Nevin Manimala

Subst Use Addctn J. 2025 Oct;46(4):880-887. doi: 10.1177/29767342251331712. Epub 2025 Apr 28.

ABSTRACT

OBJECTIVES: To estimate the effect of the passage of state laws targeting patient brokering on opioid-related outcomes.

BACKGROUND: In response to growing awareness of unethical substance use disorder (SUD) treatment practices, several states in the United States have passed laws targeting patient brokering and deceptive marketing. Patient brokering and deceptive marketing laws are intended to reduce the chances individuals with SUD interact with bad actors or suffer from adverse outcomes related to inappropriate SUD treatment, but the effectiveness of these laws is unknown.

METHODS: Matched event study analysis comparing early population-level outcomes in 6 states that passed laws targeting patient brokering between 2018 and 2019 and 24 comparison states with similar census region and presence of recovery residence regulations, anti-kickback laws, state SUD task forces. Outcomes, analyzed through 2019, included monthly rates of opioid-related mortality and quarterly rates of opioid-related emergency department visits and hospitalizations per 100,000 residents, and state-year prevalence of unusual patterns of claims for SUD-related services.

RESULTS: In 2018, there was a mean of 326.9 (SD = 72.0) opioid-related hospitalizations/100k state residents, 234.6 (SD = 37.7) opioid-related ED visits/100k state residents, and 122.9 (SD = 73.6) opioid-related deaths/100k state residents in the states in our treatment group. We did not observe evidence that passage of state laws targeting patient brokering or deceptive marketing was associated with changes in any of our outcomes.

CONCLUSIONS: The passage of state laws targeting patient brokering is not associated with significant changes in opioid-related outcomes. Additional resources may be needed to accompany implementation and enforcement efforts before desired policy effects are realized.

PMID:40913376 | DOI:10.1177/29767342251331712

Subst Use Addctn J. 2025 Oct;46(4):901-912. doi: 10.1177/29767342251336035. Epub 2025 Apr 28.

ABSTRACT

BACKGROUND: To address the opioid use disorder (OUD) public health crisis, the ADvancing Pharmacological Treatments for OUD (ADaPT-OUD) external facilitation randomized trial was conducted in 8 intervention and 27 matched control low-performing Veterans Health Administration (VHA) facilities to increase the prescribing of medications for OUD (MOUD). Facilities were considered low-performers if they were in the bottom quartile of the facility ratio of Veterans with OUD who received MOUD. The objective of this analysis was to evaluate the healthcare expenditures of Veterans with OUD who received care in ADaPT-OUD intervention facilities compared to those receiving care in matched control facilities.

METHODS: Difference-in-differences (DID) design was used to compare the overall, outpatient, and inpatient expenditures (extracted from the VHA data warehouse) of Veterans diagnosed with OUD or receiving MOUD between the 2 groups 12 months before and after the intervention.

RESULTS: A total of 7348 Veterans with a diagnosis of OUD or prescribed MOUD on at least 1 encounter 12 months after ADaPT-OUD intervention at all sites (92.39% male and 83.26% white) were included for analysis. ADaPT-OUD intervention did not have a substantial impact on overall healthcare costs. However, we reported 4% fewer total encounters in the intervention sites (DID, 95% confidence intervals [CI]: 0.96 [0.92-1.00]) compared to the control sites, driven by a decline in non-VA services. Notably, the outpatient psychiatric-related costs were $391 (95% CI: $49-$733) higher per Veteran within the year after the intervention sites received external facilitation compared to control sites.

CONCLUSIONS: Veterans at intervention sites with an OUD history had higher outpatient psychiatric-related costs, which could be explained by increased access to optimal mental health services at VHA. Improving access to OUD treatment at VA may lead to more coordinated and comprehensive treatment of both OUD and other associated mental health and physical comorbidities.

PMID:40913373 | DOI:10.1177/29767342251336035

Eur J Neurol. 2025 Sep;32(9):e70355. doi: 10.1111/ene.70355.

ABSTRACT

BACKGROUND: No standardized strategy for integrating κ-free light chain (κ-FLC) index into routine cerebrospinal fluid (CSF) diagnostics has yet been established.

OBJECTIVE: To determine agreement between κ-FLC index and CSF-restricted oligoclonal bands (OCB), and to identify κ-FLC index range where second-line OCB testing is needed.

METHODS: A retrospective analysis was conducted in patients who had κ-FLC measurement between December 2023 and December 2024 at the Medical University of Innsbruck. κ-FLC in CSF and serum was determined by nephelometry; OCB by isoelectric focusing and immunoblotting. The threshold for positivity was defined as ≥ 3 CSF-restricted bands for OCB and ≥ 6.1 for κ-FLC index.

RESULTS: In 632 included samples, κ-FLC index ranged from 0.5 to 971. Among 213 samples with κ-FLC index ≥ 3.5, 180 (85%) samples had a positive κ-FLC index and 148 (69%) positive OCB. Thirty-four (16%) samples showed discordant results. One sample was OCB positive/κ-FLC index negative, showing markedly elevated serum κ-FLC values. Thirty-three samples were OCB negative/κ-FLC index positive; of those, 4 samples had isolated intrathecal immunoglobulin M or A synthesis, and the remaining 29 discordant samples showed a median κ-FLC index of 8.7 (75th percentile: 10.3). The predictive value for OCB positivity exceeded 95% in the case of κ-FLC index > 20.

CONCLUSION: κ-FLC index shows high agreement with OCB. Discordant results were largely confined to κ-FLC index between 3.5 and 20 (“gray zone”). A reflex approach, that is, initial screening with κ-FLC index and in case of values within the “gray zone” performing OCB, seems reasonable.

PMID:40913362 | DOI:10.1111/ene.70355

J Clin Periodontol. 2025 Sep 5. doi: 10.1111/jcpe.70032. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease driven by immune dysfunction and microbial imbalance. This study aims to identify circulating druggable proteins causally linked to the disease.

MATERIALS AND METHODS: We integrated proteomics data from deCODE genetics with periodontitis genome-wide association studies (GWAS) from the Million Veteran Program to identify proteins associated with periodontitis. Findings were replicated using GWAS data from the Gene-Lifestyle Interactions in Dental Endpoints consortium. Causal associations were validated using genetic and statistical methods, and the identified proteins were assessed for biological relevance and druggability.

RESULTS: Among the 2088 evaluated proteins, three showed robust evidence of causal association with periodontitis: FGF2 (fibroblast growth factor 2) (odds ratio [OR]: 1.06, 95% confidence interval [CI] 1.032-1.082), AZGP1 (zinc-alpha-2-glycoprotein) (OR: 1.12, 95% CI 1.058-1.189) and BTC (betacellulin) (OR: 0.86, 95% CI 0.789-0.942). Replication analysis confirmed associations for 18 proteins, with 16 showing high colocalisation. Further evaluation of drug target databases revealed indirect links between the identified proteins and approved therapies for inflammatory conditions, suggesting potential therapeutic relevance.

CONCLUSION: This study identifies three circulating proteins-FGF2, AZGP1 and BTC-as causally associated with periodontitis, highlighting their potential as therapeutic targets. These results provide a foundation for future research into targeted therapies for periodontitis.

PMID:40913361 | DOI:10.1111/jcpe.70032

Ophthalmic Physiol Opt. 2025 Sep 5. doi: 10.1111/opo.70015. Online ahead of print.

ABSTRACT

PURPOSE: To gain a better understanding of corneal Stress-Strain Index (SSI) maps in healthy eyes and to determine their changes with age.

METHOD: The eyes of 72 participants (age 43.1 ± 20.9 years, 69.5% female) were included in the analysis, considering the left and right eyes separately. Corneal biomechanics were assessed using a combination of the Pentacam and Corvis instruments, whose data enabled the production of the SSI maps. The corneas were divided into nine zones to facilitate zone-specific analysis of biomechanical behaviour. Regression analyses were conducted to evaluate the relationship between age and SSI values in each corneal zone.

RESULTS: The mean overall SSI value of the cornea for all participants was 1.075. Considering different age groups, significant differences in SSI were seen between the young and older groups in the overall map from 0.938 ± 0.067 in 20-50-year-olds to 1.143 ± 0.064 in 50-80-year-olds (ANOVA, p < 0.001). The same effect was seen for each zone separately (ANOVA, p < 0.001). The corneal central apex and peripheral zones showed higher mean SSI values (1.153 ± 0.079) and hence, higher corneal stiffness compared with paracentral zones (0.890 ± 0.057).

CONCLUSION: This paper showcases a series of maps depicting corneal elasticity and explores the differences in corneal stiffening with age across various regions of healthy corneas. The results reveal that stiffening tends to accelerate in areas that are already stiffer and decelerate in weaker regions. This deeper insight into ocular physiology could enhance clinical care by enabling more personalised treatments based on the patient’s age and the specific corneal regions being addressed.

PMID:40913331 | DOI:10.1111/opo.70015

Ophthalmic Physiol Opt. 2025 Sep 5. doi: 10.1111/opo.70013. Online ahead of print.

ABSTRACT

PURPOSE: Few studies have comprehensively investigated the effect of low dose atropine on the binocular vision system beyond accommodative amplitude. This study examined the effect of 0.05% atropine eye drops on a range of accommodation and vergence parameters across a 10-day period.

METHODS: Twenty myopic, adult participants (mean age [SD] 22.3 [1.0] years, mean spherical equivalent refraction [SD] -1.9 [1.0] D) were randomised to receive either atropine (0.05% atropine sulphate, n = 10) or control (0.9% sodium chloride, n = 10) eye drops for nightly use for nine consecutive nights. Accommodative posture, monocular and binocular accommodative amplitude (AA), positive and negative relative accommodation (PRA/NRA), binocular accommodative facility (BAF), distance and near heterophoria, positive and negative fusional vergences (PFV/NFV), near point of convergence (NPC) and gradient accommodative convergence to accommodation ratios (AC/A) were measured at baseline, day-3 and day-10.

RESULTS: By day-10, accommodative lag had increased significantly and AA, PRA and BAF had all decreased significantly in the atropine group, while there were no significant changes in any of the control group measurements. Near heterophoria shifted significantly towards esophoria and the NFV break and recovery points were decreased significantly in the atropine group by day-10. Additionally, NPC reduced by a clinically significant amount (that bordered on statistical significance), with no changes found in the control group. There was no significant change in distance heterophoria, AC/A, NRA or PFV (all p > 0.05) at day-3 or day-10 in either treatment group.

CONCLUSIONS: Atropine (0.05%) use disrupted accommodation significantly over 10 days and increased convergence at near. While near heterophoria shifted towards esophoria, participants’ ability to counteract this was also diminished by a reduction in NFV. This suggests that the near heterophoria and fusional reserves of children using 0.05% atropine for myopia control should be monitored closely.

PMID:40913324 | DOI:10.1111/opo.70013

HGG Adv. 2025 Sep 5:100501. doi: 10.1016/j.xhgg.2025.100501. Online ahead of print.

ABSTRACT

Pleiotropy, the phenomenon where a genetic region confers risk to multiple traits, is widely observed, even among seemingly unrelated traits. Knowledge of pleiotropy can improve understanding of biological mechanisms of diseases/traits, and can potentially guide identification of molecular targets or help predict side-effects in drug development. However, statistical approaches for identifying pleiotropy genome-wide are limited, particularly for two correlated traits or case-control traits with unknown sample overlap or for disease traits from family studies. We proposed PLACO+, an improved version of our pleiotropic analysis under composite null hypothesis method based on GWAS summary statistics from two traits. PLACO+ uses an inflated variance model to allow for fractions of variants to be associated with none or only one trait under the null. It is genome-wide scalable, where analytical p-value is computed as a weighted sum of extreme tail probabilities of bivariate normal product distribution. Simulations for both population-based and family-based designs demonstrate well-calibrated type I errors at stringent levels and substantially improved power of PLACO+ over conventional approaches. We illustrate PLACO+ on inflammatory bowel disease subtypes with shared controls and on correlated lipid traits with unknown sample overlap. In particular, PLACO+ revealed pleiotropic regions between triglyceride and high-density lipoprotein levels that conventional approaches missed and all of which were replicated in larger GWAS of these lipid traits. This further demonstrates the utility of PLACO+ in discovering genetic associations of traits with modest sample sizes by leveraging information from another correlated trait.

PMID:40913314 | DOI:10.1016/j.xhgg.2025.100501

Am J Health Promot. 2025 Sep 5:8901171251375977. doi: 10.1177/08901171251375977. Online ahead of print.

ABSTRACT

ObjectiveTo characterize individual- and structural-level stigma associated with government (ie, SNAP, WIC) and emergency food program (ie, food banks, pantries, cupboards, soup kitchens) utilization in the US.Data Source5 databases (PubMed, PsychINFO, Web of Science, CINAHL, Sociological Abstracts) were searched in June 2024.Study Inclusion and Exclusion CriteriaIncluded peer-reviewed articles (January 2004 – June 2024), in the US, in English, original research or systematic reviews, and report on data closely related to general food insecurity, government and emergency food program participation, and stigma manifestations among adults.Data ExtractionData on study characteristics and stigma were extracted using a structured template.Data SynthesisDescriptive statistics and thematic analysis were used.ResultsOur search yielded 99 articles. A majority studied individual-level stigma (57.4%) and used qualitative designs (62.6%). Among the 9 identified populations, food insecure adults were the most frequently studied (25.2%). Anticipated stigma (29.8%) was the most commonly reported stigma manifestation, deterring program participation.ConclusionThis review underscores the significance of addressing food insecurity-related stigma to enhance the effectiveness of food assistance programs. Given the extensive evidence of the impact of stigma on program participation, policymakers and program administrators should design, implement and test strategies to address stigma. Future research should explore intersectional stigma, develop a food insecurity-related stigma measure, and evaluate stigma-reduction interventions longitudinally and across program settings.

PMID:40913286 | DOI:10.1177/08901171251375977

J Am Heart Assoc. 2025 Sep 5:e039381. doi: 10.1161/JAHA.123.039381. Online ahead of print.

ABSTRACT

BACKGROUND: Traditional cardiovascular risk assessment entails investigator-defined exposure levels and individual risk markers in multivariable analysis. We sought to determine whether an alternative unbiased learning analysis might provide further insights into vascular risk.

METHODS: We conducted an unsupervised learning (k-means cluster) analysis in the Women’s Health Study (N=26 443) using baseline levels of triglycerides, high-sensitivity C-reactive protein, and low-density lipoprotein cholesterol to form novel exposures. We then evaluated cluster-based risk of incident coronary, cerebrovascular, and limb events using the Kaplan-Meier method and multivariable Cox models, followed by comparison with established clinical biomarker thresholds. Finally, we illustrated clinical applicability to a nonvascular outcome (type 2 diabetes).

RESULTS: Four clusters emerged and were named according to aggregate biomarker profiles: Cluster 1 (“healthy,” n=12 101), cluster 2 (“hypercholesterolemic,” n=7424), cluster 3 (“inflammatory,” n=5056), and cluster 4 (“triglyceride-rich,” n=1862). Triglyceride-rich cluster identity conferred the highest risk of future cardiovascular events (adjusted hazard ratio [HR_adj], 2.24 [95% CI, 1.93-2.60]) compared with those in the healthy cluster (reference group). Risk was intermediate in the hypercholesterolemic (predominantly elevated low-density lipoprotein cholesterol) and inflammatory (predominantly elevated high-sensitivity C-reactive protein) clusters (HR_adj, 1.44 [95% CI, 1.28-1.61]; and 1.54 [95% CI, 1.35-1.75], respectively). Clustering yielded stronger total cardiovascular disease risk associations than traditionally defined mixed dyslipidemia with modest improvement in reclassification statistics. Cluster identities also predicted incident type 2 diabetes, with the greatest risk among the triglyceride-rich cluster (HR_adj, 3.78 [95% CI, 3.29-4.35]).

CONCLUSIONS: Unsupervised learning analyses demonstrated associations that may be useful when refining cardiovascular risk and may inform atherosclerosis development in healthy individuals better than traditional classification methods.

REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT00000479.

PMID:40913283 | DOI:10.1161/JAHA.123.039381

J Am Heart Assoc. 2025 Sep 5:e040058. doi: 10.1161/JAHA.124.040058. Online ahead of print.

ABSTRACT

BACKGROUND: Supervised treadmill exercise improves walking performance in people with lower extremity peripheral artery disease, but benefits are not immediate. This study identified the time course of attaining meaningful improvement in 6-minute walk distance and patient-reported outcome measures during a 6-month supervised exercise intervention in people with peripheral artery disease.

METHODS: Participants with peripheral artery disease were randomized to supervised treadmill exercise 3 time weekly or a nonexercise control group for 6 months. Six-minute walk distance (large clinically important difference: 20 meters) and the Walking Impairment Questionnaire distance score (0-100 scale, 100 is best, clinically important difference: 5 points) were measured at the 6-week, 12-week, and 26-week follow-up using a mixed-effects model for repeated measures.

RESULTS: Of 210 randomized participants (mean age, 67.0±8.6 years, 82 [39%] women, 141 [66%] Black), 200 (95%) completed at least 1 follow-up visit. Compared with controls, supervised exercise significantly improved 6-minute walk distance by 13.0 m (P=0.049) at the 6-week, 31.8 m (P<0.001) at the 12-week, and 33.9 m (P<0.001) at the 26-week follow-up. Compared with controls, supervised exercise increased the Walking Impairment Questionnaire distance score by +2.63 (P=0.37) at the 6-week, +6.59 (P=0.049) at the 12-week, and +2.37 (P=0.49) at the 26-week follow-up.

CONCLUSIONS: In people with peripheral artery disease, >6 weeks of supervised treadmill exercise was necessary to attain a large meaningful gain in 6-minute walk, and large meaningful gains were measurable by week 12 of supervised exercise. Meaningful improvement in participant reported walking ability was first observed at the 12-week follow-up, but this statistically significant benefit was gone by the 26-week follow-up.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01408901.

PMID:40913279 | DOI:10.1161/JAHA.124.040058