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Nevin Manimala Statistics

Effect of dapagliflozin on COVID-19 infection and risk of hospitalization

J Antimicrob Chemother. 2023 Aug 7:dkad241. doi: 10.1093/jac/dkad241. Online ahead of print.

ABSTRACT

BACKGROUND: Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection.

METHODS: We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model.

RESULTS: We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65-1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34-4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53-3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40-1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05-1.62; P = 0.015).

CONCLUSIONS: Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.

PMID:37549309 | DOI:10.1093/jac/dkad241

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Nevin Manimala Statistics

Documented Penicillin Allergies on Antibiotic Selection at Pediatric Emergency Department Visits

Pediatr Emerg Care. 2023 Aug 8. doi: 10.1097/PEC.0000000000003023. Online ahead of print.

ABSTRACT

BACKGROUND: Penicillin or amoxicillin are the recommended treatments for the most common pediatric bacterial illnesses. Allergies to penicillin are commonly reported among children but rarely true. We evaluated the impact of reported penicillin allergies on broad-spectrum antibiotic use overall and for the treatment of common respiratory infections among treat-and-release pediatric emergency department (ED) visits.

METHODS: Retrospective cohort study of pediatric patients receiving antibiotics during a treat-and-release visit at a large, pediatric ED in the northeast from 2014 to 2016. Study exposure was a reported allergy to penicillin in the electronic medical record. Study outcomes were the selection of broad-spectrum antibiotics and alternative (second-line) antibiotic therapy for the treatment of acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis. We used unadjusted and adjusted generalized estimating equation models to analyze the impact of reported penicillin allergies on the selection of broad-spectrum antibiotics. We used unadjusted and adjusted logistic regression models to determine the probability of children with a documented penicillin allergy receiving alternative antibiotic treatments for AOM and GAS.

RESULTS: Among 12,987 pediatric patients, 810 (6.2%) had a documented penicillin allergy. Penicillin allergies increased the odds of children receiving a broad spectrum versus narrow spectrum antibiotic (adjusted odds ratio, 13.55; 95% confidence interval (CI), 11.34-16.18). In our adjusted logistic regression model, the probability of children with a documented penicillin allergy receiving alternative antibiotic treatment for AOM was 0.97 (95% CI, 0.94-0.99) and for GAS was 0.97 (95% CI, 0.92-0.99).

CONCLUSIONS: Antibiotic stewardship efforts in pediatric EDs may consider the delabeling of penicillin allergies particularly among children receiving antibiotics for an acute respiratory infection as a target for intervention.

PMID:37549307 | DOI:10.1097/PEC.0000000000003023

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Nevin Manimala Statistics

sccomp: Robust differential composition and variability analysis for single-cell data

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2203828120. doi: 10.1073/pnas.2203828120. Epub 2023 Aug 7.

ABSTRACT

Cellular omics such as single-cell genomics, proteomics, and microbiomics allow the characterization of tissue and microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical to revealing markers of disease progression, such as cancer and pathogen infection. A dedicated statistical method for differential variability analysis is lacking for cellular omics data, and existing methods for differential composition analysis do not model some compositional data properties, suggesting there is room to improve model performance. Here, we introduce sccomp, a method for differential composition and variability analyses that jointly models data count distribution, compositionality, group-specific variability, and proportion mean-variability association, being aware of outliers. sccomp provides a comprehensive analysis framework that offers realistic data simulation and cross-study knowledge transfer. Here, we demonstrate that mean-variability association is ubiquitous across technologies, highlighting the inadequacy of the very popular Dirichlet-multinomial distribution. We show that sccomp accurately fits experimental data, significantly improving performance over state-of-the-art algorithms. Using sccomp, we identified differential constraints and composition in the microenvironment of primary breast cancer.

PMID:37549298 | DOI:10.1073/pnas.2203828120

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Nevin Manimala Statistics

Collaborative privacy-preserving analysis of oncological data using multiparty homomorphic encryption

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2304415120. doi: 10.1073/pnas.2304415120. Epub 2023 Aug 7.

ABSTRACT

Real-world healthcare data sharing is instrumental in constructing broader-based and larger clinical datasets that may improve clinical decision-making research and outcomes. Stakeholders are frequently reluctant to share their data without guaranteed patient privacy, proper protection of their datasets, and control over the usage of their data. Fully homomorphic encryption (FHE) is a cryptographic capability that can address these issues by enabling computation on encrypted data without intermediate decryptions, so the analytics results are obtained without revealing the raw data. This work presents a toolset for collaborative privacy-preserving analysis of oncological data using multiparty FHE. Our toolset supports survival analysis, logistic regression training, and several common descriptive statistics. We demonstrate using oncological datasets that the toolset achieves high accuracy and practical performance, which scales well to larger datasets. As part of this work, we propose a cryptographic protocol for interactive bootstrapping in multiparty FHE, which is of independent interest. The toolset we develop is general-purpose and can be applied to other collaborative medical and healthcare application domains.

PMID:37549296 | DOI:10.1073/pnas.2304415120

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Nevin Manimala Statistics

Climate determines transmission hotspots of Polycystic Echinococcosis, a life-threatening zoonotic disease, across Pan-Amazonia

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2302661120. doi: 10.1073/pnas.2302661120. Epub 2023 Aug 7.

ABSTRACT

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE’s key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.

PMID:37549288 | DOI:10.1073/pnas.2302661120

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Nevin Manimala Statistics

Sterically driven current reversal in a molecular motor model

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2210500120. doi: 10.1073/pnas.2210500120. Epub 2023 Aug 7.

ABSTRACT

Simulations can help unravel the complicated ways in which molecular structure determines function. Here, we use molecular simulations to show how slight alterations of a molecular motor’s structure can cause the motor’s typical dynamical behavior to reverse directions. Inspired by autonomous synthetic catenane motors, we study the molecular dynamics of a minimal motor model, consisting of a shuttling ring that moves along a track containing interspersed binding sites and catalytic sites. The binding sites attract the shuttling ring while the catalytic sites speed up a reaction between molecular species, which can be thought of as fuel and waste. When that fuel and waste are held in nonequilibrium steady-state concentrations, the free energy from the reaction drives directed motion of the shuttling ring along the track. Using this model and nonequilibrium molecular dynamics, we show that the shuttling ring’s direction can be reversed by simply adjusting the spacing between binding and catalytic sites on the track. We present a steric mechanism behind the current reversal, supported by kinetic measurements from the simulations. These results demonstrate how molecular simulation can guide future development of artificial molecular motors.

PMID:37549273 | DOI:10.1073/pnas.2210500120

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Nevin Manimala Statistics

Comparison of turbidometric immunoassay, refractometry, and gamma-glutamyl transferase to radial immunodiffusion for assessment of transfer of passive immunity in high-risk beef calves

J Vet Intern Med. 2023 Aug 7. doi: 10.1111/jvim.16831. Online ahead of print.

ABSTRACT

BACKGROUND: Attainment of adequate transfer of passive immunity (TPI) is critical to health of calves; however, studies comparing available tools for measurement of TPI in individual beef animals are limited.

OBJECTIVES: To report agreement between 4 tests evaluating individual TPI status in beef calves.

ANIMALS: One hundred ninety-six beef calves born to cows and heifers presenting for calving management or dystocia.

METHODS: Retrospective study to assess serum immunoglobulin (IgG) concentrations via turbidimetric immunoassay (TI), gamma-glutamyl transferase (GGT), serum total protein (TP), and single radial immunodiffusion (RID; reference standard). Test agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis, Cohen’s kappa, and receiver operating characteristic (ROC) curves with and without covariate adjustment to determine optimal thresholds.

RESULTS: Correlation between RID and test results varied: TI, ρ = 0.757; TP, ρ = 0.715; GGT: ρ = 0.413. For the TI compared to RID, regression analysis identified a constant (intercept = -0.51 [CI: -2.63, 3.05]) and proportional (slope = 1.87 [CI: 1.69, 2.08]) bias. Based on ROC, TI concentrations of ≤9.89 and ≤13.76 g/L, and TP concentrations of ≤5.5 and ≤6.0 g/dL, indicated IgG concentrations <18.0 and <25.0 g/L, respectively.

CONCLUSIONS AND CLINICAL IMPORTANCE: Within this cohort of calves, TI demonstrated the best correlation with RID; however, significant bias was identified which led to frequent underestimation of IgG concentration. Serum total protein demonstrated less correlation with RID but had less misclassification than TI. Both TI and TP demonstrated less correlation for calves that received colostrum replacement prompting clinical awareness of colostrum type when evaluating individual TPI in beef calves.

PMID:37549250 | DOI:10.1111/jvim.16831

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Nevin Manimala Statistics

Herpes zoster reactivation after mRNA and adenovirus-vectored coronavirus disease 2019 vaccination: Analysis of National Health Insurance Database

J Infect Dis. 2023 Aug 7:jiad297. doi: 10.1093/infdis/jiad297. Online ahead of print.

ABSTRACT

BACKGROUND: Our study aimed to determine the risk of herpes zoster reactivation and COVID-19 vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]).

METHODS: This retrospective study analyzed herpes zoster cases diagnosed between February 26, 2021 and June 30, 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio, and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed.

RESULTS: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose, adjusted odds ratio [aOR]: 1.11 [95% confidence interval {CI}: 1.06-1.15]; second dose, aOR: 1.17 [95% CI: 1.12-1.23]). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR]: 1.09 [95% CI: 1.02-1.16]). BNT162b2 was associated with an increased risk at 18 days post-vaccination (aHR: 1.65 [95% CI: 1.35-2.02]) and second dose (aHR: 1.10 [95% CI: 1.02-1.19]). However, the risk did not increase in both analysis of ChAdOx1 vaccination.

CONCLUSIONS: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.

PMID:37549237 | DOI:10.1093/infdis/jiad297

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Dance movement therapy for dementia

Cochrane Database Syst Rev. 2023 Aug 7;8:CD011022. doi: 10.1002/14651858.CD011022.pub3.

ABSTRACT

BACKGROUND: Dementia is a syndrome of acquired cognitive impairment which is severe enough to interfere with independent living. Over the course of the illness, people with dementia also experience changes in emotions, behaviour and social relationships. According to Alzheimer’s Disease International, dementia affects approximately 55 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia, including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. A growing literature highlights the capacity of the arts and has embodied practices to address this complexity. Dance movement therapy (DMT) is an embodied psychological intervention that can address complexity and thus may be useful for people with dementia, but its effectiveness remains unclear.

OBJECTIVES: To assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement) SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group’s register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization’s meta-register of the International Clinical Trials Registry Portal until 8 December 2022.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included people with dementia, of any age and in any setting. The DMT intervention had to be delivered by a dance movement therapy practitioner who (i) had received formal training (ii) was a dance movement therapist in training or (iii) was otherwise recognised as a dance movement therapist in the country in which the study was conducted.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and evaluated methodological quality. We expressed effect estimates using the mean difference (MD) between intervention groups and presented associated confidence intervals (CIs). We used GRADE methods to rate our certainty in the results.

MAIN RESULTS: We found only one study eligible for inclusion in this review. This was a 3-arm parallel-group RCT conducted in Hong Kong involving 204 adults with mild neurocognitive disorder or dementia. The study examined the effects of short-term (12 weeks) group DMT in comparison with exercise and a waiting-list control group immediately post-intervention and three and nine months later. We found that, at the end of the intervention, DMT may result in little to no difference in neuropsychiatric symptoms assessed with the 12-item Neuropsychiatric Inventory when compared with waiting list (MD 0.3, 95% CI -0.96 to 1.56; low-certainty evidence) or exercise (MD -0.30, 95% CI -1.83 to 1.23; low-certainty evidence). Nor was there any evidence of effects at later time points. Cognitive functioning was assessed with a variety of instruments and there were no statistically significant between-group differences (low-certainty evidence). When compared to exercise or waiting list, DMT may result in little to no difference in cognitive function immediately after the intervention or at follow-up. In comparison to waiting list, DMT may result in a slight reduction in depression assessed with the 4-item Geriatric Depression Scale at the end of therapy (MD -0.60, 95% CI -0.96 to -0.24; low-certainty evidence). This slight positive effect of DMT on depression scores was sustained at three and nine months after the completion of the intervention. DMT may also reduce depression slightly in comparison with exercise at the end of therapy (MD -0.40, 95% CI -0.76 to -0.04, low-certainty evidence), an effect also sustained at three and nine months. Our fourth primary outcome, quality of life, was not assessed in the included study. There were data for two of our secondary outcomes, social and occupational functioning and dropouts (which we used as a proxy for acceptability), but in both cases the evidence was of very low certainty and hence our confidence in the results was very low. For all outcomes, we considered the certainty of the evidence in relation to our review objectives to be low or very low in GRADE terms due to indirectness (because not all participants in the included study had a diagnosis of dementia) and imprecision.

AUTHORS’ CONCLUSIONS: This review included one RCT with a low risk of bias. Due to the low certainty of the evidence, the true effects of DMT as an intervention for dementia may be substantially different from those found. More RCTs are needed to determine with any confidence whether DMT has beneficial effects on dementia.

PMID:37549216 | DOI:10.1002/14651858.CD011022.pub3

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Effectiveness of Human-supported and Self-help eHealth Lifestyle Interventions for Patients with Cardiometabolic Risk Factors: A Meta-analysis

Psychosom Med. 2023 Aug 7. doi: 10.1097/PSY.0000000000001242. Online ahead of print.

ABSTRACT

OBJECTIVE: eHealth is a useful tool to deliver lifestyle interventions for patients with cardiometabolic diseases. However, there are inconsistent findings about whether these eHealth interventions should be supported by a human professional, or whether self-help interventions are equally effective.

METHODS: Databases were searched between January 1995 and October 2021 for randomized controlled trials on cardiometabolic diseases (cardiovascular disease, chronic kidney disease, type 1 and 2 diabetes mellitus) and eHealth lifestyle interventions. A multilevel meta-analysis was used to pool clinical and behavioral health outcomes. Moderator analyses assessed the effect of intervention type (self-help vs. human-supported), dose of human support (minor vs. major part of intervention), and delivery mode of human support (remote vs. blended). 107 papers fulfilled eligibility criteria and 102 unique (N = 20,781) studies were included.

RESULTS: The analysis showed a positive effect of eHealth lifestyle interventions on clinical and behavioral health outcomes (p < .001). However, these effects were not moderated by intervention type (p = .169), dose (p = .698), or delivery mode of human support (p = .557).

CONCLUSION: This shows that self-help eHealth interventions are equally effective as human-supported ones in improving health outcomes among cardiometabolic disease patients. Future studies could investigate whether higher quality eHealth interventions compensate for a lack of human support.Meta-analysis registration: PROSPERO CRD42021269263.

PMID:37549197 | DOI:10.1097/PSY.0000000000001242