Nevin Manimala

Cancer. 2025 Nov 1;131(21):e70163. doi: 10.1002/cncr.70163.

ABSTRACT

BACKGROUND: Management of metastatic prostate cancer often requires combining androgen deprivation therapy (ADT) with novel androgen receptor signaling inhibitors (ARSIs). Although these agents improve survival, older patients may face acute care utilization from medication burden, reflected in polypharmacy and nonadherence.

METHODS: Using SEER-Medicare data, the authors identified patients ≥66 years old with de novo metastatic prostate cancer prescribed abiraterone, enzalutamide, or apalutamide (2010-2017). Polypharmacy was defined by the Youden index (≥8 medications). ARSI adherence was measured by medication possession ratio (≥0.8) from initiation to discontinuation, assessed over 6 months. Acute care use was defined as any inpatient hospitalization or emergency visit within 6 months. Demographic characteristics were compared by t-tests/χ². Negative binomial regression estimated incidence rate ratios (IRRs) for acute care use.

RESULTS: Among 2697 patients (mean age, 75 years), most were White (80.3%), married (63.1%), and received prior ADT (85.3%). Polypharmacy was present in 50.6% of patients before ARSI initiation, whereas ARSI nonadherence in the 6 months post-initiation was 34.0%. Polypharmacy and adherence were not significantly associated. In adjusted analyses controlling for demographic, clinical, and treatment factors, both polypharmacy (IRR, 1.59; 95% confidence interval [CI], 1.28-1.98) and ARSI nonadherence (IRR 2.50; 95% CI, 2.00-3.03) independently prognosticated higher acute care use.

CONCLUSIONS: Medication burden, as characterized by suboptimal adherence and polypharmacy, is an independent risk factor for acute care use among older adults initiating ARSI treatment for metastatic prostate cancer. These findings highlight an opportunity for potential interventions to reduce downstream acute care use.

PMID:41176642 | DOI:10.1002/cncr.70163

J Eval Clin Pract. 2025 Dec;31(8):e70300. doi: 10.1111/jep.70300.

ABSTRACT

RATIONALE: Skin cancer is a significant public health problem; it is one of the most commonly occurring cancers worldwide and imposes a high economic burden on society.

AIMS AND OBJECTIVES: This study aimed to elucidate the key factors affecting the cost of skin cancer in patients residing in southern Iran.

METHODS: A comprehensive list of cost-affecting factors for skin cancer was developed through a scoping review of relevant literature from multiple databases (PubMed, ProQuest, Scopus, ISI Web of Science, SID, and Magiran), supplemented by expert input from skin cancer specialists. Subsequently, the data about 216 skin cancer patients selected randomly were collected between March 2020 and March 2022. The factors affecting the costs of skin cancer were determined using SPSS 13.0 software through statistical tests and multiple regression analysis.

RESULTS: Multiple linear regression analysis identified mortality (p < 0.001), inpatient days (p < 0.001), and skin cancer type (p = 0.056) as key cost drivers. Mortality had the strongest impact, increasing costs by $78,249 per case (95% CI: ±$12,433), followed by each additional inpatient day ($4884 ± $845). Melanoma cases incurred $3727 higher costs than non-melanoma cases.

CONCLUSIONS: In conclusion, mortality, cancer type, and inpatient days were key cost drivers in skin cancer management. To mitigate these, we recommend nationwide high-risk screening, hospitalization reduction strategies, and prevention programs. Targeted mortality reduction requires early detection initiatives and public education on warning signs.

PMID:41176632 | DOI:10.1111/jep.70300

Coron Artery Dis. 2025 Oct 30. doi: 10.1097/MCA.0000000000001584. Online ahead of print.

ABSTRACT

BACKGROUND: Older adults undergoing percutaneous coronary intervention (PCI) face unique challenges due to complex anatomy and comorbidities. Intravascular imaging [including intravascular ultrasound (IVUS) and optical coherence tomography (OCT)] has been shown to improve PCI outcomes, but its benefits in older adults are less well established. We conducted a meta-analysis of randomized controlled trials (RCTs) to compare intravascular imaging with angiography alone to guide PCI in older adults.

METHODS: Cochrane, PubMed, and Scopus were searched for RCTs comparing intravascular imaging (IVUS or OCT) vs. angiography alone in adults aged ≥65 years. The outcome of interest was major adverse cardiovascular events (MACE) at the longest follow-up, as defined by each trial. Subgroup analyses were performed based on intravascular imaging modality, age group, and lesion complexity. Data were pooled using random-effects models, and heterogeneity was assessed using Higgins’ I² statistic.

RESULTS: Nine RCTs (n = 7164, intravascular imaging = 3703, angiography alone = 3461) met the inclusion criteria. Intravascular imaging significantly reduced MACE compared with angiography alone [relative risk (RR) 0.66, 95% confidence interval (CI) 0.56-0.77; P < 0.001; I² = 0%]. IVUS demonstrated superiority over angiography alone (RR 0.55, 95% CI 0.43-0.72; P < 0.001; I² = 0%), while OCT demonstrated only a trend toward MACE reduction (RR 0.80, 95% CI 0.62-1.02). Subgroup analyses indicated consistent benefits with intravascular imaging for adults aged ≥65 and ≥70 years, respectively, and among those with complex coronary lesions (RR 0.65, 95% CI 0.53-0.79; P < 0.001).

CONCLUSION: Intravascular imaging guidance, especially IVUS, reduces MACE in older adults undergoing PCI compared with angiography alone.

PMID:41176629 | DOI:10.1097/MCA.0000000000001584

BMC Anesthesiol. 2025 Nov 1;25(1):541. doi: 10.1186/s12871-025-03418-y.

ABSTRACT

BACKGROUND: Robotic-assisted minimally invasive esophagectomy (RAMIE) has become an increasingly adopted approach for the treatment of esophageal cancer. However, the impact of intraoperative fluid therapy on postoperative outcomes remains poorly defined. Whereas fluid overload has been linked to pulmonary and anastomotic complications, restrictive strategies may impair tissue perfusion and organ function. This study investigates the association between intraoperative fluid balance and postoperative morbidity in patients undergoing RAMIE.

METHODS: We conducted a retrospective single-center cohort study including 254 consecutive patients who underwent elective RAMIE between 2019 and 2024. Intraoperative fluid balance was calculated in mL/kg/h and analyzed as a continuous variable. Primary endpoints included pulmonary complications, anastomotic leakage, postoperative atrial fibrillation (POAF), and acute kidney injury (AKI). Secondary endpoints comprised ICU length of stay (LOS), postoperative delirium, delayed gastric emptying (DGE), and complication severity according to the Clavien-Dindo classification. Multivariable regression models were adjusted for age, sex, BMI, and ASA status.

RESULTS: Pulmonary complications (23.2%) were significantly associated with higher intraoperative fluid volumes (mean: 5.2 vs. 4.4 ml/kg/h; p = 0.027; OR: 1.24, 95% CI: 1.05-1.46). Anastomotic leakage (18.5%) exhibited an inverted U-shaped relationship, with the highest risk at fluid levels of 4.7-8.1 ml/kg/h). POAF (16.1%) and AKI (5.5%) were not significantly associated with fluid volume in multivariable analysis. POAF showed no significant association with intraoperative fluid volume in adjusted models. Predicted probabilities illustrated a fivefold increase in pulmonary risk across the 0 to 10 ml/kg/h range, whereas POAF declined steadily over this interval. Postoperative delirium showed a trend toward association with fluid volume (OR: 1.34; p = 0.056), while DGE, ICU-LOS, and major complications demonstrated no significant associations. Subgroup analyses suggested stronger associations between fluid volume and pulmonary complications in elderly patients, and a more pronounced POAF risk in males, indicating potential effect modification by age and sex.

CONCLUSION: Intraoperative fluid volume during RAMIE is variably associatiated with postoperative outcomes. While higher volumes are linked to increased pulmonary morbidity, lower volumes may predispose patients to arrhythmias. Anastomotic complications appear to peak at moderate fluid levels. These findings challenge binary fluid strategies and support a more individualized, risk-adapted approach to intraoperative fluid management in esophageal surgery.

PMID:41176601 | DOI:10.1186/s12871-025-03418-y

BMC Surg. 2025 Nov 1;25(1):517. doi: 10.1186/s12893-025-03152-9.

ABSTRACT

INTRODUCTION: Acute appendicitis is a common surgical emergency worldwide. While the use of preoperative antibiotics has shown clear benefits in improving outcomes for uncomplicated appendicitis, the necessity of routine postoperative antibiotics remains a topic of debate. This meta-analysis evaluates the impact of preoperative and postoperative antibiotics on patient outcomes, adverse events, and hospital stay duration.

METHODOLOGY: A systematic review and meta-analysis were conducted, including 14 studies published over the past 15 years, focusing on patients aged 14-65 with uncomplicated appendicitis. Both experimental and observational designs were included. Statistical analyses were performed using SPSS, Excel, and RevMan to assess adverse effects, hospital stays, and antibiotic duration outcomes. The risk of bias was assessed using the Cochrane tool, with all included studies showing low risk across key domains. The study received no external funding and was not registered in any clinical trial database.

RESULTS: Preoperative antibiotic prophylaxis demonstrated significant benefits, including shorter hospital stays and reduced postoperative complications. Metronidazole was the most frequently prescribed antibiotic, followed by cefoxitin and cefuroxime. Conversely, the use of postoperative antibiotics was associated with increased rates of adverse events, including Clostridium difficile infections, deep surgical site infections, and urinary tract infections. Patients receiving only preoperative antibiotics experienced fewer complications and improved overall outcomes than those receiving postoperative antibiotics.

CONCLUSION: Preoperative antibiotics, such as metronidazole and cefoxitin, are sufficient to optimize outcomes in uncomplicated appendicitis. Postoperative antibiotics offer no additional benefit and are associated with a higher risk of adverse events. These findings support limiting antibiotic use to the preoperative phase, aligning with antimicrobial stewardship principles, and ensuring safer, more cost-effective patient care. A revision of clinical guidelines is recommended to reflect these findings and enhance evidence-based practices in managing uncomplicated appendicitis. Despite some heterogeneity in study design and follow-up variability, this meta-analysis remains robust due to consistent inclusion criteria, high-quality studies, a large sample size, and rigorous methods like the Mantel-Haenszel model.

PMID:41176598 | DOI:10.1186/s12893-025-03152-9

Support Care Cancer. 2025 Nov 1;33(11):1010. doi: 10.1007/s00520-025-10062-2.

ABSTRACT

This observational cross-sectional study aimed to evaluate swallowing in volunteers with and without a history of head and neck cancer using electromyographic amplitude, salivary flow, and quality of life. We analyzed 30 volunteers, 15 with a history of cancer (test group), and 15 without (control group), all wearing bimaxillary complete dentures for at least 6 months. Electromyographic amplitude of the masseter, temporal, and suprahyoid muscles was assessed during mandibular rest and during swallowing of nectar, liquid, pudding, and solid foods, using a surface electromyograph. Salivary flow was measured by collecting unstimulated saliva from volunteers while wearing their dentures. Dysphagia and its impact on quality of life were assessed using the MD Anderson Dysphagia Inventory (MDADI). Data were analyzed using normality tests (Shapiro-Wilk) and appropriate statistical tests (T Student or Mann-Whitney). No statistically significant differences were found between the test and control groups in electromyographic amplitude of the temporal, masseter, and suprahyoid muscles during rest (p = 0.468/0.663/0.619) and swallowing (p = 0.240/0.830/0.870 for nectar, p = 0.101/0.760/0.838 for liquid, p = 0.056/0.902/0.967 for pudding, p = 0.494/0.805/0.116 for solid). There was also no significant difference in salivary flow (p = 0.438). However, significant differences were found in MDADI scores (p < 0.001), especially in the emotional domain (p < 0.001), indicating a major impact of dysphagia on quality of life in these patients.

PMID:41176586 | DOI:10.1007/s00520-025-10062-2

Intern Emerg Med. 2025 Nov 1. doi: 10.1007/s11739-025-04161-5. Online ahead of print.

ABSTRACT

People with mental health issues (MHI) are disproportionately dependent on tobacco smoking and experience higher rates of smoking-related mortality compared to the general population. Mental health workers (MHWs) are well placed to address this burden, yet many lack the knowledge, confidence, or skills to support smoking cessation or tobacco harm reduction (THR). This study aimed to evaluate the impact of a structured THR training session on the knowledge and attitudes of mental health workers in Malawi. A quasi-experimental pre-post study was conducted among 48 mental health professionals at two psychiatric hospitals in Malawi. Participants attended a structured training session on tobacco harm reduction. Baseline and end-line surveys assessed demographics, prior tobacco harm reduction exposure, knowledge, and attitudes. Knowledge scores were analysed using the Wilcoxon signed-rank test, with descriptive statistics summarising categorical shifts and attitudinal changes. Only 25% of the participants had received prior training on tobacco harm reduction. A statistically significant increase in median knowledge scores from baseline (median = 6, interquartile range [IQR] = 5-7) to end line (median = 8, IQR = 7-9), Z = -5.72, p < 0.001, with a large effect size (r = 0.62) was observed. The proportion of participants classified as having ‘Good’ knowledge increased substantially from 21.3% at baseline to 68.1% at end line, while the ‘Poor’ knowledge category decreasing from 6.4 to 0%. A brief, well-structured training on tobacco harm reduction can help improve knowledge among mental health workers. Scaling up such training could help close a major gap in patient care for people with mental illness in Malawi and similar settings.

PMID:41176585 | DOI:10.1007/s11739-025-04161-5

Target Oncol. 2025 Nov 1. doi: 10.1007/s11523-025-01184-y. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are now standard for various cancers, and preclinical studies suggest beta-blockers (BBs) may boost the efficacy of ICIs. However, prior clinical studies had small sample sizes, requiring large-scale validation.

OBJECTIVE: We aimed to evaluate the efficacy and safety of combining BBs with ICIs in patients with solid tumors through a systematic review and meta-analysis.

METHODS: A systematic search of PubMed/MEDLINE and Embase was conducted for studies on BBs plus ICIs for solid tumors up to July 2024. Outcomes of interest were overall survival, progression-free survival, and adverse events. Hazard ratios with 95% confidence intervals were pooled using a random-effects model meta-analysis, with heterogeneity assessed by I² statistics.

RESULTS: Overall, 12 clinical studies involving 4293 patients with solid tumors were included, with 1463 patients receiving both BBs and ICIs and 2830 patients receiving ICIs alone. The combination of BBs and ICIs was not associated with a longer overall survival (hazard ratio 1.02; 95% confidence interval 0.84-1.23; p = 0.87; I² = 69%) or progression-free survival (hazard ratio 0.98; 95% confidence interval 0.80-1.20; p = 0.81; I² = 71%). Subgroup analyses by cancer types and BB types showed no significant heterogeneity in the hazard ratios for overall survival across different cancer types (I² = 0%, p for heterogeneity = 0.44) and BB types ⁽I² = 0%, p for heterogeneity = 0.67). The combination of BBs plus ICIs did not seem to increase toxicity.

CONCLUSIONS: Despite positive preclinical findings, this meta-analysis showed that adding BBs to ICIs was not associated with longer survival. We await the results of ongoing prospective trials assessing this strategy. PROSPERO REGISTRATION: CRD42024574043.

PMID:41176581 | DOI:10.1007/s11523-025-01184-y

Mol Psychiatry. 2025 Nov 1. doi: 10.1038/s41380-025-03330-4. Online ahead of print.

ABSTRACT

Machine learning (ML) is revolutionising our ability to decode the complex genetic architectures of brain disorders. In this review we examine the strengths and limitations of ML methods, highlighting their applications in genetic prediction, patient stratification, and the modelling of genetic interactions. We explore how ML can augment polygenic risk scores (PRS) through advanced techniques and how integrating functional genomics and multimodal data can address challenges like rare variants and weak genetic effects. Additionally, we discuss the importance of embedding biological knowledge into ML models to enhance interpretability and uncover meaningful insights. With the ongoing expansion of phenotype-genotype datasets and advances in federated learning, ML is poised to compete with and surpass classical statistical methods in disease risk prediction and identifying genetically homogenous subgroups. By balancing the strengths and weaknesses of these approaches, we provide a roadmap for leveraging ML to unravel the genomic complexity of brain disorders and drive the next wave of discoveries.

PMID:41176580 | DOI:10.1038/s41380-025-03330-4

Eur Arch Otorhinolaryngol. 2025 Nov 1. doi: 10.1007/s00405-025-09679-0. Online ahead of print.

ABSTRACT

PURPOSE: Intraoperative identification of parathyroid adenomas can be challenging due to their anatomical variability and the limitations of preoperative imaging. This study aimed to evaluate the impact of indocyanine green (ICG) fluorescence imaging on operative efficiency and surgical outcomes in parathyroidectomy, employing a standard near-infrared (NIR) endoscopic system.

METHODS: We conducted a prospective interventional study with retrospective controls. Patients undergoing parathyroidectomy for primary hyperparathyroidism were included. The study group received intravenous ICG for intraoperative fluorescence imaging to aid parathyroid gland identification. Standard protocols, including preoperative imaging, intraoperative quick parathyroid hormone (qPTH) measurements, and frozen section analysis, were followed in both groups. Operative times and clinical outcomes were compared between ICG-assisted and standard procedures.

RESULTS: Seventy-six patients were included: 19 in the ICG group and 57 in the control group. The median net operative time (cutting-to-end) was significantly shorter in the ICG group (59 vs. 79 min; p = 0.002), while entry-to-cutting time was slightly longer (44 vs. 35 min; p = 0.014). Although the total operative time was shorter in the ICG group (109 vs. 123 min), this difference was not statistically significant (p = 0.060). A ≥ 50% reduction in qPTH was achieved in 94.7% vs. 89.5% (p = 0.672), and adenoma confirmation was 100% vs. 96.5% (p = 1.0), respectively.

CONCLUSION: ICG fluorescence is a cost-effective adjunct to standard parathyroidectomy, offering real-time gland visualization and potentially reducing operative times. Its integration into the routine surgical workflow may enhance intraoperative efficiency and outcomes.

PMID:41176564 | DOI:10.1007/s00405-025-09679-0