Nevin Manimala

Bioinformatics. 2024 Nov 25:btae707. doi: 10.1093/bioinformatics/btae707. Online ahead of print.

ABSTRACT

SUMMARY: LEfSe is a widely used Python package and Galaxy module for metagenomic biomarker discovery and visualization, utilizing the Kruskal-Wallis test, Wilcoxon Rank-Sum test, and Linear Discriminant Analysis. R/Bioconductor provides a large collection of tools for metagenomic data analysis but has lacked an implementation of this widely-used algorithm, hindering benchmarking against other tools and incorporation into R workflows. We present the lefser package to provide comparable functionality within the R/Bioconductor ecosystem of statistical analysis tools, with improvements to the original algorithm for performance, accuracy, and reproducibility. We benchmark the performance of lefser against the original algorithm using human and mouse metagenomic datasets.

AVAILABILITY AND IMPLEMENTATION: Our software, lefser, is distributed through the Bioconductor project (https://www.bioconductor.org/packages/release/bioc/html/lefser.html), and all the source code is available in the GitHub repository https://github.com/waldronlab/lefser.

CONTACT: Institute for Implementation Science in Population Health, Department of Epidemiology and Biostatistics, City University of New York School of Public Health, New York, NY, United States. E-mail: [email protected] (S.O.).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39585730 | DOI:10.1093/bioinformatics/btae707

JAMA Neurol. 2024 Nov 25. doi: 10.1001/jamaneurol.2024.4058. Online ahead of print.

ABSTRACT

IMPORTANCE: Long-term exposure to total fine particulate matter (PM2.5) is a recognized dementia risk factor, but less is known about wildfire-generated PM2.5, an increasingly common PM2.5 source.

OBJECTIVE: To assess the association between long-term wildfire and nonwildfire PM2.5 exposure and risk of incident dementia.

DESIGN, SETTING, AND PARTICIPANTS: This open cohort study was conducted using January 2008 to December 2019 electronic health record (EHR) data among members of Kaiser Permanente Southern California (KPSC), which serves 4.7 million people across 10 California counties. KPSC members aged 60 years or older were eligible for inclusion. Members were excluded if they did not meet eligibility criteria, if they had a dementia diagnosis before cohort entry, or if EHR data lacked address information. Data analysis was conducted from May 2023 to May 2024.

EXPOSURES: Three-year rolling mean wildfire and nonwildfire PM2.5 in member census tracts from January 2006 to December 2019, updated quarterly and estimated via monitoring and remote-sensing data and statistical techniques.

MAIN OUTCOME AND MEASURES: The primary outcome was incident dementia, identified using diagnostic codes in the EHR. Odds of dementia diagnoses associated with 3-year mean wildfire and nonwildfire PM2.5 exposure were estimated using a discrete-time approach with pooled logistic regression. Models adjusted for age, sex, race and ethnicity (considered as a social construct rather than as a biological determinant), marital status, smoking status, calendar year, and census tract-level poverty and population density. Stratified models assessed effect measure modification by age, sex, race and ethnicity, and census tract-level poverty.

RESULTS: Among 1.64 million KPSC members aged 60 years or older during the study period, 1 223 107 members were eligible for inclusion in this study. The study population consisted of 644 766 female members (53.0%). In total, 319 521 members identified as Hispanic (26.0%), 601 334 members identified as non-Hispanic White (49.0%), and 80 993 members received a dementia diagnosis during follow-up (6.6%). In adjusted models, a 1-μg/m3 increase in the 3-year mean of wildfire PM2.5 exposure was associated with an 18% increase in the odds of dementia diagnosis (odds ratio [OR], 1.18; 95% CI, 1.03-1.34). In comparison, a 1-μg/m3 increase in nonwildfire PM2.5 exposure was associated with a 1% increase (OR, 1.01; 95% CI, 1.01-1.02). For wildfire PM2.5 exposure, associations were stronger among members less than 75 years old upon cohort entry, members from racially minoritized subgroups, and those living in high-poverty vs low-poverty census tracts.

CONCLUSIONS AND RELEVANCE: In this cohort study, after adjusting for measured confounders, long-term exposure to wildfire and nonwildfire PM2.5 over a 3-year period was associated with dementia diagnoses. As the climate changes, interventions focused on reducing wildfire PM2.5 exposure may reduce dementia diagnoses and related inequities.

PMID:39585704 | DOI:10.1001/jamaneurol.2024.4058

JAMA Netw Open. 2024 Nov 4;7(11):e2446851. doi: 10.1001/jamanetworkopen.2024.46851.

ABSTRACT

IMPORTANCE: The practice of deprescribing antihypertensive medications is common among long-term care residents, yet the effect on cardiovascular outcomes is unclear.

OBJECTIVE: To compare the incidence of hospitalization for myocardial infarction (MI) or stroke among long-term care residents who are deprescribed or continue antihypertensive therapy.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness research study used target trial emulation with observational electronic health record data from long-term care residents aged 65 years or older admitted to US Department of Veterans Affairs community living centers between October 1, 2006, and September 30, 2019, and taking at least 1 antihypertensive medication. Analyses were conducted between August 2023 and August 2024.

EXPOSURE: A reduction in the number of antihypertensive medications or dose (by ≥30%), assessed using barcode medication administration data.

MAIN OUTCOME AND MEASURES: Incidence of MI and stroke hospitalization up to 2 years was assessed using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. A pooled logistic regression model with inverse probability of treatment weighting (IPTW) and inverse probability of censoring weighting (IPCW) was used to estimate per-protocol effects.

RESULTS: Of 13 096 long-term care residents (97.4% men; median age, 77 years [IQR, 70-84 years]) taking antihypertensive medication, 17.8% were deprescribed antihypertensive medication over a period of 12 weeks. The estimated unadjusted cumulative incidence of stroke or MI hospitalization over 2 years was similar among residents who were and were not deprescribed antihypertensives in per-protocol analyses (11.2% vs 8.8%; difference, 2.4 percentage points [95% CI, -2.3 to 7.1 percentage points]). Participant characteristics were balanced after applying IPTW and IPCW; all standardized mean differences were less than 0.05. After full adjustment for confounding and informative censoring, the per-protocol analysis results showed no association of antihypertensive deprescribing with MI or stroke hospitalization (hazard ratio, 0.93; 95% CI, 0.70-1.26).

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness research study, deprescribing antihypertensive medication was not associated with risk of hospitalization for MI or stroke in long-term care residents. These findings may be informative for long-term care residents and clinicians who are considering deprescribing antihypertensive medications.

PMID:39585693 | DOI:10.1001/jamanetworkopen.2024.46851

JAMA Netw Open. 2024 Nov 4;7(11):e2447605. doi: 10.1001/jamanetworkopen.2024.47605.

ABSTRACT

IMPORTANCE: The association between psychological resilience (PR) and frailty progression in older adults is not fully understood.

OBJECTIVE: To investigate the longitudinal associations between PR and its changes (ΔPR) with frailty progression among older adults.

DESIGN, SETTING, AND PARTICIPANTS: Data were collected from a community-based prospective cohort study conducted in Shanghai from 2020 to 2023. Older adults aged 60 years and above were recruited at baseline and completed follow-up assessments. Statistical analysis was performed from May to July 2024.

EXPOSURES: PR was assessed using the 25-item Connor-Davidson resilience scale (CD-RISC). ΔPR was calculated using the difference between 3-year follow-up and baseline CD-RISC scores. Multiple key covariates were included such as demographics, health behaviors, social participation, and chronic diseases.

MAIN OUTCOMES AND MEASURES: Frailty was evaluated using the Chinese Frailty Screening Scale-10. Frailty progression was categorized into 3 groups (improvement, stability, and deterioration) by the difference assessment between 3-year follow-up and baseline.

RESULTS: A total of 4033 participants were included in the study (mean [SD] age, 71.0 [6.1] years; 2257 [56.0%] women). Over a 3-year follow-up period, 1142 participants (28.3%) experienced an improvement in frailty, 1200 (29.8%) experienced stability, and 1691 (41.9%) exhibited deterioration. After controlling for confounding variables, a significant association was found between PR and future frailty, particularly when baseline frailty scores were at least 3 vs 2 or lower (β, -0.136 [95% CI, -0.214 to -0.057] vs -0.020 [-95% CI, -0.052 to 0.012]; P for interaction < .001). A similar association was observed between PR and frailty improvement (adjusted odds ratio [OR], 1.28 [95% CI, 1.05 to 1.57]). Furthermore, ΔPR displayed a significant association with frailty, exhibiting a nonlinear association that was stronger when ΔPR was less than 0 vs when ΔPR was greater than 0 (β,-0.186 [95% CI, -0.228 to -0.145] vs -0.068 [95% CI, -0.107 to -0.029]; P for nonlinear < .001). Similarly, ΔPR was significantly associated with frailty progression, indicating both improvement (adjusted OR, 1.30 [95% CI, 1.19 to 1.42]) and deterioration (adjusted OR, 0.74 [95% CI, 0.69 to 0.80]). These associations were more pronounced among older adults with higher levels of baseline frailty.

CONCLUSIONS AND RELEVANCE: In this cohort study of community-dwelling older adults, a longitudinal association between PR and frailty progression was found. The results suggest that monitoring changes in PR can help forecast future frailty trajectories, particularly highlighting the need to support individuals facing declines in resilience. Targeted interventions that prioritize enhancing PR have potential to prevent and ameliorate frailty.

PMID:39585692 | DOI:10.1001/jamanetworkopen.2024.47605

Cogn Emot. 2024 Nov 25:1-20. doi: 10.1080/02699931.2024.2430403. Online ahead of print.

ABSTRACT

Superior recognition of positive emotional facial expressions compared to negative expressions is well established. However, it is unclear whether this superiority effect differs between non-parents and parents, for whom emotion perception (EP) is an indispensable skill. Although EP has been shown to be modulated by the neuropeptide oxytocin, a central factor in the development of parental care, very little research has addressed the relationship between EP skills, the transition to parenthood, and plasma oxytocin levels. In the present study, we assessed EP abilities with a test battery and measured plasma oxytocin in 77 non-parent and 79 parent couples and applied structural equation modelling to the data. The results showed increased happiness perception abilities in both parents and individuals with elevated oxytocin levels. Furthermore, non-parents showed superior abilities to recognise anger expressions. No significant associations were found regarding the perception of other basic emotion categories or with a general EP factor. The findings are consistent with previous research indicating that elevated oxytocin levels are associated with enhanced EP abilities. They also extend the existing literature by demonstrating that mothers and fathers, regardless of their oxytocin levels, exhibit increased EP superiority.

PMID:39585690 | DOI:10.1080/02699931.2024.2430403

JAMA Pediatr. 2024 Nov 25. doi: 10.1001/jamapediatrics.2024.4552. Online ahead of print.

ABSTRACT

IMPORTANCE: Communicating clearly about who is included in a population group is a critical element to effective dissemination and knowledge transfer. This narrative review highlights the inconsistency as it relates to communicating about individuals with intellectual disability (ID) and developmental disability (DD).

OBSERVATIONS: There is enormous variability in the use of definitions and abbreviations in the field of intellectual disability and developmental disabilities. The lack of consistency has resulted in widely varying reported rates of prevalence and has contributed to confusion around the interpretation of research and clinical findings, population statistics, and policy decisions. The reported rates of prevalence for developmental disabilities published by different US federal agencies have ranged widely from 3% to 17%. This represents a 5-fold difference. Equally confusing is the inconsistent and ambiguous adoption of initialisms. These initialisms include ID/DD, IDD, and I/DD for which it is not always clear if these initialisms reference separate and independent populations (eg, ID or DD) or populations with co-occurring conditions (eg, persons with ID and DD). This Narrative Review discusses these issues and proposed a number of recommendations that would contribute to enhanced consistency and clarity of understanding for stakeholders, administrators, practitioners, researchers, and policy makers.

CONCLUSION: Authors of scholarly works, clinical publications, policies, and position papers are encouraged to provide a clear operational definition as well as the choice of initialisms used (eg, ID/DD, IDD, I/DD, etc) when it is first used.

PMID:39585684 | DOI:10.1001/jamapediatrics.2024.4552

JAMA Intern Med. 2024 Nov 25. doi: 10.1001/jamainternmed.2024.6212. Online ahead of print.

ABSTRACT

IMPORTANCE: Clinicians often approach urate-lowering therapy (ULT) cautiously in patients with gout and impaired kidney function because they are concerned about the risk of progression to severe or end-stage kidney disease. However, evidence from randomized clinical trials of this association remains inconclusive.

OBJECTIVE: To evaluate the association between achieving target serum urate level with ULT and progression of chronic kidney disease (CKD) to severe or end-stage in patients with gout and impaired kidney function.

DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study using the target trial emulation approach using data from a general practice database (IQVIA Medical Research Database) for 2000 to 2023. Eligible patients were 40 to 89 years old and had gout and CKD stage 3. Data analyses were performed from November 2023 to September 2024.

EXPOSURES: Lowering serum urate level to target level (<6 mg/dL) using ULT.

MAIN OUTCOMES AND MEASURES: Severe or end-stage kidney disease, determined by an estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 on at least 2 occasions more than 90 days apart within 1 year, or at least 1 Read code (per the Refined Etiology, Anatomical Site, and Diagnosis classification) for CKD stages 4 or 5, hemodialysis, peritoneal dialysis, or kidney transplant. The prespecified noninferiority margin of the hazard ratio (HR) was set at 1.2, comparing those who achieved the target serum urate level with those who did not.

RESULTS: Among the 14 792 participants (mean [SD] age, 73.1 [9.5] years; 9215 men [62.3%] and 5577 women [37.7%]) with gout and with CKD stage 3, the 5-year risk of severe or end-stage kidney disease was 10.32% for those who achieved the target serum urate level and 12.73% for those who did not. Compared with those not achieving the target level, the adjusted 5-year risk difference and HR of severe or end-stage kidney disease for patients achieving the target serum urate level was -2.41% (95% CI, -4.61% to -0.21%) and 0.89 (95% CI, 0.80 to 0.98), respectively.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study indicate that in patients with gout and CKD stage 3, lowering serum urate level to less than 6 mg/dL vs 6 mg/dL or greater using ULT was not associated with an increased risk of severe or end-stage kidney disease. These findings support optimizing ULT to achieve target serum urate levels when treating patients with gout and impaired kidney function.

PMID:39585678 | DOI:10.1001/jamainternmed.2024.6212

JAMA Intern Med. 2024 Nov 25. doi: 10.1001/jamainternmed.2024.5451. Online ahead of print.

ABSTRACT

IMPORTANCE: There is increased interest in public reporting of, and linking financial incentives to, the performance of organizations on health equity metrics, but variation across organizations could reflect differences in performance or selection bias.

OBJECTIVE: To assess whether differences across health plans in sex- and age-adjusted racial disparities are associated with performance or selection bias.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study leveraged a natural experiment, wherein a southern US state randomly assigned much of its Medicaid population to 1 of 5 plans after shifting to managed care in 2012. Enrollee-level administrative claims and enrollment data from 2011 to 2015 were obtained for self-identified Black and White enrollees. The analyses were limited to Black and White Medicaid enrollees because they accounted for the largest percentages of the population and could be compared with greater statistical power than other groups. Data were analyzed from June 2021 to September 2024.

EXPOSURES: Plan enrollment via self-selection (observational population) vs random assignment (randomized population).

MAIN OUTCOMES AND MEASURES: Annual counts of primary care visits, low-acuity emergency department visits, prescription drug fills, and total spending. For observational and randomized populations, models of each outcome were fit as a function of plan indicators, indicators for race, interactions between plan indicators and race, and age and sex. Models estimated the magnitude of racial differences within each plan and tested whether this magnitude varied across plans.

RESULTS: Of 118 101 enrollees (mean [SD] age, 9.3 [7.5] years; 53.0% female; 61.4% non-Hispanic Black; and 38.6% non-Hispanic White), 70.2% were included in the randomized population, and 29.8% were included in the observational population. Within-plan differences in primary care visits, low-acuity emergency department visits, prescription drug use, and total spending between Black and White enrollees were large but did not vary substantially and were not statistically significantly different across plans in the randomized population, suggesting minimal effects of plans on racial differences in these measures. In contrast, in the observational population, racial differences varied substantially across plans (standard deviations 2-3 times greater than in the randomized population); this variation was statistically significant after adjustment for multiple testing, except for emergency department visits. Greater between-plan variation in racial differences in the observational population was only partially explained by sampling error. Stratifying by race did not bring observational estimates of plan effects meaningfully closer to randomized estimates.

CONCLUSIONS AND RELEVANCE: This cross-sectional study showed that selection bias may mischaracterize plans’ relative performance on measures of health care disparities. It is critical to address disparities in Medicaid, but adjusting plan payments based on disparity measures may have unintended consequences.

PMID:39585673 | DOI:10.1001/jamainternmed.2024.5451

JAMA Neurol. 2024 Nov 25. doi: 10.1001/jamaneurol.2024.3976. Online ahead of print.

ABSTRACT

IMPORTANCE: Several psychiatric disorders have been found to occur more frequently in persons with epilepsy (PWE) than in persons without epilepsy.

OBJECTIVE: To summarize the prevalence of 20 psychiatric disorders in PWE compared with persons without epilepsy.

DATA SOURCES: The search included records from inception to February 2024 in Ovid, MEDLINE, Embase, and PsycINFO.

STUDY SELECTION: Published epidemiological studies examining the prevalence of psychiatric disorders among PWE compared with persons without epilepsy were systematically reviewed. There were no restrictions on language or publication date.

DATA EXTRACTION AND SYNTHESIS: Abstracts were reviewed in duplicate, and data were extracted using a standardized electronic form. Descriptive statistics and meta-analyses are presented.

MAIN OUTCOMES AND MEASURES: Data were recorded on the prevalence of 20 psychiatric disorders among PWE compared with persons without epilepsy. Meta-analyses were performed along with descriptive analyses.

RESULTS: The systematic search identified 10 392 studies, 27 of which met eligibility criteria. The meta-analyses included 565 443 PWE and 13 434 208 persons without epilepsy. The odds of most psychiatric disorders studied were significantly increased in PWE compared with those without epilepsy, including anxiety (odds ratio [OR], 2.11; 95% CI, 1.73-2.58); depression (OR, 2.45; 95% CI, 1.94-3.09); bipolar disorder (OR, 3.12; 95% CI, 2.23-4.36); suicidal ideation (OR, 2.25; 95% CI, 1.75-2.88) but not suicide attempt (OR, 3.17; 95% CI, 0.49-20.46); psychotic disorder (OR, 3.98; 95% CI, 2.57-6.15); schizophrenia (OR, 3.72; 95% CI, 2.44-5.67); obsessive-compulsive disorder (OR, 2.71; 95% CI, 1.76-4.15); posttraumatic stress disorder (OR, 1.76; 95% CI, 1.14-2.73); eating disorders (OR, 1.87; 95% CI, 1.73-2.01); alcohol misuse (OR, 3.64; 95% CI, 2.27-5.83) and alcohol dependence (OR, 4.94; 95% CI, 3.50-6.96) but not alcohol abuse (OR, 2.10; 95% CI, 0.60-7.37); substance use disorder (OR, 2.75; 95% CI, 1.61-4.72); autism spectrum disorder (OR, 10.67; 95% CI, 6.35-17.91); and attention-deficit/hyperactivity disorder (OR, 3.93; 95% CI, 3.80-4.08).

CONCLUSIONS AND RELEVANCE: In this comprehensive study, most psychiatric comorbidities examined were significantly more prevalent in PWE than in those without epilepsy. These findings show the high burden of psychiatric comorbidities in PWE. This, in turn, underscores the need for appropriately identifying and treating psychiatric comorbidity in epilepsy to manage patients effectively and improve quality of life.

PMID:39585664 | DOI:10.1001/jamaneurol.2024.3976

JAMA Pediatr. 2024 Nov 25. doi: 10.1001/jamapediatrics.2024.4782. Online ahead of print.

ABSTRACT

IMPORTANCE: Taxation of sweetened beverages is a proposed strategy to reduce excess sugar consumption. The association of such taxes with health outcomes is not well studied. Philadelphia, Pennsylvania, is the largest US city with a beverage tax.

OBJECTIVE: To assess whether the 2017 Philadelphia beverage tax was associated with changes in pediatric weight outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This study used difference-in-differences models weighted by inverse probability of treatment weights to adjust for differences between youth in Philadelphia (tax exposed) and in the surrounding counties (control) on age, sex, race, ethnicity, Medicaid insurance status, health care use, and census-tract socioeconomic index. Mixed-effects linear and logistic regression models estimated differences in posttax changes in standardized body mass index (zBMI) and prevalence of obesity (a BMI 95th percentile or higher for age and sex) between Philadelphia and control. Stratified analyses assessed differences by age, sex, race, Medicaid insurance status, and baseline weight. Data came from electronic health records of a primary care network operating in the Philadelphia region. A panel analysis included youth 2 to 18 years old with 1 or more BMI measurement pretax (2014 to 2016) and 1 or more BMI measurement posttax (2018 to 2019). A cross-sectional analysis included youth 2 to 18 years old with 1 or more BMI measurement at any time from 2014 to 2019. These data were analyzed from December 2020 through July 2024.

EXPOSURE: Living in Philadelphia after implementation of the beverage tax.

MAIN OUTCOMES AND MEASURES: zBMI and obesity prevalence.

RESULTS: In panel analysis of 136 078 youth, the tax was associated with a difference in zBMI change of -0.004 (95% CI, -0.009 to 0.001) between Philadelphia and the control and a 1.02 odds ratio (95% CI, 0.97-1.08) of BMIs in the 95th percentile or higher. In cross-sectional analysis of 258 584 youth, the difference in zBMI change was -0.004 (95% CI, -0.009 to 0.001) and the odds ratio of a BMI in the 95th percentile or higher was 1.01 (95% CI, 0.95-1.07). In subgroup analyses, some differences in zBMI change were evident by race, age, Medicaid insurance status, and baseline weight but these differences were small and inconsistent across samples.

CONCLUSIONS AND RELEVANCE: These results show that 2 years after implementation, the Philadelphia beverage tax was not associated with changes in youth zBMI or obesity prevalence. Though certain subgroups demonstrated small statistically significant changes in zBMI, they are of low clinical significance.

PMID:39585659 | DOI:10.1001/jamapediatrics.2024.4782