Tag: nevin manimala

JAMA Netw Open. 2025 Apr 1;8(4):e257733. doi: 10.1001/jamanetworkopen.2025.7733.

ABSTRACT

IMPORTANCE: Clinical trials represent the gold standard to test the safety and efficacy of new or updated approaches to treatments that will inform quality cancer care. However, cancer trials enroll few patients in low- and middle-income countries (LMICs), are often led by investigators from high-income countries, and do not adequately reflect global disease burden or population diversity.

OBJECTIVE: To identify key challenges and strategies to advance contextually relevant, quality cancer trials in LMICs.

DESIGN, SETTING, AND PARTICIPANTS: The survey used in this survey study was available in English, Arabic, French, Portuguese, and Spanish and was conducted by the US National Cancer Institute from October 18 to December 22, 2023. Clinicians with experience in cancer therapeutic clinical trials in LMICs were eligible. The survey covered their professional background and views on challenges and strategies for improving clinical trial opportunities in LMICs. Analysis was performed from April 2 to August 26, 2024.

MAIN OUTCOMES AND MEASURES: Respondents were asked to rate 34 challenges by impact on their ability to conduct cancer trials using a 4-point Likert scale and 8 strategies by importance using a 5-point Likert scale. Descriptive statistics summarized participants’ backgrounds, challenges, and priorities.

RESULTS: Of 453 respondents who began the survey, a total of 223 (49%) were eligible for inclusion, and 131 of those (59%) completed the survey in full. Among the 133 respondents who provided gender data, 81 (61%) were male. In all, 107 of 130 respondents (82%) were affiliated with LMIC institutions, 65 of 223 (29%) were medical oncologists, and 52 of 133 (39%) were midcareer. Financial challenges were rated as the most impactful, with 133 of 170 respondents (78%) rating difficulty obtaining funding for investigator-initiated trials as having a large impact on ability to carry out a trial. Human capacity issues followed, with 105 of 192 respondents (55%) rating lack of dedicated research time as having a large impact. Increasing opportunities for funding and improving human capacity were reported as key strategies to advance capacity to conduct clinical trials in LMICs.

CONCLUSIONS AND RELEVANCE: This survey study of clinicians with clinical trial experience in LMICs suggests that adequate funding and a well-trained research workforce are 2 predominant challenges to advancing cancer therapeutic clinical trials in LMICs. Understanding these obstacles can inform efforts to support cancer clinical trials that better reflect worldwide needs and diversity by prioritizing and sustaining research led by LMIC investigators.

PMID:40293747 | DOI:10.1001/jamanetworkopen.2025.7733

JAMA Netw Open. 2025 Apr 1;8(4):e257766. doi: 10.1001/jamanetworkopen.2025.7766.

ABSTRACT

IMPORTANCE: Older children awaiting a heart transplant (HT) sometimes receive a heart offer from a donor with a history of drug use (HDU). The effect of using such donor hearts on posttransplant survival in pediatric recipients is unclear.

OBJECTIVE: To assess the association of using hearts from donors with HDU on posttransplant graft survival in pediatric HT recipients.

DESIGN, SETTING, AND PARTICIPANTS: For this retrospective cohort study, all pediatric HT recipients (aged <18 years) in the Organ Procurement and Transplantation Network database during January 1, 2000, to December 31, 2020, were identified. Among the recipients who received a heart from a donor with HDU, nearly all donors were aged 11 years or older. A propensity score (PS) model was developed to assess the probability of receiving a heart from a donor with HDU using baseline recipient and donor variables, limiting the study cohort to donors aged 11 years or older. Data were analyzed from October 2023 to November 2024.

EXPOSURE: HT using a heart from a donor with HDU (exposure group) vs from a donor without HDU (control group).

MAIN OUTCOMES AND MEASURES: The main outcome was graft loss (death or retransplant) assessed at 90 days after transplant and long term among 90-day survivors. Kaplan-Meier survival curves and a Cox proportional hazards regression model that accounted for matching of exposure and control groups were used to compare risk of graft loss.

RESULTS: This study included 2730 pediatric HT recipients. Their median age at HT was 14 years (IQR, 11-16 years), and most (1642 [60.1%]) were male. Overall, the exposure group comprised 822 children who received a heart from a donor with HDU; of these, 765 (93.1%) were PS matched to the control group. There was no difference in risk of graft loss within 90 days (hazard ratio [HR], 0.93 [95% CI, 0.55-1.57]; P = .78) or at long-term follow-up (HR, 1.04 [95% CI, 0.87-1.25]; P = .68) between PS-matched groups. Risk of graft loss within 90 days was not significantly different in children who received a heart from a donor with a history of cocaine use (157 pairs) vs children in the control group (HR, 0.55 [95% CI, 0.19-1.54]; P = .25); however, the risk of long-term graft loss among 90-day survivors was significantly higher (HR, 2.03 [95% CI, 1.35-3.06]; P = .001).

CONCLUSIONS AND RELEVANCE: In this cohort study of pediatric HT recipients, there was no association of 90-day graft survival with donor HDU; however, donor history of cocaine use was associated with a higher risk of long-term graft loss. These findings may be important when considering a donor with HDU for pediatric HT candidates.

PMID:40293746 | DOI:10.1001/jamanetworkopen.2025.7766

Environ Toxicol Chem. 2025 Apr 28:vgaf111. doi: 10.1093/etojnl/vgaf111. Online ahead of print.

ABSTRACT

Microplastics (MPs) are pervasive pollutants due to their extensive dispersion across terrestrial, marine, freshwater environments, and even the atmosphere. Beyond the common sources of MPs from the degradation of larger plastic items, an often-overlooked primary source is glitter. Widely incorporated into everyday products, glitter not only poses a significant environmental risk due to its ease of dispersion but also holds cultural importance in regions like Brazil, where it is extensively used in festivities. Understanding glitter as a type of microplastic can offer valuable insights into the effects of MPs on aquatic ecosystems, particularly concerning freshwater macroinvertebrates. Given the ecological significance of this issue, our study investigated the ingestion and potential bioaccumulation of MPs by macroinvertebrates in the phytotelmata of Aechmea blanchetiana bromeliads. Organisms were exposed to a microplastic treatment (0.1 g/L glitter) for seven days, followed by taxonomic identification and analysis of MP distribution across body segments. Statistical tests assessed variations in MP distribution among taxa and body regions. Results revealed significant MP ingestion, with the highest concentrations in Culicidae and Chironomidae, suggesting that their generalist feeding behaviors facilitate MP intake. Observations also pointed to preferential accumulation of MPs in certain body parts, indicating potential bioaccumulation. Additionally, the presence of fragmenting MP particles within these taxa highlights their potential role in enhancing MP bioavailability in aquatic environments. Chironomidae and Culicidae, through ingestion and fragmentation, may increase MP dispersal across trophic levels, which could exacerbate bioaccumulation risks within the food web. This evidence supports the use of Chironomidae and Culicidae as effective biomonitors for MPs and calls attention to the ecological implications of glitter pollution in tropical freshwater ecosystems.

PMID:40293741 | DOI:10.1093/etojnl/vgaf111

J Pediatr Orthop B. 2025 Apr 29. doi: 10.1097/BPB.0000000000001253. Online ahead of print.

ABSTRACT

Opioids are the mainstay of pain management in scoliosis surgery. We hypothesized that in adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF) surgery, perioperative intravenous (IV) lidocaine would reduce postoperative opioid requirement and pain scores. In this retrospective observational before-and-after study, we identified AIS patients who underwent single-stage PSF at a tertiary university hospital from 2020 to 2022. All patients received total intravenous anesthesia. The Lidocaine group received a bolus of 1.5 mg/kg IV lidocaine prior to induction, followed by infusion at 2 mg/kg/h. At wound closure, the rate was reduced to 1 mg/kg/h and continued for 30 min in recovery. All patients received patient-controlled analgesia (PCA) morphine postoperatively. The primary outcome was total morphine consumption in the first 24 h. The secondary outcome was mean pain scores over 48 h using a numerical rating scale. We included 115 patients: 59 in the Usual Care group and 56 in the Lidocaine group. Postoperative morphine use in the first 24 h showed no significant difference (Lidocaine: 13.5 ± 8.9 mg vs Usual Care: 13.9 ± 10.6 mg; P = 0.821). The cumulative morphine milligram equivalents per kilogram bodyweight at 48 h was 0.43 mg/kg. Mean pain scores were higher in the Lidocaine group in the first 48 h (4.25 ± 0.37 vs 3.67 ± 1.46; P = 0.03). Perioperative IV lidocaine administered as an analgesic adjunct for AIS surgery did not reduce postoperative morphine requirement. Although pain scores were statistically higher in patients receiving intravenous lidocaine, the difference was minimal and lacked clinical significance.

PMID:40293731 | DOI:10.1097/BPB.0000000000001253

J Strength Cond Res. 2025 Apr 29. doi: 10.1519/JSC.0000000000005116. Online ahead of print.

ABSTRACT

Nakamura, H, Yamashita, D, Nishiumi, D, Nakaichi, N, and Hirose, N. Factors influencing change of direction performance in youth soccer players: velocity-time profile analysis of the Pro-Agility test. J Strength Cond Res XX(X): 000-000, 2025-The purpose of this study was to assess factors influencing change of direction (COD) deficit (CODD) and total time completion (CODTT) in adolescent soccer players through velocity-time profile analysis of the Pro-Agility Test. We enrolled 71 junior high school male soccer players and measured the 20-m sprint time and CODTT of the Pro-Agility Test, calculating CODD by subtracting the 20-m sprint time from CODTT. In addition, 3-dimensional motion data were collected using a markerless motion capture system during the Pro-Agility Test. Each section (5 m in the first, 10 m in the second, and 5 m in the third) was divided into acceleration and deceleration phases based on center of mass (COM) velocity, which were further divided into early and late halves. The mean COM acceleration during the acceleration phase (Acc) and deceleration during the deceleration phase (Dec) were calculated. Stepwise multiple regression analysis was performed to identify phases affecting CODTT and CODD. Statistical significance was set at p < 0.05. Total time completion of a COD task was explained by the second early Acc (β = -0.500), second late Dec (β = 0.433), and 20-m sprint time (β = 0.226) (adjusted R2 = 0.858), whereas CODD was explained by the second late Dec (β = 0.561) and second early Acc (β = -0.271) (adjusted R2 = 0.459). Maturity offset significantly correlated with CODTT (r = -0.456) but not with CODD (r = -0.119). The results indicated that deceleration and reacceleration during the Pro-Agility Test can be evaluated in adolescents by combining CODTT and CODD.

PMID:40293724 | DOI:10.1519/JSC.0000000000005116

J Strength Cond Res. 2025 Apr 29. doi: 10.1519/JSC.0000000000005089. Online ahead of print.

ABSTRACT

McBride, JM, Bauer, EC, Kaufmann, NC, Triplett, NT, and Shanely, RA. Handgrip strength associated with leg strength, power, and muscle mass in 18-64-year-old males and females. J Strength Cond Res XX(X): 000-000, 2025-The purpose of this investigation was to determine the association between handgrip strength (HGS) and measures of leg strength, power, and muscle mass. Twenty-one men (age = 32.9 ± 11.4 years, height = 175.7 ± 8.3 cm, body mass = 83.6 ± 14.4 kg, body fat = 22.6 ± 6.2%) and 24 women (age = 35.5 ± 14.0 years, height = 164.6 ± 6.8 cm, body mass = 65.2 ± 8.6 kg, body fat = 30.0 ± 5.7%) performed a HGS test, a squat and leg press 1 repetition maximum (1RM), a countermovement jump (CMJ) on a force plate, and a dominant leg peripheral quantitative computed tomography thigh scan to calculate muscle cross-section area (CSA). Lean body mass was determined through dual x-ray absorptiometry. Jump height and impulse were calculated from force time curves from the CMJ as a representation of leg muscular power. Strong statistically significant correlations were found between HGS and squat 1RM (r = 0.80, p ≤ 0.0001), leg press 1RM (r = 0.79, p ≤ 0.0001), CMJ height (r = 0.78, p ≤ 0.0001), CMJ impulse (r = 0.84, p ≤ 0.0001), and thigh muscle CSA (r = 0.75, p ≤ 0.0001 and lean body mass (r = 0.79, p ≤ 0.0001). This study indicates that HGS could be used as a preliminary screening tool for determination of leg strength, power, and muscle mass. These variables have been determined to be components to overall fitness that increase quality of life and overall health. Thus, health care providers may be able to use this simple test as an early indication of possible risk factors for poor health and well-being.

PMID:40293720 | DOI:10.1519/JSC.0000000000005089

Cell Biochem Biophys. 2025 Apr 28. doi: 10.1007/s12013-025-01764-9. Online ahead of print.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking hormonal and HER2 receptors, making it highly resistant to treatment. Apo2L/TRAIL, a tumor necrosis factor-related ligand, induces apoptosis in cancer cells via the death receptor DR4. However, TNBC often develops resistance to TRAIL-mediated apoptosis, limiting its therapeutic potential. This study investigates whether arsenic trioxide (ATO) can overcome TRAIL resistance by modulating the Apo2L/TRAIL pathway and enhancing the effects of carboplatin (CP) and cyclophosphamide (CY). TNBC cell lines BT-20 and MDA-MB-231 were treated with ATO, CP, CY, and their combinations. Cell viability was measured using the MTT assay, while real-time PCR and Western blot analysis assessed Apo2L/TRAIL and DR4 expression. Statistical analysis was performed using ANOVA with Dunnett’s post hoc test. ATO induced dose-dependent cytotoxicity in TNBC cells, which was significantly enhanced in combination treatments. The highest reductions in cell viability were observed with 3 µM ATO plus 5000 µM CP or 500 µM CY (p < 0.0001). ATO markedly upregulated Apo2L/TRAIL and DR4 at both mRNA and protein levels, with the most pronounced effects seen in ATO-CY combinations. These findings indicate that ATO sensitizes TNBC cells to TRAIL-mediated apoptosis by upregulating DR4 and Apo2L/TRAIL, while also exhibiting strong synergistic cytotoxicity with CP and CY. This highlights ATO’s potential as an adjuvant therapy to improve TNBC treatment efficacy and overcome chemoresistance, warranting further clinical exploration.

PMID:40293700 | DOI:10.1007/s12013-025-01764-9

J Racial Ethn Health Disparities. 2025 Apr 28. doi: 10.1007/s40615-025-02455-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Black patients have the worst survival outcomes from colorectal cancer (CRC) in the US. In addition, disparities and differences in mortality outcomes among Black and NHW patients across the four US census regions (Northeast [NE], South, West, Midwest [MW]) remain unexplored. We hypothesized that survival outcomes for Black patients would differ across the US census regions and might correlate with socioeconomic factors.

METHODS: Black and Non-Hispanic White (NHW) patients ≥ 45 years of age with a diagnosis of colon or rectal adenocarcinoma between 2010 and 2018 were identified in the National Cancer Database for survival analysis. Survival differences were further validated using the Surveillance, Epidemiology, and End Results (SEER) database to investigate 5-year cause-specific survival (CSS).

RESULTS: For colon adenocarcinoma, the largest difference in median overall survival (OS) between NHW and Black patients was in the MW (67 months Black vs. 74 months NHW, P < 0.001). For rectal cancer, the largest difference was in the West (60 months Black vs. 84 months NHW, P < 0.001). Black patients receiving care in the MW had the lowest median OS for CRC, while those in the NE had the highest (colon: 67 months MW vs. 100 months NE; rectum: 55 months MW vs. 79 months NE). In multivariable analyses of the Black patient cohort, cancer care in the NE was associated with decreased mortality risk compared to other regions.

CONCLUSION: Geographic region of care appears to correlate with survival differences for CRC. Exploring these differences may facilitate improved understanding of systemic and structural drivers of health inequities and aid improved resource allocation.

PMID:40293690 | DOI:10.1007/s40615-025-02455-0

Pharmacoeconomics. 2025 Apr 28. doi: 10.1007/s40273-025-01491-2. Online ahead of print.

ABSTRACT

OBJECTIVE: In this study we aimed to identify possible changes over time in validation efforts and the way in which they are reported for model-based health economic (HE) evaluations, given the introduction of several new validation tools and methods in the past decade.

METHODS: A systematic review was conducted using PubMed and Embase on published HE models for early breast cancer (EBC) for the period 2016 to 2024. AdViSHE-consisting of four validation categories that cover the main HE model aspects-was utilized to systematically evaluate the reported evaluation efforts. The percentage of studies reporting validation per category was compared with the review by de Boer et al. that covers the years 2008 to 2015.

RESULTS: Of the 2199 records, 78 studies fulfilled the eligibility criteria. Reported validation efforts did not significantly improve compared with the previous period, except for the validation of input data by experts. Reporting on the validation of the conceptual model remained low with around 10% of the studies providing validation. Validation of the computerized model and validation against outcomes using alternative input data were the most underreported validation categories with < 4% of the studies. The validation of model outcomes, specifically cross validity and the comparison with empirical data, remained the most reported categories in this review also, with 52% and 36%, respectively. When validation efforts were reported, this was done in a non-systematic manner, and the tests and results were rarely detailed.

CONCLUSION: Overall reporting of validation efforts for model-based HE evaluations in the past decade did not significantly change compared with the previous decade.

PMID:40293688 | DOI:10.1007/s40273-025-01491-2

J Neurooncol. 2025 Apr 28. doi: 10.1007/s11060-025-05047-4. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the feasibility of introducing additional Mixed Reality (MR) visualisation of patient-specific imaging during the neurosurgical consultation to improve patients’ understanding, as well as the potential benefits from a patient’s perspective to the consultation process.

METHODS: An IDEAL Stage 2a feasibility randomised controlled trial was conducted involving patients with radiologically suspected brain tumours at a large, tertiary UK neurosurgery institution. Patients were randomised into two groups: standard 2D monitor versus additional MR visualisation. Primary feasibility outcomes included recruitment rates, MR intervention adherence, fidelity, and acceptability. Secondary outcomes included patient-reported experiences. Quantitative and qualitative analyses were performed via validated questionnaires.

RESULTS: A total of 36 patients were randomised over 12 months, 17 to a Mixed Reality (MR) Group and 19 to a standard 2D monitor-only group, with no significant baseline differences. MR intervention was deemed feasible for further clinical evaluation with high fidelity and user acceptability. Patients in the MR group reported statistically higher satisfaction with information received, an improved patient-doctor relationship, greater confidence in decision-making, and a better understanding of their condition compared to the standard 2D monitor-only group. No major technological issues were encountered. No adverse effects were reported or observed (including cybersickness). Patients found the MR technology easy to use.

CONCLUSIONS: Our findings suggest that incorporating MR visualisation into routine neurosurgical consultations is feasible and offers potential benefits for patients. With minor modifications to the intervention and assessments, we aim to perform a larger-scale, multi-centre randomised feasibility trial, which will also address implementation challenges for widespread adoption and provide more indication of efficacy.

PMID:40293673 | DOI:10.1007/s11060-025-05047-4