bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing “people-like-me” and linear mixed model predictions of functional recovery following knee arthroplasty
Authors: Graber Jeremy , Kittelson Andrew , Juarez-Colunga Elizabeth , Jin Xin , Bade Michael , Stevens-Lapsley Jennifer
Published: March 2022

Objective

Prediction models can be useful tools for monitoring patient status and personalizing treatment in health care. The goal of this study was to compare the relative strengths and weaknesses of two different approaches for predicting functional recovery after knee arthroplasty: a neighbors-based “people-like-me” (PLM) approach and a linear mixed model (LMM) approach.

Materials and Methods

We used two distinct datasets to train and then test PLM and LMM prediction approaches for functional recovery following knee arthroplasty. We used Timed Up and Go (TUG)—a commonly used test of mobility—to operationalize physical function. Both approaches used patient characteristics and baseline postoperative TUG values to predict TUG recovery from days 1-425 following surgery. We compared the accuracy and precision of PLM and LMM predictions in the testing dataset.

Results

A total of 317 patient records with 1379 TUG observations were used to train PLM and LMM approaches, and 456 patient records with 1244 TUG observations were used to test the predictions. The approaches performed similarly in terms of mean squared error and bias, but the PLM approach provided more accurate and precise estimates of prediction uncertainty.

Discussion and Conclusion

Overall, the PLM approach more accurately and precisely predicted TUG recovery following knee arthroplasty. These results suggest PLM predictions may be more clinically useful for monitoring recovery and personalizing care following knee arthroplasty. However, clinicians and organizations seeking to use predictions in practice should consider additional factors (e.g., resource requirements) when selecting a prediction approach.
Parkinson’s disease causality and heterogeneity: a proteogenomic view
Authors: Kaiser Sergio , Zhang Luqing , Mollenhauer Brit , Jacob Jaison , Longerich Simonne , Del-Aguila Jorge , Marcus Jacob , Raghavan Neha , Stone David , Fagboyegun Olumide , Galasko Douglas , Dakna Mohammed , Bilican Bilada , Dovlatyan Mary , Kostikova Anna , Li Jingyao , Peterson Brant , Rotte Michael , Sanz Vinicius , Foroud Tatiana , Hutten Samantha J. , Frasier Mark , Iwaki Hirotaka , Singleton Andrew , Marek Ken , Crawford Karen , Elwood Fiona , Messa Mirko , Serrano-Fernandez Pablo
Published: March 2022

The pathogenesis and clinical heterogeneity of Parkinson’s disease have been evaluated from molecular, pathophysiological, and clinical perspectives. High-throughput proteomic analysis of CSF has opened new opportunities for scrutinizing this heterogeneity. To date, this is the most comprehensive CSF-based proteomics profiling study in Parkinson’s disease (1103 patients, 4135 proteins). Combining CSF aptamer-based proteomics with genetics we determined protein quantitative trait loci (pQTLs). Analyses of pQTLs together with summary statistics from the largest Parkinson’s disease genome wide association study (GWAS) identified 68 potential causal proteins by Mendelian randomization. The top causal protein, GPNMB was previously reported to be upregulated in the substantia nigra of Parkinson’s disease patients.

We also compared the CSF proteomes of patients and controls. The Parkinson’s disease cohort comprised not only LRRK2+ and GBA+ mutation carriers but also idiopathic patients. Proteome differences between GBA+ patients and unaffected GBA+ controls suggest degeneration of dopaminergic neurons, altered dopamine metabolism and increased brain inflammation. The proteins discriminating LRRK2+ patients from unaffected LRRK2+ controls, revealed dysregulated lysosomal degradation, as well as altered alpha-synuclein processing, and neurotransmission. Proteome differences between idiopathic patients and controls suggest increased neuroinflammation, mitochondrial dysfunction / oxidative stress, altered iron metabolism and potential neuroprotection mediated by vasoactive substances.

Finally, we used proteomic data to stratify idiopathic patients into “endotypes”. The identified endotypes show differences in cognitive and motor disease progression based on the use of previously reported protein-based risk scores.

In summary, we: i) identified causal proteins for Parkinson’s disease, ii) assessed CSF proteome differences in Parkinson’s disease patients of genetic and idiopathic etiology, and. iii) stratified idiopathic patients into robust clinically relevant subtypes. Our findings not only contribute to the identification of new therapeutic targets but also to shaping personalized medicine in CNS neurodegeneration.
Bacterial culture use, etiology and antibiotic susceptibility of common bacterial infections in Indonesian hospitals in 2019
Authors: de Brabander Justin , Nelwan Erni J. , Limato Ralalicia , Alamanda Monik , Mudia Manzilina , Tjoa Enty , Mauleti Ifael Y. , Mayasari Maria , Firmansyah Iman , Jayati T. Mannaria , van Vugt Michèle , van Doorn H. Rogier , Hamers Raph L.
Published: March 2022

Objectives

To describe the use of bacterial cultures, and the etiology and antibiotic susceptibility of common high-priority bacteria isolated from hospitalized patients in Jakarta, Indonesia.

Methods

We conducted a hospital-wide cross-sectional study of all inpatients receiving systemic antibiotic treatment (WHO ATC J01) in six hospitals in 2019, capturing routine data on antibiotic treatment and cultures. We reported bug-drug combinations for Escherichia coli and the ESKAPE group of bacteria.

Results

562 patients (52% women, median age 46 years) had 587 diagnoses, with pneumonia (258, 44%) most common. One or more culture specimens were taken in 38% (215/562) overall, a sputum culture in 25% (64/258) of pneumonia patients; and a blood culture in 52% (16/31) of sepsis patients. 50% of positive blood culture results were reported after 4 days. From 670 culture specimens, 279 bacteria were isolated, 214 (77%) were Gram-negative, including Klebsiella pneumoniae (70, 25%), Pseudomonas aeruginosa (36, 13%), and E. coli (21, 11%). Resistance included third-generation cephalosporin-resistant K. pneumoniae (77%), E. coli (65%) and Enterobacter spp (81%); carbapenem-resistant K. pneumoniae (26%), P. aeruginosa (24%), E. coli (33%), Acinetobacter spp (57%), and Enterobacter spp (60%); and meticillin-resistant S. aureus (71%). Vancomycin-resistant S. aureus (0%) and Enterococcus faecalis (12%) were uncommon. Multi-drug resistance was 30% for K. pneumoniae, 29% for P. aeruginosa, 49% for E. coli, 42% for Acinetobacter spp, and 71% for S. aureus.

Conclusions

In Indonesian hospitals, bacterial cultures were underused and antibiotic resistance is at alarming levels. Enhanced context-specific infection prevention, diagnostic and antibiotic stewardship interventions are urgently needed.
Associations between maternal infections during pregnancy and childhood IQ scores using the ALSPAC birth cohort
Authors: Kwok Janell , Hall Hildigunnur Anna , Murray Aja Louise , Lombardo Michael Vincent , Auyeung Bonnie
Published: March 2022

Maternal prenatal infections have been linked to children’s neurodevelopment and cognitive outcomes. It remains unclear, however, whether infections occurring during specific vulnerable gestational periods can affect children’s cognitive outcomes. The study aimed to examine maternal infections in each trimester of pregnancy and associations with children’s verbal, performance, and total IQ scores. The ALSPAC birth cohort was used to investigate associations between maternal infections in pregnancy and childhood IQ outcomes. Infection data from mothers and cognition data from children were included with the final study sample size comprising 7,410 mother-child participants. Regression analysis was used to examine links between maternal infections occurring at each trimester of pregnancy and children’s cognitive IQ scores at 18 months, 4 years, and 8 years. Infections in the third trimester were significantly associated with decreased verbal IQ at age 4 (p<.05, adjusted R2 = .004); decreased verbal IQ (p<.01, adjusted R2 = .001), performance IQ (p<.01, adjusted R2 = .0008), and total IQ at age 8 (p<.01, adjusted R2 = .001). Results suggest that later maternal infections could have a latent effect on cognitive development, only emerging when cognitive load increases over time, though magnitude of effect appears to be small. Performance IQ may be more vulnerable to trimester-specific exposure to maternal infection as compared to verbal IQ. Future research could include examining potential mediating mechanisms on childhood cognition, such as possible moderating effects of early childhood environmental factors, and if effects persist in future cognitive outcomes.
Reversal of increases in methadone distribution for opioid use disorder in the US during the COVID-19 pandemic
Authors: Kennalley Amy L. , Fanelli Jessica L. , Furst John A. , Mynarski Nicholas J. , Jarvis Margaret A. , Nichols Stephanie D. , McCall Kenneth L. , Piper Brian J.
Published: March 2022

Opioid use disorder (OUD) is a major public health concern in the United States (US), resulting in high rates of overdose and other negative outcomes. Methadone, a treatment for OUD, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life. This study analyzed the distribution of methadone for the treatment of OUD across the US using data from the Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System, Medicaid’s State Drug Utilization Data, and the US Census Bureau. Analysis revealed that methadone distribution for OUD has expanded significantly over the past decade, with an average state increase of +96.96% from 2010 to 2020, and there was a significant increase in overall distribution of methadone to opioid treatment programs (OTP) in the US from 2010 to 2020 (+61.00%) and from 2015 to 2020 (+26.22%). However, the distribution to OTPs did not significantly change from 2019 to 2021 (−5.15%). Furthermore, pronounced variation in methadone distribution among states were observed, with some states having no OTPs or Medicaid coverage. New policies are urgently needed to increase access to methadone treatment and address the opioid overdose crisis in the US.
Identification and Quantification of Bioactive Compounds Suppressing SARS-CoV-2 Signals in Wastewater-based Epidemiology Surveillance
Authors: Bayati Mohamed , Hsieh Hsin-Yeh , Hsu Shu-Yu , Li Chenhui , Rogers Elizabeth , Belenchia Anthony , Zemmer Sally A. , Blanc Todd , LePage Cindy , Klutts Jessica , Reynolds Melissa , Semkiw Elizabeth , Johnson Hwei-Yiing , Foley Trevor , Wieberg Chris G. , Wenzel Jeff , Lyddon Terri , LePique Mary , Rushford Clayton , Salcedo Braxton , Young Kara , Graham Madalyn , Suarez Reinier , Ford Anarose , Lei Zhentian , Sumner Lloyd , Mooney Brian P. , Wei Xing , Greenlief C. Michael , Johnson Marc C. , Lin Chung-Ho
Published: March 2022

Recent SARS-CoV-2 wastewater-based epidemiology (WBE) surveillance have documented a positive correlation between the number of COVID-19 patients in a sewershed and the level of viral genetic material in the wastewater. Efforts have been made to use the wastewater SARS-CoV-2 viral load to predict the infected population within each sewershed using a multivariable regression approach. However, reported clear and sustained variability in SARS-CoV-2 viral load among treatment facilities receiving industrial wastewater have made clinical prediction challenging. Several classes of molecules released by regional industries and manufacturing facilities, particularly the food processing industry, can significantly suppress the SARS-CoV-2 signals in wastewater by breaking down the lipid-bilayer of the membranes. Therefore, a systematic ranking process in conjugation with metabolomic analysis was developed to identify the wastewater treatment facilities exhibiting SARS-CoV-2 suppression and identify and quantify the chemicals suppressing the SARS-COV-2 signals. By ranking the viral load per diagnosed case among the sewersheds, we successfully identified the wastewater treatment facilities in Missouri, USA that exhibit SARS-CoV-2 suppression (significantly lower than 5 × 1011gene copies/reported case) and determined their suppression rates. Through both untargeted global chemical profiling and targeted analysis of wastewater samples, 40 compounds were identified as candidates of SARS-CoV-2 signal suppression. Among these compounds, 14 had higher concentrations in wastewater treatment facilities that exhibited SARS-CoV-2 signal suppression compared to the unsuppressed control facilities. Stepwise regression analyses indicated that 4-nonylphenol, palmitelaidic acid, sodium oleate, and polyethylene glycol dioleate are positively correlated with SARS-CoV-2 signal suppression rates. Suppression activities were further confirmed by incubation studies, and the suppression kinetics for each bioactive compound were determined. According to the results of these experiments, bioactive molecules in wastewater can significantly reduce the stability of SARS-CoV-2 genetic marker signals. Based on the concentrations of these chemical suppressors, a correction factor could be developed to achieve more reliable and unbiased surveillance results for wastewater treatment facilities that receive wastewater from similar industries.
The impact of the one child policy on China’s infant mortality from 1970-1989: a quasi-experimental study
Authors: Chakrabarti Suman , Choo Esther , He Yao
Published: March 2022

Background

China’s One Child Policy (OCP), enforced in 1980, was the largest fertility control policy in human history, and its effects are still widely debated. Previous analyses of the OCP have focused on population reduction and sex ratios, among others. This study evaluates the impact of the OCP on infant mortality in China using quasi-experimental methods.

Methods

Country-level panel data for China and 106 other countries were extracted from the World Bank data repository for the years 1970-1989. The primary outcome was infant mortality rate (IMR) defined as deaths among children <1 year of age per 1000 live births. The impact of the OCP was estimated using uncontrolled and controlled interrupted time series (ITS) designs that control for within group time varying characteristics. Models were further adjusted for a comprehensive set of covariates and corrected for first-order autocorrelation. Countries included in the control groups were identified using the method of synthetic controls and propensity score matching (PSM). Valid control groups reduced threats from selection bias and unobserved time invariant confounders.

Results

Adjusting for GDP per capita, GDP growth, women’s education, and population density, IMR decreased on average by 2.5 deaths per 1,000 annually before the OCP was enforced in China. The pre-OCP trends in IMR moved in tandem across China, synthetic and PSM controls, validating the parallel trends assumption. After the OCP, the trend in IMR in China increased by 2.24 (95% CI 1.39-3.09) per year, compared to the IMR trend in the pre-OCP period, comparing differences in China to synthetic controls. Results were similar and confirmed across PSM (1.96, 0.56-3.37) and uncontrolled ITS (2.14, 1.39-2.89) models. No significant immediate level change in IMR was observed in the controlled ITS models.

Conclusions

The reduction in IMR slowed down significantly after the OCP was enforced in China. The slowdown is likely due to a relative increase in the ratio of the IMR of females to males suggesting that practices such as female infanticide, abandonment, and neglect, stemming from a strong son preference were primary contributors. Coercive policies to reduce fertility can have unintended consequences.
Cross-sector Decision Landscape in Response to COVID-19: A Qualitative Analysis of North Carolina Decision-Makers
Authors: Biddell Caitlin B. , Johnson Karl T. , Patel Mehul D. , Smith Raymond L. , Hecht Hillary K. , Swann Julie L. , Mayorga Maria E. , Lich Kristen Hassmiller
Published: March 2022

Context

The COVID-19 pandemic response has demonstrated the interconnectedness of individuals, organizations, and other entities jointly contributing to the production of community health. This response has involved stakeholders from numerous sectors who have been faced with new decisions, objectives, and constraints.

Objective

We aimed to examine the cross-sector organizational decision landscape that formed in response to the COVID-19 pandemic.

Design

We applied a systems approach to the qualitative analysis of semi-structured interviews on the cross-sector, organizational response to the COVID-19 pandemic. We analyzed transcribed interviews using conventional content analysis to synthesize key themes.

Setting

Semi-structured interviews were conducted via secure, video-conferencing platform between October 2020 and January 2021.

Participants

Forty-four state and local decision-makers representing organizations from nine sectors in North Carolina participated.

Main Outcome Measures

We defined the decision landscape as including decision-maker roles, key decisions, and inter-relationships involved in producing community health.

Results

Decision-maker roles were characterized by underlying tensions between balancing organizational mission with employee/community health and navigating organizational versus individual responsibility for reducing transmission. Key Decisions fell into several broad categories, including how to translate public health guidance into practice; when to institute, and subsequently loosen, public health restrictions; and how to address downstream social and economic impacts of public health restrictions. Lastly, given limited and changing information, as well as limited resources and expertise, the COVID-19 response required cross-sector collaboration, which was commonly coordinated by local health departments.

Conclusions

By documenting the local, cross-sector decision landscape that formed in response to COVID-19, we illuminate the impacts different organizations may have on information/misinformation, prevention behaviors, and, ultimately, health. Public health researchers and practitioners must understand, and work within, this complex decision landscape when responding to COVID-19 and future community health challenges.
Preliminary Rasch analysis of the Multidimensional Assessment of Interoceptive Awareness in adults with stroke
Authors: Blackwood Jena , Carpentier Sydney , Deng Wei , Van de Winckel Ann
Published: March 2022

Purpose

The Multidimensional Assessment of Interoceptive Awareness (MAIA) measures interoceptive body awareness, which includes aspects such as attention regulation, self-regulation, and body listening. Our purpose was to validate the MAIA in adults with stroke using Rasch Measurement Theory.

Methods

The original MAIA has 32 items grouped into 8 separately scored subscales that measure aspects of body awareness. Using Rasch Measurement Theory we evaluated the unidimensionality of the entire scale and investigated person and item fit, person separation reliability, targeting, local item dependence, and principal components analysis of residuals.

Results

Forty-one adults with chronic stroke (average 3.8 years post-stroke, 13 women, average age 57±13 years) participated in the study. Overall fit (χ2=62.26,p=0.26) and item fit were obtained after deleting 3 items and rescoring 26 items. One participant did not fit the model (2.44%). There were no floor (0.00%) or ceiling effects (0.00%). Local item dependence was found in 42 pairs. The person separation reliability was 0.91, and the person mean location was 0.06±1.12 logits.

Conclusions

The MAIA demonstrated good targeting and reliability, as well as good item and person fit in adults with chronic stroke. A study with a larger sample size is needed to validate our findings.
Accumulation of dihydrosphingolipids and neutral lipids is related to steatosis and fibrosis damage in human and animal models of non-alcoholic fatty liver disease
Authors: Babiy Bohdan , Ramos-Molina Bruno , Ocaña Luis , Sacristán Silvia , Burgos-Santamaría Diego , Martínez-Botas Javier , Villa-Turégano Gemma , Busto Rebeca , Perna Cristian , Frutos M. Dolores , Albillos Agustín , Pastor Óscar
Published: March 2022

Background

Dihydrosphingolipids are lipid molecules biosynthetically related to ceramides. An increase in ceramides is associated with enhanced fat storage in the liver and inhibition of their synthesis is reported to prevent the appearance of steatosis in animal models. However, the precise association of dihydrosphingolipids with non-alcoholic fatty liver disease (NAFLD) is yet to be established. We employed a diet-induced NAFLD mouse model to study the association between this class of compounds and disease progression.

Methods

Mice were fed a high-fat diet enriched in cholesterol and supplemented with glucose and fructose up to 40 weeks. A mouse subgroup was treated with carbon tetrachloride to accelerate fibrosis development. Animals were sacrificed at different time-points to reproduce the full spectrum of histological damage found in human disease, including steatosis (NAFL) and steatohepatitis (NASH) with and without significant fibrosis. Blood and liver tissue samples were obtained from patients (n=195) whose NAFLD severity was assessed histologically. Lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry.

Results

Triglyceride, cholesterol ester and dihydrosphingolipid levels were increased in the liver of model mice in association with the degree of steatosis. Dihydroceramide concentrations increased with the histological severity of the disease in liver samples of mice (0.024 ± 0.003 vs 0.049 ± 0.005, non-NAFLD vs NASH-fibrosis, p<0.0001) and patients (0.105 ± 0.011 vs 0.165 ± 0.021, p=0.0221). Several dihydroceramide and dihydrosphingomyelin species were increased in plasma of NAFLD patients and correlated with accumulation of liver triglycerides.

Conclusions

Dihydrosphingolipids accumulate in the liver in response to increased free fatty acid overload and are correlated with progressive histological damage in NAFLD. The increase in dihydrosphingolipids is related to upregulation of hepatic expression of enzymes involved inde novosynthesis of ceramides.

HIGHLIGHTS

Neutral lipids and dihydrosphingolipids accumulate in liver in correlation with the histological severity of NAFLD in both mice and humans.

The ceramide pathway is stimulated to alleviate the free fatty acid excess in liver of NAFLD models.

Appearance of significant fibrosis is associated with reduced concentrations of neutral lipids but not dihydrosphingolipids in a mouse model of NAFLD.
SARS-CoV-2 seroconversion in response to infection and vaccination: A time series local study in Brazil
Authors: Huergo Luciano F. , Paula Nigela M. , Gonçalves Ana C.A. , Kluge Carlos H.S. , Marins Paulo H.S.A. , Camargo Haxley S.C. , Sant’Ana Thamyres P. , Farias Lucas R.P. , Aldrighi Juliane D. , Lima Ênio S. , Jacotenski Guiomar T. , Vargas Letícia R. , Costa Gisele , Weissheimer Karin V. , Nazário Maria G. , Teixeira Kádima N. , Conzentino Marcelo S.
Published: March 2022

The investigation of antibodies raised against different SARS-CoV-2 antigens can help to determine the extent of previous SARS-CoV-2 infections in the population and track the humoral response to vaccination. Therefore, serological surveys can provide key information to better manage the pandemic and/or to implement the most effective vaccination program. Here we describe a time series anti-Nucleocapsid, anti-Spike IgG serological survey analysis in the city of Matinhos, PR, Brazil during the year of 2021. Seroconversion rates to the Nucleocapsid antigen was not influenced by gender or age. Comparison of the serological data with official COVID-19 cases in the city suggest that case sub notification is higher than 47%. Furthermore, by applying serological data, the corrected infection fatality rate was estimated to be lower than 2.4 % in contrast with the official estimative of 3.6 %. The rates of IgG reactive to Spike antigen resembled the curve of the fraction the population that had taken the second vaccine dose. Up to 82% of Spike seroconversion was detected in the end of 2021 confirming the effective of the COVID-19 vaccination program in the city. This SARS-CoV-2 serological study unraveled the SARS-CoV-2 infection rates and the response to vaccination in the city of Matinhos. It is likely that the numbers reported here may be similar in other cities in Brazil.
The Gastric Cancer Registry: A Genomic Translational Resource for Multidisciplinary Research in Stomach Malignancies
Authors: Almeda Alison F , Grimes Sue , Lee HoJoon , Greer Stephanie U , Shin GiWon , McNamara Madeline , Hooker Anna C , Arce Maya , Kubit Matthew , Schauer Marie , Van Hummelen Paul , Ma Cindy , Mills Meredith , Huang Robert J , Hwang Joo Ha , Amieva Manuel R , Han Summer , Ford James M. , Ji Hanlee P.
Published: March 2022

Background

Gastric cancer (GC) is a leading cause of global cancer morbidity and mortality. Developing information systems which integrate clinical and genomic data may accelerate discoveries to improve cancer prevention, detection, and treatment. To support translational research in GC, we developed the GC Registry (GCR), a North American repository of clinical and cancer genomics data.

Methods

GCR is a national registry with online self-enrollment. Entry criteria into the GCR included the following: (1) diagnosis of GC, (2) history of GC in a first-or second-degree family member or (3) known pathogenic or likely pathogenic germline mutation in the gene CDH1. Participants provided demographic and clinical information through a detailed (412-item) online survey. A subset of participants provided specimens of saliva and tumor samples. These tumor samples underwent exome sequencing, whole genome sequencing and transcriptome sequencing.

Results

From 2011-2021, 567 individuals registered for the GCR and returned the clinical questionnaire. For this cohort 65% had a personal history of GC, 36% reported a family history of GC and 14% had a germline CDH1 mutation. Eighty-nine GC patients provided tumor tissue samples. For the initial pilot study, 41 tumors were sequenced using next generation sequencing. The data was analyzed for cancer mutations, copy number variations, gene expression, microbiome presence, neoantigens, immune infiltrates, and other features. We developed a searchable, web-based interface (the GCR Genome Explorer) to enable researchers access to these datasets.

Conclusions

The GCR is a unique, North American GC registry which integrates both clinical and genomic annotation.

Impact

Available for researchers through an open access, web-based explorer, we hope the GCR Genome Explorer accelerates collaborative GC research across the United States.
Novel Application of a Multistate Model to Evaluate the Opioid Use Disorder Care Cascade: A Retrospective Cohort Study
Authors: Murillo Anarina L. , Sun Tianyu , Aroke Hilary , Bratberg Jeffrey , Kogut Stephen , Marshall Brandon D.L. , Yedinak Jesse L. , Rich Josiah D. , Lebeau Rebecca , Hogan Joseph W. , Buchanan Ashley
Published: March 2022

Background

Evaluating the opioid use disorder (OUD) care cascade can improve OUD treatment retention and care.

Objectives

To identify risk and protective factors for retention among patients in OUD treatment.

Methods

We conducted a retrospective cohort study among patients diagnosed with OUD using data from the Rhode Island (RI) All-Payer Claims Database from 2011 to 2019. Patients who initiated treatment (Stage 2) were classified into sub-stages of retention (Stage 3) corresponding to multistate modeling states capturing early retention (sub-stage 1), short and long-term retention (sub-stage 2), and short and long-term disengagement (sub-stage 3). The association of baseline characteristics with state transitions were evaluated.

Results

A cohort of 6,939 RI residents diagnosed with OUD included 41% aged 40 to 60 years, 57.6% male, and 70.8% Medicaid beneficiaries. In sub-stage 1, cannabis (Relative risk ratios (RRR) = 1.16; 95% confidence interval (CI) = 1.04,1.29) and cocaine use disorders (RRR=1.15; 95% CI=1.05,1.25) increased early disengagement risk after engagement. Medicaid beneficiaries were less likely to experience early disengagement (RRR=0.81; 95% CI =0.76,0.87). In sub-stage 2, alcohol (RRR=1.29; 95% CI=1.13,1.47) or cocaine use disorders (RRR=1.18; 95% CI=1.01,1.40) increased risk of disengagement among patients in the retention states. In sub-stage 3, tobacco (RRR=1.10; 95% CI=1.01,1.21) and alcohol (RRR=1.14; 95% CI=1.03,1.27) use disorders were associated with re-engagement from disengaged states.

Conclusion

The multistate model applied to a cohort of patients initiating medication for OUD led to the identification of factors associated with treatment engagement and retention. These results may guide strategies to sustain treatment among OUD patients.
Digital gait biomarkers, but not clinical ataxia scores, allow to capture 1-year longitudinal change in Spinocerebellar ataxia type 3 (SCA3)
Authors: Ilg Winfried , Müller Björn , Faber Jennifer , van Gaalen Judith , Hengel Holger , Vogt Ina R. , Hennes Guido , van de Warrenburg Bart , Klockgether Thomas , Schöls Luger , Synofzik Matthis
Published: March 2022

Measures of step variability and body sway during gait have shown to correlate with clinical ataxia severity in several cross-sectional studies. However, to serve as a valid progression biomarker, these gait measures have to prove their sensitivity to robustly capture longitudinal change, ideally within short time-frames (e.g. one year). We present the first multi-center longitudinal gait analysis study in spinocerebellar ataxias (SCAs). We performed a combined cross-sectional (n=28) and longitudinal (1-year interval, n=17) analysis in SCA3 subjects (including 7 pre-ataxic mutation carriers). Longitudinal analysis revealed significant change in gait measures between baseline and 1-year follow-up, with high effect sizes (stride length variability: p=0.01, effect size rprb=0.66; lateral sway: p=0.007, rprb=0.73). Sample size estimation for lateral sway reveals a required cohort size of n=43 for detecting a 50% reduction of natural progression, compared to n=240 for the clinical ataxia score SARA. These measures thus present promising motor biomarkers for upcoming interventional studies.
Polymorphism in IFNAR contributes to glucocorticoid response and outcome in ARDS and COVID-19
Authors: Jalkanen Juho , Khan Sofia , Elima Kati , Huttunen Teppo , Wang Ning , Hollmén Maija , Elo Laura L. , Jalkanen Sirpa
Published: March 2022

The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). Here we report a novel disease association of a SNP rs9984273, which is situated in the interferon alpha/beta receptor (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, lower IFN-gamma and IL-6 levels and less severe form of coronavirus diseases (COVID-19) according to the COVID-19 Host Genetics Initiative database, and better outcome in interferon (IFN) beta treated patients with ARDS. Thus, the distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signalling and glucocorticoids.

One-Sentence Summary

Single nucleotide polymorphism in interferon receptor contributes to corticosteroid response and outcome in ARDS and COVID-19
Effect of working from home on the association between job demands and psychological distress
Authors: Eguchi Hisashi , Inoue Akiomi , Hino Ayako , Tsuji Mayumi , Tateishi Seiichiro , Ikegami Kazuhiro , Nagata Tomohisa , Matsugaki Ryutaro , Fujino Yoshihisa ,   the CORoNaWork project
Published: March 2022

Purpose

Limited information is available about the association between workplace psychosocial factors and general mental health status among workers during the COVID-19 pandemic. This study examined how working from home affected the association between job demands and psychological distress (PD).

Method

A cross-sectional online survey was conducted in December 2020 (N=27,036). The dependent variable (PD) was assessed using the Kessler Psychological Distress Scale. Job demands were assessed using the Job Content Questionnaire. Working from home was determined by participants’ responses to the question: “Do you currently work from home?” We used a two-level regression analysis adjusted for prefecture; each individual-level variable at level 1 was nested into each prefecture at level 2, stratified by working from home or not.

Results

Overall, 21.3% of participants worked from home. The interaction between working from home and job demands was significant. Job demands were positively associated with PD. The stratified analysis showed the associations were weaker among employees who worked from home compared with those who did not.

Conclusion

The association between job demands and PD may be weakened by working from home.
The Omicron SARS-CoV-2 epidemic in England during February 2022
Authors: Chadeau-Hyam Marc , Tang David , Eales Oliver , Bodinier Barbara , Wang Haowei , Jonnerby Jakob , Whitaker Matthew , Elliott Joshua , Haw David , Walters Caroline E. , Atchinson Christina , Diggle Peter J. , Page Andrew J. , Ashby Deborah , Barclay Wendy , Taylor Graham , Cooke Graham , Ward Helen , Darzi Ara , Donnelly Christl A , Elliott Paul
Published: March 2022

Background: The third wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron variant. However, rates of hospitalisations and deaths were substantially lower than in the first and second waves
Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).
Findings: We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76-3.00), with a within-round reproduction number (R) overall of 0.94 (0.91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,195 positive samples with sublineages determined, only one (0.1% [0.0-0.5]) corresponded to AY.39 Delta sublineage and the remainder were Omicron: N=390, 32.7% (30.0-35.4) were BA.1; N=473, 39.6% (36.8-42.5) were BA.1.1; and N=331, 27.7% (25.2-30.4) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1 or BA.1.1) of 0.40 (0.36-0.43). The highest proportion of BA.2 among positives was found in London.
Interpretation: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.
Funding: Department of Health and Social Care, England.
Positive association between country-level screening rates for chlamydia and gonorrhea and self-reported diagnoses in MSM: an ecological analysis
Authors: Thibaut Vanbaelen , Eric Florence , Chris Kenyon
Published: March 2022

We assessed if there was a country-level association between intensity of screening MSM for Neisseria gonorrhoeae and Chlamydia trachomatis and self-reported incidence of these infections in 2010 and 2017. Unexpectedly, we found that screening intensity was associated with a higher incidence of these infections.

Short summary

We found a positive association between intensity of screening for chlamydia and gonorrhoea and the self-reported incidence of these infections in MSM in European countries.
Smoking, e-cigarettes and the effect on respiratory symptoms among a population sample of youth: retrospective study
Authors: Chaiton M , Pienkowski M , Musani I , Bondy SJ , Cohen JE , Dubray J , Eissenberg TE , Kaufman P , Stanbrook MB , Schwartz R
Published: March 2022

Introduction

E-cigarettes have been steadily increasing in popularity, both as cessation methods for smoking and for recreational and social reasons. This increase in vaping may pose cardiovascular and respiratory risks. We aimed to assess respiratory symptoms in youth users of e-cigarettes and cigarettes.

Methods

A cross-sectional survey design was utilized to assess Canadian youth aged 16-25 years old. Participants were recruited from the Ontario Tobacco Research Unit Youth and Young Adult Research Registration Panel November 2020 to March 2021. A total of 3,082 subjects completed the baseline survey. Of these, 2660 individuals who did not have asthma were included in the analysis. The exposure of interest was vaping dose, pack equivalent years, equivalent to cigarette pack years incorporating number of puffs per day, number of days vaped per month, and number of years vaped. Respiratory symptoms were measured using the five-item Canadian Lung Health Test. Poisson regression analyses were performed while adjusting for demographic confounders, stratified by smoking status. A non-stratified model tested the interaction of status and vaping dose and the effect of vaping device used was assessed among ever vapers. Analyses controlled for demographic characteristics, use of cannabis and alcohol, and survey date.

Results

Each additional puff year increased the rate ratio of respiratory symptoms by a factor of 11.36 (95%CI: 4.61-28.00; p<0.001) for never smokers, but among current daily smokers higher pack equivalent years were not associated with more respiratory symptoms (0.83; 95% CI: 0.23., 3.11). Among current vapers, those using pod-style devices were more likely to have more respiratory symptoms (1.25; 95% CI: 1.08, 1.45) after adjusting for dose.

Conclusions

Vaping is associated with an increased risk of reporting respiratory symptoms among never smoking youth and non-daily ever cigarette smokers. Use of e-cigarettes among non-smokers should be discouraged.

Funding

Canadian Institutes of Health Research
Comparing survival in urinary tract cancer patients with various second primary malignancies: A population-based study
Authors: Gao Xiang , Cao Hui , Zhou Liang , Li Xiaopan , Zou Yongbin , Yu Dehua , Geng Jinsong , Jia Haiyi , Lv Yipeng , Yu Wenya , Chen Yichen , Wang Zhaoxin , Shi Jianwei , Jin Hua
Published: March 2022

Purpose

We aimed to identify the patterns and combinations of second primary malignancies (SPMs) observed in patients with malignant neoplasms of the urinary tract (MNUT) and to explore the independent risk factors for survival outcomes in these patients.

Materials and Methods

We analysed the data of MNUT patients with SPM in 25 hospitals in Shanghai between 2002 and 2015. A life table was used to calculate the survival rates, Kaplan–Meier analysis was used to determine the survival status of MNUT patients, and Cox regression analysis was used to perform multivariate analysis of survival risk factors in MNUT patients with SPM.

Results

Among the 154 patients included, the first primary malignancy (PM) most commonly occurred in the bladder (50.65%) and kidney (41.56%), and the SPM most commonly occurred in the lung (22.73%) and stomach (13.64%). The most common combinations included the bladder + lung and bladder + stomach. The Cox regression results showed that age older than 60 years (HR = 2.36 [95% CI 1.30–4.28] vs. age ≤60 years, p = 0.005), TNM 1 stage III+IV disease (HR = 2.19 [95% CI 1.37-4.57] vs. I+ II), p = 0.037), TNM 2 stage III+IV disease (HR = 7.43 [95% CI 1.49-19.68] vs. I + II), p <0.001), and SPM in the lung (HR = 4.36 [95% CI 1.74-18.69], p = 0.047) were associated with a significantly worse cancer-specific survival.

Conclusion

The survival of MNUT patients with SPM may be related to the SPM site, first and second PM staging and latency time.
Milder disease trajectory among COVID-19 patients hospitalised with the SARS-CoV-2 Omicron variant compared with the Delta variant in Norway
Authors: Stålcrantz Jeanette , Bråthen Kristoffersen Anja , Bøås Håkon , Veneti Lamprini , Seppälä Elina , Aasand Nina , Hungnes Olav , Kvåle Reidar , Bragstad Karoline , Buanes Eirik Alnes , Whittaker Robert
Published: March 2022

Using individual-level national registry data, we conducted a cohort study to estimate differences in the length of hospital stay, and risk of admission to an intensive care unit and in-hospital death among patients infected with the SARS-CoV-2 Omicron variant, compared to patients infected with Delta variant in Norway. We included 409 (38%) patients infected with Omicron and 666 (62%) infected with Delta who were hospitalised with COVID-19 as the main cause of hospitalisation between 6 December 2021 and 6 February 2022. Omicron patients had a 48% lower risk of intensive care admission (aHR: 0.52, 95%CI: 0.34–0.80) and a 56% lower risk of in-hospital death (aHR: 0.44, 95%CI: 0.24–0.79) compared to Delta patients. Omicron patients had a shorter length of stay (with or without ICU stay) compared to Delta patients in the age groups from 18–79 years and those who had at least completed their primary vaccination. This supports growing evidence of reduced disease severity among hospitalised Omicron patients compared with Delta patients.
Blood group O and post-COVID-19 syndrome
Authors: Díaz-Salazar Sara , Navas Raquel , Sainz-Maza Laura , Fierro Patricia , Maamar Meryam , Artime Arancha , Basterrechea Héctor , Petitta Benedetta , Lamadrid Carlota , Pedraja Lucía , Gándara-Samperio Claudia , Pini Stefanie , Olmos José Manuel , Ramos Carmen , Pariente Emilio , Hernández José Luis
Published: March 2022

Objective

The ABO blood group system modulates the inflammatory response and has been involved in COVID-19. O-group protects against SARS-CoV-2 infection, but there are no data regarding post-COVID-19 syndrome (PCS). Our aim was to assess this possible association.

Subjects and methods

Case-control study in a community setting, with subjects who had experienced mild COVID-19. Cases were PCS+, controls were PCS-, and the exposure variable, O-group. Epidemiological data (age, sex, BMI, smoking, comorbidities), laboratory parameters (inflammatory markers, IgG antibodies, blood type) and clinical data were collected. Composite inflammatory indices were developed. Multivariate analyses were performed.

Results

We analyzed 121 subjects (56.2% women), mean age 45.7 ± 16 years. Blood group frequencies were 43.3%, 7.7%, 5.7%, and 43.3% for A, B, AB and O, respectively. Thirty-six patients were PCS+. There were no significant differences between cases and controls. Compared to non-O, a higher prevalence of PCS (p=0.036), number of symptoms (p=0.017) and myalgia (p=0.030) were noted in O-group. Concerning inflammatory markers, PCS+ and PCS-showed no differences in A, B, and AB groups. In contrast, O-group PCS+ patients had significantly higher lymphocyte count, higher levels of fibrinogen and CRP, and higher percentages of 3 composite indices, than PCS-subjects. The O-group showed a 4-fold increased risk of PCS compared to non-O (adjusted OR=4.20 [95%CI, 1.2-14]; p=0.023).

Conclusion

An increased risk of PCS has shown to be associated with O-group, after controlling for confounders. In O-group subjects with PCS, slightly albeit significant, raised levels of fibrinogen, CRP, and lymphocyte count, have been demonstrated.
Arterial Oxygen and Carbon Dioxide Tension and Acute Brain Injury in Extracorporeal Cardiopulmonary Resuscitation Patients: Analysis of the Extracorporeal Life Support Organization Registry
Authors: Shou Benjamin L , Ong Chin Siang , Premraj Lavienraj , Brown Patricia , Tonna Joseph E. , Dalton Heidi J , Kim Bo Soo , Keller Steven P , Whitman Glenn JR , Cho Sung-Min
Published: March 2022

Objective

Acute brain injury remains common after extracorporeal cardiopulmonary resuscitation. Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO2) and carbon dioxide (PaCO2) on ABI occurrence.

Design

Retrospective cohort study.

Setting

Data in the Extracorporeal Life Support Organization Registry from 2009 to 2020.

Patients

Adult patients (≥18 years old) who underwent extracorporeal cardiopulmonary resuscitation.

Interventions

None.

Measurements and Main Results

Of 3,125 patients with extracorporeal cardiopulmonary resuscitation (median age=58, 69% male), 488 (16%) experienced at least one form of acute brain injury, which included ischemic stroke, intracranial hemorrhage, seizures, and brain death. 217 (7%) experienced ischemic stroke and 88 (3%) experienced intracranial hemorrhage. The registry collects two blood gas data pre- (6 hours before) and on- (24 hours after) extracorporeal membrane oxygenation (ECMO) cannulation. Blood gas parameters were classified as: hypoxia (<60mmHg), normoxia (60-119mmHg), and mild (120-199mmHg), moderate (200-299mmHg), and severe hyperoxia (≥300mmHg); hypocarbia (<35mmHg), normocarbia (35-44mmHg), mild (45-54mmHg) and severe hypercarbia (≥55mmHg). In multivariable logistic regression analysis, pre-ECMO hypoxia (aOR=1.46, 95%CI: 1.03-2.08, p=0.04) and on-ECMO severe hyperoxia (aOR=1.55, 95%CI: 1.02-2.36, p=0.04) were associated with composite ABI. Also, on-ECMO severe hyperoxia was associated with intracranial hemorrhage (aOR=1.88, 95%CI: 1.02-3.47, p=0.04) and in-hospital mortality (aOR=3.51, 95%CI: 1.98-6.22, p<0.001). Pre- and on-ECMO PaCO2levels were not significantly associated with composite ABI or mortality, though mild hypercarbia pre- and on-ECMO were protective of ischemic stroke and intracranial hemorrhage, respectively.

Conclusions

Early severe hyperoxia (≥300mmHg) on ECMO was a significant risk factor for acute brain injury and mortality for patients undergoing extracorporeal cardiopulmonary resuscitation. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.
Cov2clusters: genomic clustering of SARS-CoV-2 sequences
Authors: Sobkowiak Benjamin , Kamelian Kimia , Zlosnik James E. A. , Tyson John , da Silva Anders Gonçalves , Hoang Linda M. N. , Prystajecky Natalie , Colijn Caroline
Published: March 2022

Background

The COVID-19 pandemic remains a global public health concern. Advances in sequencing technologies has allowed for high numbers of SARS-CoV-2 whole genome sequence (WGS) data and rapid sharing of sequences through global repositories to enable almost real-time genomic analysis of the pathogen. WGS data has been used previously to group genetically similar viral pathogens to reveal evidence of transmission, including methods that identify distinct clusters on a phylogenetic tree. Identifying clusters of linked cases can aid in the regional surveillance and management of the disease. In this study, we present a novel method for producing stable genomic clusters of SARS-CoV-2 cases, cov2clusters, and compare the sensitivity and stability of our approach to previous methods used for phylogenetic clustering using real-world SARS-CoV-2 sequence data obtained from British Columbia, Canada,

Results

We found that cov2clusters produced more stable clusters than previously used phylogenetic clustering methods when adding sequence data through time, mimicking an increase in sequence data through the pandemic. Our method also showed high sensitivity when compared to epidemiologically informed clusters.

Conclusions

Our new approach allows for the identification of stable clusters of SARS-CoV-2 from WGS data. Producing high-resolution SARS-CoV-2 clusters from sequence data alone can a challenge and, where possible, both genomic and epidemiological data should be used in combination.