Nevin Manimala

Elife. 2025 May 13;13:RP101369. doi: 10.7554/eLife.101369.

ABSTRACT

Bulk transcriptomic analyses of high-grade serous ovarian cancer (HGSOC) so far have not uncovered potential drug targets, possibly because subtle, disease-relevant transcriptional patterns are overshadowed by dominant, non-relevant ones. Our aim was to uncover disease-outcome-related patterns in HGSOC transcriptomes that may reveal novel drug targets. Using consensus-independent component analysis, we dissected 678 HGSOC transcriptomes of systemic therapy naïve patients-sourced from public repositories-into statistically independent transcriptional components (TCs). To enhance c-ICA’s robustness, we added 447 transcriptomes from non-serous histotypes, low-grade serous, and non-cancerous ovarian tissues. Cox regression and survival tree analysis were performed to determine the association between TC activity and overall survival (OS). Finally, we determined the activity of the OS-associated TCs in 11 publicly available spatially resolved ovarian cancer transcriptomes. We identified 374 TCs, capturing prominent and subtle transcriptional patterns linked to specific biological processes. Six TCs, age, and tumor stage stratified patients with HGSOC receiving platinum-based chemotherapy into ten distinct OS groups. Three TCs were linked to copy-number alterations affecting expression levels of genes involved in replication, apoptosis, proliferation, immune activity, and replication stress. Notably, the TC identifying patients with the shortest OS captured a novel transcriptional pattern linked to synaptic signaling, which was active in tumor regions within all spatially resolved transcriptomes. The association between a synaptic signaling-related TC and OS supports the emerging role of neurons and their axons as cancer hallmark-inducing constituents of the tumor microenvironment. These constituents might offer a novel drug target for patients with HGSOC.

PMID:40359002 | DOI:10.7554/eLife.101369

J Med Internet Res. 2025 May 13;27:e63030. doi: 10.2196/63030.

ABSTRACT

BACKGROUND: It is important to explain early diagnosis and treatment plans to patients of prostate cancer due to the different stages that diagnosis is made at and the corresponding stage-specific treatment options, as well as the varying prognoses depending on the choices made. Although various studies have implemented metaverse-based interventions across diverse clinical settings for medical education, there is a lack of publications addressing the implementation and validation of patient education using this technology.

OBJECTIVE: This study explored the potential of the metaverse as an educational and informational tool for prostate cancer. We measured and analyzed participants’ satisfaction and perceptions following a metaverse-based prostate cancer awareness campaign. We also evaluated the feasibility and potential effectiveness of the metaverse as a platform for hosting a virtual patient association and delivering health education.

METHODS: The study was conducted via a questionnaire administered from September 15 to October 20, 2023, during the Blue Ribbon Campaign organized by the Korean Urological Association and the Korean Society of Urological Oncology. The postevent questionnaire was designed to assess the effectiveness of using the metaverse to increase awareness of prostate cancer. A total of 119 participants, including patients, caregivers, and members of the general population, completed the survey within the metaverse space and assessed their satisfaction and perceived awareness using a 5-point Likert scale.

RESULTS: The mean educational satisfaction score was 4.17 (SD 0.65), the mean psychological satisfaction score was 4.06 (SD 0.70), the mean overall satisfaction score was 4.12 (SD 0.72), and the mean awareness score was 4.09 (SD 0.72) out of a possible 5 points. Among responses rated 4 or higher (“agree” or “strongly agree”), 82.8% (394/476) were in the educational aspect, 76.6% (365/476) in psychological satisfaction, 81% (289/357) in overall satisfaction, and 80.4% (287/357) in awareness. Statistical analysis revealed significant differences in psychological (median 4.0, IQR 3.50-4.63, vs median 4.50, IQR 4.0-4.56) and overall (median 4.0, IQR 3.67-4.83, vs median 4.33, IQR 4.0-4.67) aspects between the general population group and patients and caregivers (median 4.0, IQR 3.33-4.33, vs median 4.67, IQR 4.0-4.67).

CONCLUSIONS: The findings suggest that the metaverse holds promise as a platform for health care education and patient support, offering accessible and engaging experiences for patients, caregivers, and members of the general population. Our approach demonstrated a positive influence on participants’ satisfaction and perceived awareness, highlighting its potential to enhance health communication and patient engagement. Despite these encouraging results, limitations, such as the sample being skewed toward younger participants and reliance on self-reported data, underscore the need for more rigorous and multidimensional assessment strategies. Future studies should incorporate objective knowledge assessments, behavioral follow-ups, and qualitative methods to better evaluate the intervention’s effectiveness. This study provides early evidence that metaverse-based interventions can support disease awareness and promote preventive health behaviors, contributing to the ongoing evolution of digital health education.

PMID:40359001 | DOI:10.2196/63030

J Orthop Trauma. 2025 May 12. doi: 10.1097/BOT.0000000000003013. Online ahead of print.

ABSTRACT

OBJECTIVES: To discover postoperative symptom differences between nerve-sparing and nerve-sacrificing techniques during ORIF of clavicle fractures.

METHODS: Design: Prospective, partially blinded randomized controlled trial.

SETTING: Single academic Level I Trauma Center.

PATIENT SELECTION CRITERIA: Patients with closed, isolated, displaced, midshaft clavicle fractures (OTA/AO 15-2A, -2B, -2C) underwent ORIF and were consented and randomized to a “nerve-sacrificing” or “nerve-sparing” group.

OUTCOME MEASURES AND COMPARISONS: Semmes-Weinstein monofilament used to test for sensation changes around the supraclavicular area, single assessment numerical evaluation (SANE) scores and symptom severity level (SSL) providing patient self-reported changes, and patient morbidity questionnaires were issued at follow-up. One trained research fellow measured and mapped area of anesthesia. Outcomes between “nerve-sacrificing” and “nerve-sparing” groups were compared.

RESULTS: 21 patients (median age 41.5, 28.6% female) were randomized to “nerve-sacrificed” and 16 (median age 45.6, 18.8% female) to the “nerve-spared” group. There were no statistical differences in age or gender ratio (p=0.304 and 0.702 respectively). Longitudinal models including an interaction between group and time, showed cohort differences being driven by 12-weeks (49.3 (95% CLM 7.68, 90.92)) and 24-weeks (23.92 (95%CLM 1.70, 46.14)). While point estimates for the spare group were still lower at 2- and 52-weeks, they were not significantly different between groups. SANE scores and SSL data showed improvements in both cohorts over time, however; there were no statistically significant differences between the groups (p=0.176 and 0.155, respectively).

CONCLUSIONS: Sparing the supraclavicular nerve during open reduction and internal fixation of clavicle fractures significantly decreased chest-wall area of anesthesia at 12- and 24-weeks postoperatively. However, nerve sparing did not provide clinically significant differences in other symptoms compared to sacrificing the nerve.

LEVEL OF EVIDENCE: Level I, Therapeutic.

PMID:40358991 | DOI:10.1097/BOT.0000000000003013

Ann Plast Surg. 2025 Jun 1;94(6):647-652. doi: 10.1097/SAP.0000000000004395.

ABSTRACT

Flexor tendon injury in the hand is an injury that can be associated with significant morbidity, prolonged outpatient care, and potential revision surgery. We aimed to establish whether delayed healing is a risk factor for poorer functional outcomes for patients undergoing repair of zone 1/2 injuries. The records of patients treated for flexor tendon injuries were analyzed retrospectively. Patient demographics, comorbidities, injury mechanism, surgical details, and outpatient outcomes were recorded including total active movement and repair rupture. Sixty-one injuries were identified. Linear regression demonstrated a statistically significant negative relationship between days to healed wound and total active movement at 6 and 12 weeks. Increased time to healing is associated with poorer functional outcomes. We advise careful consideration of surgical exploration to reduce the burden of healing and allow improved outcomes.

PMID:40358960 | DOI:10.1097/SAP.0000000000004395

JAMA Netw Open. 2025 May 1;8(5):e259481. doi: 10.1001/jamanetworkopen.2025.9481.

ABSTRACT

IMPORTANCE: Patient-staff interactions in clinical trials may influence future enrollment decisions among racial and ethnic minority patients, who remain underrepresented in clinical research. A scale that measures common patient-staff interactions encountered by racial and ethnic minority patients in clinical trials may help improve patient experience and enrollment outcomes.

OBJECTIVE: To develop and validate a scale that measures common interactions encountered by racial and ethnic minority patients in clinical trials.

DESIGN, SETTING, AND PARTICIPANTS: This mixed-methods survey study involved interviews and online surveys for data collection between April 1, 2023, and June 30, 2024. Adult (aged ≥18 years) racial and ethnic minority patients were interviewed to identify common interactions with research staff. The survey was validated across potential clinical trial participants and among former clinical trial participants.

MAIN OUTCOMES AND MEASURES: Fit statistics for exploratory factor analysis and confirmatory factor analysis were used to confirm the validity of the scale. Structural equation modeling coefficients were used to assess the validity of the scale for measuring patients’ trust toward the research staff and willingness to participate in future studies.

RESULTS: The sample include 1113 participants. The scale item derivation cohort comprised 16 racial and ethnic minority participants with clinical trial experience (mean [SD] age, 44.9 [12.9] years; 10 female [62.5%]; 3 identifying as Asian or Pacific Islander [18.8%], 9 as Black [56.3%], 3 as Latino [18.8%], and 1 as multiracial [6.3%]). The scale structure validation cohort of potential clinical trial participants comprised 479 survey respondents (mean [SD] age, 35.5 [11.9] years; 219 women [45.7%]; 1 identifying as American Indian [0.2%], 59 as Asian or Pacific Islander [12.3%], 266 as Black [55.5%], 59 as Latino [12.3%], and 86 as multiracial [19.7%]). The concurrent validation cohort included 618 participants (mean [SD] age, 45.3 [16.3] years; 53% male; 63 identifying as Asian or Pacific Islander [10.2%], 228 as Black [36.9%], 75 as Latino [12.1%], 223 as White [36.1%], and 29 as multiracial [4.7%]). The 22-item Clinical Research Interaction Scale had high reliability (α = 0.96) and validity (comparative fit index, 0.92; Tucker-Lewis index, 0.91; root mean square error of approximation, 0.08). Patient experience of frequent low-quality interactions was significantly associated with lowered trust toward research staff (β, -0.56; 95% CI, -0.74 to -0.37), which in turn significantly lowered patients’ willingness to return to the site for future studies (β, 0.80; 95% CI, 0.70-0.90).

CONCLUSIONS AND RELEVANCE: These findings suggest that low-quality interactions with research staff may reduce racial and ethnic minority patients’ willingness to return for future studies, mediated by lowered trust toward the staff. The Clinical Research Interaction Scale may be a useful tool to improve the experience and enrollment outcomes for racial and ethnic minorities in clinical trials.

PMID:40358951 | DOI:10.1001/jamanetworkopen.2025.9481

JAMA Netw Open. 2025 May 1;8(5):e259599. doi: 10.1001/jamanetworkopen.2025.9599.

ABSTRACT

IMPORTANCE: Language used in clinical documentation can reflect biases, potentially contributing to health disparities. Understanding associations between patient race and ethnicity and documentation of stigmatizing and positive language in clinical notes is crucial for addressing health disparities and improving patient care.

OBJECTIVE: To examine associations of race and ethnicity with stigmatizing and positive language documentation in clinical notes from hospital birth admission.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included birthing patients at 2 metropolitan hospitals in the Northeastern US between 2017 and 2019. Eligible participants were admitted for labor and birth and had at least 1 free-text clinical note. Analysis was conducted using natural language processing. Data were analyzed between March and December 2024.

EXPOSURES: Patient race and ethnicity, categorized into mutually exclusive groups of Asian or Pacific Islander, Black, Hispanic, and White.

MAIN OUTCOME AND MEASURES: Presence of 4 stigmatizing language categories (marginalized language or identities, difficult patient, unilateral or authoritarian decisions, and questioning patient credibility) and 2 positive language categories (preferred and/or autonomy, power and/or privilege).

RESULTS: Among the 18 646 patients included in the study (mean [SD] age, 30.5 [6.2] years), 2121 were Black (11.4%), 11 078 were Hispanic (59.4%), and 4270 were White (22.9%). The majority (10 559 patients [56.6%]) were insured by Medicaid. Compared with White patients, Black patients had higher odds of having any stigmatizing language (model 2: odds ratio [OR], 1.25; 95% CI, 1.05-1.49; P < .001), after adjustment for demographic characteristics. Black patients also had higher odds of any positive language documented (model 2: OR, 1.18; 95% CI, 1.05-1.32; P = .006). Hispanic patients had lower odds of documented positive language (model 2: OR, 0.90; 95% CI, 0.82-0.99; P = .03). Asian or Pacific Islander patients had lower odds of language documented in the power and/or privilege category (model 2: OR, 0.71; 95% CI, 0.57-0.88; P = .002).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study examining clinical notes of 18 646 patients admitted for labor and birth, there were notable disparities in how stigmatizing and positive language was documented across racial and ethnic groups. This underscores the necessity for improving documentation and communication practices to reduce the use of stigmatizing language.

PMID:40358949 | DOI:10.1001/jamanetworkopen.2025.9599

JAMA Netw Open. 2025 May 1;8(5):e259852. doi: 10.1001/jamanetworkopen.2025.9852.

ABSTRACT

IMPORTANCE: Value-based health care increasingly requires electronic patient-reported outcome-based remote symptom monitoring (RSM) to improve health care utilization in patients with cancer. However, data on the impact of RSM in clinical practice are lacking.

OBJECTIVE: To evaluate the association of RSM with 3- and 6-month health care utilization among patients receiving systemic cancer treatment.

DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized controlled trial used a hybrid, type 2 implementation-effectiveness design. Participants were patients with cancer at 2 Alabama-based academic institutions receiving chemotherapy, targeted therapy, or immunotherapy; the exposure group received standard-of-care delivered RSM from 2021 to 2024, and historical controls were patients who received cancer treatment prior to RSM implementation from 2017 to 2021. Data were analyzed from May to October 2024.

EXPOSURE: RSM using electronic patient-reported outcomes.

MAIN OUTCOMES AND MEASURES: Health care utilization at 3 and 6 months after RSM enrollment (intensive care unit [ICU] admissions, hospitalizations, emergency department [ED] visits). Adjusted modified Poisson models estimated the relative risk (RR) and 95% CI of health care utilization overall. Penalized logistic regression was used for stratified analyses by patient race, residence, neighborhood deprivation, insurance type, and comorbid conditions.

RESULTS: A total of 5949 patients were assessed. From May 2021 to May 2024, 1392 patients (median [IQR] age at index date, 61 [51-69] years; 933 [67%] female) were enrolled in RSM, including 378 Black patients (27%) and 922 White patients (66%), with 262 patients (19%) living in rural areas and 372 patients (27%) living in areas with high neighborhood disadvantage; RSM patients were compared with 4557 controls (median [IQR] age at index date, 62 [53-69] years; 2654 [58%] female), including 1177 Black patients (26%) and 3151 White patients (69%), with 1012 patients (22%) living in rural areas, and 1281 patients (28%) living in areas with high neighborhood disadvantage. Compared with historical controls, hospitalizations among patients receiving RSM were 19% lower at 3 months (RR, 0.81; 95% CI, 0.73-0.91) and 13% lower at 6 months (RR, 0.87; 95% CI, 0.80-0.96). ICU admissions were not significantly different among the RSM populations compared with controls (3 months: RR, 0.82; 95% CI, 0.59-1.13; 6 months: RR, 0.83; 95% CI, 0.65-1.06). ED visits were similar for both groups (3 months: RR, 1.02; 95% CI, 0.89-1.16; 6 months: RR, 1.03; 95% CI, 0.92-1.15). Subset analyses showed similar patterns in 3- and 6-month RR for hospitalizations, ED visits, and ICU admissions.

CONCLUSIONS AND RELEVANCE: In this nonrandomized controlled trial, RSM implementation was associated with reduced risk of hospitalizations for patients with cancer, supporting the need to expand implementation nationally.

PMID:40358948 | DOI:10.1001/jamanetworkopen.2025.9852

JAMA Netw Open. 2025 May 1;8(5):e2510016. doi: 10.1001/jamanetworkopen.2025.10016.

ABSTRACT

IMPORTANCE: Although structural and social determinants of health (SSDH) have been consistently associated with health disparities, percentage African genetic ancestry (AGA) has been suggested as a risk factor associated with common diseases in Black populations. Appropriate use and interpretation of percentage AGA in understanding health disparities has been complicated by the fact that percentage AGA is correlated with genetic and nongenetic factors.

OBJECTIVE: To evaluate associations of SSDH with mortality in the context of percentage AGA and how percentage AGA is correlated with SSDH.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study investigated data from the Multiethnic Cohort (MEC) Study, in which participants were enrolled from 1993 through 1996 and followed up until death or censoring on December 31, 2019. Participant data were analyzed between March and June 2023. The population-based sample was predominantly from Los Angeles County, California, consisting of self-identified Black adults aged 45 to 75 years who enrolled into the MEC Study; completed a baseline demographic, clinical, and lifestyle questionnaire; and provided biospecimens.

EXPOSURES: The Index of Concentration at the Extremes (ICE), capturing social polarization based on income and racial composition, and a neighborhood socioeconomic status (NSES) index were computed from the 1990 Census, scaled to county-specific quintiles, and linked to residential census tracts at study enrollment. Percentage AGA was estimated using 21 431 single-nucleotide variations based on similarity with African continental referent data.

MAIN OUTCOMES AND MEASURES: Multivariable hazard ratios (HRs) for all-cause mortality were estimated from Cox models. Correlation of percentage AGA with SSDH measures was described.

RESULTS: After exclusions, 9685 participants were included (mean [SD] age, 61.0 [8.9] years; 5593 female [57.7%]), with a mean (SD) percentage AGA of 75.0% (14.0%). There were 5504 deaths over 204 463 person-years of follow-up. Comparing the most with least advantaged quintile, income ICE (adjusted HR [aHR], 1.30; 95% CI, 1.16-1.45) and NSES (aHR, 1.37, 95% CI, 1.20-1.56) were associated with lower all-cause mortality. Minimal changes were observed after adjusting for percentage AGA; for example, comparing the most with least advantaged quintile, NSES (aHR, 1.36; 95% CI, 1.19-1.55) remained associated with lower all-cause mortality. There was no association between percentage AGA and mortality after adjustment (aHR per 10-percentage point change in percentage AGA, 1.01; 95% CI, 0.99-1.03).

CONCLUSIONS AND RELEVANCE: In this study, associations of SSDH with mortality persisted with adjustment for percentage AGA. Findings support the hypothesis that SSDH should be the primary factors to consider for eliminating health disparities.

PMID:40358946 | DOI:10.1001/jamanetworkopen.2025.10016

JAMA Netw Open. 2025 May 1;8(5):e2510077. doi: 10.1001/jamanetworkopen.2025.10077.

ABSTRACT

IMPORTANCE: Illegal fentanyl is driving overdose mortality, and fentanyl test strips (FTS) can be used to test drugs for fentanyl at the point of consumption. Evidence on whether FTS use is associated with overdose risk reduction behaviors is encouraging, but largely limited to smaller, single-site studies.

OBJECTIVE: To determine whether self-reported baseline FTS use among people who use drugs (PWUD) was associated with overdose risk reduction behaviors and nonfatal overdose over a 28-day follow-up.

DESIGN, SETTING, AND PARTICIPANTS: Multisite, observational cohort study of PWUD conducted from May to December 2023 as an ancillary study of the HEALing Communities Study, which consists of fixed and mobile direct service provision sites in 14 community partner organizations distributing FTS. Participants lived in Kentucky, New York, or Ohio and reported using heroin, fentanyl, cocaine, methamphetamine, or nonprescribed opioids, benzodiazepines, or stimulants within 30 days before baseline. Participants were followed up for a maximum of 37 days.

EXPOSURE: Baseline FTS use.

MAIN OUTCOME AND MEASURES: The primary outcome was a composite score measuring the self-reported number and frequency of using 8 overdose risk reduction behaviors. Secondary outcomes included multiple measures (eg, self-reported nonfatal overdose).

RESULTS: The study included 732 participants (median [IQR] age, 41 [34.0-48.0] years; 369 [50.4%] male; 64 [8.9%] Black or African American, 587 [81.3%] White, and 71 [9.8%] other races); 414 reported baseline FTS use and 318 did not. Compared with nonusers, a higher percentage of baseline FTS users were from Ohio and White, while a lower percentage were from New York and Hispanic and/or Black. In adjusted analyses, PWUD who used FTS had a mean daily composite score for overdose risk reduction behaviors that was 0.86 (95% CI, 0.34-1.38) units higher across follow-up compared with nonusers (score for FTS users, 7.37; nonusers, 6.51). There was no difference in self-reported nonfatal overdoses between the 2 groups (mean daily risk for FTS users, 0.02; nonusers, 0.02; risk ratio, 1.20; 95% CI, 0.70-2.06).

CONCLUSIONS AND RELEVANCE: In this cohort study, baseline FTS use was associated with greater engagement in overdose risk reduction behaviors during follow-up, but not with the risk of nonfatal overdose during follow-up, suggesting PWUD who use FTS may also engage in a broader set of harm reduction strategies.

PMID:40358945 | DOI:10.1001/jamanetworkopen.2025.10077

JAMA Netw Open. 2025 May 1;8(5):e2510083. doi: 10.1001/jamanetworkopen.2025.10083.

ABSTRACT

IMPORTANCE: School-based health centers (SBHCs) provide students with convenient access to physical, mental, and dental health services, which is particularly important in rural areas with long travel distances and limited availability of primary care.

OBJECTIVE: To examine the association between SBHCs and school attendance in a rural region.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study compared attendance rates among students in school districts with and without SBHCs in rural upstate New York. Student attendance data from the 2015 to 2016 through the 2018 to 2019 school years were obtained for 52 schools in 32 districts within a regional education service area. Analysis included students in kindergarten through 12th grade from 18 schools in 14 districts with SBHCs and 34 schools in 18 districts without SBHCs. Multivariable logistic regression was used to model the association between SBHC access and risk of chronic absenteeism. Statistical analysis was performed from May 2024 to February 2025.

EXPOSURE: Access vs no access to an SBHC based on which district a student was enrolled in. In districts with SBHCs, all schools had SBHCs.

MAIN OUTCOMES AND MEASURES: Absenteeism was calculated as the number of days absent divided by the total days enrolled and classified by federal and state chronic absenteeism categories: not at risk (0%-4.99% absent), at risk of chronic absenteeism (5%-9.99% absent), and chronically absent (≥10% absent).

RESULTS: Attendance data were available for 66 303 students (kindergarten through 12th grade; 49.4% female) during 4 years: 30 046 from SBHC districts and 36 257 from non-SBHC districts. Across all but 1 school year, non-SBHC students were significantly more likely than SBHC students to be classified as chronically absent or at risk for chronic absenteeism. Students in SBHC districts had 12% greater odds of being not at risk for chronic absenteeism after accounting for grade, sex, school year, economic disadvantage, and community characteristics of wealth and district size (odds ratio, 1.12; 95% CI, 1.08-1.16). Evidence of a stronger association was found between SBHC access and reduced absenteeism among elementary school students and among children attending schools with higher student poverty and higher community wealth.

CONCLUSIONS AND RELEVANCE: This cross-sectional study of rural students in kindergarten through 12th grade found that students in SBHC districts had significantly fewer absences than students in non-SBHC districts in the same region. These findings suggest that by providing primary care services at school, SBHCs may help decrease absenteeism among students in rural communities.

PMID:40358944 | DOI:10.1001/jamanetworkopen.2025.10083