Nevin Manimala

Curr Eye Res. 2025 Oct 27:1-8. doi: 10.1080/02713683.2025.2577767. Online ahead of print.

ABSTRACT

PURPOSE: Use of illicit substances such as cocaine is associated with alteration in catecholamine-mediated neurotransmission throughout the CNS, including the eye. One of the most accessible physiologic parameters associated with neuromodulatory features of substance abuse is the pupillary light reflex (PLR). In this study, we examined a domain of the PLR characterized by melanopsin-driven intrinsically photosensitive retinal ganglion cells (ipRGCs) to assess the impact of substance abuse on ipRGC function.

METHODS: An exploratory PLR examination on ten subjects with a documented history of substance use (HSU) without preexisting ocular disease was conducted with a comparator control cohort. Cases included assessment of cognitive function, depression, insomnia, and retinal nerve fiber thickness. IpRGC functionality was demonstrated by the PLR using a pedagogical-based methodology centered on response parameters with the introduction of a complementary analysis employing pseudo-one-phase modeling. Discriminant analysis employing the area under the receiver operating characteristic curve (AUC of ROC) categorized normal vs. abnormal ipRGC response.

RESULTS: There was no statistical association between ipRGC function and insomnia; however, insomnia was more prevalent among those with ipRGC abnormality. Indication of clinical depression was seen in 70% of study participants and was unrelated to ipRGC function. Pseudo-one-phase modeling demonstrated a significantly higher plateau in the HSU group as well as a slower initial rate of pupil recovery consistent with abnormal PIPR dynamics and complementary to AUC metrics. Discriminant analysis identified that 60% of HSU demonstrated ipRGC abnormality.

CONCLUSION: Abnormal ipRGC functionality was demonstrated among those with HSU in this small exploratory study utilizing both AUC-ROC analysis as well as assessment of PLR waveform characteristics using features of a pseudo-first-order model.

PMID:41143850 | DOI:10.1080/02713683.2025.2577767

JAMA Netw Open. 2025 Oct 1;8(10):e2539451. doi: 10.1001/jamanetworkopen.2025.39451.

ABSTRACT

IMPORTANCE: The Defense Health Agency Procedural Instruction (DHA-PI) 6200.02, introduced in May 2019, aimed to improve contraception access and knowledge among eligible beneficiaries. However, the policy’s association with contraception prescribing and dispensing practices has not been fully evaluated.

OBJECTIVE: To evaluate changes in contraceptive prescribing and dispensing practices associated with DHA-PI 6200.02, focusing on extended day supply of long-acting reversible contraception (LARC), short-acting reversible contraception (SARC), and permanent contraception.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted utilizing interrupted time-series analysis to examine changes in contraception care practices before and after policy implementation. The study period was between January 1, 2016, and September 30, 2022. Participants were active-duty servicewomen (ADSW) aged 18 to 55 years, with an assigned sex of female in medical records who were enrolled in TRICARE.

EXPOSURE: The implementation of the DHA-PI 6200.02 policy in May 2019.

MAIN OUTCOMES AND MEASURES: The primary outcomes included rates of extended contraceptive supply and utilization of LARC, SARC, and permanent contraception. Five performance measures were employed to assess the associations between DHA-PI 6200.02 and changes in contraceptive supply. Segmented regression models were unadjusted and used to estimate level and trend changes in monthly MOPs.

RESULTS: Among 429 194 ADSWs (mean [SD] age 24.5 [7.0] years; 148 104 [34.5%] Army, 101 299 [32.6%] Navy, 115 288 [26.86%] Air Force, and 35 352 [8.24%] Marine Corps), the proportion of SARC users receiving extended supply increased from 1.1% prepolicy to 5.3% postpolicy. Extended SARC use increased from 16.3% (95% CI, 16.0%-16.7%) at baseline to 19.7% (95% CI, 17.9%-21.6%) at the end of follow-up, and dispensed extended SARC rose from 8.2% (95% CI, 7.9%-8.5%) to 9.3% (95% CI, 7.4%-11.1%), both reflecting significant post-policy upward trends. The overall proportion of ADSW with any extended contraceptive supply showed no meaningful change and declined significantly in trend. Prescriber provision of extended supply rose modestly without sustained trend change, and among contraceptive users extended supply increased but without significant policy-related effects.

CONCLUSIONS AND RELEVANCE: In this cohort study of ADSWs, DHA-PI 6200.02 was associated with increased access to extended day supply for SARC but no corresponding increases were observed in overall extended contraceptive supply across all methods (SARC, LARC placement, and permanent contraception). These findings underscore challenges in policy uptake and highlight the need for enhanced efforts to ensure comprehensive implementation of DHA-PI 6200.02.

PMID:41143794 | DOI:10.1001/jamanetworkopen.2025.39451

AIDS. 2025 Oct 27. doi: 10.1097/QAD.0000000000004380. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy has demonstrated safety and efficacy in a variety of malignancies, including cancers affecting patients with human immunodeficiency virus (PWH). However, there is limited data directly comparing efficacy of ICI use between cancer patients with versus without HIV.

METHODS: Real-world retrospective data were used to compare clinical outcomes between 24 PWH and cancer 24 matched cancer patients without HIV, all treated with ICI therapy.

RESULTS: Adverse event rates did not differ by HIV status. Overall response (complete or partial response) to ICI therapy was observed in 29% of PWH compared to 38% of people without HIV (PWoH), but this difference was not statistically significant. The overall survival at end of study follow-up by HIV status was similar between both groups (63% in PWH and 67% in PWoH).

CONCLUSIONS: These findings suggest that HIV status alone should not preclude use of ICI therapy to improve prognosis among PWH and cancer.

PMID:41143744 | DOI:10.1097/QAD.0000000000004380

Health Technol Assess. 2025 Oct;29(51):1-28. doi: 10.3310/JHGD7339.

ABSTRACT

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Formal psychological therapies are not routinely part of United Kingdom standard motor neuron disease care due to a lack of evidence-based guidance resulting from a paucity of clinical trials. We aimed to evaluate the clinical and cost-effectiveness of Acceptance and Commitment Therapy plus usual care compared to usual care alone for improving psychological health in people living with motor neuron disease.

METHODS: We conducted qualitative interviews with 15 people living with motor neuron disease, 10 caregivers and 12 healthcare professionals. Findings were used to develop an Acceptance and Commitment Therapy intervention specifically for people living with motor neuron disease. Next, we examined its acceptability and feasibility in an uncontrolled feasibility study with 29 people living with motor neuron disease. Findings from qualitative interviews with 14 people living with motor neuron disease and 11 therapists were used to revise the intervention. Finally, we conducted a multicentre, parallel, two-arm randomised controlled trial in 16 United Kingdom motor neuron disease care centres/clinics. Eligible participants were aged ≥ 18 years with motor neuron disease. Participants were randomly assigned (1 : 1) to receive up to eight sessions of Acceptance and Commitment Therapy plus usual care or usual care alone and followed up at 6 and 9 months post randomisation by blinded outcome assessors. The primary outcome was total score on the McGill Quality of Life Questionnaire-Revised at 6 months. Secondary outcomes included health status using the EuroQol-5 Dimensions, five-level version. Primary analyses were by intention to treat.

RESULTS: Acceptance and Commitment Therapy was acceptable to people living with motor neuron disease, and it was feasible to recruit participants, hence trial progression criteria were met. From September 2019 to August 2022, 191 participants were recruited: 97 were allocated to Acceptance and Commitment Therapy plus usual care and 94 to usual care alone. Mean age was 61.9 years (standard deviation 11.4), 58% were male and 95% were White/White British. Acceptance and Commitment Therapy plus usual care was superior to usual care alone on the McGill Quality of Life Questionnaire-Revised at 6 months [adjusted mean difference 0.66 (95% confidence interval 0.22 to 1.10); Cohen’s d = 0.46 (95% confidence interval 0.16 to 0.77); p = 0.003] and 9 months [adjusted mean difference 0.76 (95% confidence interval 0.30 to 1.22); Cohen’s d = 0.53 (95% confidence interval 0.21 to 0.85); p = 0.001]. Mean differences in total costs and quality-adjusted life-years at 9 months between Acceptance and Commitment Therapy plus usual care versus usual care alone were not statistically significant [costs: £1019 (95% confidence interval -£34 to £2074); quality-adjusted life-years: 0.019 (95% confidence interval -0.07 to 0.05)]. The incremental cost-effectiveness ratio was £88,507/quality-adjusted life-year: this decreased to £13,817/quality-adjusted life-year in those with medium disease-related deterioration in subgroup analyses.

CONCLUSION: Acceptance and Commitment Therapy plus usual care is clinically effective at maintaining or improving psychological health, as measured by the McGill Quality of Life Questionnaire-Revised, in people living with motor neuron disease compared to usual care alone. It was not cost-effective overall when calculated using a standard health status measure (EuroQol-5 Dimensions, five-level version). However, it was cost-effective in a subgroup of people experiencing a medium rate of disease-related deterioration.

LIMITATIONS: Participants from ethnic minorities were under-represented, despite recruiting from sites with diverse communities. Between-group differences in outcomes may have been partly attributable to expectancy or non-specific therapeutic effects due to the lack of an active control. Cost-effectiveness analyses may have been underpowered to detect significant between-group differences.

FUTURE WORK: Studies should examine the effectiveness of Acceptance and Commitment Therapy in diverse populations, compared to an active control, using a more appropriate measure to assess cost-effectiveness, and in those with different rates of disease-related deterioration.

FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/81/01.

PMID:41143590 | DOI:10.3310/JHGD7339

Ann Behav Med. 2025 Jan 4;59(1):kaaf082. doi: 10.1093/abm/kaaf082.

ABSTRACT

BACKGROUND: While intergenerational caregiving is increasingly prevalent among older individuals, longitudinal evidence on its associations with multidimensional health outcomes remains limited.

PURPOSE: This study examined the associations between childcare engagement in older adults and various health and behavioral outcomes at follow-up.

METHODS: We analyzed data from a cohort of >12 000 (range: 12 124-12 896) community-dwelling adults aged 70+ years, categorizing childcare engagement as never, <weekly, and ≥weekly. Using an outcome-wide approach, we assessed 42 outcomes across physical, cognitive/major health events, psychological, social, and behavioral domains. Follow-up assessments occurred at ∼2 years for most outcomes, with extended follow-up (median 6-9 years) for time-to-event outcomes. We performed gender-disaggregated regressions, adjusting for multiple covariates.

RESULTS: Participants were aged 70-95 years (mean: 75.2 ± 4.3) at baseline, and 54.5% were women. Childcare engagement was more common among women (46% vs. 40%). Key findings included: (1) social domain: both genders showed increased social contacts and community participation, with women additionally demonstrating reduced social isolation; (2) mortality: lower mortality was observed in men with a dose-response pattern, while only <weekly childminding was associated with lower mortality in women; (3) physical domain: men showed increased moderate-to-vigorous physical activity while women had higher pain reports and slower gait speed; and (4) null associations: most psychological outcomes, as well as certain physical and health events, showed no significant relationships.

CONCLUSION: Childcare engagement during older adulthood was linked to not only selected health outcomes, including notable social benefits and lower mortality, but also some physical trade-offs in women. These findings support considering intergenerational engagement in healthy ageing initiatives.

PMID:41143543 | DOI:10.1093/abm/kaaf082

J Chem Phys. 2025 Oct 28;163(16):164509. doi: 10.1063/5.0292952.

ABSTRACT

It is experimentally well-established that non-equilibrium long-range correlations of concentration fluctuations appear in free diffusion of a solute in a solvent, but it remains unknown how such correlations are established dynamically. We address this problem in a model of Donev, Fai, and Vanden-Eijnden (DFV), obtained from the high-Schmidt limit of the Landau-Lifshitz fluctuating hydrodynamic equations for a binary mixture. We consider an initial planar interface of the mean concentration field in an infinite space domain, idealizing prior experiments. Using methods borrowed from turbulence theory, we show both analytically and numerically that a quasi-steady regime with self-similar time decay of concentration correlations appears at long time. In addition to the expected “giant concentration fluctuations” with correlations ∝r for r ≲ L(t) = (Dt)1/2, with diffusivity D, a new regime with spatial decay ∝1/r appears for r ≳ L(t). The quasi-steady regime arises from an initial stage of transient growth ∝t, confirming the prediction of DFV for r ≳ L(t) and discovering an analogous result for r ≲ L(t). Our results give new insight into the emergence of non-equilibrium long-range correlations and provide novel predictions that may be investigated experimentally.

PMID:41143499 | DOI:10.1063/5.0292952

Physiother Theory Pract. 2025 Oct 27:1-12. doi: 10.1080/09593985.2025.2575073. Online ahead of print.

ABSTRACT

BACKGROUND: The estrogen reduction caused by endocrine therapy can lead to symptoms associated with pelvic floor dysfunction in patients with breast cancer. Identifying medication-related symptoms can help prevent or mitigate adverse effects.

PURPOSE: The objective of this study was to compare pelvic floor muscle function among women treated with tamoxifen, aromatase inhibitors, and cancer-free controls.

METHODS: Cross-sectional observational study comparing three groups of women: tamoxifen users, aromatase inhibitor users, and healthy controls. Pelvic floor muscle function was assessed through vaginal inspection and palpation. Symptoms of dysfunction and vaginal complaints were evaluated through the Pelvic Floor Bother Questionnaire and Incontinence Questionnaire Vaginal Symptoms Module. Descriptive statistics included frequencies and medians. Group comparisons used Kruskal-Wallis and Mann-Whitney U tests. Associations were assessed via odds ratios, Chi-square, Phi coefficient, and Spearman’s correlation. Multiple correspondence analysis, multiple linear regression, and binary logistic regression were also performed.

RESULTS: Ninety-three women were included – 31 in each group. A significantly higher prevalence of descended perineum was observed in the aromatase inhibitors group compared to the tamoxifen and control groups (12.9% vs 0% vs 0% respectively, p = .034). The prevalence of pelvic organ prolapse was higher in the groups on endocrine therapy (IA 19.4%, TAM 16.1%, control 0%, p = .037). The remaining pelvic floor muscle functions and dysfunctions were similar between the groups, as was the associated bother.

CONCLUSION: Women treated with endocrine therapy showed a higher prevalence of pelvic organ prolapse, with a descended perineum observed in the aromatase inhibitor group.

PMID:41143489 | DOI:10.1080/09593985.2025.2575073

Platelets. 2025 Dec;36(1):2572982. doi: 10.1080/09537104.2025.2572982. Epub 2025 Oct 27.

ABSTRACT

Platelets are increasingly recognized as key players not only in hemostasis, but also in immunity and inflammation. However, the mechanisms and markers underlying their activation remain incompletely understood. This study aimed to decipher how platelets respond to different stimuli and to identify specific molecular signatures using computational approaches. Platelets from 10 healthy donors were stimulated under seven conditions, including TRAP (PAR-1), AYPGKF (PAR-4), ADP, collagen, sCD40L, fibrinogen, and a control. A total of 47 markers-encompassing membrane proteins, soluble mediators, and intracellular signals-were analyzed. Statistical and machine learning methods, including hierarchical clustering and random forest algorithms, were used to classify and interpret the data. Distinct activation profiles emerged for each agonist. A reduced panel of six markers (AKT, CD40L, CD62P, PKC, RANTES, and TSLP) enabled identification of the stimulus with 86.8% accuracy. Machine learning further improved classification (87.9% multiclass accuracy). Differences were also observed across donors, highlighting inter-individual variability. This work supports a new paradigm in which platelets act as “biological sensors,” fine-tuning their responses to environmental cues. The identified biomarker panel provides a basis for further investigation into the characterization of platelet activation profiles, with potential relevance for future diagnostic and therapeutic applications in thromboinflammatory and immune-mediated conditions.

PMID:41143469 | DOI:10.1080/09537104.2025.2572982

JMIR Res Protoc. 2025 Oct 27;14:e76668. doi: 10.2196/76668.

ABSTRACT

BACKGROUND: Many mental health professionals face work-related stress due to high job demands, limited control, and inadequate institutional support. Connected mental health (CMH) technologies such as mobile apps and teletherapy platforms are increasingly being proposed as tools to alleviate these job demands. However, their actual influence on clinicians’ work environments-here understood as the organizational, social, and psychological conditions that shape their workload, job demands, autonomy, and overall well-being-remains underexplored. Existing reviews have primarily focused on traditional organizational interventions, leaving a critical gap in understanding how CMH technologies specifically influence the work environment of mental health clinicians.

OBJECTIVE: This systematic literature review aims to identify and summarize knowledge about the impact of CMH on the work environment of mental health clinicians.

METHODS: A systematic literature review will be performed. The review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and has been registered in PROSPERO on April 23, 2025. A comprehensive search strategy was developed using the population, intervention, comparison, and outcome (PICO) framework in collaboration with an academic librarian. Studies will be sourced from the PubMed, Scopus, IEEE Xplore, and ACM Digital Library databases. Inclusion criteria are limited to empirical studies involving mental health clinicians using CMH tools, where outcomes explicitly relate to the work environment (eg, job demands, workload, autonomy, stress, or well-being). Eligible studies must be published in English. Data extraction will include publication trends, study methods, and types of CMH technologies. Additionally, the extraction will capture the study results, including qualitative and quantitative findings, along with the measurement instruments used. Two reviewers will independently select articles for review and extract data. Conflicts will be discussed, and a third reviewer will be consulted if a consensus cannot be reached. Descriptive statistics and thematic analysis (via NVivo) will be used to synthesize the findings.

RESULTS: This systematic literature review seeks to explore and synthesize existing research on how CMH technologies affect clinicians’ work environments and is expected to be completed by December 2025.

CONCLUSIONS: This review will offer a comprehensive overview of how CMH technologies affect the professional work environment of clinicians.

TRIAL REGISTRATION: PROSPERO CRD420251018685; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251018685.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/76668.

PMID:41143459 | DOI:10.2196/76668

Turk J Ophthalmol. 2025 Oct 27;55(5):296-297. doi: 10.4274/tjo.galenos.2025.27715.

NO ABSTRACT

PMID:41143456 | DOI:10.4274/tjo.galenos.2025.27715