Tag: pubmed

JMIR Res Protoc. 2025 Sep 8;14:e64057. doi: 10.2196/64057.

ABSTRACT

BACKGROUND: Various media are used to enhance public understanding about diseases. While mobile health apps are widely used, there is little proof for using such apps to raise awareness of skin diseases.

OBJECTIVE: We intend to develop an app, called DEDIKASI-app, to raise awareness of skin diseases, including leprosy. The study will explore baseline awareness, assess the app’s acceptance by community members and health care workers, and evaluate its effectiveness in enhancing awareness about skin diseases.

METHODS: The study will be conducted in four phases: (1) development of DEDIKASI-app, (2) questionnaire development for an awareness study, (3) acceptability testing, and (4) effect measurement of DEDIKASI-app. We will adopt design thinking methodology to develop the app, involving systematic reviews, expert consultations, focus group discussions, and validation of the questionnaire on skin disease awareness. We will recruit 50 members of the community for the awareness and acceptability study and 1 health care worker per community health center to assess their perception of the app. A pilot study will assess the acceptability of DEDIKASI-app among community members and health care workers based on various constructs, with responses categorized as positive, negative, or undecided. The validity and reliability of a newly developed questionnaire on skin disease awareness will be tested, with validity results analyzed qualitatively and reliability measured using Cronbach α. The effectiveness of DEDIKASI-app in improving community awareness will be evaluated through a randomized controlled trial, using total scores, means, and SDs for control and intervention groups. Statistical significance of awareness level changes will be determined by delta change (P value), with P<.01 considered significant.

RESULTS: This study received ethical approval from the Ethics Review Board of the Faculty of Public Health, Universitas Airlangga (160/EA/KEPK/2023) and was registered in the Indonesia Clinical Research Registry (INA-O8EX278). Funding for the field research was secured in the period of May 2022-December 2024 from NLR Indonesia and Erasmus University Medical Center. As of manuscript submission, phase 1 (app development) and phase 2 (questionnaire development) have been completed. Data collection for the randomized controlled trial has just finished and data analysis is ongoing, with publication of the study results expected in late 2025.

CONCLUSIONS: Innovative approaches are required to enhance awareness in the community. This study will introduce new tools and insights to address the limited knowledge about detecting skin problems.

TRIAL REGISTRATION: INA-CRR Indonesia Clinical Research Registry INA-O8EX278; https://tinyurl.com/ms3k5yvn.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64057.

PMID:40920442 | DOI:10.2196/64057

Rheumatology (Oxford). 2025 Sep 8:keaf478. doi: 10.1093/rheumatology/keaf478. Online ahead of print.

NO ABSTRACT

PMID:40920420 | DOI:10.1093/rheumatology/keaf478

JAMA Neurol. 2025 Sep 8. doi: 10.1001/jamaneurol.2025.3316. Online ahead of print.

ABSTRACT

IMPORTANCE: Exposure to fine particulate matter air pollution (PM2.5) may increase risk for dementia. It is unknown whether this association is mediated by dementia-related neuropathologic change found at autopsy.

OBJECTIVE: To examine associations between PM2.5 exposure, dementia severity, and dementia-associated neuropathologic change.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data associated with autopsy cases collected from 1999 to 2022 at the Center for Neurodegenerative Disease Research Brain Bank at the University of Pennsylvania. Data were analyzed from January to June 2025. Participants included 602 cases with common forms of dementia and/or movement disorders and older controls after excluding 429 cases with missing data on neuropathologic measures, demographic factors, APOE genotype, or residential address.

EXPOSURES: One-year mean PM2.5 concentration prior to death or prior to last Clinical Dementia Rating Sum of Boxes (CDR-SB) assessment was estimated using a spatiotemporal prediction model at residential addresses.

MAIN OUTCOMES AND MEASURES: Dementia severity was measured by CDR-SB scores. Ten dementia-associated neuropathologic measures representing Alzheimer disease, Lewy body disease, limbic-predominant age-related transactive response DNA-binding protein (TDP)-43 encephalopathy, and cerebrovascular disease were graded or staged. Linear, logistic, and structural equation models were used to examine the associations between PM2.5, CDR-SB, and neuropathologic measures, adjusting for demographic factors and APOE ε4 allele status.

RESULTS: In a total of 602 autopsy cases (median [IQR] age at death, 78 [71-85] years; 328 male [54.5%] and 274 female [45.5%]), higher PM2.5 exposure prior to death was associated with increased odds of more severe Alzheimer disease neuropathologic change (ADNC) (odds ratio, 1.19; 95% CI, 1.11-1.28). In a subset of 287 cases with CDR-SB records (median [IQR] age at death, 79 [72-86] years; 154 [53.7%] male and 133 female [46.3%]), higher PM2.5 exposure prior to CDR-SB assessment was associated with greater cognitive and functional impairment (β = 0.48; 95% CI, 0.22-0.74). Lastly, 63% of the association between higher PM2.5 exposure and greater cognitive and functional impairment was statistically mediated by ADNC (β = 0.30; 95% CI, 0.04-0.53).

CONCLUSIONS AND RELEVANCE: In this study, PM2.5 exposure was associated with increased dementia severity and increased ADNC. Population-based studies are needed to better understand this relationship.

PMID:40920417 | DOI:10.1001/jamaneurol.2025.3316

JAMA Intern Med. 2025 Sep 8. doi: 10.1001/jamainternmed.2025.4421. Online ahead of print.

ABSTRACT

IMPORTANCE: There is an unmet need for long-term, safe, effective, and hormone-free treatments for menopausal symptoms, including vasomotor symptoms (VMS) and sleep disturbances.

OBJECTIVE: To evaluate the 52-week efficacy and safety of elinzanetant, a dual neurokinin-targeted therapy, for treating moderate to severe VMS associated with menopause.

DESIGN, SETTING, AND PARTICIPANTS: OASIS-3 was a double-blind, placebo-controlled, randomized phase 3 clinical trial that was conducted at 83 sites in North America and Europe from August 27, 2021, to February 12, 2024, and included postmenopausal women aged 40 to 65 years who were seeking treatment for moderate to severe VMS (no requirement for a minimum number of VMS events per week). The data were analyzed on March 11, 2024.

INTERVENTION: Once-daily oral elinzanetant, 120 mg, or matching placebo for 52 weeks.

MAIN OUTCOMES AND MEASURES: The primary outcome was mean change from baseline to week 12 in the frequency of daily moderate to severe VMS, which was analyzed using a mixed model with repeated measures. Secondary end points included changes over 52 weeks in measures evaluating sleep disturbance and the effect on menopause-related quality of life. Exploratory end points included mean changes over 50 weeks in frequency and severity of daily moderate to severe VMS. Exploratory and secondary end points were analyzed using descriptive statistics. Safety was also assessed.

RESULTS: Overall, 313 women (mean [SD] age, 54.6 [4.7] years; 51 [16.3%] were Black or African American, and 240 [76.7%] were White individuals; 34 [10.9%] were Hispanic or Latina) were randomized to receive elinzanetant and 315 (mean [SD] age, 54.9 [5.0] years; 44 [14.0%] Black or African American, 34 [10.8%] Hispanic or Latina, and 253 [80.3%] White individuals) to receive placebo. At week 12, the mean change from baseline in daily moderate to severe VMS frequency was -5.4 (95% CI, -6.3 to -4.5) for elinzanetant and -3.5 (95% CI, -4.1 to -2.9) for placebo; the least-squares mean difference for elinzanetant vs placebo was -1.6 (95% CI, -2.0 to -1.1; P < .001). Although no statistical hypotheses were defined, nor was the study powered to detect between-group differences for the secondary and exploratory end points, descriptive analyses showed numerical advantages for elinzanetant vs placebo for improving VMS frequency and severity over 50 weeks and sleep disturbances and menopause-related quality of life over 52 weeks. Regarding safety, elinzanetant was not associated with hepatotoxic effects, endometrial hyperplasia, or meaningful changes in bone density or bone turnover markers. Treatment-related adverse events were more common with elinzanetant than placebo (30.4% vs 14.6%); the most frequent were somnolence, fatigue, and headache.

CONCLUSIONS AND RELEVANCE: The OASIS-3 randomized clinical trial expanded on findings from the 26-week OASIS-1 and OASIS-2 trials, exploring the use of elinzanetant over a longer duration and in a broader population. Elinzanetant shows promise as a treatment for moderate to severe VMS.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05030584.

PMID:40920404 | DOI:10.1001/jamainternmed.2025.4421

Clin Transl Sci. 2025 Sep;18(9):e70328. doi: 10.1111/cts.70328.

ABSTRACT

Since the first decentralized clinical trial (DCT) was conducted in 2011, there has been an increased usage of DCT due to its benefits of patient-centricity and generalizability of findings. This trend was further expedited by the global COVID-19 pandemic. We identified 23 case studies across various therapeutic areas and grouped them into different categories according to their purposes-by necessity, for operational benefits, to address unique research questions, to validate innovative digital endpoints, or to validate decentralization as a clinical research platform. We leveraged the estimand framework from ICH E9(R1) including its five attributes (population, treatment, variable, intercurrent event, and summary measure) to critically assess their design and conduct. Common trends, opportunities, and challenges were reported along with recommendations for future DCT. Of note, intercurrent events and associated handling strategies are largely not present when reporting DCT. This is an area that can impact study conclusions and require more dedicated efforts when designing new DCTs.

PMID:40920390 | DOI:10.1111/cts.70328

JAMA Netw Open. 2025 Sep 2;8(9):e2529399. doi: 10.1001/jamanetworkopen.2025.29399.

ABSTRACT

IMPORTANCE: The cost-effectiveness of adding early in-bed cycling to usual physiotherapy among adults receiving mechanical ventilation in the intensive care unit (ICU) compared with usual physiotherapy alone is unknown.

OBJECTIVE: To evaluate the cost-effectiveness of in-bed cycling plus usual physiotherapy compared with usual therapy alone in the Critical Care Cycling to Improve Lower Extremity Strength (CYCLE) randomized clinical trial.

DESIGN, SETTING, AND PARTICIPANTS: This trial-based economic evaluation with a 90-day time horizon compared early cycling plus usual physiotherapy vs usual physiotherapy alone from a societal perspective. Adult ICU patients (aged ≥18 years) receiving mechanical ventilation were recruited from 16 ICUs in Canada, the US, and Australia. Enrollment occurred from November 1, 2016, to May 30, 2023, with the last follow-up on August 3, 2023.

INTERVENTIONS: Intervention group participants were offered 30 minutes per day of cycling in addition to usual physiotherapy on weekdays, starting within the first 4 days of mechanical ventilation. Cycling continued until the patient could march on the spot for 2 consecutive days, ICU discharge, or for 28 days, whichever occurred first. Usual care participants were offered individualized physiotherapy according to local practices and patient alertness.

MAIN OUTCOMES AND MEASURES: Differences in costs (in 2024 Canadian dollars [CA$]) and quality-adjusted life-years (QALYs) between the groups were calculated. In the absence of dominance (ie, 1 strategy is associated with higher costs and fewer QALYs), the results were reported in terms of incremental cost per QALY gained.

RESULTS: The CYCLE trial recruited 360 patients (mean [SD] age, 61.5 [15.6] years; 205 male [56.9%]). The estimated per-patient cost associated with providing early in-bed cycling (CA$321) represented 0.5% of the index hospitalization costs (CA$66 554). The per-patient differences in 90-day costs (CA$5841; 95% CI, -CA$7666 to CA$18 797) and QALYs (-0.0009; 95% CI, -0.0185 to 0.0182) between cycling plus usual physiotherapy vs usual physiotherapy alone were not statistically different from 0. The probability of cycling plus usual physiotherapy to be cost-effective was 0.19 at a willingness-to-pay threshold of $50 000 per QALY gained.

CONCLUSIONS AND RELEVANCE: In this trial-based economic evaluation, the differences in costs and QALYs between adding early in-bed cycling to usual physiotherapy and usual physiotherapy alone for adults receiving mechanical ventilation were not significantly different from 0. These results highlight the need for additional cost-effectiveness studies considering the full body of evidence regarding in-bed cycling for critically ill patients.

PMID:40920382 | DOI:10.1001/jamanetworkopen.2025.29399

JAMA Netw Open. 2025 Sep 2;8(9):e2529885. doi: 10.1001/jamanetworkopen.2025.29885.

ABSTRACT

IMPORTANCE: Trisomy 13 (T13) and trisomy 18 (T18) are chromosomal abnormalities with high mortality rates in the first year of life. Understanding differences in long-term survival between children with full vs mosaic or partial trisomy is crucial for prognosis and health care planning.

OBJECTIVE: To examine the differences in 10-year survival between children with full T13 and T18 vs those with mosaic or partial trisomy.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study assessed liveborn infants with T13 and T18 in the Texas Birth Defects Registry (deliveries from January 1, 1999, to December 31, 2008). Follow-up was through December 31, 2018 (the last date available at the time of analyses) to allow for 10 years of follow-up for all infants. All analyses were conducted from January 1, 2022, to December 31, 2024.

EXPOSURES: Cytogenetic status (full trisomy vs mosaic or partial trisomy).

MAIN OUTCOMES AND MEASURES: The primary outcome was survival to 10 years of age, assessed using Kaplan-Meier survival estimates. The association between cytogenetic status and mortality by 10 years of age was assessed using Cox proportional hazards regression to generate hazard ratios (HRs). Population attributable fraction was calculated to determine the percentage of survival attributable to mosaic or partial trisomy status.

RESULTS: The study cohort included 798 infants (463 female infants [58.0%]; mean [SD] maternal age, 30.9 [8.0] years) with T13 (n = 295) or T18 (n = 503). Among all cases with T13, 25 infants (8.5%; 95% CI, 5.5%-12.3%) survived to 10 years of age. Similarly, among all infants with T18, 43 (8.6%; 95% CI, 6.3%-11.3%) survived to 10 years of age. Kaplan-Meier survival estimates to 10 years of age were statistically significantly higher among children with mosaic or partial trisomy (13 [25.0%] and 14 [43.8%], respectively) compared with full trisomy (12 [4.9%] and 29 [6.6%], respectively) (both P < .001). Infants with full trisomy had statistically significantly increased 10-year mortality hazards compared with those with mosaic or partial trisomy for both T13 (HR, 2.00; 95% CI, 1.42-2.82) and T18 (HR, 3.34; 95% CI, 2.08-5.38). The results of the calculated proportion of 10-year survival due to the presence of nonfull trisomy status (population attributable fraction) was 41.7% for children with T13 and 27.9% for children with T18.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study of infants with T13 and T18 support differences in long-term survival based on cytogenetic status and emphasize the need to potentially reassess the context of these conditions generally being considered incompatible with life, particularly for those with mosaic trisomies. These findings offer context surrounding treatment decisions, such as withholding interventions, for affected infants in the future.

PMID:40920381 | DOI:10.1001/jamanetworkopen.2025.29885

JAMA Netw Open. 2025 Sep 2;8(9):e2530804. doi: 10.1001/jamanetworkopen.2025.30804.

ABSTRACT

IMPORTANCE: Approximately 35% of individuals seeking abortion care use Medicaid for health insurance. Although the Hyde Amendment restricts use of federal funds for most abortions, states can supplement coverage using state funds. Understanding the scope of abortion coverage across states and potential barriers to access may help address health care inequities and inform interventions.

OBJECTIVE: To characterize state Medicaid abortion policies by conducting a qualitative analysis of publicly available state documents on Medicaid policy.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study analyzed Medicaid abortion policies across all 50 states and the District of Columbia (hereinafter, states). Data were systematically collected from publicly available Medicaid documents and state websites from May 2023 to February 2024.

MAIN OUTCOMES AND MEASURES: The main outcomes were key themes and descriptive statistics reporting on the scope of Medicaid abortion coverage and requirements for coverage across states, including documentation and procedures required of patients and physicians. Thematic analysis was performed to extract key themes found in abortion coverage policies, and descriptive statistics were used to show prevalence of identified themes across states.

RESULTS: The analysis of 94 documents revealed 3 key themes. First, the scope of coverage across states was heterogeneous. Eighteen states aligned with the current wording of the Hyde Amendment, 10 states described life endangerment without use of current Hyde Amendment wording, 17 states outlined additional coverage for other specified conditions for abortions, 6 states covered all abortions, and 1 state’s policy did not mention required federal coverage for rape or incest exceptions. Second, states imposed various patient restrictions and requirements with regard to abortion care coverage, with 22 states mandating reporting requirements for abortions due to rape or incest, along with other administrative hurdles for patients seeking care. Third, physicians were tasked with many responsibilities, such as determining eligibility for Medicaid abortion coverage and complying with documentation and administrative requirements. Thirty-eight states explicitly required physician certification and justification for clinical conditions warranting coverage.

CONCLUSIONS AND RELEVANCE: The findings of this qualitative study of state Medicaid abortion policies suggest that there is substantial heterogeneity among states regarding the scope of Medicaid abortion coverage and that there are numerous obstacles for patients and physicians in accessing this coverage. This heterogeneity and burden may impose an additional layer of complexity to abortion access. Measures and policies that improve transparency, clarity, and efficiency may enhance access to essential abortion care for vulnerable populations.

PMID:40920379 | DOI:10.1001/jamanetworkopen.2025.30804

JAMA Netw Open. 2025 Sep 2;8(9):e2530946. doi: 10.1001/jamanetworkopen.2025.30946.

ABSTRACT

IMPORTANCE: Black individuals have a twofold higher rate of prostate cancer death in the US compared with the average population with prostate cancer. Few guidelines support race-conscious screening practices among at-risk Black individuals.

OBJECTIVE: To examine structural factors that facilitate or impede access to prostate cancer screening among Black individuals in the US.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative, mixed-methods study was conducted between September 1, 2021, and December 31, 2023, in clinical and community settings across Washington, Wyoming, Alaska, Montana, Idaho, and Oregon. It included semistructured interviews with Black adults (aged ≥18 years) at risk for prostate cancer with or without a history of prostate-specific antigen (PSA) testing and a survey of primary care practitioners (PCPs) and urologists.

MAIN OUTCOMES AND MEASURES: Patient and physician experiences, knowledge, attitudes, and practices of PSA testing and prostate cancer screening were evaluated. Consensus coding and thematic analysis were used to analyze interviews; surveys were analyzed using descriptive statistics.

RESULTS: A total of 29 Black men (median [range] age, 59 [32-72] years) participated in the interviews, and 31 PCPs (including 30 phyicians and 1 physician assistant) and 32 urologists (45 of 63 aged 30-59 years [71.4%]; 40 male [63.5%]) participated in the survey. Interview participants perceived that PCPs function as gatekeepers in accessing PSA testing but may lack knowledge specific to Black men’s risk for prostate cancer and hold attitudes about PSA testing that do not support its use. Interview participants also reported a lack of trusted relationships with PCPs to support shared decision-making. While both urologists and PCPs were highly aware of US Preventive Services Task Force guidelines, PCPs were much less likely than urologists to believe in the value of PSA testing or the role of early detection to prevent prostate cancer-related mortality (2 [6.5%] vs 24 [75.0%], respectively).

CONCLUSIONS AND RELEVANCE: In this qualitative study examining structural factors associated with access to prostate cancer screening among Black individuals, findings from the survey supported participants’ perceptions that PCPs do not value PSA testing for prostate cancer early detection or appreciate its role in reducing the risk of prostate cancer-related mortality. Primary care practitioner reliance on USPSTF guidelines, which currently do not provide guideline recommendations for screening high-risk groups, including Black individuals, suggests that incorporating evidence-driven guidance for PSA screening among Black individuals into these guidelines may substantially improve prostate cancer early detection among this high-risk population.

PMID:40920378 | DOI:10.1001/jamanetworkopen.2025.30946

Environ Toxicol Chem. 2025 Sep 8:vgaf224. doi: 10.1093/etojnl/vgaf224. Online ahead of print.

ABSTRACT

Several micro- and nanoplastic particle (MNP) traits, like polymer type, size, and shape, have been shown to influence MNP toxicity. However, the direction and strength of these moderating effects are often unclear, and generalizations from single studies are challenging to establish. Meta-analyses increase generalizability and derive more accurate and precise effect size estimates by combining measurements from published studies. We conducted a meta-analysis to investigate the effects of MNP exposure on the reproductive output of water fleas of the genus Daphnia by aggregating 369 data points from 64 studies. We show that daphnids exposed to MNP produce, on average, 13.6 less neonates, a reduction of 20.8% compared to the particle-free controls (control mean = 65.37 neonates). This effect is moderated by MNP concentration, exposure duration, experimental temperature, and size category, with microplastics eliciting a stronger negative effect than nanoplastic particles. Shape category, species, age, polymer type, size (µm), fluorescence, modification type, presence of surfactant, and dissolved organic matter (DOM) did not influence effect sizes significantly. Based on the high residual heterogeneity in the data, we suggest that additional factors likely influence observed effects and discuss how better particle characterization could improve our understanding of the drivers of MNP toxicity.

PMID:40920353 | DOI:10.1093/etojnl/vgaf224