Tag: pubmed

Pharmaceut Med. 2026 Mar 31. doi: 10.1007/s40290-026-00606-0. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Survival benefit constitutes the primary pillar of therapeutic efficacy in oncology. However, the survival benefits observed in registrational trials broadly range from significant to marginal, even for US Food and Drug Administration (FDA)-approved drugs. This study explores the association between survival benefits and the likelihood of FDA approval and estimates the boundary effect size that distinguishes FDA-approved from non-approved drugs.

METHODS: We screened 3463 phase 3 trials initiated between 1990 and 2021 on ClinicalTrials.gov. Eligibility was restricted to randomized phase 3 trials for novel anticancer agents with overall survival (OS) as a primary or co-primary endpoint. Included trials required published results, including the OS hazard ratio (HR) and 95% confidence interval (CI). A total of 189 eligible trials were identified, encompassing 208 arm-pairs and 158,250 participants. Clinical data were extracted from published reports, while regulatory outcomes were adjudicated at the trial-and-indication level using US Prescribing Information on Drugs@FDA database. The association between OS benefit and approval status was modeled using logistic regression, with generalized estimating equations (GEE) to account for trial-level clustering. Publication bias was assessed via funnel plots and the trim-and-fill method.

RESULTS: Of the 208 arm-pairs, 79 (38%) supported FDA approval, and 129 (62%) did not. The dataset spanned 27 cancer types, with a mean sample size of 761 participants. The pooled OS HR was 0.70 (95% CI 0.68-0.73) for approved drugs and 0.95 (95% CI 0.93-0.97) for non-approved drugs. Logistic regression revealed a sharp sensitivity of approval probability to the HR for OS. A boundary was observed ranging from 0.74 to 0.86 in the HR for OS, with a 50% probability of FDA approval at HR 0.80. GEE analysis confirmed the robustness of these estimates against trial-level clustering. While funnel plot asymmetry suggested potential publication bias in the non-approved group, trim-and-fill analysis confirmed that the relative disparity in OS HR between approved and non-approved drugs remained consistent.

CONCLUSION: FDA approval for anticancer drugs is characterized by distinct OS HR patterns. While these findings provide a clear efficacy benchmark for OS-driven trials, they should be interpreted cautiously given the evolving therapeutic landscape and potential publication bias in negative trials. Our results underscore the central role of survival benefit in regulatory decisions and provide a quantitative metric to support oncology drug development.

FUNDING: This study was funded by the Ministry of Education, Culture, Sports, Science and Technology (MEXT): Shunsuke Ono KAKEN-HI: 25K10043.

PMID:41915314 | DOI:10.1007/s40290-026-00606-0

Clin Transplant. 2026 Apr;40(4):e70523. doi: 10.1111/ctr.70523.

ABSTRACT

BACKGROUND: In out-of-sequence (OOS) allocation of deceased donor kidney transplants (DDKTs), providers are allowed to choose recipients irrespective of waitlist priority. Whether candidate obesity affects OOS recipient selection is unknown.

METHODS: We examined access to OOS-DDKT by candidate body mass index (BMI) using kidney offers from Organ Procurement and Transplantation Network data (1/2022-12/2023). We compared characteristics of OOS-DDKT versus being last-skipped candidate at the same center using donor-level conditional logistic regression and multilevel modeling among the top-20 OOS-performing centers.

RESULTS: We identified 4970 OOS-placements and 4588 list-skipped candidates. OOS candidates were older and less likely to be Black. We found a dose-response relationship between weight class and odds of OOS-DDKT. Compared to normal weight candidates, candidates with Class 1, 2, and 3 obesity had 32%, 50%, and 69% lower odds of receiving OOS-DDKT. Mediation analysis suggested candidate BMI partially explained higher access among Asian and Hispanic candidates. There was substantial center-level variation; a 10-unit increase in BMI was associated with >50% lower odds of OOS-DDKT at 3/20 centers, 20%-50% lower odds at 12/20 centers, and comparable odds at 5/20 centers.

CONCLUSIONS: DDKT candidates with obesity have lower access to OOS kidney allocation. However, equitable distribution irrespective of candidate obesity was observed at a small number of top-performing centers.

PMID:41915312 | DOI:10.1111/ctr.70523

J Nurs Manag. 2026;2026(1):e1459619. doi: 10.1155/jonm/1459619.

ABSTRACT

BACKGROUND: Medical staff in Chinese tertiary hospitals experience excessive workloads, increasing burnout vulnerability. Traditional cultural resources may influence their job attitudes, but this area remains unexplored.

PURPOSE: Based on the job demands-resources model, this study investigates how Confucian coping, as a personal culture resource, moderates the relationships among job demands, resources, engagement and burnout in Chinese medical staff.

METHODS: Using an online self-administered survey, we collected data from 1653 medical staff members across 14 tertiary hospitals in China. Structural equation modelling was used to test the hypothesised moderating pathways.

RESULTS: Confucian coping demonstrated a significant positive moderating effect on the job resources-job engagement relationship and a significant negative moderating effect on the job demands-job burnout relationship.

CONCLUSION: Confucian coping serves as a significant personal resource for medical staff, mitigating burnout by buffering job demands and enhancing engagement by amplifying job resources.

ORIGINALITY: By employing empirical analysis with the job demands-resources model, this study unravels how medical staff draw on Confucian coping functions and provides a new theoretical perspective for further study of the influence of cultural and psychological factors.

PMID:41915299 | DOI:10.1155/jonm/1459619

Appl Health Econ Health Policy. 2026 Mar 31. doi: 10.1007/s40258-026-01040-8. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Publicly funded healthcare systems that consider a trade-off between efficiency and equity by allowing a higher cost per patient benefit in patients with more severe conditions must somehow assess disease severity. Some countries employ quantitative measures of shortfall, whereas others rely on qualitative assessments. Despite its importance in pharmaceutical reimbursement and pricing, the operationalisation of disease severity in real-world decision making has rarely been scrutinized. The aim of this study was to investigate the relationship and agreement between qualitative disease severity assessments and quantitative measures of disease severity in Swedish pharmaceutical reimbursement.

METHODS: Information from 36 pharmaceutical reimbursement decisions made by the Dental and Pharmaceutical Benefits Agency (TLV) in Sweden from 2018 to 2023 was extracted, including the qualitative assessment of disease severity (moderate, high, or very high). Based on publicly available decision documents from the agency, we calculated absolute QALY shortfall (AS) and proportional QALY shortfall (PS). Linear regression was used to describe the mean shortfall across severity classifications. Ordinal logistic regression was used to analyse the role of AS and PS as predictors of TLV’s qualitative disease-severity assessments and the predictive ability of both measures was compared using the coefficient of discrimination (D’).

RESULTS: The mean AS and PS was 12.2 and 0.796, respectively, in the very high disease severity category, which was approximately twice the mean shortfall observed in the moderate and high severity categories (Moderate: AS = 6.0, PS = 0.340; High: AS = 6.2, PS = 0.405). When the quantitative measures of severity were used as predictors of the qualitative assessments, PS was better able to discriminate between TLV’s severity classifications than was AS (D’ = 34.6% vs 22.3%). However, both measures frequently predicted low probabilities of the qualitative assessments that were observed and there was both substantial variation in shortfall for diseases with the same qualitative assessment (AS, R² = 35.8%; PS, R² = 61.0%) and overlaps in observed shortfall across different severity classifications.

CONCLUSION: Proportional QALY shortfall agrees more closely than AS with qualitatively assessed disease severity applied in the Swedish reimbursement system but there are large variations in the qualitative assessments that cannot be explained by either measure. Further investigation is warranted to understand if this is an intended and desired outcome.

PMID:41915293 | DOI:10.1007/s40258-026-01040-8

Environ Monit Assess. 2026 Mar 31;198(4):390. doi: 10.1007/s10661-026-15214-3.

ABSTRACT

Heavy metal pollution in groundwater poses global environmental and public health risks, particularly in agricultural regions relying on groundwater for irrigation and drinking. Here we quantify 11 heavy metals (Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Cd, Ba) in the Fengpei Plain, China, and apportion their sources and health impacts using the APCS-MLR receptor model coupled with health risk assessment. Mean concentrations ranked as: Sr (521.5 μg/L) > Ba (50.45 μg/L) > Fe (15.37 μg/L) > As (1.080 μg/L) > Zn (0.887 μg/L) > Cu (0.294 μg/L) > Cr (0.083 μg/L) > Ni (0.064 μg/L) > Co (0.032 μg/L) > Mn (0.027 μg/L) > Cd (0.011 μg/L). Source apportionment using the APCS-MLR model revealed five major sources of heavy metals in the study area, with their respective contributions as follows: iron ore mining (22.8%), traffic emissions (24.4%), agricultural activities (18.9%), industrial activities (6.4%), and unidentified sources (27.5%). The health risks associated with heavy metals in groundwater were mainly attributed to As ingestion through drinking water. At approximately 6.7% of sampling sites, the non-carcinogenic hazard index (HI) for children exceeded 1 (maximum 1.31), while adult carcinogenic risk (TCR) exceeded the acceptable threshold, reaching 1.39 × 10⁻4 for females and 1.13 × 10⁻4 for males. This study provides a comprehensive understanding of the distribution, sources, and health risks of groundwater heavy metals, offering valuable guidance for groundwater management and contributing to the protection of drinking water safety for residents in agriculture-dominated regions.

PMID:41915285 | DOI:10.1007/s10661-026-15214-3

Environ Monit Assess. 2026 Mar 31;198(4):388. doi: 10.1007/s10661-026-15261-w.

ABSTRACT

Pit latrines are widely used sanitation systems in underdeveloped countries. However, poor construction and maintenance often allow pathogenic bacteria to contaminate surrounding soil and water, facilitating the spread of enteric diseases. Young children are particularly vulnerable because geophagy (soil ingestion) increases exposure to fecal pathogens, leading to higher incidences of diarrhea, growth impairment, and mortality. This review investigates the association between pit latrine-derived contamination of water (surface and groundwater) and soil (including sludge) and its impacts on child health. Relevant studies were systematically collected, summarized, and compared. The health effects of pathogens, particularly among children aged 6-24 months, are discussed, along with reported child mortality rates linked to fecal contaminated soil and water. Common pathogens identified in contaminated soils include Escherichia coli, Salmonella, Bacteroides (HF183), and rotavirus, with several studies reporting multidrug-resistant strains. High child mortality from diarrhea and pneumonia has been consistently associated with poor sanitation and open defecation. Pit latrines promote aerobic decomposition at the sludge surface and anaerobic decomposition at depth, enabling pathogen survival, greenhouse gas emissions, and soil contamination. Improved latrine designs incorporating impermeable linings, along with phytoremediation strategies, may offer effective solutions to mitigate pathogen persistence and environmental contamination.

PMID:41915284 | DOI:10.1007/s10661-026-15261-w

Palliat Support Care. 2026 Mar 31;24:e87. doi: 10.1017/S1478951526102089.

ABSTRACT

PURPOSE: This study aimed to investigate the mediating role of perceived stigma in the relationship between cancer-related symptoms and social relationships among cancer patients.

METHODS: This cross-sectional descriptive study was conducted with 250 cancer patients undergoing chemotherapy in an oncology hospital in Ankara, Türkiye. Data were collected using a sociodemographic form, the Nightingale Symptom Assessment Scale, the Cataldo Lung Cancer Stigma Scale, and the Social Relationship Scale. Descriptive analyses, group comparisons, Pearson correlation, and mediation analysis were performed with SPSS v27.0 and DataTab web-based analysis platform.

RESULTS: The findings revealed significant positive correlations between cancer-related symptoms and perceived stigma (r = 0.51, p < .001), and negative correlations between both cancer-related symptoms and social relationships (r = -0.24, p < .001) and stigma and social relationships (r = -0.54, p < .001). The mediation analysis suggested that perceived stigma may play a mediating role in the relationship between cancer-related symptoms and social relationships, as indicated by a non-significant direct effect and a significant indirect effect. Cancer-related symptoms significantly predicted perceived stigma (B = 0.58, p < .001), and stigma was a significant predictor of decreased social relationship quality (B = -0.72, p < .001). The indirect effect of cancer-related symptoms on social relationships via stigma was statistically significant (B = -0.42, p < .001), while the direct effect was not (B = -0.27, p = .182).

CONCLUSIONS: Perceived stigma is a critical psychosocial factor that may mediate the adverse impact of cancer-related symptoms on social relationships in this study. Therefore, addressing stigma may play a crucial role in maintaining social functioning in cancer care.

PMID:41914306 | DOI:10.1017/S1478951526102089

J Integr Neurosci. 2026 Mar 25;25(3):44233. doi: 10.31083/JIN44233.

ABSTRACT

BACKGROUND: The subjective limitations of neurobehavioral assessment cause a high misdiagnosis rate for disorders of consciousness (DoC). The purpose of this study was to identify the DoC level based on an analysis of multi-dimensional electroencephalogram (EEG) signals to assist with establishing a clinical diagnosis.

METHODS: Sixty-seven patients with DoC [coma, n = 19; vegetative state (VS), n = 23; and minimally conscious state (MCS), n = 25] were included to analyze resting state EEG characteristics. The EEG features were statistically compared among five band powers (delta, theta, alpha, beta, and gamma) and five brain regions (prefrontal, frontal, parietal, temporal, and occipital) by multidimensional analyses, including time-domain analysis, spectral analysis, and functional brain connectivity.

RESULTS: Amplitude-integrated electroencephalography (aEEG) center amplitude showed significant differences between coma and MCS (p = 0.02688), with no significant differences observed for the other comparison. Spectral analysis revealed that delta and theta power decreased with higher consciousness levels, whereas alpha, beta, and gamma power increased. Relative power differed among groups across specific brain regions (prefrontal, frontal, parietal, temporal, and occipital) and frequency bands. Weighted Phase Lag Index (wPLI) based functional connectivity demonstrated frequency-specific network reorganization with theta band connectivity strongest in VS and alpha/beta/gamma band connectivity enhanced in MCS. Absolute power topographic maps showed expanding high-power regions from coma-to-MCS in high-frequency bands and the left dorsolateral prefrontal cortex (DLPFC) (F3 electrode) exhibited a consistent power gradient of coma < MCS < VS across all bands.

CONCLUSIONS: Multidimensional EEG features have significant value in differentiating the levels of consciousness disorders. aEEG center amplitude discriminated MCS from coma; delta/gamma relative power separated VS from MCS, and alpha/beta relative power separated coma, VS, and MCS. Parieto-occipital connectivity matrix in the theta band distinguishes coma from VS, while absolute power topography of the left DLPFC shows potential for grading levels of impaired consciousness. These electrophysiologic biomarkers complement behavioral assessments, enhancing diagnostic accuracy.

PMID:41914245 | DOI:10.31083/JIN44233

J Prim Care Community Health. 2026 Jan-Dec;17:21501319251412650. doi: 10.1177/21501319251412650. Epub 2026 Mar 31.

ABSTRACT

OBJECTIVES: This quasi-experimental study investigates the effects of the first-ever home treatment (HT), equivalent to inpatient care, for individuals with dual diagnoses: severe alcohol and/or substance use disorder plus major psychiatric illness. Outcomes are compared to those of regular inpatient treatment (IT) of the same addiction service. The primary objective was to evaluate feasibility and safety of HT. Secondary outcomes measures included discontinuation of treatment and service utilization during the 12-month follow-up period as defined by the number of emergency department visits and hospitalization days.

METHODS: Our Geneva model was introduced to meet local needs. In 2023, 39 individuals received home treatment (HT) for the first time, either in their own homes or in residential settings. They were retrospectively compared to a group of individuals who had undergone regular IT. Matching was based on age and gender. Allocation to IT or HT was determined by individual preferences as well as predefined inclusion and exclusion criteria following an evaluation interview. Electronic patient records were reviewed 1 year later to collect data on service use.

RESULTS: The primary outcome criteria were met. Treatment withdrawal occurred among IT patients only. At 1-year follow-up, a clear difference in addiction-related hospital days emerged in favor of HT, with smaller but still favorable for HT differences for sequelae and somatic problems. At intake, the HT and IT groups differed regarding stimulant and opioid use, as well as in the presence of the exclusion criteria history of complicated withdrawal and suicidality, which were only present in the IT group. Health of the Nations Outcome Scale (HoNOS) scores at admission and discharge did not differ between groups. Sociodemographic factors showed small differences for partnership status and housing, more pronounced ones for employment, in favor of HT patients.

CONCLUSIONS: This first study on HT for dual-diagnosis patients suggests that such treatment is feasible and safe, as demonstrated for HT in general psychiatry, and may offer certain advantages over inpatient care. Key limitations include the lack of randomization, the retrospective design, limited statistical power, and the fact that data can currently only be compared with HT from general adult psychiatry.

PMID:41914242 | DOI:10.1177/21501319251412650

Arch Ital Urol Androl. 2026 Mar 31;98(1):14883. doi: 10.4081/aiua.2026.14883.

ABSTRACT

INTRODUCTION: Antibiotic resistance represents a major public health problem driven by inappropriate antimicrobial use. Cystoscopy is a common urological procedure associated with a low risk of urinary tract infection (UTI), and the role of routine antibiotic prophylaxis remains controversial.

OBJECTIVE: To evaluate the effectiveness of antibiotic prophylaxis in preventing post-cystoscopy UTI.

MATERIALS AND METHODS: A prospective observational comparative study including 297 patients undergoing outpatient cystoscopy. Patients were assigned to Group A (no prophylaxis, n=161) and Group B (cefuroxime 500 mg prophylaxis, n=136). Urine cultures were obtained one hour before and one week after cystoscopy. Significant bacteriuria was defined as >104 CFU/ml. Risk factors were analyzed according to current literature. Fisher’s exact test and multivariate logistic regression were performed. Statistical analysis was performed using SPSS/R.

RESULTS: UTI occurred in 5.59% of patients without prophylaxis and 5.88% with prophylaxis (p=1.00). Antibiotic prophylaxis did not reduce infection risk (OR 0.95; 95% CI 0.36-2.53). Baseline characteristics and risk factors were similar between groups. No independent predictor reached statistical significance.

CONCLUSIONS: Routine antibiotic prophylaxis does not reduce post-cystoscopy UTI incidence in low-risk patients, supporting restrictive and rational antimicrobial use.

PMID:41914232 | DOI:10.4081/aiua.2026.14883