Tag: nevin manimala

J Clin Oncol. 2025 Oct 13:JCO2500036. doi: 10.1200/JCO-25-00036. Online ahead of print.

ABSTRACT

PURPOSE: Immunotherapy targeting PD-L1 improves outcomes in patients with unresectable stage III non-small cell lung cancer (NSCLC) and no progression after definitive, concurrent chemoradiotherapy (cCRT). Earlier administration of immunotherapy, simultaneously with cCRT, may improve outcomes further.

METHODS: Eligible patients were randomly assigned (2:1) to receive either durvalumab or placebo administered from the start of cCRT. Patients without progression after completing cCRT received consolidation durvalumab or placebo (per initial random assignment) until progression. The primary end point was progression-free survival (PFS) by blinded independent central review. Key secondary end points included objective response rate (ORR), overall survival (OS), the proportion of patients alive at 24 months (OS24), and safety.

RESULTS: In total, 328 patients were randomly assigned to receive durvalumab (n = 219) or placebo (n = 109). There was no statistically significant difference with durvalumab versus placebo in PFS (hazard ratio [HR], 0.85 [95% CI, 0.65 to 1.12]; P = .247) or OS (HR, 1.03 [95% CI, 0.78 to 1.39]; P = .823); OS24 was 58.4% versus 59.5%, respectively. Confirmed ORR was 60.7% with durvalumab versus 60.6% with placebo (difference, 0.2% [95% CI, -15.2 to 16.3%]; P = .976). With durvalumab versus placebo, respectively, maximum grade 3 or 4 adverse events (AEs) occurred in 53.4% versus 59.3% of patients, pneumonitis or radiation pneumonitis (group term) in 28.8% (grade ≥3: 4.6%) versus 28.7% (grade ≥3: 5.6%), AEs leading to discontinuation of durvalumab or placebo in 25.6% versus 12.0%, and fatal AEs in 13.7% versus 10.2%.

CONCLUSION: Among patients with unresectable stage III NSCLC, durvalumab administered from the start of cCRT failed to demonstrate additional benefit compared with cCRT plus placebo. Consolidation durvalumab following definitive cCRT remains the standard of care in this setting.

PMID:41082707 | DOI:10.1200/JCO-25-00036

Neurology. 2025 Nov 11;105(9):e214309. doi: 10.1212/WNL.0000000000214309. Epub 2025 Oct 13.

NO ABSTRACT

PMID:41082698 | DOI:10.1212/WNL.0000000000214309

Neurology. 2025 Nov 11;105(9):e214250. doi: 10.1212/WNL.0000000000214250. Epub 2025 Oct 13.

ABSTRACT

BACKGROUND AND OBJECTIVES: Preclinical-to-clinical translational failure is common in neurologic research. Reasons for translational failure are complex and multifaceted, but it is increasingly recognized that translational decision making may be influenced by preclinical work that is overly optimistic, due to a lack of scientific rigor. Previous research has demonstrated that statistical errors are common in preclinical research, yet results of preclinical null hypothesis significance testing contribute to the body of evidence used to evaluate whether a new intervention is a candidate for translation. However, no empirical investigations exist yet that compare positive and negative clinical trials on the statistical soundness of contributing studies. The aim of this study was to explore, for 3 neurologic indications (multiple sclerosis, Parkinson disease, epilepsy), whether negative clinical trials show a higher prevalence of statistical misapplication in preceding animal experiments, compared with positive human trials.

METHODS: A modified meta-research, case-control design with multistep systematic search was used. Phase 2 clinical trials (completed January 1, 2010-October 31, 2020) were identified on ClinicalTrials.gov. Best practice methods were used to systematically search MEDLINE and Embase for animal experiments preceding the start of each human trial, for each intervention and disease. Statistical reporting and decision-making data were gathered from animal articles by collectors blinded to human trial outcome. Rates of statistical mistakes were compared between animal articles preceding positive vs negative human trials using weighted percentages and CIs.

RESULTS: The final sample included 24 trials (8 negative) and 70 associated rodent studies. Animal studies preceding negative human trials had higher rates of misapplication of solely cross-sectional statistical tests to longitudinal data (93% [95% CI 83-100] vs 66% [95% CI 47-82]) and of the use of plots that concealed continuous data distributions (98% [95% CI 95-100] vs 71% [95% CI 51-91]), indicating possible mishandling of continuous data.

DISCUSSION: Statistical practice in animal studies was generally poor or not well reported, with rates of some statistical mistakes occurring more frequently before negative trials than positive trials. This was an exploratory study with a highly selected sample, yet it suggests that translational decision making should include evaluation of the quality of preclinical statistical practice.

PMID:41082697 | DOI:10.1212/WNL.0000000000214250

Ecol Lett. 2025 Oct;28(10):e70219. doi: 10.1111/ele.70219.

ABSTRACT

The phenotypes of individuals within a population create a dynamic social environment that influences phenotypic selection and population growth. Fluctuations in the frequencies of these phenotypes can influence population mean fitness and the relative fitness of phenotypes, and thus impact both population dynamics and phenotypic evolution. Various theoretical frameworks have been used to study the impact of frequency dependence on ecological and evolutionary dynamics. However, their diversity and mathematical complexity have obscured the relationship between theoretical models and empirical work. To bridge this gap, we discuss the effects of frequency dependence on phenotypic selection and population growth from a statistical perspective. We classify frequency-dependent effects on fitness according to their additive, relative or multiplicative effects, and explore how their interaction with population density can affect the eco-evolutionary dynamics of continuous traits. We show how these different effects can be mapped onto the parameters of simple linear regression models and derive how their magnitude is expected to affect the population carrying capacity and equilibrium mean phenotype. We then use individual-based simulations to complement our analytical results and demonstrate that quantifying frequency-dependent effects on fitness is key for understanding how populations will respond to environmental change.

PMID:41082684 | DOI:10.1111/ele.70219

J Physician Assist Educ. 2025 Oct 14. doi: 10.1097/JPA.0000000000000716. Online ahead of print.

ABSTRACT

INTRODUCTION: Physician associates/assistants (PAs) require extensive clinical training through supervised clinical practice experiences (SCPEs) to meet accreditation standards. While PA programs must document student performance during rotations, there is considerable variability in assessment methods. Many programs use a 2-pronged approach: end-of-rotation (EOR) exams and preceptor evaluations. This study aims to evaluate whether SCPE preceptor evaluations are associated with student performance on EOR exams or Physician Assistant National Certifying Examination (PANCE).

METHODS: This retrospective study analyzed data from 782 students across 3 PA programs over 5 years (2020-2024). The study focused on Family Medicine, Emergency Medicine, and Internal Medicine rotations, comparing preceptor evaluations with EOR and PANCE scores.

RESULTS: Mean PANCE score was 468.2 ± 73.9, with mean EOR scores of 410.6 ± 23.2 for internal medicine, 409.3 ± 22.7 for family medicine, and 410.2 ± 22.1 for emergency medicine. Preceptor evaluations averaged 4.36 ± 0.7 on a 5-point Likert scale. While some statistically significant correlations were identified between preceptor evaluations and standardized exam performance, correlation coefficients were weak (-0.11 to 0.17).

DISCUSSION: Despite some statistically significant correlations, the practical utility of preceptor evaluations in predicting standardized exam performance is negligible. This suggests that preceptor evaluations, although essential to evaluate for clinical competencies beyond standardized evaluations, may not be predictive of academic student success. Preceptor evaluations reveal a weak correlation, when present, with standardized examinations. These findings prompt reflection upon the traditional reliance on preceptor evaluations and suggest that future research is needed at both the programmatic and national levels to capture a comprehensive understanding of student competence as a future clinician.

PMID:41082682 | DOI:10.1097/JPA.0000000000000716

Microsurgery. 2025 Oct;45(7):e70120. doi: 10.1002/micr.70120.

ABSTRACT

BACKGROUND AND OBJECTIVES: The tongue is the most common site of oral malignancy, and surgical treatment may result in impaired feeding, swallowing, and speech. Free tissue transfer is the preferred method for reconstructing complex defects. Evidence remains unclear on whether sensory reinnervation improves function. The objective of this review is to evaluate the outcome of patients undergoing innervated versus noninnervated free flap reconstruction following tongue cancer surgery.

METHODS: A systematic review was performed to determine the role of sensory neurotization in lingual reconstruction. Only studies with comparative designs were eligible for inclusion. Primary outcome measures included static two-point discrimination (S2PD), pinprick sensation, swallowing, and speech. A meta-analysis was performed using key data analysis to calculate weighted effect sizes for reconstruction with or without neurotization using random-effects models. The statistical heterogeneity was determined using the Higgins’ method.

RESULTS: Nine studies were included which produced 107 reinnervated flaps and 117 non-innervated flaps for pooled analysis. Objective measures of sensation were significant, favoring the reinnervation group for pinprick sensation and S2PD (p < 0.05), with the pooled difference in proportions being 0.25 and -13.88 (0.06-0.45, 95% CI, -26.66 mm to -1.11, 95% CI), respectively. Functional outcome measures revealed significantly improved speech in the reinnervated group (p < 0.05, non-weighted means 74.8 vs. 62.5%).

CONCLUSIONS: This study found a strong association favoring the sensory neurotization for tongue reconstruction. Higher quality studies are required to further define the role of reinnervation for the restoration of swallow, relative differences between type of free flap selected, and measure changes in patients’ quality of life.

PMID:41082276 | DOI:10.1002/micr.70120

JAMA Netw Open. 2025 Oct 1;8(10):e2537160. doi: 10.1001/jamanetworkopen.2025.37160.

ABSTRACT

IMPORTANCE: Uncertainty exists about whether women of West African ancestry have increased rates of estrogen receptor (ER)-negative breast tumors, which commonly have earlier age onsets than ER-positive tumors and are aggressive. High-quality population-based studies in Africa with tumor pathology data are generally unavailable, and there is speculation that younger population age structures may explain the increased frequencies of reported ER-negative tumors.

OBJECTIVE: To estimate age-standardized and age-specific rates of ER-negative breast cancer among Ghanaian women and non-Hispanic Black and non-Hispanic White women in the US.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used 2013 through 2015 data from a population-based case-control study conducted in 2 metropolitan areas of Ghana, Accra and Kumasi, to estimate ER-specific breast cancer incidence rates among women 18 to 74 years of age. Incidence rates were recovered by applying sampling weights for controls calculated by district, 5-year age groups, and nonresponse rates from the 2010 census-based enumeration area listings. US Breast Cancer Registry data were retrieved from 17 registries in the Surveillance, Epidemiology, and End Results (SEER) program for non-Hispanic Black and non-Hispanic White women with breast cancer 20 to 74 years of age. Analyses were conducted January 2020 through May 2025.

EXPOSURES: Age, sex, race and ethnicity, ER tumor status, and country (US and Ghana).

MAIN OUTCOMES AND MEASURES: For each of 3 populations, crude, age-standardized, and age-specific breast cancer incidence rates were calculated overall and by ER status.

RESULTS: Analyses were performed for 1071 women (age range, 18-74 years; 468 [51%] ER-negative) in Ghana and 18 321 non-Hispanic Black women (age range, 20-74 years; 5117 [29%] ER-negative) and 103 227 non-Hispanic White women (age range, 20-74 years; 15 040 [15%] ER-negative) in SEER. From 2013 through 2015, ER-negative age-standardized incidence rates were 42.3 (95% CI, 38.7-46.3) per 100 000 women for Ghanaian participants and 43.1 (95% CI, 42.0-44.3) per 100 000 for US non-Hispanic Black women, both higher rates than that of 24.0 (95% CI, 23.6-24.4) per 100 000 for US non-Hispanic White women. ER-positive age-standardized incidence rates were 42.1 (95% CI, 38.4-46.1) per 100 000 women for Ghanaian participants, 105.4 (95% CI, 103.6-107.3) per 100 000 for non-Hispanic Black women, and 128.5 (95% CI, 127.9-129.7) per 100 000 for non-Hispanic White women.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of Ghanaian and US non-Hispanic Black and non-Hispanic White women with breast cancer, age-standardized tumor incidence rates for women with ER-negative tumors in Ghana were similar to those for US non-Hispanic Black women, and both rates were higher than for US non-Hispanic White women. This finding may suggest increased susceptibility requiring elucidation in US non-Hispanic Black and West African populations.

PMID:41082230 | DOI:10.1001/jamanetworkopen.2025.37160

JAMA Intern Med. 2025 Oct 13. doi: 10.1001/jamainternmed.2025.5263. Online ahead of print.

ABSTRACT

IMPORTANCE: An estimated 70% to 80% of older adults develop delirium in the intensive care unit (ICU).

OBJECTIVE: To determine if a slow-tempo music (60-80 beats/min) listening intervention decreases delirium duration, delirium severity, pain, or anxiety in older adults undergoing mechanical ventilation.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial with concealed outcomes assessments was conducted in older adults undergoing mechanical ventilation from February 2020 to December 2023. Patients were enrolled from the ICUs of 2 hospitals affiliated with the Indiana University School of Medicine and from the Mayo Clinic in Rochester, Minnesota.

INTERVENTION: A music intervention comprising classical and contemporary tracks, delivered twice daily through noise-canceling headphones and tablets for up to 7 days, was compared to active control listening to a silence track delivered under identical conditions.

MAIN OUTCOMES AND MEASURES: The primary outcome was delirium/coma-free days during the 7-day intervention period assessed by the Confusion Assessment Method for the ICU (CAM-ICU) and the Richmond Agitation-Sedation Scale. The secondary outcomes were delirium severity assessed by the CAM-ICU-7, pain assessed by the Critical Care Pain Observation Tool, and anxiety assessed by the visual analog scale for anxiety (VAS-A).

RESULTS: A total of 158 patients were randomized (mean [SD] age, 68 (9.2) years; 72 [45.5%] female and 86 [54.4%] male). In an intention-to-treat analysis, no differences were found in the number of delirium/coma-free days in the music intervention group compared with control (median [IQR] days, 2.5 [0-5] vs 3 [0-5]; P = .66). There were also no statistically significant differences in the mean CAM-ICU-7 scores, mean pain scores, or mean VAS-A scores over the 7-day intervention period. By end of the 7-day period, both music intervention and control groups had similar mean (SD) CAM-ICU-7 scores (2.72 [2.80] vs 2.56 [2.72]), Critical Care Pain Observation Tool scores (0.20 [0.55] vs 0.61 [1.29]), and VAS-A scores (43.6 [24.7] vs 28.8 [38.4]).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial among older adults undergoing mechanical ventilation, a slow-tempo music intervention did not demonstrate a statistically significant decrease in delirium duration, delirium severity, pain, or anxiety symptoms.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04182334.

PMID:41082215 | DOI:10.1001/jamainternmed.2025.5263

Psychooncology. 2025 Oct;34(10):e70306. doi: 10.1002/pon.70306.

ABSTRACT

BACKGROUND: Valid and reliable measurement tools are needed to plan programs that address the stigmatization of adolescents and to monitor the effectiveness of these programs in childhood cancers, where early diagnosis and treatment are decisive for prognosis. In this context, the development of a stigmatization scale for childhood cancers in adolescents will provide an objective tool for health professionals and researchers to assess stigma and evaluate the effectiveness of interventions designed to reduce it.

OBJECTIVES: This study aims to develop a valid and reliable measurement tool to determine adolescents’ stigma of childhood cancer and to examine its psychometric properties.

METHODS: This methodological study was conducted with 500 adolescents in Türkiye between November 2024 and December 2024. Data were collected with the “The Information Form and the Stigmatization Scale for Childhood Cancers for Adolescents (STS-CA)”. IBM SPSS 25.0 and IBM AMOS 25.0 software programs were used for data analysis, and descriptive statistics were used to analyze numeric variables. Exploration and confirmatory factor analyses were performed to determine the scale’s factorial structure.

RESULTS: The factorial analysis was used to test the structural validity of the scale. A three-factor structure consisting of 22 items was developed. The Cronbach’s alpha coefficients for the Avoidance of Friendship and Social Relationships sub-scale, Health Status and Perception of Difference sub-scale, Emotional Burden and Social Isolation sub-scale and total Cronbach’s alpha coefficients were 0.642, 0.744, 0.579 and 0.910, respectively. Fit indices resulting from the study were χ²/sd: 2.725, RMSEA: 0.075, GFI: 0.90, CFI: 0.90, and NFI: 0.90.

CONCLUSIONS: The Stigmatization Scale for Childhood Cancers for Adolescents (STS-CA) is a valid and reliable scale to determine the stigma level of adolescents toward childhood cancers.

IMPLICATIONS FOR PRACTICE: The scale provides a practical tool for health professionals to assess adolescents’ stigmatization levels, plan and implement interventions to reduce stigma, and evaluate their effectiveness. It may also be used to guide educational activities and awareness programs that support psychosocial well-being in adolescents affected by childhood cancer.

PMID:41082211 | DOI:10.1002/pon.70306