Category: Statistics

Neurology. 2025 May 27;104(10):e213599. doi: 10.1212/WNL.0000000000213599. Epub 2025 Apr 23.

ABSTRACT

BACKGROUND AND OBJECTIVES: Young-onset dementia (YOD) poses substantial societal and health care burdens. Although metabolic syndrome (MetS) is recognized as a contributor to late-onset dementia, its effect on YOD remains unclear. This study aimed to determine whether MetS and its individual components increase the risk of YOD, including all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD).

METHODS: We conducted a nationwide population-based cohort study using data from the Korean National Insurance Service. Individuals aged 40-60 who underwent national health check-ups in 2009 were included and followed until December 31, 2020, or age 65, whichever came first. MetS was defined according to established guidelines, incorporating measurements of waist circumference, blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Covariates included age, sex, income level, smoking status, alcohol consumption, and comorbidities such as hypertension, diabetes, dyslipidemia, and depression. The primary outcome was incident all-cause YOD, defined as a dementia diagnosis before age 65; secondary outcomes included young-onset AD and VaD. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs.

RESULTS: A total of 1,979,509 participants (mean age, 49.0 years; 51.3% men; 50.7% with MetS) were included. Over an average follow-up of 7.75 years, 8,921 individuals (0.45%) developed YOD. MetS was associated with a 24% higher risk of all-cause YOD (adjusted HR 1.24, 95% CI 1.19-1.30), a 12.4% increased risk of AD (HR 1.12, 95% CI 1.03-1.22), and a 20.9% increased risk of VaD (HR 1.21, 95% CI 1.08-1.35). Significant interactions were noted with younger age (40-49 vs 50-59), female sex, drinking status, obesity, and depression.

DISCUSSION: In this large Korean cohort, MetS and its individual components were significantly associated with an increased risk of YOD. These findings suggest that interventions targeting MetS may help mitigate YOD risk. However, the observational design precludes definitive causal inferences, and reliance on claims data could introduce misclassification bias. Future research using longitudinal designs and comprehensive data collection is needed to validate and expand on these associations.

PMID:40267374 | DOI:10.1212/WNL.0000000000213599

Microb Genom. 2025 Apr;11(4). doi: 10.1099/mgen.0.001394.

ABSTRACT

Salmonella enterica serotype Enteritidis (SE) is a common foodborne pathogen that can cause human salmonellosis. Identifying closely related cases is essential to control the pathogen through, e.g. outbreak investigation, but it is often challenging due to the low genetic diversity of SE, particularly with traditional typing methods. This study aimed to investigate the population structure of SE genomes collected during routine surveillance in the Netherlands using whole-genome sequencing (WGS), their clustering, temporal distribution and the association between epidemiological and phenotypic antimicrobial resistance (AMR) factors and the persistence of SE clusters. We also investigated the distribution of genotypic AMR markers among these isolates. The study collection comprised 1,669 unique SE isolates from human infections collected from Dutch surveillance between 2019 and 2023, and their relatedness was derived using core-genome multi-locus sequence typing and Hamming distances. Based on the results, the 216 clusters comprised 1,085 sequences, in addition to 584 sequences depicted as singletons. These clusters predominantly fell within three major lineages, of which two were the previously described Global and Atlantic lineages. Of these clusters, approximately a third persisted for more than 1 year during the 5-year study period. However, no statistically significant associations were found between epidemiological factors, such as age, gender and travel history, or phenotypic AMR and the persistence of SE clusters. The most common AMR genetic markers observed were related to antimicrobial classes of (fluor)quinolones, β-lactamases and aminoglycosides. This study provides a better understanding of the genomic epidemiology of SE in the Netherlands based on WGS. Further analysis that includes samples from the food-chain supply, along with higher resolution methods during a post-Coronavirus Disease of 2019 (COVID-19) period, may provide more insights into the possible causes of the persistence of SE clusters.

PMID:40266678 | DOI:10.1099/mgen.0.001394

J Neurophysiol. 2025 Apr 23. doi: 10.1152/jn.00059.2024. Online ahead of print.

ABSTRACT

Psychophysical reverse correlation is an established technique for retrieving perceptual templates. Its application is best suited to a scenario in which 1) the human observer operates as a template matcher, and 2) the perceptual system is probed using radially symmetric noise, such as Gaussian white noise. When both conditions apply, the resulting estimate of the perceptual template directly reflects the actual template engaged by observers. However, when either condition fails, template estimates can be highly distorted to the point of becoming uninterpretable. This limitation is particularly relevant when ecological validity is under consideration, because natural signals are clearly nothing like white noise. Template distortions associated with natural statistics may be corrected using a number of methods, many of which have been tested in single neurons, but none of which has been tested in human observers. We studied the applicability (or lack thereof) of five such methods to multiple experimental conditions under which the human visual system approaches a template matcher to different degrees of approximation. We find that methods based on minimizing/maximizing loss/information, such as logistic regression and maximally informative dimensions, outperform other approaches under the conditions of our experiments, and therefore represent promising tools for the retrieval of human perceptual templates under ecologically valid conditions. However, we also identify plausible scenarios under which those same approaches produce misleading outcomes, urging caution when interpreting results from those and related methods.

PMID:40266668 | DOI:10.1152/jn.00059.2024

J Strength Cond Res. 2025 May 1;39(5):e706-e710. doi: 10.1519/JSC.0000000000005092.

ABSTRACT

Cabarkapa, D, Cabarkapa, DV, Batra, A, and Fry, AC. Postpractice neuromuscular performance changes in 3 × 3 professional female basketball players. J Strength Cond Res 39(5): e706-e710, 2025-The purpose of this investigation was to examine changes in lower body neuromuscular performance characteristics across multiple testing time points within a cohort of professional 3 × 3 female basketball players. Ten athletes volunteered to participate in this study (x̄ ± SD; age = 29.1 ± 4.3 years; height = 181.4 ± 7.0 cm; body mass = 77.4 ± 6.2 kg). Each athlete completed 3 countermovement vertical jumps while standing on a portable force plate system on 4 different occasions: before team practice, immediately postpractice, and the next morning and afternoon. Twenty-two force-time metrics were analyzed, 8 within braking and propulsive and 2 within landing phases of the jumping motion, including 4 performance metrics. Repeated measures analysis of variance was used to examine statistically significant differences (p < 0.05). The findings reveal an absence of significant changes in all force-time metrics of interest pre-post practice. However, a notable decrease in jump height (-5.8%), average and peak propulsive force (-4.3% and -4.7%), propulsive net impulse (-3.5%), average and peak propulsive power (-6.1% and -6.0%), and reactive strength index modified (-11.8%) was observed the following morning when compared with baseline measurements. The reactive strength index modified was shown to be the most sensitive metric in detecting fatigue-induced changes in athletes’ performance, because it experienced the largest drop between these 2 testing time points (p = 0.011; g = 0.727). Also, the observed performance suppression disappeared by the afternoon training session because all of the aforementioned force-time metrics returned to the baseline levels, indicating that the athletes were adequately recovered to participate in team training activities.

PMID:40266643 | DOI:10.1519/JSC.0000000000005092

J Strength Cond Res. 2025 May 1;39(5):570-578. doi: 10.1519/JSC.0000000000005052.

ABSTRACT

Soriano, MA, Flores, FJ, Alonso-Aubín, DA, García-Sánchez, C, Ceniza-Villacastín, JA, Jiménez-Ormeño, E, Lama-Arenales, J, and Comfort, P. Associations between maximum isometric strength and weightlifting performance in youth weightlifters. J Strength Cond Res 39(5): 570-578, 2025-The aim of this study was to explore the differences between the isometric start position pull (ISPP) and mid-thigh pull (IMTP) peak forces in youth weightlifters and their associations with weightlifting performance. Forty-six male and female youth weightlifters (age: 15.4 ± 1.3 years, height: 1.66 ± 0.91 m, body mass: 65.7 ± 10.0 kg, weightlifting experience: 2.5 ± 1.6 years) participated. Weightlifting performance was evaluated as the sum of the heaviest snatch and clean and jerk. Isometric start position pull and IMTP kinetics were calculated using a force plate. Weightlifting performance, ISPP, and IMTP were evaluated in 3 different sessions and were calculated in absolute, relative, and allometrically scaled forms. Paired samples t-tests were conducted to analyze the differences between the ISPP and IMTP. Pearson’s r correlation coefficient was used to determine the relationship between weightlifting performance and the ISPP and IMTP. Fisher’s r-z transformation was performed to determine the differences in the magnitude of correlations between the ISPP and IMTP with weightlifting performance. Statistical significance was set at p ≤ 0.05. All subjects had a significantly (p < 0.001) lower performance when performing the ISPP compared with IMTP. Significant (p < 0.001) and strong correlations were found between ISPP and IMTP with weightlifting performance (r = 0.56-0.91). Weightlifting performance was more strongly associated with ISPP than IMTP, although only significant in the relative and allometrically scaled forms (z = 2.19, p = 0.01, z = 2.34, p = 0.01, respectively). The ISPP is highly associated with weightlifting performance in youth weightlifters and should be included in talent identification and development testing batteries.

PMID:40266638 | DOI:10.1519/JSC.0000000000005052

Med Care. 2025 Apr 22. doi: 10.1097/MLR.0000000000002145. Online ahead of print.

ABSTRACT

OBJECTIVES: To demonstrate an innovative method combining machine learning with comparative effectiveness research techniques and to investigate a hitherto unstudied question about the effectiveness of common prescribing patterns.

DATA SOURCES: United States Veterans Health Administration Corporate Data Warehouse.

STUDY DESIGN: For Operation Enduring Freedom/Operation Iraqi Freedom veterans with major depressive disorder, we generate pharmacotherapy pathways (of antidepressants) using process mining and machine learning. We select the medication episodes that were started at subtherapeutic doses by the first assigned primary care physician and observe the paths that those medication episodes follow. Using 2-stage least squares, we test the effectiveness of starting at a low dose and staying low for longer versus ramping up fast while balancing observable and unobservable characteristics of patients and providers through instrumental variables. We leverage predetermined provider practice patterns as instruments.

DATA COLLECTION: We collected outpatient pharmacy data for selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, patient and provider characteristics (as control variables), and the instruments for our cohort. All data were extracted for the period between 2006 and 2020.

PRINCIPAL FINDINGS: There is a statistically significant positive effect (0.68, 95% CI 0.11-1.25) of “ramping up fast” on engagement in care. When we examine the effect of “ramping up slow”, we see an insignificant negative impact on engagement in care (-0.82, 95% CI -1.89 to 0.25). As expected, the probability of drop-out also seems to have a negative effect on engagement in care (-0.39, 95% CI -0.94 to 0.17). We further validate these results by testing with medication possession ratios calculated periodically as an alternative engagement in care metric.

CONCLUSIONS: Our findings contradict the “Start low, go slow” adage, indicating that ramping up the dose of an antidepressant faster has a significantly positive effect on engagement in care for our population.

PMID:40266632 | DOI:10.1097/MLR.0000000000002145

JAMA Netw Open. 2025 Apr 1;8(4):e255635. doi: 10.1001/jamanetworkopen.2025.5635.

ABSTRACT

IMPORTANCE: Care decisions for long-term care (LTC) residents should be frailty-informed to maximize well-being and avoid burdensome treatments that do not align with patient wishes.

OBJECTIVE: To investigate the incidence and time spent living with severe impairment among LTC residents to help inform person-centered decision-making.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted among a population-based cohort of incident admissions to LTC facilities between April 1, 2013, and March 31, 2018, determined using administrative health data in Ontario, Canada. Ontario residents aged 65 years or older who were admitted to LTC were included. Participants were followed up until death, discharge, or April 1, 2023. Data analysis was completed from October 17, 2023, to March 31, 2024.

MAIN OUTCOMES AND MEASURES: Outcomes were states of impairment that care partners identified as meaningful and some considered worse than death. The incidence of total care dependence, inability to make any decisions, inability to communicate, and incontinence of stool or urine was described. Survival after becoming impaired, characteristics of residents when they became impaired, and characteristics of those who survived for more than 1 year with each impairment were described. Residents at risk of a specific impairment (at-risk residents) were those who did not already have the impairment at admission.

RESULTS: A total of 120 238 residents admitted to LTC (mean [SD] age, 84.3 [7.7] years; 77 868 female [64.8%]) were included. By the end of follow-up, 22 018 of 109 830 at-risk residents (20.0%) had become permanently unable to make decisions, 9138 of 118 132 at-risk residents (7.7%) had become permanently unable to communicate, 15 711 of 116 848 at-risk residents (13.4%) had developed total care dependence, and 30 449 of 92 974 at-risk residents (32.8%) had developed incontinence of stool or urine. Median (IQR) survival time was shortest for residents who entered a state of total care dependence (45 [5-310] days) and longest for those with newly developed incontinence of stool or urine (356 [79-1031] days). Younger residents (eg, median [IQR] survival after developing total care dependence, 133 (17-735) days for ages <80 years vs 30 (4-217) days for ages ≥80 years) and those with dementia at admission (eg, median [IQR] survival after developing the inability to make decisions, 318 [40-1020] days with dementia vs 74 [4-474] days without dementia) had longer median survival after entering a state of severe impairment.

CONCLUSIONS AND RELEVANCE: In this study, severe permanent impairment in function and cognition were common and often present near the end of life for LTC residents, but a minority of residents lived in these states for years. These results suggest that building shared understanding and open communication about the natural course of frailty trajectories for LTC residents may support resident-centered medical decision-making.

PMID:40266620 | DOI:10.1001/jamanetworkopen.2025.5635

JAMA Netw Open. 2025 Apr 1;8(4):e256219. doi: 10.1001/jamanetworkopen.2025.6219.

ABSTRACT

IMPORTANCE: Asthma affects an estimated 7.7% of the US population and 262 million people worldwide. Symptom monitoring has demonstrated benefits but has not achieved widespread use.

OBJECTIVE: To assess the effect of a scalable asthma symptom monitoring intervention on asthma outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted between July 2020 and March 2023 at 7 primary care clinics affiliated with an academic medical center (Brigham and Women’s Hospital in Boston, Massachusetts). Candidate patients with a diagnosis of asthma over a 20-month recruitment period (July 2020 to March 2022) were identified and categorized into tiers of varying disease activity based on electronic health record data. Eligible patients were adults (aged ≥18 years) and had a primary care practitioner in 1 of the 7 participating clinics.

INTERVENTION: Intervention group patients were asked to use a mobile health app to complete weekly symptom questionnaires; track notes, peak flows, and triggers; and view educational information. Patients who reported worsening or severe symptoms were offered clinical callback requests. App data were available in the electronic health record. Usual care group patients received general asthma guidance.

MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change in Mini Asthma Quality of Life Questionnaire (MiniAQLQ) score for the intended 12-month study period. A change of 0.5 on a scale of 1 to 7 was considered a minimally important change. The secondary outcome was the mean number of asthma-related health care utilization events (urgent care visits, emergency department visits, or hospitalizations). Mean differences for all outcomes between groups were compared using robust linear regression models (generalized estimating equations) with treatment group as the only covariate.

RESULTS: Baseline questionnaires were completed by 413 patients (mean [SD] age, 52.2 [15.4] years; 321 women [77.7%]). Of these, 366 patients completed final questionnaires and were included in the primary analysis. MiniAQLQ scores increased 0.34 (95% CI, 0.19-0.49) in the intervention group and 0.11 (95% CI, -0.11 to 0.33) in the usual care group from baseline to final questionnaire completion (adjusted difference-in-difference, 0.23 [95% CI, 0.06-0.40]; P = .01); although the difference was statistically significant, it did not reach the threshold for a minimally important change. Intervention subgroups showed positive differences in MiniAQLQ scores relative to the usual care group, with noteworthy increases among individuals aged 18 to 44 years (adjusted difference-in-difference, 0.40 [95% CI, 0.13-0.66]), those with low baseline patient activation (adjusted difference-in-difference, 0.77 [95% CI, 0.30-1.24]), those with a low baseline MiniAQLQ score (adjusted difference-in-difference, 0.33 [95% CI, 0.07-0.59]), and those with uncontrolled asthma at baseline (adjusted difference-in-difference, 0.30 [95% CI, 0.05-0.54]). The intervention group had a mean of 0.59 (95% CI, 0.42-0.77) nonroutine asthma-related utilization events compared with 0.76 (95% CI, 0.55-0.96) in the usual care group (adjusted effect size, -0.16 [95% CI, -0.42 to 0.17]; P = .23).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of a scalable symptom monitoring intervention, the increase in asthma-related quality of life did not reach the threshold for a minimally important change. Exploratory analyses suggest possible benefits for patients with low levels of activation.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04401332.

PMID:40266619 | DOI:10.1001/jamanetworkopen.2025.6219

JAMA Netw Open. 2025 Apr 1;8(4):e256637. doi: 10.1001/jamanetworkopen.2025.6637.

ABSTRACT

IMPORTANCE: Detection bias occurs when an exposure is associated with a systematic difference in outcome ascertainment or diagnosis. For dementia research, diagnosed health conditions that bring patients into frequent interaction with health care may increase the chance that an individual receives a dementia diagnosis.

OBJECTIVE: To evaluate potential detection bias or misdiagnosis bias in evaluation of clinical factors associated with dementia using electronic health record (EHR) data.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from 2 population-based volunteer cohorts: UK Biobank (UKB) and All of Us (AOU). Participants were aged 55 years or older, were dementia-free at baseline, and had linked EHRs. Participants in UKB were followed up from baseline (2006-2010) until December 2022, and in AOU, from baseline (2017-2022) until July 2022. Data were analyzed from November 2023 through February 2025.

EXPOSURES: Diagnoses of type 2 diabetes, depression, hypertension, urinary tract infection, kidney stones, forearm fracture, and gastrointestinal (GI) bleeding.

MAIN OUTCOMES AND MEASURES: Rate of incident all-cause dementia diagnosis from EHRs and associations between clinical exposures and incident dementia diagnosis, assessed using Cox proportional hazards regression models.

RESULTS: Among 228 392 participants from UKB (n = 137 374; mean [SD] age at baseline, 62.5 [4.1] years; 53.8% female) and AOU (n = 91 018; mean [SD] age at baseline, 66.9 [7.8] years; 57.1% female), those with a history of a clinical exposure at baseline had higher dementia incidence rates compared with those without such history. For example, among participants with a history of GI bleeding, the dementia incidence rates were 3.0 (UKB) and 7.7 (AOU) per 1000 person-years compared with 2.2 (UKB) and 2.4 (AOU) per 1000 person-years among those without a history of GI bleeding. All exposures were significantly associated with incident dementia, with hazard ratios (HRs) ranging from 1.18 (95% CI, 1.00-1.40) to 3.51 (95% CI, 3.08-4.01). Risk of incident dementia was typically highest in the first year following exposure diagnosis and attenuated thereafter. For example, in the first year after GI bleeding, there were larger elevations in risk of incident dementia (HR, 2.17 [95% CI, 1.46-3.22] in UKB; HR, 2.56 [95% CI, 1.62-4.04] in AOU) compared with 1 to 5 years after bleeding (HR, 1.46 [95% CI, 1.15-1.86] in UKB; HR, 2.14 [95% CI, 1.63-2.81] in AOU).

CONCLUSIONS AND RELEVANCE: In this cohort study of 2 large datasets, diagnoses of several conditions associated with varying risks of dementia were associated with a higher short-term likelihood of dementia diagnosis. This finding suggests that diagnostic bias or misdiagnoses may lead to spurious associations between conditions requiring clinical care and subsequent dementia diagnoses.

PMID:40266617 | DOI:10.1001/jamanetworkopen.2025.6637

JAMA Netw Open. 2025 Apr 1;8(4):e256781. doi: 10.1001/jamanetworkopen.2025.6781.

ABSTRACT

IMPORTANCE: The prevalence of diabetes is increasing over time, fueling an epidemic of diabetic foot ulcers (DFUs) and subsequent risk of leg amputation. However, little is known about the variation in outcomes for patients with DFUs according to the health care facilities treating them.

OBJECTIVE: To examine facility-level variation in major leg amputation among veterans with incident DFUs using the Veterans Health Administration (VHA) cohort.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted from January 1, 2016, to December 31, 2021, of all veterans with a new diagnosis of DFU at 140 VHA facilities across the US. Patients were followed up to 1 year from DFU diagnosis. Analyses were conducted between March 22, 2024, and January 13, 2025.

EXPOSURE: A facility was assigned to each patient corresponding to the health care site where the initial DFU diagnosis was made.

MAIN OUTCOMES AND MEASURES: The primary outcome was major leg amputation during the follow-up period. A multivariable mixed-effects regression model with random facility intercepts was applied to assess variation in major leg amputation rates across facilities, adjusting for social drivers of health, comorbidities, and complicated DFU at initial diagnosis. The median odds ratio (MOR) was calculated to quantify facility-level variation in outcomes.

RESULTS: A total of 86 094 veterans (98.3% male; mean [SD] age, 73.0 [8.1] years; age range, 55-102 years) were included. Major leg amputation was performed for 3279 veterans (3.8%) within a year of DFU diagnosis. The MOR for facility-level variation in major leg amputation was 1.85, indicating that the odds of major leg amputation were 1.85 times higher between 2 randomly selected facilities for an average patient (P < .001). In contrast, the MOR for facility-level variation in 1-year mortality was 1.16 (P < .001).

CONCLUSIONS AND RELEVANCE: This cohort study of veterans with newly diagnosed DFU found significant facility-level variation in major leg amputation rates within 1 year of DFU diagnosis. Facility-level variation in 1-year mortality rates was much smaller, suggesting variation in leg amputation was likely to stem from variation in DFU-specific care. The VHA should strive to minimize the odds of major leg amputation and interfacility variation.

PMID:40266616 | DOI:10.1001/jamanetworkopen.2025.6781