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Melatonin for neuropathic pain: a double-blind, placebo-controlled, randomized, crossover trial

Pain. 2025 May 13. doi: 10.1097/j.pain.0000000000003651. Online ahead of print.

ABSTRACT

Neuropathic pain (NP) is a common challenging problem, and there is a growing need to develop safe and effective nonopioid treatments. Sleep disturbance is commonly associated with NP because pain intensity of NP conditions is often worse at night. Some evidence suggests that the pineal hormone, melatonin, may reduce pain in clinical settings. We conducted a clinical trial to evaluate the efficacy of melatonin for NP. Using a double-blind, placebo-controlled, crossover design, 31 adults with NP were randomly allocated to 1 of 2 sequences of treatment with melatonin and placebo. During each of 2 treatment periods, participants took capsules containing melatonin or placebo for 4 weeks, followed by a 7-day washout period. The primary outcome was mean daily pain intensity (0-10) at maximally tolerated doses (MTD) during each period. Secondary outcomes, assessed at MTD, included adverse events, and measures of sleep, mood, and quality of life. Thirty-one participants were recruited, and 30 participants completed both treatment periods of the trial. The mean maximal tolerated dose of melatonin in this trial was 11.9 mg/day. Treatment-emergent adverse events with melatonin were infrequent and not statistically different from placebo. At MTD, mean daily pain (standard error) was 4.1 (0.3) for melatonin and 4.2 (0.3) for placebo (P = 0.8). There were no statistically significant differences between placebo and melatonin for any secondary outcomes. Overall, the results of this trial do not provide any evidence to suggest promise for melatonin as an effective treatment for NP.

PMID:40359364 | DOI:10.1097/j.pain.0000000000003651

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Efficacy and safety of ureterorenoscopy in the elderly: A systematic review axnd meta-analysis

PLoS One. 2025 May 13;20(5):e0323237. doi: 10.1371/journal.pone.0323237. eCollection 2025.

ABSTRACT

OBJECTIVE: Ureterorenoscopy (URS) is a common procedure performed for renal or upper ureteric stones. Nevertheless, the efficacy and safety of URS in the elderly is unclear. We conducted the first meta-analysis of literature comparing outcomes of URS between elderly and non-elderly patients.

METHODS: Embase, PubMed, Web of Science, and Scopus databases were searched for studies relevant to the review. The last date was 2nd September 2024. The elderly were defined as ≥ 65 or 60 years of age. Outcomes compared were stone-free rates (SFR), complications, and length of hospital stay (LOS).

RESULTS: Nine studies met the inclusion criteria. Pooled analysis showed that there was no difference in SFR between elderly and non-elderly groups after URS (OR: 0.96 95% CI: 0.81, 1.14 I2 = 3%). Meta-analysis failed to show any statistical significant in all complication rates (OR: 1.04 95% CI: 0.77, 1.40 I2 = 51%) as well as infectious (OR: 1.27 95% CI: 0.84, 1.92 I2 = 0%), medical (OR: 2.01 95% CI: 0.23, 17.57 I2 = 93%), surgical (OR: 1.18 95% CI: 0.68, 2.03 I2 = 0%) or Clavein Dindo grade ≥2 (OR: 1.02 95% CI: 0.60, 1.75 I2 = 0%) complications between elderly and non-elderly groups. Meta-analysis showed that the elderly had significantly longer LOS as compared to non-elderly patients (MD: 0.75 95% CI: 0.05, 1.45 I2 = 90%).

CONCLUSIONS: URS seems to efficacious and safe in the elderly. Patients ≥60 or 65 years of age have similar SFR and complication rates as younger patients. However, LOS may be increased in the elderly. More robust studies taking into account baseline characteristics and importantly presenting rates are needed to validate the current results.

PMID:40359352 | DOI:10.1371/journal.pone.0323237

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Circulating Antioxidant Nutrients and Brain Age in Midlife Adults

Biopsychosoc Sci Med. 2025 May 9. doi: 10.1097/PSY.0000000000001399. Online ahead of print.

ABSTRACT

OBJECTIVE: Due to population aging, the increasing prevalence of Alzheimer’s Disease (AD) and related dementias are major public health concerns. Dietary consumption of antioxidant nutrients, in particular the carotenoid β-carotene, has been associated with lower age-related neurocognitive decline. What is unclear, however, is the extent to which antioxidant nutrients may exert neuroprotective effects via their influence on established indicators of age-related changes in brain tissue. This study thus tested associations of circulating β-carotene and other nutrients with a structural neuroimaging indicator of brain age derived from cross-validated machine learning models trained to predict chronological age from brain tissue morphology in independent cohorts.

METHODS: Midlife adults (N=132, aged 30.4 to 50.8 years, 59 female at birth) underwent a structural magnetic resonance imaging (MRI) protocol and fasting phlebotomy to assess plasma concentrations of β-carotene, retinol, γ-tocopherol, ⍺-tocopherol, and β-cryptoxanthin.

RESULTS: In regression analyses adjusting for chronological age, sex at birth, smoking status, MRI image quality, season of testing, annual income, and education, greater circulating levels of β-carotene were associated with a lower (i.e., younger) predicted brain age (β=-0.23, 95% CI=-0.40 to -0.07, P=0.006). Other nutrients were not statistically associated with brain age, and results persisted after additional covariate control for body mass index, cortical volume, and cortical thickness.

CONCLUSIONS: These cross-sectional findings are consistent with the possibility that dietary intake of β-carotene may be associated with slower biological aging at the level of the brain, as reflected by a neuroimaging indicator of brain age.

PMID:40359351 | DOI:10.1097/PSY.0000000000001399

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Otopathologic Patterns of Cellular Degeneration in the Peripheral Vestibular Organ Secondary to Head Trauma

Laryngoscope. 2025 May 13. doi: 10.1002/lary.32258. Online ahead of print.

ABSTRACT

OBJECTIVE: This study examined patterns of cellular and neural degeneration in the peripheral vestibular system following head trauma, comparing cases with and without skull/temporal bone fractures.

METHODS: We analyzed 26 temporal bones (17 cases) with head trauma with fractures (six cases, nine ears) and ones without fractures (11 cases, 17 ears). Appropriate age-matched control groups comprising temporal bones without temporal bone pathology were included for comparative purposes. Histopathological analyses included counts of Scarpa’s ganglion cells (ScGCs) in the superior and inferior vestibular nerves (SVN and IVN), and counts of vestibular hair cells (HCs) in the utricle, saccule, lateral semicircular canal (LSCC), and posterior semicircular canal (PSCC). Mann-Whitney U tests were used for statistical analyses.

RESULTS: The group without fractures showed a significant reduction in total ScGCs (SVN + IVN) compared to controls (p = 0.040), with a pronounced decrease in the SVN (p = 0.014). Significant reductions in type I and type II HCs were observed in the utricle (p = 0.008 and p = 0.035) and in type I HCs in the LSCC (p = 0.037). In the group with fractures, only type I HCs in the utricle were significantly reduced (p = 0.038).

CONCLUSION: Head trauma without fractures is associated with more severe vestibular cell degeneration and greater loss of ganglion cells in the SVN in our specimens. These findings suggest that head trauma without fractures may pose a higher risk for vestibular cell damage compared with trauma with fractures.

LEVEL OF EVIDENCE: NA.

PMID:40359321 | DOI:10.1002/lary.32258

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Transcriptional pattern enriched for synaptic signaling is associated with shorter survival of patients with high-grade serous ovarian cancer

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

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Analyzing Usage of the Metaverse by Associations of Patients With Prostate Cancer During the 2023 Blue Ribbon Campaign: Cross-Sectional Survey Study

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

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Preservation versus Sacrifice of the Supraclavicular Nerves during Clavicle ORIF: A Randomized Controlled Trial

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

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Delayed Wound Healing Worsens Outcomes in Flexor Tendon Repair Surgery

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

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A Clinical Research Interaction Scale for Racial and Ethnic Minority Participants

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

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Stigmatizing and Positive Language in Birth Clinical Notes Associated With Race and Ethnicity

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