Category: Nevin Manimala

JAMA Netw Open. 2026 Jan 2;9(1):e2552787. doi: 10.1001/jamanetworkopen.2025.52787.

ABSTRACT

IMPORTANCE: Outcomes for people with low back pain (LBP) may be improved through targeting treatments to subgroups with particular experiences, characteristics, or symptoms and clinical factors.

OBJECTIVE: To investigate potential treatment effect modifiers of graded sensorimotor retraining affecting pain intensity and disability level in the short and long terms for people with chronic LBP.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc exploratory secondary analysis of the RESOLVE randomized clinical trial in Sydney, Australia, was conducted from November 5, 2024, to May 27, 2025. Trial participants were recruited from primary care settings and randomly allocated (1:1) to receive either graded sensorimotor retraining (treatment group) or attention control and sham procedures (sham control group). Eligible participants were adults aged 18 to 70 years who reported chronic nonspecific LBP (lasting ≥12 weeks), with or without leg pain, that was rated at least a 3 out of 10 in pain intensity. Statistical analyses were conducted from November 11 to December 6, 2024.

INTERVENTIONS: The treatment group completed 12 weekly clinical sessions of the graded sensorimotor retraining package, which consisted of pain science education, premovement training, and graded movement and loading. The sham control group completed 12 weekly sessions, without advice or education, of sham electrotherapy to the back and sham noninvasive brain stimulation.

MAIN OUTCOMES AND OUTCOME MEASURES: Primary outcomes were pain intensity (measured with the 11-point Numerical Rating Scale ranging from 0 [no pain] to 10 [worst imaginable pain]) and disability level (measured with the 24-item Roland-Morris Disability Questionnaire with scores ranging from 0-24 [higher scores indicating greater levels of disability]) assessed at 18 weeks and 52 weeks after randomization. A formal moderation analysis was performed using a test for statistical interaction. Eight baseline variables-psychoactive medication use, pain intensity, disability level, beliefs about back pain consequences, kinesiophobia, pain catastrophizing, pain self-efficacy, and back perception-were investigated for their potential treatment effect modification.

RESULTS: The study included 276 participants (mean [SD] age, 46 [14.3] years; 138 females [50.0%]), 138 of whom were randomized to the treatment group and 138 of whom were randomized to the sham control group. Pain self-efficacy, pain catastrophizing, pain intensity, and psychoactive medication use showed no evidence of modifying the effect of the intervention. Impaired back perception was identified as a potential treatment effect modifier of pain intensity (β-coefficient = 0.18 [95% CI, 0.05-0.32]; P = .007) at the 52-week follow-up time point. Hypothesis-generating evidence (P < .20) indicated potential effect modification by kinesiophobia (on pain intensity at 18-week follow-up: β-coefficient = 0.06 [95% CI, -0.02 to 0.14], P = .15; 52-week follow-up: β-coefficient = 0.07 [95% CI, -0.02 to 0.16], P = .12), baseline disability level (on disability level at 18-week follow-up: β-coefficient = -0.15 [95% CI, -0.38 to 0.07], P = .17), beliefs about back pain consequences (on disability level at 52-week follow-up: β-coefficient = 0.16 [95% CI, -0.05 to 0.37], P = .14) and back perception (on pain intensity at 18-week follow-up: β-coefficient = 0.10 [95% CI, -0.02 to 0.22], P = .09; on disability level at 18-week follow-up: β-coefficient = 0.22 [95% CI, -0.04 to 0.48], P = .10; 52-week follow-up: β-coefficient = 0.27 [95% CI, 0.00-0.55], P = .05).

CONCLUSIONS AND RELEVANCE: This secondary analysis found that the benefits of graded sensorimotor retraining are likely to be similar for all people with chronic nonspecific LBP presenting for care. Future clinical trials are needed to further explore and assess the role of the potential treatment effect modifiers identified in this analysis.

TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12615000610538.

PMID:41528747 | DOI:10.1001/jamanetworkopen.2025.52787

JAMA Netw Open. 2026 Jan 2;9(1):e2553504. doi: 10.1001/jamanetworkopen.2025.53504.

ABSTRACT

IMPORTANCE: Black and Hispanic patients have lower survival rates for in-hospital cardiac arrest (IHCA) than White patients. Whether this is because do not attempt resuscitation (DNAR) orders for successfully resuscitated patients with IHCA are variable among different races and ethnicities remains unknown.

OBJECTIVE: To understand whether American Indian or Alaskan Native, Black, or Hispanic patients have different rates of early DNAR orders compared with White patients, and to examine whether survival differences by race and ethnicity persist among patients with early entry of DNAR orders.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the American Heart Association’s Get With the Guidelines – Resuscitation database, which includes IHCA data from more than 350 hospitals in the US from 2018 to 2013. Patients were aged at least 18 years, experienced an index IHCA, and were successfully resuscitated while on an admitted unit. Data were analyzed from September 26, 2024, through February 8, 2025.

EXPOSURE: IHCA.

MAIN OUTCOMES AND MEASURES: Main outcomes were associations of race and ethnicity with entry of early DNAR orders and, among patients early DNAR orders, the associations of race with survival to hospital discharge.

RESULTS: From 2018 to 2023, 93 843 patients (25 386 patients [27.1%] aged 60-69 years; 56 533 [60.2%] male) achieved ROSC after IHCA, including 2380 American Indian or Alaska Native patients (2.5%), 764 Asian patients (0.8%), 21 261 Black patients (22.7%), 6998 Hispanic patients (7.5%), and 56 989 White patients (60.7%). Overall, 25.3% and 37.4% of White patients had DNAR orders at 12 hours and 72 hours, respectively, compared with 21.3% and 33.4% of American Indian or Alaska Native patients, 21.4% and 32.7% of Black patients, and 22.2% and 33.2% of Hispanic patients. Compared with White patients, American Indian or Alaska Native, Black, and Hispanic patients were less likely to have DNAR orders entered within 12 hours (American Indian or Alaska Native: odds ratio [OR], 0.78 [95% CI, 0.67-0.91]; Black: OR, 0.74 [95% CI, 0.69-0.79]; Hispanic: OR, 0.90 [95% CI, 0.82-0.99]) or within 72 hours (American Indian or Alaska Native: OR. 0.86 [95% CI, 0.76, 0.98]; Black: OR, 0.73, [95% CI, 0.69-0.77]; Hispanic: OR, 0.89 [95% CI, 0.83, 0.97]). A total of 813 American Indian or Alaska Native patients (34.2%), 7168 Black patients (33.7%), and 2417 Hispanic patients (34.5%) with return of spontaneous circulation survived to discharge, compared with 22 226 White patients (39.0%). In adjusted analyses, among patients with an early DNAR order entered before 72 hours, there was no significant difference in survival to hospital discharge compared with White patients.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients successfully resuscitated from IHCA, American Indian or Alaska Native, Black, and Hispanic patients were less likely to have early DNAR orders than White patients. There were no differences in survival among patients with early DNAR orders placed.

PMID:41528746 | DOI:10.1001/jamanetworkopen.2025.53504

JAMA Netw Open. 2026 Jan 2;9(1):e2553687. doi: 10.1001/jamanetworkopen.2025.53687.

ABSTRACT

IMPORTANCE: Excess body weight, which is associated with poor survival after breast cancer (BC) diagnosis, is a heritable trait.

OBJECTIVE: To investigate whether genetic predisposition to excess body weight is associated with the risk of mortality among BC survivors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study is part of the Cancer Prevention Study-II Nutrition Cohort, a large study in which participants responded to a survey in 1992 and to biennial follow-up surveys starting in 1997. The cohort includes adults residing in 21 US states. Women diagnosed with a first primary nonmetastatic BC between 1992 and 2017 with genetic data were included in this study. Analyses were restricted to postmenopausal women at the time of cancer diagnosis who had genetically determined European ancestry. Data analysis was conducted from July 2023 to July 2025.

EXPOSURE: A polygenic score for body mass index (BMI-PGS), computed using summary statistics from 941 single nucleotide variants reported in a meta-analysis of genome-wide association studies that included approximately 700 000 individuals.

MAIN OUTCOMES AND MEASURES: Deaths through 2020 were identified via linkage with the National Death Index. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for the association between BMI-PGS and all-cause mortality.

RESULTS: This analysis included 4177 women diagnosed with BC. The median (IQR) age at diagnosis was 71.5 (66.3-76.7) years. BC survivors with a BMI-PGS in the top tertile were more likely to have a BMI of 30 or greater (345 [24.8%]) compared with survivors in the lowest tertile (172 [12.4%]). During a median (IQR) follow-up time of 14.5 (9.7-19.7) years, 2114 BC survivors (50.6%) died. Compared with BC survivors in the lowest tertile of the BMI-PGS, those in the highest tertile had a 15% increased risk of all-cause mortality (HR, 1.15, 95% CI, 1.04-1.28). BC survivors with BMI-PGS in the highest tertile needed to walk approximately 1.7 hours per week more to be at a similar risk level as BC survivors in the lowest tertile of the BMI-PGS, which corresponds to approximately an extra 15 minutes of walking each day of the week.

CONCLUSIONS AND RELEVANCE: In this cohort of nonmetastatic BC survivors, women who were genetically predisposed to having a higher BMI were at increased risk of all-cause mortality. Targeted lifestyle recommendations to mitigate their genetic predisposition should be considered to lower this risk.

PMID:41528745 | DOI:10.1001/jamanetworkopen.2025.53687

JAMA Netw Open. 2026 Jan 2;9(1):e2553704. doi: 10.1001/jamanetworkopen.2025.53704.

ABSTRACT

IMPORTANCE: Hospital closures pose persistent concerns about health care access, yet the extent to which closures are associated with cancer surgical care and patient outcomes remains unknown.

OBJECTIVE: To examine the association between undergoing colon or lung cancer surgery in hospitals that subsequently closed and postoperative and travel outcomes among Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used Medicare administrative data from 2008 to 2019. A national sample of hospital closures was identified using the Provider of Service files from the Centers for Medicare & Medicaid Services. Closed cancer surgical hospitals were those performing at least 1 colon or lung cancer surgery in the period from 2008 to 2019 and that also stopped inpatient care in 2008 to 2019. Participants were Medicare fee-for-service beneficiaries who underwent colon or lung cancer surgery from 2008 to 2019. Analyses were conducted separately by cancer type. Data were analyzed from December 2023 through February 2025.

EXPOSURE: Undergoing cancer surgery at hospitals that subsequently closed.

MAIN OUTCOMES AND MEASURES: The primary outcomes were postoperative outcomes, including 90-day mortality, 90-day complications, and length of stay. Secondary outcomes were travel measures, including distance to surgical hospital and distance to the nearest alternative surgical hospital. Logistic regression was used to analyze 90-day postoperative mortality and complications, and linear regression was used to analyze length of stay. Travel measures were analyzed descriptively.

RESULTS: The total sample was 558 708 participants, with 360 564 beneficiaries (64.5%) who underwent colon cancer surgery (median [IQR] age, 77 [71-83] years; 195 862 [54.3%] female) and 198 144 beneficiaries (35.5%) who underwent lung cancer surgery (median [IQR] age, 73 [69-78] years; 102 418 [51.7%] female) from 2008 to 2019. Of those, 6018 beneficiaries (1.7%) who underwent colon cancer surgery and 1938 beneficiaries (1.0%) who underwent lung cancer surgery underwent those surgical procedures at hospitals that subsequently closed. Beneficiaries treated at hospitals that subsequently closed were more often dually eligible (colon: 1047 [17.4%] closing vs 37228 [10.5%] nonclosing; lung: 234 [12.1%] closing vs 14426 [7.4%] nonclosing) and Black, Hispanic, or other race (ie, American Indian or Alaska Native, Asian, other, and unknown) (colon: 1450 [24.1%] closing vs 53640 [15.1%] nonclosing; lung: 388 [20.0%] closing vs 22048 [11.2%] nonclosing), with urgent admission (colon: 2559 [42.5%] closing vs 123830 [34.9%] nonclosing; lung: 228 [11.8%] closing vs 13394 [6.8%] nonclosing) than those treated at hospitals that did not close. Most beneficiaries bypassed their nearest hospital, but the majority treated at their nearest hospital that subsequently closed (colon, 1967 beneficiaries [79.0%]; lung, 465 beneficiaries [90.6%]) had an alternative surgical hospital within a 15-minute driving distance. Undergoing surgery at hospitals that subsequently closed was significantly associated with higher likelihood of 90-day mortality for colon cancer (adjusted odds ratio [aOR] 1.11; 95% CI, 1.01-1.22) and 90-day complications for both cancer types (colon aOR, 1.10; 95% CI, 1.01-1.21; lung aOR, 1.43, 95% CI, 1.17-1.76). The odds ratio for 90-day mortality after lung cancer surgery was not statistically significant, 1.26 (95% CI, 0.96-1.64). Lengths of stay were similar for both cancers.

CONCLUSIONS AND RELEVANCE: In this cohort study, undergoing colon and lung cancer surgery at hospitals that subsequently closed was associated with worse postoperative outcomes, but most beneficiaries treated at their nearest hospital had a nearby alternative hospital, suggesting that hospital closures may improve postoperative outcomes for cancer surgery, with minimal increase in travel burden, by directing patients to nearby, better-performing hospitals.

PMID:41528743 | DOI:10.1001/jamanetworkopen.2025.53704

Hum Reprod Update. 2026 Jan 13:dmaf030. doi: 10.1093/humupd/dmaf030. Online ahead of print.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) affects women globally, but its prevalence across World Health Organization (WHO) regions has not previously been reported.

OBJECTIVE AND RATIONALE: We aimed to synthesize evidence on the prevalence of PCOS by diagnostic criteria and by WHO geographic regions to inform the International Evidence-Based PCOS Guideline.

SEARCH METHODS: A systematic search of OVID MEDLINE, All EBM, PsycInfo, EMBASE, and Cumulative Index to Nursing and Allied Health Literature was conducted from 1990 to November 2024. Studies assessing PCOS prevalence in an unselected population were included. Non-primary studies or those with unclear diagnostic criteria were excluded. The primary outcome was PCOS prevalence among adult women. The secondary outcome was PCOS prevalence among women of all ages. Random effects meta-analysis using the DerSimonian and Laird method was applied for estimating the overall effect size. Two reviewers independently assessed risk-of-bias (RoB) and evidence certainty.

OUTCOMES: The search yielded 16 664 articles, of which 119 unique studies (in 137 articles) were eligible, and 92 (including 157 181 participants) were pooled in a meta-analysis. By diagnostic criteria, PCOS global prevalence among adult women only was 12.1% (95% CI: 9.8, 14.8; I2: 98.8%) using Rotterdam criteria, 7.9% (95% CI: 6.2, 9.9; I2: 96.2%) using the original National Institute of Health (NIH) criteria, 12.7% (95% CI: 8.2, 17.9; I2: 98.0%) using the Androgen Excess (AE)-PCOS criteria, and 7.8% (95% CI: 5.8, 10.0; I2: 99.4%) by self-report. By WHO regions, PCOS prevalence among adult women when using Rotterdam criteria was highest in the Eastern Mediterranean region (15.1%; 95% CI: 11.1, 19.7) and the South-East Asian region (14.3%; 95% CI: 5.8, 25.9), followed by the European region (11.7%; 95% CI: 5.1, 20.3), the region of the Americas (10.5%; 95% CI: 3.0, 21.7), and the Western Pacific region (9.1%; 95% CI: 6.2, 12.5), with no data from Africa. Subgroup analysis using Cochran’s Q test indicated a statistically significant difference in prevalence by WHO region (P = 0.022). Subgroup analyses including adolescents yielded a lower prevalence globally, with a global prevalence of 11.4% (95% CI: 9.5, 13.5) by Rotterdam criteria, 7.1% (95% CI: 5.7, 8.7) by NIH criteria, 11.2% (95% CI: 7.4, 15.5) by AE-PCOS criteria, and 7.6% (95% CI: 5.8, 9.6) on self-report. Of the 119 studies, 30 had low, 49 had moderate, and 40 had high RoB. Certainty of evidence ranged from very low to low.

WIDER IMPLICATIONS: This is the most comprehensive and contemporary review of PCOS prevalence and highlights past inconsistencies in diagnostic criteria and individual diagnostic features. Pooled PCOS prevalence was 12.1% by the Rotterdam criteria and was highest in the Eastern Mediterranean and the South-East Asian regions, with a potentially different health burden of PCOS across world regions. These findings directly inform International PCOS Guidelines, including updated guideline diagnostic criteria and refined individual features, emphasizing early, accurate diagnosis.

REGISTRATION NUMBER: PROSPERO CRD42022372029.

PMID:41528735 | DOI:10.1093/humupd/dmaf030

Drugs Aging. 2026 Jan 13. doi: 10.1007/s40266-025-01273-7. Online ahead of print.

ABSTRACT

BACKGROUND: The scientific literature, including systematic reviews and meta-analyses, has frequently described associations between aging, medication use, and frailty, without evaluation of their independent causation. The Bradford Hill Criteria, a framework consisting of nine principles for assessing epidemiological causation, is ideally suited to unconfound and assess the independent causal effect of aging versus medication use, in frailty progression.

METHODS: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, searched MEDLINE, EMBASE, and CENTRAL with no restrictions on date or study design. Studies were selected based on predefined inclusion criteria and assessed for quality using the Joanna Briggs Institute critical appraisal tool. Where appropriate, meta-analyses of collated data were performed in RStudio, including effect sizes accounting for minimum age and polypharmacy to reduce confounding bias. Causal relationships between aging, medication use, and frailty were then evaluated independently using the nine principles of the Bradford Hill Criteria.

RESULTS: Data from 105 moderate-to-high quality studies based on the Joanna Briggs Institute assessment were extracted, formatted, and compiled to allow evaluation via the Bradford Hill Criteria. Evidence supported a strong independent causal relationship between aging, medication use, and frailty progression across eight of the nine principles. Strength of association, consistency, and a clear biological gradient were observed, with frailty increasing alongside age and medication count, respectively. Temporality was addressed as aging and medication exposure often preceded frailty, while interventions reducing medication supported the experiment criterion. Biological plausibility, biological coherence, and analogy were reinforced by clear biological mechanism, scientific reasoning, and epidemiological patterns. However, specificity could not be fully met, as frailty is influenced by multiple factors beyond aging and medication use, making the relationship inherently non-specific.

CONCLUSIONS: An independent causal link between aging and frailty, as well as between medication use and frailty, is well supported by the framework of Bradford Hill Criteria. Given the limited availability of randomized controlled trials or interventional studies in older adults, these findings offer valuable insights where evidence has been lacking and serve as a strategic starting point for future investigations into factors driving frailty progression.

CLINICAL TRIAL REGISTRATION: PROSPERO Registration Number CRD42024614144.

PMID:41528721 | DOI:10.1007/s40266-025-01273-7

Phys Eng Sci Med. 2026 Jan 13. doi: 10.1007/s13246-025-01688-x. Online ahead of print.

ABSTRACT

Wrist pulse measurement offers significant insights into cardiovascular health. However, the application of various sensors, such as optical, pressure, image, and ultrasonic, is limited due to issues like bright environments, incompatibility with pressure adjustments, and system complexity. Recent studies suggest condenser microphones as promising alternatives, though the optimal type among various condenser microphones remains unclear. This study explores the application of three different condenser microphones using four regression-based machine learning models (Partial Least Square Regression, Ridge Regression, Principal Component Regression, and Nu-Support Vector Regression) for wrist pulse measurement based on pulse rate accuracy. One omnidirectional condenser microphone, previously used for wrist pulse measurement, and two commonly available unidirectional condenser microphones were evaluated. A mechanical system for pulse acquisition was developed, and data were collected from 27 healthy subjects using each microphone alternatingly. Extracted time-domain and statistical features were used as inputs to compare the predicted pulse rates with the ground truth pulse rate values. Results indicated that unidirectional condenser microphones were more accurate than the omnidirectional type. Among the unidirectional microphones, the one with a sensitivity range of – 50 to – 44 dB outperformed the microphone with a sensitivity range of – 40 to – 34 dB. The Nu-Support Vector Regression model exhibited the least errors, indicating superior predictive capabilities compared to the other models. In conclusion, this study provides valuable insights into selecting appropriate condenser microphones for wrist pulse measurement, offering a guiding framework for future research in this domain.

PMID:41528717 | DOI:10.1007/s13246-025-01688-x

J Behav Med. 2026 Jan 13. doi: 10.1007/s10865-025-00624-4. Online ahead of print.

ABSTRACT

Sleep health disparities are well documented, whereas racial differences in treatment response to sleep interventions, are not. This single arm sleep intervention study explored treatment-response differences in sleep behaviors, quality of life, well-being, depressive symptoms, and daytime sleepiness between White and Underrepresented racial groups, as well as racial differences in pre-treatment sleep-relevant characteristics. Middle-aged adults at risk for the metabolic syndrome with short sleep duration (N = 41; 49% Underrepresented racial group [n = 20], 51% White [n = 21]) participated in a virtually-delivered, 12-week personalized systematic sleep time extension informed by cognitive behavioral therapy for insomnia. Sleep behaviors were estimated using wrist actigraphy. Quality of life, emotional well-being, daytime sleepiness, chronotype preference, daytime sleepiness, depressive symptoms, quality of life, and well-being were assessed using validated surveys. Sleep environment, race, and socio-demographic characteristics were self-reported. Underrepresented participants had a greater increase in fragmentation indexes and a greater improvement in emotional well-being from pre to post-intervention compared to their White counterparts of medium and medium-to-large magnitude, respectively. Within each racial group, statistically and clinically significant improvements in sleep duration and daytime sleepiness were found. Within the Underrepresented group, the sleep regularity index increased and sleep onset times advanced significantly. These exploratory findings suggest that future studies with larger samples should investigate the modulating effects of chronotype on sleep intervention treatment response for Underrepresented racial groups and the upstream contextual and systemic factors impacting sleep.Trial registration numberTrial registration number ClincalTrials.gov NCT03596983.

PMID:41528656 | DOI:10.1007/s10865-025-00624-4

J Occup Rehabil. 2026 Jan 13. doi: 10.1007/s10926-025-10361-9. Online ahead of print.

ABSTRACT

PURPOSE: Firefighting is widely recognized as a physically demanding profession, in which working until the statutory retirement age is considered highly challenging. However, increasing societal pressure to extend working lives highlights the need to gain more insight into how sustainable employability (SE) can be supported in such occupations. This study aims to examine cross-sectional associations between overall and task-specific physical work demands and SE among Dutch career firefighters.

METHODS: Data from the SEmFire Cohort Study questionnaire for Dutch career firefighters (n = 1371) were used. SE was assessed using nine indicators across three domains: health (health status, work ability, need for recovery, prolonged fatigue), well-being (job satisfaction, motivation to work), and employability (employability, skill gap, job performance). Physical work demands-overall and task-specific-were used as independent variables. Multiple logistic regression models were applied, adjusting for personal, occupational, and health-related factors.

RESULTS: Dutch career firefighters reported high physical work demands and unfavorable outcomes across multiple SE indicators. Both overall and task-specific physical demands were cross-sectionally associated with adverse SE outcomes across all three domains. Statistically significant associations were observed in all three distinguished function groups-operational, hybrid, and non-operational-though patterns (i.e., which indicators and the strength of associations) varied between groups. The frequency of incident responses per month also influenced the strengths of these associations.

CONCLUSION: This study shows that physical work demands are associated with multiple indicators of SE among Dutch career firefighters. These findings provide an important first step toward identifying actionable areas to enhance SE among firefighters.

PMID:41528644 | DOI:10.1007/s10926-025-10361-9

Clin Rheumatol. 2026 Jan 13. doi: 10.1007/s10067-026-07929-y. Online ahead of print.

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation. Growing evidence suggests a link between insulin resistance (IR) and RA. However, the association of specific lipid-based IR indices, such as the Mffm/I index (Metabolic Score for Insulin Sensitivity), with RA prevalence remains underexplored. This study aimed to investigate the associations of the Mffm/I index and the Quantitative Insulin Sensitivity Check Index (QUICKI) with the prevalence of RA in a large, nationally representative population.

METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018. A total of 8,477 adult participants were included and categorized based on their RA status. The associations between Mffm/I, QUICKI (as both continuous variables and quartiles), and RA were evaluated using multivariable logistic regression models, adjusting for a comprehensive set of sociodemographic and clinical covariates. Results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses, interaction tests, and mediation analyses were conducted to explore the consistency of these associations and the potential mediating role of obesity.

RESULTS: Of the 8,477 participants, 549 (6.5%) reported a diagnosis of RA. After full adjustment for potential confounders, both the Mffm/I index and QUICKI demonstrated a significant inverse association with RA. In the fully adjusted model (Model 3), participants in the highest quartile (Q4) of Mffm/I had a 40% lower odds of RA (OR = 0.60, 95% CI: 0.45-0.79) compared to the lowest quartile (Q1). Similarly, the highest quartile of QUICKI was associated with a 28% lower odds of RA (OR = 0.72, 95% CI: 0.55-0.94). These negative associations were consistent across most predefined subgroups. Mediation analysis revealed that obesity significantly mediated the relationships, accounting for 43.87% of the total effect for Mffm/I and 51.04% for QUICKI.

CONCLUSION: This study establishes a stable and robust inverse association between both the Mffm/I index and QUICKI and the prevalence of rheumatoid arthritis in the U.S. adult population. These findings highlight the potential role of insulin sensitivity in the pathophysiology of RA and suggest that obesity is a critical mediator in this relationship. These easily accessible indices may serve as valuable tools for risk assessment in clinical practice. Key Points • High insulin sensitivity is strongly associated with lower rheumatoid arthritis prevalence. • The novel lipid-based Mffm/I index is a robust indicator of RA prevalence. • Obesity mediates over 40% of the link between insulin resistance and RA. • Accessible insulin sensitivity indices may aid in clinical RA risk assessment.

PMID:41528638 | DOI:10.1007/s10067-026-07929-y