factors for persisting symptoms following infection with SARS-CoV-2.

DiscussionA better understanding regarding the nature of persisting symptoms following SARS-CoV-2 infection will enable better diagnosis, management and will consequently minimize negative consequences on quality of life.


title: Environmental risk factors associated with the presence of Mycobacterium ulcerans in Victoria, Australia

abstract:
In recent years reported cases of Buruli ulcer (BU), caused by Mycobacterium ulcerans (MU), have increased substantially in Victoria, Australia, with the epidemic also expanding geographically. To develop an understanding of how MU circulates in the environment and transmits to humans we analyzed environmental samples collected from 115 properties of recent BU cases and from 115 postcode-matched control properties, for the presence of MU. Environmental factors associated with increased odds of MU presence at a property included certain native plant species and native vegetation in general, more alkaline soil, lower altitude, the presence of common ringtail possums (Pseudocheirus peregrinus) and overhead powerlines. However, only powerlines and the absence of the native plant Melaleuca lanceolata were associated with BU case properties. Samples positive for MU were more likely to be found at case properties and were associated with detections of MU in ringtail possum feces, supporting the hypothesis that MU is zoonotic, with ringtail possums the strongest reservoir host candidate. However, the disparity in environmental risk factors associated with MU positive properties versus case properties indicates a strong human behavioral component or the influence of other environmental factors in disease acquisition that requires further study.

Article Summary LinePossums, powerlines, and native vegetation are associated with the presence of Mycobacterium ulcerans in residential properties in Victoria, Australia.


title: Hydroxychloroquine/Chloroquine for the Treatment of Hospitalized Patients with COVID-19: An Individual Participant Data Meta-Analysis

abstract:
ImportanceResults from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data (IPD), including unanalyzed data from trials terminated early, enables further investigation of the efficacy and safety of HCQ/CQ.

ObjectiveTo assess efficacy of HCQ/CQ in patients hospitalized with COVID-19, both overall and in prespecified subgroups.

Data SourcesClinicalTrials.gov was searched multiple times in May-June 2020. Principal investigators of US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients were invited to collaborate in this IPD meta-analysis.

Study SelectionRCTs in which: (1) HCQ/CQ was a treatment arm; (2) patient informed consent and/or individual study IRB approval allowed for data sharing; (3) principal investigators/their institutions signed a data use agreement for the present study; and (4) the outcomes defined in this study were recorded or could be extrapolated.

Data Extraction and SynthesisWherever possible, harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator, then shared via a secure online data sharing platform to create a pooled data set. When this was not possible, individual study data were harmonized and merged manually. Data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions.

Main Outcome(s) and Measure(s)7-point ordinal scale, measured between day 28 and 35 post-enrollment.

ResultsEight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We found no evidence of a difference in ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively).

Conclusions and RelevanceThe findings of this IPD meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

Key PointsO_ST_ABSQuestionC_ST_ABSDoes hydroxychloroquine/chloroquine benefit hospitalized patients with COVID-19, overall or within prespecified subgroups?

FindingsIn this individual participant data meta-analysis of 770 hospitalized COVID-19 patients across 8 clinical trials, we did not find evidence of a benefit of hydroxychloroquine/chloroquine, measured by a 7-point ordinal COVID-19 severity score at 28-35 days post-enrollment, in the pooled study population. We also found no substantial treatment effect heterogeneity among prespecified patient subgroups.

MeaningThis study supports the consensus that hydroxychloroquine/chloroquine should not be used to treat hospitalized patients with COVID-19.


title: Healthcare workers' views on mandatory SARS-CoV-2 vaccination in the United Kingdom: findings from the UK-REACH prospective longitudinal cohort study

abstract:
BackgroundSeveral countries now have mandatory SARS-CoV-2/COVID-19 vaccination for healthcare workers (HCWs) or the general population. HCWs views on this are largely unknown.

MethodsWe administered an online questionnaire to 17891 United Kingdom (UK) HCWs in Spring 2021 as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question "What should society do if people dont get vaccinated against COVID-19?" using content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not and used logistic regression to calculate its demographic predictors, and occupational, health and attitudinal predictors adjusted for demographics.

FindingsOf 5633 questionnaire respondents, 3235 answered the freetext question; 18% (n=578) of those favoured mandatory vaccination but the most frequent suggestion was education (32%, n=1047). Older HCWs, HCWs vaccinated against influenza (OR 1.48; 95%CI 1.10 - 1.99, vs none) and with more positive vaccination attitudes generally (OR 1.10; 95%CI 1.06 - 1.14) were more likely to favour mandatory vaccination (OR 1.26; 95%CI 1.17 - 1.37, per decade increase), whereas female HCWs (OR= 0.80, 95%CI 0.65 - 0.99, vs male), Black HCWs (OR= 0.48, 95%CI 0.26 - 0.87, vs White), those hesitant about COVID-19 vaccination (OR= 0.56; 95%CI 0.43 - 0.71, vs not hesitant), in an Allied Health Profession (OR 0.67; 95%CI 0.51 - 0.88, vs Medical), or who trusted their organisation (OR 0.78; 95%CI 0.63 - 0.96) were less likely to.

InterpretationOnly one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating and supporting HCWs who are hesitant about vaccination may be more acceptable, effective and equitable.

FundingMRC-UK Research and Innovation grant (MR/V027549/1) and the Department of Health and Social Care via the National Institute for Health Research.


title: Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron

abstract:
BackgroundViral load (VL) is one determinant of secondary transmission of SARS-CoV-2. Emergence of variants of concerns (VOC) Alpha and Delta was ascribed, at least partly, to higher VL. Furthermore, with parts of the population vaccinated, knowledge on VL in vaccine-breakthrough infections is crucial. As RNA VL is only a weak proxy for infectiousness, studies on infectious virus presence by cell culture isolation are of importance.

MethodsWe assessed nasopharyngeal swabs of COVID-19 patients for quantitative infectious viral titres (IVT) by focus-forming assay and compared to overall virus isolation success and RNA genome copies. We assessed IVTs during the first 5 symptomatic days in a total of 384 patients: unvaccinated individuals infected with pre-VOC SARS-CoV-2 (n= 118) or Delta (n= 127) and vaccine breakthrough infections with Delta (n= 121) or Omicron (n=18).

FindingsCorrelation between RNA copy number and IVT was low for all groups. No correlation between IVTs and age or sex was seen. We observed higher RNA genome copies in pre-VOC SARS-CoV-2 compared to Delta, but significantly higher IVTs in Delta infected individuals. Vaccinated Delta infected individuals had significantly lower RNA genome copies and IVTs compared to unvaccinated subjects and cleared virus faster. In addition, vaccinated individuals with Omicron infection had comparable IVTs to Delta breakthrough infections.

InterpretationQuantitative IVTs can give detailed insights into virus shedding kinetics. Vaccination was associated with lower infectious titres and faster clearance for Delta, showing that vaccination would also lower transmission risk. Omicron vaccine-breakthrough infections did not show elevated IVTs compared to Delta, suggesting that other mechanisms than increase VL contribute to the high infectiousness of Omicron.

FundingThis work was supported by the Swiss National Science Foundation 196644, 196383, NRP (National Research Program) 78 Covid-19 Grant 198412, the Fondation Ancrage Bienfaisance du Groupe Pictet and the Fondation Privee des Hopitaux Universitaires de Geneve.


title: Long-lasting effects of insufficient sleep on neurocognitive development in early adolescence

abstract:
ImportanceAdolescents nowadays often get insufficient sleep. Yet, the long-term adverse effects of sleep loss on developing brain and behavior remains unknown.

ObjectiveTo determine whether insufficient sleep leads to long-lasting impacts on mental health, cognition, and brain development in adolescents across two years.

DesignThis longitudinal study utilized a public dataset, the Adolescent Brain Cognitive Development (ABCD) study, which is an ongoing study starting from 2016.

SettingData were collected from 21 research sites in the U.S.

Participants11,875 9-10-year-olds were recruited using stratified sampling in order to reflect the diversity of the U.S. population.

InterventionIndividuals with sufficient versus insufficient sleep (< 9 hours per day for adolescents) were compared after controlling for age (months), sex, race, puberty status, and other 7 covariates based on propensity score matching.

Main Outcomes and MeasuresBehavior problems, cognition, mental health assessments, resting-state functional connectivity, gray matter volume, cortical area, cortical thickness, and structural connectivity (Fractional anisotropy) were collected and preprocessed by the ABCD study. Independent-sample t-tests and meditation analysis were performed to investigate the effects of insufficient sleep.

Results3021 matched pairs (50.7% male) were identified based on baseline assessment, with mean (SD) age of 119.5 (7.5) months. In baseline, sufficient sleep is associated less behavioral problems on 18 of 20 assessments, e.g. depress (95% CI of mean difference: -0.28 to -0.47, false discovery rate (FDR)-corrected p{square}<{square}.001, Cohens d = -0.20), better cognitive performance on 7 of 10 assessments, such as crystal cognition (95% CI: 0.81 to 1.50, FDR-corrected p{square}<{square}.001, Cohens d = 0.17), better functional connection between cortical regions and basal ganglia (all FDR-corrected p{square}<{square}.05, Cohens d >0.15), and large structure in ACC and temporal pole (all FDR-corrected p{square}<{square}.05, Cohens d >0.09). Similar patterns of effect of sufficient sleep were found in FL2 (749 pairs remained) e.g. Cohens d of function connectivity at baseline was correlated with Cohens d of that at FL2 (r = 0.54, 95% CI: 0.45 to 0.61, p < 1e-10). Mediation and longitudinal mediation analysis revealed that identified brain measures (e.g. gray matter volume of left temporal pole) at baseline mediated the effect of sufficient sleep on behavioral assessments (e.g. crystal cognition) at baseline and at FL2 (95% CI did not encompass 0, p < 0.05 on 100,000 random-generated bootstrapped samples).

Conclusions and RelevanceThese results provide strong population-level evidence for the long-lasting detrimental effects of insufficient sleep on mental health, cognition, and brain function and structure in adolescents. The current study identified potential neural mechanisms of adverse effect of insufficient sleep in adolescents, which might provide a theoretical grounding for sleep intervention programs to improve the long-term developmental outcomes in adolescents.

Key pointsO_ST_ABSQuestionC_ST_ABSWhat are the long-lasting effects of insufficient sleep on neurocognitive development in early adolescents?

FindingsIn this propensity score matching study that included 11,875 9-10-year-old participants, we identified long-lasting adverse effects of insufficient sleep on depression, thought problems, crystal cognition, neural network connectivity, cortical areas, and gray matter volume across 2 years.

MeaningThis study elucidated the neural mechanisms underlying the long-term detriments of insufficient sleep on mental health and cognition, suggesting potential intervention targets to improve sleep-related outcomes.

category: pediatrics


title: Impact of COVID-19 Pandemic on Utilization of Facility-Based Essential Maternal and Child Health Services in North Shewa Zone, Ethiopia

abstract:
IntroductionEthiopia registered its first case of COVID-19 on March 13, 2020. We aimed to assess maternal, newborn, and child health care (MNCH) utilization during the first six months of the COVID-19 pandemic, as well as potential barriers and enablers of service utilization from health care providers and clients.

MethodsMixed study design was conducted as part of the Birhan Health and Demographic Surveillance System in Ethiopia. The trend of service utilization during the first six months of COVID-19 was compared to corresponding time and data points of the preceding year.

ResultService utilization of new family planning visits (43.2 to 28.5/month, p = 0.014) and sick under five child visits (225.0 to 139.8/month, P = 007) declined during the initial six months of the pandemic compared to the same period in the preceding year. Antenatal and postnatal care visits, facility delivery rates, and child routine immunization visits also decreased although this did not reach statistical significance. Interviews with health care providers and clients highlighted several barriers to service utilization during COVID-19, including fear of disease transmission, economic hardship, and transport service disruptions and restrictions. Enablers of service utilization included communities decreased fear of COVID-19, and awareness-raising activities.

ConclusionProvision of essential MNCH services is crucial to ascertain favorable maternal and child health outcomes. In low- and middle-income country settings like Ethiopia, health systems might be fragile to withstand the caseloads and priority setting due to the pandemic. Our study presents early findings on the utilization of MNCH services that were maintained except sick child and new family planning visits. Government leaders, policy makers, and clinicians who wish to improve the resilience of their health system will need to continuously monitor service utilization and clients evolving concerns during the pandemic to prevent increases in maternal and child morbidity and mortality.

What is already known?Facility-based essential MNCH services utilization decreased during the initial phase of the pandemic and similarly facility-based healthcare utilizations were reduced in the 2014-2015 Ebola outbreak in west Africa.

What are the new findings?Facility based essential MNCH services such as antenatal care, postnatal care, family planning, facility deliveries, routine immunization and repeat family planning utilization were maintained in the initial six month of the pandemic unlike other similar studies elsewhere.

What do the new findings imply?In light of a pandemic, essential MNCH services such as antenatal and postnatal care, family planning, facility deliveries, repeat family planning and routine immunizations can be sustained in a health system. More attention may be given to better understand the reduction of sick under five visits. Further research can be conducted on the utilization of essential MNCH services on maternal and child health outcomes. Our results emphasize the importance of health systems and clinicians to sustain the resilience of their health system. Among those the Ministry of Health (MoH) directive to avail MNCH services in all facilities during the pandemic and the maturity level of some programs (Even though new family planning utilizers are limited, they know the benefit and would want to continue the repeat family planning utilization, benefits of facility delivery, routine immunization, antenatal care and postnatal care).

Strengths and limitations of this studyO_ST_ABSStrengths of the studyC_ST_ABS{checkmark} We present primary data on service utilization during the early months of the pandemic in an area of Ethiopia, one of the agrarian regions, which is generalizable to 80% of the countrys population.
{checkmark}The mixed methods approach integrated both quantitative service utilization coverage data with sociocultural, contextual, and exploratory qualitative to better understand our findings and reasons for changes in service utilization.
{checkmark}The study highlights success stories in community-based care and government leadership for key services like routine immunization that may benefit other settings.

Limitation of the study{checkmark} Our study focused on service utilization and may not have been powered to detect significant differences. Furthermore, we focused on coverage of service utilization as the primary outcome rather than mortality or morbidity.
{checkmark}We do not have detailed data on service provision (e.g., which services were restricted and for how long, in what manner).
{checkmark}There is the potential of recall bias were possible limitation since qualitative data was collected three months later than the initial six months of the pandemic (March to August 2020).


title: Independent morphological variables correlate with Aging, Mild Cognitive Impairment, and Alzheimer's Disease

abstract: This manuscript presents a study with recruited volunteers that comprehends three sorts of events present in Alzheimers Disease (AD) evolution (structural, biochemical, and cognitive) to propose an update in neurodegeneration biomarkers for AD. The novel variables, K, I, and S, suggested based on physics properties and empirical evidence, are defined by power-law relations between cortical thickness, exposed and total area, and natural descriptors of brain morphology. Our central hypothesis is that variable K, almost constant in healthy human subjects, is a better discriminator of a diseased brain than the current morphological biomarker, Cortical Thickness, due to its aggregated information. We extracted morphological features from 3T MRI T1w images of 123 elderly subjects: 77 Healthy Cognitive Unimpaired Controls (CTL), 33 Mild Cognitive Impairment (MCI) patients, and 13 Alzheimers Disease (AD) patients. Moreover, Cerebrospinal Fluid (CSF) biomarkers and clinical data scores were correlated with K, intending to characterize health and disease in the cortex with morphological criteria and cognitive-behavioral profiles. K distinguishes Alzheimers Disease, Mild Cognitive Impairment, and Healthy Cognitive Unimpaired Controls globally and locally with reasonable accuracy (CTL-AD, 0.82; CTL-MCI, 0.58). Correlations were found between global and local K associated with clinical behavioral data (executive function and memory assessments) and CSF biomarkers (t-Tau, A{beta}-40, and A{beta}-42). The results suggest that the cortical folding component, K, is a premature discriminator of healthy aging, Mild Cognitive Impairment, and Alzheimers Disease, with significant differences within diagnostics. Despite the non-concomitant events, we found correlations between brain structural degeneration (K), cognitive tasks, and biochemical markers.


title: Whole genome analysis reveals the genomic complexity in metastatic cutaneous squamous cell carcinoma

abstract:
Metastatic cutaneous squamous cell carcinoma (cSCC) is a highly morbid disease requiring radical surgery and adjuvant therapy that is associated with reduced overall survival. Yet compared to other advanced malignancies, relatively little is known of the genomic landscape of metastatic cSCC. We have previously reported the mutational signatures and mutational patterns of CCCTC-binding factor (CTCF) regions in metastatic cSCC. However, many other genomic components (indel signatures, non-coding drivers, and structural variants) of metastatic cSCC have not been reported. To this end, we performed whole genome sequencing on lymph node metastases and blood DNA from 25 cSCC patients with regional metastases of the head and neck. We designed a multifaceted computational analysis at the whole genome level to provide a more comprehensive perspective of the genomic landscape of metastatic cSCC.

In the noncoding genome, 3UTR regions of EVC (48% of specimens), PPP1R1A (48% of specimens) and ABCA4 (20% of specimens) along with the tumor-suppressing lncRNA LINC01003 (64% of specimens) were significantly functionally altered (Q-value < 0.05) and represent potential noncoding biomarkers of cSCC. Recurrent copy number loss in the tumor suppressor gene PTPRD was observed. Gene amplification was much less frequent and few genes were recurrently amplified. Single nucleotide variants driver analyses from 3 tools confirmed TP53 and CDKN2A as recurrently mutated genes but also identified C9 as potential novel driver in this disease. Further, indel signature analysis highlighted the dominance of ID signature 13 (ID13) followed by ID8 and ID9. ID 9 has previously been shown to have no association with skin melanoma, unlike ID 13 and 8, suggesting a novel pattern of indel variation in metastatic cSCC. The enrichment analysis of various genetically altered candidates shows enrichment of  TGF-beta regulation of extracellular matrix and  Cell cycle G1 to S check points. These enriched terms are associated with genetic instability, cell proliferation, and migration providing mechanisms of genomic drivers of metastatic cSCC.


title: Changes in foot progression angle during gait reduce the knee adduction moment and do not increase hip moments in individuals with knee osteoarthritis

abstract: People with knee osteoarthritis who adopt a modified foot progression angle (FPA) during gait often benefit from a reduction in the knee adduction moment and knee pain. It is unknown, however, whether changes in the FPA increase hip moments, a surrogate measure of hip loading, which may increase the risk of hip pain or osteoarthritis. This study examined how altering the FPA affects hip moments. Individuals with knee osteoarthritis walked on an instrumented treadmill with their baseline gait, 10{degrees} toe-in gait, and 10{degrees} toe-out gait. A musculoskeletal modeling package was used to compute joint moments from the experimental data. Fifty participants were selected from a larger study who reduced their peak knee adduction moment with a modified FPA. In this group, participants reduced the first peak of the knee adduction moment by 7.6% with 10{degrees} toe-in gait and reduced the second peak by 11.0% with 10{degrees} toe-out gait. Modifying the FPA reduced the early-stance hip abduction moment, at the time of peak hip contact force, by 4.3% {+/-} 1.3% for 10{degrees} toe-in gait (p=0.005) and by 4.6% {+/-} 1.1% for 10{degrees} toe-out gait (p<0.001) without increasing the flexion and internal rotation moments (p>0.15). In summary, when adopting a FPA modification that reduced the knee adduction moment, participants did not increase surrogate measures of hip loading.

category: orthopedics


title: IMU-derived kinematics detect gait differences with age or knee osteoarthritis but differ from marker-derived inverse kinematics

abstract:
Common in-lab, marker-based gait analyses may not represent daily, real-world gait. Real-world gait analyses may be feasible using inertial measurement units (IMUs), especially with recent advancements in open-source methods (e.g., OpenSense). Before using OpenSense to study real-world gait, we must determine whether these methods: (1) estimate joint kinematics similarly to traditional marker-based motion capture (MoCap) and (2) differentiate groups with clinically different gait mechanics.

Healthy young and older adults and older adults with knee osteoarthritis completed this study. We captured MoCap and IMU data during overground walking at participants self-selected and faster speeds. MoCap and IMU kinematics were computed with appropriate OpenSim workflows. We tested whether sagittal kinematics differed between MoCap- and IMU-derived data, whether tools detected between-group differences similarly, and whether kinematics differed between tools by speed.

MoCap data showed more flexion than IMU data (hip: 0-47 and 65-100% stride, knee: 0-38 and 58-91% stride, ankle: 18-100% stride). Group kinematics differed at the hip (young extension > knee osteoarthritis at 30-47% stride) and ankle (young plantar flexion > older healthy at 62-65% stride). Group-by-tool interactions occurred at the hip (61-63% stride). Significant tool-by-speed interactions were found, with hip and knee flexion increasing more for MoCap than IMU data with speed (hip: 12-15% stride, knee: 60-63% stride).

While MoCap- and IMU-derived kinematics differed, our results suggested that the tools similarly detected clinically meaningful differences in gait. Results of the current study suggest that IMU-derived kinematics with OpenSense may enable the valid and reliable evaluation of gait in real-world, unobserved settings.


title: EFFECT OF FULL VACCINATION AND POST-COVID OLFACTORY DYSFUNCTION IN RECOVERED COVID-19 PATIENT. A RETROSPECTIVE LONGITUDINAL STUDY WITH PROPENSITY MATCHING.

abstract:
BackgroundSymptoms after COVID-19 infection affect the quality of life of its survivor especially to the special senses including olfactory function. It is important to prevent the disability at an earlier stage. Vaccination as key prevention has been proven to be effective in reducing symptomatic disease and severity. However, the effects of vaccination on post COVID symptoms have not been evaluated. This study aimed to evaluate the possible protection of full vaccination and the occurrence of post-COVID olfactory dysfunction, specifically anosmia and hyposmia in patients who were diagnosed with COVID19.

MethodA longitudinal analysis using the retrospective cohort of the Indonesian patient-based Post-COVID survey collected from July 2021 until December 2021, involving COVID-19 Patients confirmed by RT-PCR and/or Antigen test. Variables including demography, comorbidities, health behavior, type of vaccine, symptoms, and treatment were collected through an online questionnaire based on the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). Participants were matched (1:1) using propensity matching score into two exposure statuses, infected 1)>14 days of full vaccination and 2)<14 days or incomplete or unvaccinated. The olfactory dysfunction was assessed two weeks and four weeks after negative conversion with PCR using a self-measured olfactory questionnaire (MOQ). The Generalized Estimating Equation (GEE) was performed to assess the effect of full vaccination on post-COVID olfactory dysfunction. The Receiver Operating Characteristic determined the sensitivity and specificity of the cutoff value of the days from fully vaccinated to diagnosis and the olfactory dysfunction.

ResultsA total of 442 participants were extracted from the cohort and inoculated with the inactivated viral vaccine (99.5%). The prevalence of olfactory dysfunction in two weeks was 9.95% and 5.43% after four weeks. Adjusted by other variables, people who were infected >14 days after being fully vaccinated had a 69% (adjusted OR 0.31 95% CI 0.102-0.941) probability of developing olfactory dysfunction. Longer days of fully vaccinated to infection associated with increased risk (adjusted OR 1.012 95% CI 1.002-1.022 p-value 0.015). A cut-off of 88 days of full vaccination-to-diagnosis duration has Area Under Curve (AUC) of 0.693 (p=0.002), the sensitivity of 73.9%, and specificity of 63.3% in differentiating the olfactory dysfunction event in two weeks after COVID with a crude odds ratio of 4.852 (95% CI 1.831-12.855 p=0.001)

ConclusionAfter 14 days of full vaccination, the protective effect could reduce the chance of post-COVID olfactory dysfunction although a longer full vaccination-to-diagnosis duration increases the risk. It is important to consider a booster shot starting from 89 days after the last dose in those who received the inactivated viral regimen.

category: otolaryngology


title: Genomic Machine Learning Meta-regression: Insights on Associations of Study Features with Reported Model Performance

abstract:
BackgroundMany studies have been conducted with the goal of correctly predicting diagnostic status of a disorder using the combination of genetic data and machine learning. The methods of these studies often differ drastically. It is often hard to judge which components of a study led to better results and whether better reported results represent a true improvement or an uncorrected bias inflating performance.

MethodsIn this systematic review, we extracted information about the methods used and other differentiating features in genomic machine learning models. We used the extracted features in mixed-effects linear regression models predicting model performance. We tested for univariate and multivariate associations as well as interactions between features.

ResultsIn univariate models the number of hyperparameter optimizations reported and data leakage due to feature selection were significantly associated with an increase in reported model performance. In our multivariate model, the number of hyperparameter optimizations, data leakage due to feature selection, and training size were significantly associated with an increase in reported model performance. The interaction between number of hyperparameter optimizations and training size as well as the interaction between data leakage due to optimization and training size were significantly associated reported model performance.

ConclusionsOur results suggest that methods susceptible to data leakage are prevalent among genomic machine learning research, which may result in inflated reported performance. The interactions of these features with training size suggest that if data leakage susceptible methods continue to be used, modelling efforts using larger data sets may result in unexpectedly lower results compared to smaller data sets. Best practice guidelines that promote the avoidance and recognition of data leakage may help the field advance and avoid biased results.


title: Cohort-specific serological recognition of SARS-CoV-2 variant RBD antigens

abstract:
BackgroundEstimating the response of different cohorts (e.g. vaccinated or critically ill) to new SARS-CoV-2 variants is important to customize measures of control. Thus, our goal was to evaluate binding of antibodies from sera of infected and vaccinated people to different antigens expressed by SARS-CoV-2 variants.

MethodsWe compared sera from vaccinated donors with sera from four patient/donor cohorts: critically ill patients admitted to an intensive care unit (split in sera collected between 2 and 7 days after admission and more than ten days later), a NIBSC/WHO reference panel of SARS-CoV-2 positive individuals, and ambulatory or hospitalized (but not critically ill) positive donors. Samples were tested with an anti-SARS-CoV-2 IgG serological assay designed with microplates coated with a SARS-CoV-2 RBD recombinant antigen. The same sample sets were also tested with microplates coated with antigens harbouring RBD mutations present in eleven of the most widespread variants.

ResultsSera from vaccinated individuals exhibited higher antibody binding (P<0.001) than sera from infected (but not critically ill) individuals when tested against the WT and each of 11 variants RBD.

The optical density generated by sera from non-critically ill convalescence individuals upon binding to variants antigens was different (P<0.05) from that of the WT in some variants--noteworthy, Beta, Gamma, Delta, and Delta Plus variants.

ConclusionsUnderstanding differences in binding and neutralizing antibody titers against WT vs variant RBD antigens from different donor cohorts can help design variant-specific immunoassays and complement other diagnostic and clinical data to evaluate the epidemiology of new variants.


title: Detection and categorization of severe cardiac disorders based solely on pulse interval measurements

abstract: Cardiac disorders are common conditions associated with a high mortality rate. Due to their potential for causing serious symptoms, it is desirable to constantly monitor cardiac status using an accessible device such as a smartwatch. While electrocardiograms (ECGs) can make the detailed diagnosis of cardiac disorders, the examination is typically performed only once a year for each individual during health checkups, and it requires expert medical practitioners to make comprehensive judgments. Here we describe a newly developed automated system for alerting individuals about cardiac disorders solely based on pulse interval measurements. For this purpose, we examined two metrics of heart rate variability (HRV) and analyzed 1-day ECG recordings of more than 1,000 subjects in total. We found that a newly introduced metric of local variation was more efficient than conventional HRV metrics for detecting premature contraction, and furthermore, that a suitable combination of the old and new metrics resulted in much superior detectability particularly for atrial fibrillation, which requires more attention. Even with a 1-minute recording of pulse intervals, our new detection system had a diagnostic performance even better than that of the conventional analysis method applied to a 1-day recording.


title: A Coupled Experimental and Statistical Approach for an Assessment of the Airborne Infection Risk in Event Locations

abstract: Operators of event locations are particularly affected by a pandemic. Resulting restrictions may cause uneconomical business. With previous models, only an incomplete quantitative risk assessments is possible, whereby no suitable restrictions can be derived. Hence, a mathematical and statistical model has been developed in order to link measurement data of substance dispersion in rooms with epidemiological data like incidences, reproduction numbers, vaccination rates and test qualities. This allows a first time overall assessment of airborne infection risks in large event locations. In these venues displacement ventilation concepts are often implemented. In this case simplified theoretical assumptions fail for the prediction of relevant airflows for infection processes. Thus, with locally resolving trace gas measurements and specific data of infection processes, individual risks can be computed more detailed. Via inclusion of many measurement positions, an assessment of entire event locations is possible. Embedding the overall model in a flexible application, daily updated epidemiological data allow latest calculations of expected new infections and individual risks of single visitors for a certain event. With this model, an instrument has been created that can help policymakers and operators to take appropriate measures and to check restrictions for their effect.


title: Covid-19 disease dynamics with vaccination: The effect of uncertainty

abstract: Rate parameters are critical in estimating the covid burden using mathematical models. In the Covid-19 mathematical models, these parameters are assumed to be constant. However, uncertainties in these rate parameters are almost inevitable. In this paper, we study a stochastic epidemic model of the SARS-CoV-2 virus infection in the presence of vaccination in which some parameters fluctuate around its average value. Our analysis shows that if the stochastic basic reproduction number (SBRN) of the system is greater than unity, then there is a stationary distribution, implying the long-time disease persistence. A sufficient condition for disease eradication is also prescribed for which the exposed class goes extinct, followed by the infected class. The disease eradication criterion may not hold if the rate of vaccine-induced immunity loss increases or/and the force of infection increases. Using the Indian Covid-19 data, we estimated the model parameters and showed the future disease progression in the presence of vaccination. The disease extinction time is estimated under various conditions. It is revealed that the mean extinction time is an increasing function of both the force of infection and immunity loss rate and shows the lognormal distribution. We point out that disease eradication might not be possible even at a higher vaccination rate if the vaccine-induced immunity loss rate is high. Our observation thus indicates the endemicity of the disease for the existing vaccine efficacy. The disease eradication is possible only with a higher vaccine efficacy or a reduced infection rate.


title: Plasma sgp130 is an independent predictor of non-alcoholic fatty liver disease severity

abstract:
BackgroundInterleukin-6 (IL-6) plays important and dynamic roles in inflammation associated with fatty liver disease over all stages, from simple steatosis to steatohepatitis, cirrhosis and cancer. IL-6 signals locally, but also circulates with multiple co-factors that control paracrine and endocrine signaling. As inflammation is a main driver of liver fibrosis, we investigated relationships between circulating components of the interleukin-6 signaling pathway (IL-6, sIL-6R and sgp130) and liver pathology in subjects with metabolically associated fatty liver disease (MAFLD) or steatohepatitis (MASH).

MethodsPredictive performances of plasma IL-6, sIL-6R and sgp130 were investigated in two independent cohorts: 1) patients with biopsy-confirmed MASH (n=49), where magnetic resonance spectroscopy (MRS), imaging (MRI) and elastography (MRE) assessed liver fat, volume and stiffness; and 2) patients with morbid obesity (n=245) undergoing bariatric surgery where histological staging of steatosis, activity, and fibrosis determined MASH severity. Correlations were evaluated between IL-6, sIL-6R and sgp130 and anthropomorphic characteristics, plasma markers of metabolic disease or liver pathology.

ResultsIn patients with MASH, plasma IL-6 and sgp130 strongly correlated with liver stiffness, which for sgp130 was independent of age, sex, BMI, diabetes, hyperlipidemia, hypertension or history of HCC. Plasma sgp130 was the strongest predictor of liver stiffness compared to common predictors and risk scores. Plasma sIL-6R correlated with liver volume independent of age, sex, and BMI. In patients with morbid obesity, circulating sgp130 correlated with advanced liver fibrosis.

ConclusionLevels of circulating sgp130 can predict progressing MASH and may be used alone or in combination with other predictors as a non-invasive measure of liver disease severity.

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title: Development of tool for assessment of performance motivation and job satisfaction among the Community Health Workers of Central India.

abstract:
IntroductionAmong the various factors influencing the performance of Community health workers, motivation and job satisfaction serves as a potential drive to perform better. Hence, this study aimed at constructing a motivation and job satisfaction tool in a systematic method that would serve as a potential tool for further research considering the heterogeneity in the study population.

ObjectiveTo develop a tool to measure how well the CHWs are motivated and satisfied pertaining to individual, community and health system determinants.

MethodsThis cross-sectional study from rural block of Madhya Pradesh in Central India included relatively high performing and low performing CHWs based on their annual performance-based incentives for the year (April 2017-March 2018). The CHWs were administered a self-reported questionnaire that contained a 5-point Likert scale with individual, health system and community determinants of motivation and job satisfaction.

ResultsThe performance motivation scale with 18 items and job satisfaction scale with 15 items were administered to the 92 CHWs. Their item content validity index was 0.66 and 0.83 respectively. The finalized tool consisted of 11 items in motivation scale and all the 15 items in job satisfaction scale following the Explanatory factor analysis. All the individual constructs in both the scales showed good internal consistency with Cronbachs alpha ranging from 0.62-0.88. The overall median (IQR) score of both RLP and RHP CHWs were 4(4-5) in both the questionnaires.

ConclusionThe CHWs in our study were intrinsically motivated and were satisfied with their performance as voluntary village health workers. Further research would be planned to validate the constructs using confirmatory factor analysis.

category: primary care research


title: Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

abstract: Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.64 years (95% CI: 3.01, 4.26; I2 = 55.28%) compared to controls, after adjusting for age and sex (Cohens d = 0.50). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.


title: Clustering-based COPD Subtypes Have Distinct Longitudinal Outcomes and Multi-omics Biomarkers

abstract:
IntroductionChronic obstructive pulmonary disease (COPD) can progress across several domains, complicating the identification of the determinants of disease progression. In our previous work, we applied k-means clustering to spirometric and chest radiologic measures to identify four COPD-related subtypes: "Relatively resistant smokers (RRS)", "mild upper lobe predominant emphysema (ULE)", "airway-predominant disease (AD)", and "severe emphysema (SE)". In the current study, we examined longitudinal spirometric and radiologic emphysema changes and prospective risks of COPD exacerbations, incident comorbidities, and mortality of these clusters. We also compared their associations to protein and transcriptomic biomarkers.

MethodsWe included 8,266 non-Hispanic white and African-American smokers from the COPDGene study. We used linear regression to investigate associations to five-year prospective changes in spirometric and radiologic measures and to plasma protein and blood gene expression levels. We used Cox-proportional hazard modeling to test for associations to prospective exacerbations, comorbidities, and mortality.

ResultsThe RRS, ULE, AD, and SE clusters represented 39%, 15%, 26%, and 20% of the studied cohort at baseline, respectively. The SE cluster had the greatest 5-year FEV1 and emphysema progression, and the highest risks of exacerbations, cardiovascular disease (CVD), and mortality. The AD cluster had the highest diabetes risk. After adjustments, only the ULE and AD clusters had elevated CVD mortality risks, while only the ULE cluster had the highest cancer-related mortality risk. These clusters also demonstrated differential protein and gene expression biomarker associations.

ConclusionCOPD k-means subtypes demonstrate varying rates of disease progression, prospective comorbidities, mortality, and associations to proteomic and transcriptomic biomarkers.

Funding SourcesThis work was supported by NHLBI K08 HL141601, K08 HL146972, R01 HL116931, R01 HL124233, R01 HL126596, R01 HL116473, U01 HL089897, R01 HL147326, R01 HL130512, and U01 HL089856. The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee comprised of AstraZeneca, Bayer, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.