Nevin Manimala

JCO Precis Oncol. 2025 Jun;9:e2500062. doi: 10.1200/PO-25-00062. Epub 2025 Jun 6.

ABSTRACT

PURPOSE: The Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends screening for four common DPYD variants to prevent severe toxicity in patients with cancer treated with fluoropyrimidines. A 50% starting dose followed by toxicity-based dose titration is advised for patients heterozygous for these variants. In this study, the appropriateness of the CPIC-recommended 5-fluorouracil (5-FU) starting dose was evaluated.

PATIENTS AND METHODS: Patients were grouped into four variant categories (DPYD*2A [c.1905+1G>A], DPYD*13 [c.1679T>G], c.2846A>T [p.D949V], c.1236G>A/HapB3 [p.E412E]) and a DPYD wild-type control group. Uracil loading tests were used for phenotyping. Variant patients started on a 50% reduced 5-FU dose. On the basis of steady-state 5-FU plasma concentrations, dose adjustments were made during cycles 2-4 until an 5-FU target AUC_0-46h of 20-30 mg × h/L was achieved, if tolerated.

RESULTS: Twenty-six wild-type controls and 34 DPYD variant patients were included: 16 with c.1236G>A/HapB3, eight with c.1905+1G>A, eight with p.D949V, and two with c.1679T>G. Heterozygous carriers of c.1905+1G>A (DPYD*2A) and c.1679T>G (DPYD*13) displayed significant reduced uracil metabolism. The impact on uracil clearance was highly variable in p.D949V but only minor in c.1236G>A/HapB3 variants. In all, 65% of wild-type controls had 5-FU exposure within target range on a 100% dose (mean, 23.2; IQR, 6.6). In 97% of all variant patients, the 50% reduced dose resulted in 5-FU underexposure, with a median AUC of 10.6 mg × h/L (IQR, 3.2). Dose escalation to 70% or higher was tolerated in most patients, reaching the target AUC in 68% of patients.

CONCLUSION: The current CPIC guidelines are overly conservative for c.1236G>A/HapB3 and most p.D949V variants. A 75% starting dose is more appropriate for most c.1236G>A/HapB3 carriers. We recommend 5-FU therapeutic drug monitoring in all patients with DPYD variants to achieve optimal 5-FU exposure.

PMID:40479625 | DOI:10.1200/PO-25-00062

Age Ageing. 2025 May 31;54(6):afaf156. doi: 10.1093/ageing/afaf156.

ABSTRACT

BACKGROUND: Machine learning (ML) models in healthcare are crucial for predicting clinical outcomes, and their effectiveness can be significantly enhanced through improvements in accuracy, generalisability, and interpretability. To achieve widespread adoption in clinical practice, risk factors identified by these models must be validated in diverse populations.

METHODS: In this cohort study, 86 870 community-dwelling older adults ≥65 years from the UK Biobank database were used to train and test three ML models to predict 30-day emergency hospitalisation. The three ML models, Random Forest (RF), XGBoost (XGB), and Logistic Regression (LR), utilised all extracted variables, consisting of demographic and geriatric syndromes, comorbidities, and the Drug Burden Index (DBI), a measure of potentially inappropriate polypharmacy, which quantifies exposure to medications with anticholinergic and sedative properties. 30-day emergency hospitalisation was defined as any hospitalisation related to any clinical event within 30 days of the index date. The model performance metrics included the area under the receiver operating characteristics curve (AUC-ROC) and the F1 score.

RESULTS: The AUC-ROC for the RF, XGB and LR models was 0.78, 0.86 and 0.61, respectively, signifying good discriminatory power. The DBI, mobility, fractures, falls, hazardous alcohol drinking and smoking were validated as important variables in predicting 30-day emergency hospitalisation.

CONCLUSIONS: This study validated important risk factors for predicting 30-day emergency hospitalisation. The validation of important risk factors will inform the development of future ML studies in geriatrics. Future research should prioritise the development of targeted interventions to address the risk factors validated in this study, ultimately improving patient outcomes and alleviating healthcare burdens.

PMID:40479613 | DOI:10.1093/ageing/afaf156

Age Ageing. 2025 May 31;54(6):afaf157. doi: 10.1093/ageing/afaf157.

ABSTRACT

OBJECTIVES: Falls have long been recognised as a frequent problem among older adults and have been cited in literature since the 1950s. Given extensive research on risk factors, prevention, and implementation strategies, one might expect a decline in fallers prevalence. The aim of this review is to explore the epidemiology of falls in Europe, focusing on healthy, community-dwelling individuals aged 65 years or older.

METHODS: Articles for this systematic review and meta-analysis were sourced from PubMed and Web of Science in June 2023, with screening completed by August 2023 and an update in January 2024. Risk of bias assessment used the Standard quality assessment criteria and potential outliers were identified. Publication bias was assessed using Egger’s regression test. Data analysis was performed in R.

RESULTS: Thirty-eight articles were included, comprising a sample of 71 245 European, community-dwelling older adults. The average fallers prevalence among European older adults was 30% (95% CI 0.26-0.34). Meta-regression analysis showed no significant change in fallers prevalence over the years (P = .66), in contrast with meta-regression for average age (P < .01). In the subgroup analysis, differences in fallers prevalence were seen for gender (P < .01), country (P < .01), and length of follow-up (P = .02).

CONCLUSION: Despite decades of evidence supporting effective fall prevention, there is no significant change in the prevalence of fallers among community-dwelling older adults in Europe. Future research should focus on systematically identifying the factors contributing to the persistent fall rates. Additionally, efforts must be made to ensure effective implementation of existing knowledge on fall prevention.

PMID:40479612 | DOI:10.1093/ageing/afaf157

J Pediatr Hematol Oncol. 2025 Jun 2. doi: 10.1097/MPH.0000000000003037. Online ahead of print.

ABSTRACT

The deregulation of WNT signaling has been shown to be important in the development of hematologic malignancies. The genetic variation of key WNT signaling pathway genes may affect the development of leukemia. In the present study, a total of 20 single nucleotide polymorphisms (SNPs) in 6 genes (CTNNB1, AXIN2, SFRP2, SFRP4, SFRP5, and DKK3) involved in the WNT signaling pathway were selected to investigate the influence of SNPs on the prognosis of 379 Chinese children with acute lymphoblastic leukemia (ALL). Both χ2 test and Kaplan-Meier survival curve estimation showed that AXIN2 rs7591, rs3923086, and rs11867417 were associated with the risk of relapse with statistical significance. The multifactorial analyses showed that the 3 SNPs of rs7591, rs3923086, and rs11867417 in AXIN2 still had a significant effect on prognosis with statistical significance (P=0.004, 0.019, and 0.013, respectively). In addition, SFRP4 rs1802073 and rs1802074 were also significantly associated with the risk of relapse after excluding the effect of confounding variables. Taken together, our findings show that polymorphisms in AXIN2 and SFRP4 were independent prognostic predictors for pediatric ALL patients. Further studies are needed to validate these findings and clarify the underlying mechanism.

PMID:40479595 | DOI:10.1097/MPH.0000000000003037

JMIR Mhealth Uhealth. 2025 Jun 6;13:e58597. doi: 10.2196/58597.

ABSTRACT

BACKGROUND: Mobile phone apps powered by artificial intelligence (AI) have emerged as powerful tools to address mental health challenges faced by children.

OBJECTIVE: This study aimed to comprehensively review AI-driven apps for child mental health, focusing on their availability, quality, readability, characteristics, and functions.

METHODS: This study systematically analyzed AI-based mobile apps for child mental health. Quality was evaluated using the Mobile Application Rating Scale, which assessed various dimensions of app quality, including subjective quality, engagement, functionality, aesthetics, and information. An automatic readability index calculator was implemented to assess readability by using the count of words, syllables, and sentences to generate a score indicative of the reading difficulty level. Content analysis was conducted to examine the apps’ availability, characteristics, and functionality.

RESULTS: Out of 369 apps initially identified, 27 met the eligibility criteria for inclusion. The quality of the apps was assessed using Mobile Application Rating Scale, with an average score of 3.45 out of 5 (SD 0.5), indicating a need for quality improvement. The readability analysis revealed suboptimal scores, with an average grade level of 6.62 (SD 2.2) for in-app content and 9.93 (SD 2.6) for app store descriptions. These results, combined with a monotonous user interface, suggest that many apps lack a child-friendly design, potentially hindering their usability and engagement for young users. Content analysis categorized the apps into 3 functional groups-chatbot-based apps (15 apps), journal logging apps (9 apps), and psychotherapeutic treatment apps (3 apps). While 20 out of 27 apps (74%) used clinically validated technologies, rigorous clinical tests of the apps were often missing, with only 2 apps undergoing clinical trials. Of the 27 apps analyzed, only 7 (26%) were free to use, while the majority, 20 apps, required a subscription or one-time payment. Among the paid apps, the average cost was US $20.16 per month, which may pose a financial barrier and limit accessibility for some users, particularly those from lower-income households.

CONCLUSIONS: AI-based mental health apps hold significant potential to address the unique challenges of child mental health but face critical limitations in design, accessibility, and validation. To fully realize their benefits, future research and development should focus on integrating child-centric design principles, ensuring affordability, and prioritizing rigorous clinical testing. These efforts are essential to harness the power of AI technologies in creating equitable, effective, and engaging solutions for improving child mental health outcomes.

PMID:40479582 | DOI:10.2196/58597

J Med Internet Res. 2025 Jun 6;27:e73336. doi: 10.2196/73336.

ABSTRACT

BACKGROUND: The proliferation of health-related content on social media platforms has changed the way people access and interpret information about cosmetic medicine. TikTok (ByteDance) has become an important platform for sharing breast enhancement content, yet little is known about the quality, credibility, and impact of such information on user perceptions and decision-making.

OBJECTIVE: This paper aims to analyze the characteristics of breast enhancement videos, including uploader demographics, product details, promotional claims, and user engagements, to better understand the nature of the claims and products encountered by users.

METHODS: We conducted a cross-sectional content analysis of the top 150 most-liked breast enhancement videos via TikTok’s web interface. The videos were coded according to the uploader’s traits (gender expression and account type), product details (type and scientific evidence), and promotional strategies (testimonials and sponsorship disclosures). Engagement metrics (likes and shares) were recorded, and nonparametric tests (Mann-Whitney U test) were used to compare the engagement between licensed physicians and uncertified content creator uploaders. Descriptive statistics were calculated for all the variables.

RESULTS: Overall, 85 videos were included in the final analysis, with most uploaders presenting a feminine gender expression (59/85, 69.4%) and using uncertified content creator accounts (59/85, 69.4%). The most promoted product types were breast enhancement creams or oils (32/85, 37.6%) and breast implants (22/85, 25.9%). Most videos (71/85, 83.5%) depicted the products positively; however, most videos (78/85, 91.8%) provided no scientific evidence of the product’s efficacy. Engagement metrics revealed that videos by licensed physicians received significantly higher thumbs up (median 9761, IQR 4975-19,492) than uncertified content creator uploaders (median 701, IQR 280-2604; P=.002). Only one video (1.2%) of the 85 videos included a “before and after” visual component, and most videos (75/85, 88.2%) omitted product purchasing details. Sponsorship disclosures were absent in most of posts (79/85, 92.9%).

CONCLUSIONS: TikTok’s short video format fosters widespread and rapid dissemination of breast enhancement information, representing a key strength in democratizing health communication. Its user-friendly interface and visual appeal also offer a valuable avenue for medical professionals to engage audiences more dynamically. However, the lack of rigorous content checks can amplify misleading or unverified claims. To address these weaknesses, implementing dual-mode content review could be essential for maximizing TikTok’s capacity to support informed public health decision-making.

PMID:40479581 | DOI:10.2196/73336

Healthc Manage Forum. 2025 Jun 6:8404704251343260. doi: 10.1177/08404704251343260. Online ahead of print.

ABSTRACT

Our Canadian multi-site academic health sciences centre uses a standardized process to review critical patient safety incidents and develop recommendations to prevent incident reoccurrence. We recognized an opportunity to enhance recommendation development by integrating the Hierarchy of Intervention Effectiveness (HIE), a human factors framework, into the incident review process. This project aimed to increase the proportion of system-focused recommendations from critical incident reviews from 16 to 30% over 16 months. A multi-intervention strategy included (1) standardizing the incident analysis review template; (2) earmarking time for recommendation development during reviews; (3) providing participants with just-in-time education and tools; and (4) initiating HIE-based recommendation classification during incident reviews. Statistical process control p-Chart analysis showed an increase in system-focused recommendations from 16 to 30% over 16 months. The HIE promotes system-level change to prevent critical incidents, which other organizations may benefit from incorporating in their patient safety reviews.

PMID:40479578 | DOI:10.1177/08404704251343260

J Am Acad Orthop Surg. 2025 Jun 15;33(12):e657-e664. doi: 10.5435/JAAOS-D-23-01243. Epub 2024 Oct 29.

ABSTRACT

INTRODUCTION: Total hip arthroplasty (THA) is a treatment used for both elective (eg, osteoarthritis) and nonelective (eg, fracture) indications. Patients undergoing nonelective THA may not be able to undergo the same preoperative optimization protocols as those undergoing elective THA. We aimed to determine differences in 30-day, 90-day, and 1-year surgical site infection (SSI) rates; 90-day and 1-year periprosthetic joint infection (PJI)-related revision; and 90-day and 1-year PJI-related surgery (ie, revision or irrigation and débridement) between nonelective and elective THA status.

METHOD: This retrospective cohort study using the Medicare Limited Data Set included fee-for-service Medicare beneficiaries aged 65+ years who underwent inpatient primary THA in 2017 to 2020. Propensity score matching (1:5, nonelective: elective) was used. We assessed differences in surgical site infection (SSI), periprosthetic joint infection (PJI) outcomes by nonelective versus elective surgery status using mixed-effects logistic regression models, reporting adjusted odds ratios (OR) and 95% confidence intervals (CI).

RESULTS: From a total of 433,326 patients, 88,940 (19,094 nonelective; 69,846 elective) were successfully matched. Nonelective surgery status was associated with markedly higher odds of 30-day SSI (OR 1.55, 95% CI 1.25 to 1.92, P < 0.001), 90-day SSI (OR 1.53, 95% CI 1.30 to 1.78, P < 0.001), and 1-year SSI (OR 1.41, 95% CI 1.25 to 1.59, P < 0.001). Nonelective status was also associated with higher odds of 1-year PJI-related revision (OR 1.33, 95% CI 1.08-1.63, P = 0.006) but not 90-day PJI-related revision. Similarly, nonelective status was associated with higher odds of 1-year PJI-related surgery (OR 1.33, 95% CI 1.09 to 1.62, P = 0.004) but not 90-day PJI-related surgery.

CONCLUSION: Nonelective THA status was an independent risk factor for SSI throughout the first postoperative year and for 1-year PJI-related revision and PJI-related surgery. Additional research is necessary to elucidate the etiology of observed differences in infection risk between patients undergoing nonelective and elective THA and to define strategies to mitigate this difference in infection risk.

PMID:40479559 | DOI:10.5435/JAAOS-D-23-01243

J Am Acad Orthop Surg. 2025 May 9;33(12):655-662. doi: 10.5435/JAAOS-D-25-00160.

ABSTRACT

BACKGROUND: Metallic implants are widely used in orthopaedic surgery. These implants may have carcinogenic properties, but the incidence of associated malignancies appears to be low, and to date, only case reports and small case series have been reported. We describe a series of patients with soft-tissue sarcoma adjacent to orthopaedic implant.

METHODS: Cases of soft-tissue sarcomas treated at our institution were reviewed to identify tumors arising next to orthopaedic implant. We collected diagnostic, therapeutic, surgical, and outcome data and conducted genetic testing on the implant-associated tumors and control tumors.

RESULTS: We identified 4 cases, all of which were high-grade sclerosing rhabdomyosarcoma. Median age at diagnosis was 50 years (range: 35 to 58 years). Three tumors were in the lower extremity following internal fixation of the tibia and/or fibula, whereas the fourth was posterior to spinal implant. Mean time from implant placement to diagnosis was 19.0 years (range: 10.9 to 24.3 years). Three patients underwent wide surgical resection, whereas one had metastatic disease at diagnosis and declined surgery. All were treated with chemotherapy and radiation. Genetic testing revealed a MYOD1 mutation in all four tumors. The tumor mutational burden and fraction of genome altered were slightly higher in the control tumors than in the implant-adjacent tumors, although the differences were not statistically significant. Median follow-up was 1.7 years (range: 0.8 to 2.6 years). Of the three patients with localized disease, two had no evidence of disease at latest follow-up and one died of unknown cause at 2.6 years. The patient with metastatic disease died of disease at 0.8 years.

CONCLUSIONS: We found no genetic differences between implant-associated and non-implant-associated rhabdomyosarcomas. Further investigation is needed to understand the contribution of metallic implants to tumorigenesis. Physicians should be aware of this diagnosis when a new mass arises in a patient with long-standing orthopaedic implants.

PMID:40479555 | DOI:10.5435/JAAOS-D-25-00160

ATS Sch. 2025 Jun 6. doi: 10.34197/ats-scholar.2024-0134OC. Online ahead of print.

ABSTRACT

Background: Interprofessional teaching (IPT) has the potential to promote teamwork and collaborative patient care, but few studies have explored physician attitudes about the role of nonphysician clinical teachers in graduate medical education. Objective: This study aimed to elucidate critical care attending physician perspectives about the role of nurses, pharmacists, and respiratory therapists in teaching medical residents. Methods: Using a concurrent mixed methods approach, surveys and focus groups were administered to attendings in an urban tertiary academic medical center. Survey data were analyzed with descriptive statistics; focus group data were analyzed using the Framework method of content analysis. Results: Of attendings surveyed, 23/26 (88%) responded. Attendings reported positive attitudes about IPT; highly cited benefits included capitalizing on the unique expertise held by interprofessional providers (21/22, 95%), modeling respectful interprofessional relationships (21/22, 95%), and promoting collaborative patient care (20/22, 91%). Ten attendings participated in focus groups. Qualitative analysis revealed four major themes: overall low rates of IPT that vary by profession, potential role of attending as facilitator of IPT, multiple interpersonal and environmental characteristics that influence IPT, and impacts of IPT on education, patient care, and teamwork. Conclusion: Study results suggest that attending physicians are enthusiastic about the concept of IPT and their potential role in its promotion.

PMID:40479547 | DOI:10.34197/ats-scholar.2024-0134OC