Category: Nevin Manimala

JAMA Netw Open. 2025 May 1;8(5):e2512763. doi: 10.1001/jamanetworkopen.2025.12763.

ABSTRACT

IMPORTANCE: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

OBJECTIVE: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

DESIGN, SETTING, AND PARTICIPANTS: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults who received the intended number of doses, experienced COVID-19-like symptoms, and obtained SARS-CoV-2 testing. Start dates ranged from July 27, 2020, to October 19, 2021; data cutoff dates ranged from March 26, 2021, to March 15, 2022. Statistical analysis was performed from May 11, 2023, to February 25, 2025.

INTERVENTIONS: Participants received vaccines consisting of messenger RNA-1273 (COVE; 2 doses 28 days apart), ChAdOx1 nCoV-19 (AZD1222; 2 doses 28 days apart), Ad26.COV2.S (ENSEMBLE; 1 dose), NVX-CoV2373 (PREVENT-19; 2 doses 21 days apart), CoV2 preS dTM-AS03 (VAT00008; D614) (2 doses 21 days apart), or CoV2 preS dTM-AS03 (D614 plus B.1.351) (VAT00008; 2 doses 21 days apart) or placebo.

MAIN OUTCOMES AND MEASURES: Main outcomes were symptomatic COVID-19 according to each trial’s primary efficacy definition and the Centers for Disease Control and Prevention definition. Vaccine effectiveness was estimated using targeted maximum likelihood estimation under a semiparametric logistic regression model and ordinary logistic regression. Noncase exchangeability, a core TND assumption for unbiased estimation, was also assessed by estimating vaccine efficacy against non-COVID-19 illness.

RESULTS: Among the 12 157 participants included in the analysis, mean (SD) age was 45 (15) years, 6414 were female (53%), 5858 were vaccinated (48%), 2835 experienced primary COVID-19 (23%), and 2992 experienced Centers for Disease Control and Prevention-defined COVID-19 (25%). TND vaccine effectiveness estimates were concordant with RCT vaccine efficacy estimates (concordance correlation coefficient, 0.86 [95% CI, 0.58-0.96] for both outcomes). The semiparametric method had 48% smaller variance estimates than ordinary logistic regression. Noncase exchangeability was generally supported with a median vaccine efficacy against non-COVID-19 illness of 7.7% (IQR, 2.7%-16.8%) across trial cohorts and most 95% CIs including 0.

CONCLUSIONS AND RELEVANCE: In this cross-protocol analysis, the TND provided reliable inferences on COVID-19 vaccine effectiveness in health care-seeking populations for multiple vaccines and symptom definitions when confounding and selection bias were absent. A machine-learning approach for robust confounding control in postmarketing TND studies was also introduced.

PMID:40434773 | DOI:10.1001/jamanetworkopen.2025.12763

Urol Res Pract. 2025 May 21;51(1):38-42. doi: 10.5152/tud.2025.24152.

ABSTRACT

Objective: To evaluate the efficacy of the Quadruple-D scoring system in predicting stone-free rate (SFR) using the newer Generation Piezoelectric lithotripter. Methods: A prospective observational study was conducted from January to December 2023, involving patients who underwent extracorporeal shock wave litho- tripsy (ESWL) for renal stones sized 5-20 mm. Evaluation parameters included stone density, skin-to-stone distance (SSD), stone size (ellipsoid stone volume), and location, with Quadruple-D scores calculated based on predetermined cutoffs. Extracorporeal shock wave lithotripsy sessions utilized the “Piezolith 3000 Plus” lithotripter, and SFR was assessed 4 weeks post-procedure. Statistical analysis included Student’s t-test and receiver operating characteristic curve analysis. Results: Of the 40 eligible patients, 75% achieved stone-free status post-ESWL. Stone density and SSD emerged as leading predictors of SFR, with new cut-off values identi- fied. Comparative analysis demonstrated improved predictive power of the Piezolith Q-D score over the previous Quadruple-D score (AUC: 84% and 80% respectively). Although stone location and size also influenced outcomes, their significance varied in this study. Conclusion: The Piezolith Q-D score system exhibits promise in predicting SFR post- ESWL with piezoelectric lithotripters. External validation and larger-scale studies are warranted to establish the scoring system’s reliability and applicability across diverse populations.

PMID:40434748 | DOI:10.5152/tud.2025.24152

Int J Surg. 2025 May 28. doi: 10.1097/JS9.0000000000002460. Online ahead of print.

ABSTRACT

Dementia is a leading cause of death worldwide. This study examines trends and risk factors for dementia mortality in India and projects the future burden. Mortality and risk factors for Alzheimer’s disease and other dementias (ADOD) in India between 1990 and 2021 were extracted from the Global Burden of Disease (GBD) 2021 database. Spatial autocorrelation analysis was calculated using ArcGIS 10.8. The age-period-cohort (APC) model was applied to analyze the independent effects of age, period and cohort. A bidirectional Mendelian randomization (MR) analysis assessed causality between risk factors and ADOD. The Bayesian APC model was conducted to predict future trends. From 1990 to 2021, deaths, crude mortality rates (CMRs) and age-standardized mortality rates (ASMRs) for ADOD increased gradually. Females had higher CMRs and ASMRs than males, and the burden persisted mainly in the elderly. In 2021, Uttar Pradesh, Maharashtra and Tamil Nadu were the top three states for deaths, but the top three states for ASMR were Meghalaya, Orissa and Telangana. Moreover, Meghalaya, Orissa and Telangana were also the three fastest growing states for ASMR. High fasting plasma glucose (FPG), high body mass index (BMI) and tobacco were the primary drivers of this increase. The MR analysis showed a statistically significant causal association of these three risk factors with ADOD. Projections showed that mortality in the elderly would continue to rise until 2050. Overall, the burden of dementia mortality in India has increased dramatically. There is an urgent need for targeted prevention and control strategies to reduce this burden.

PMID:40434737 | DOI:10.1097/JS9.0000000000002460

Int J Surg. 2025 May 28. doi: 10.1097/JS9.0000000000002592. Online ahead of print.

ABSTRACT

BACKGROUND: Probiotics could reduce postoperative infections and intestinal inflammation, and increase the prognostic survival rate in patients undergoing abdominal surgery. Despite its therapeutic efficacy, probiotics are also associated with some adverse drug reactions (ADRs). The FDA Adverse Event Reporting System (FAERS) database could offer several significant advantages for pharmaceutical monitoring and research. Thus, the aim of this study was to analyze the ADRs associated with probiotics using the FAERS database to guide clinical safe treatment.

METHODS: We analyzed the ADR reports related to probiotics from the FAERS database retrospectively. After removing duplicate entries, the final dataset comprised 8,150,023 records. ADRs related to probiotics were identified, and statistical analyses were conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM).

RESULTS: A total of 55 ADRs induced by probiotics were found. Significant findings include high ROR and PRR values for gastrointestinal disorders, such as abdominal discomfort (ROR = 17.68, PRR = 16.87), abdominal distension (ROR = 20.88, PRR = 20.21), flatulence (ROR = 28.34, PRR = 27.68), abdominal pain upper (ROR = 7.21, PRR = 7.06), abdominal pain (ROR = 4.91, PRR = 4.84), gastrointestinal pain (ROR = 109.48, PRR = 107.36). Uncommon disorder, including anxiety (ROR = 5.69, PRR = 5.56), agitation (ROR = 17.88, PRR = 17.55), tremor (ROR = 7.23, PRR = 7.11), suggesting very high probability of associations emerging.

CONCLUSION: The analysis provides a detailed overview of the ADRs associated with probiotics, and both new and unexpected significant ADRs were identified, which enriched its safety profile. A process of continuous vigilance and additional investigations are imperative to verify these results, and to increase our knowledge on how probiotics should be handled in terms of its safety.

PMID:40434728 | DOI:10.1097/JS9.0000000000002592

Med Oncol. 2025 May 28;42(7):222. doi: 10.1007/s12032-025-02759-5.

ABSTRACT

Pancreatic cancer is a highly aggressive malignancy with rising incidence and mortality rates, often diagnosed at advanced stages. Conventional imaging methods, such as computed tomography (CT) and magnetic resonance imaging (MRI), struggle to assess tumor characteristics and vascular involvement, which are crucial for treatment planning. This paper explores the potential of diffusion magnetic resonance imaging (dMRI) in enhancing pancreatic cancer diagnosis and treatment. Diffusion-based techniques, such as diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI), combined with emerging AI‑powered analysis, provide insights into tissue microstructure, allowing for earlier detection and improved evaluation of tumor cellularity. These methods may help assess prognosis and monitor therapy response by tracking diffusion and perfusion metrics. However, challenges remain, such as standardized protocols and robust data analysis pipelines. Ongoing research, including deep learning applications, aims to improve reliability, and dMRI shows promise in providing functional insights and improving patient outcomes. Further clinical validation is necessary to maximize its benefits.

PMID:40434720 | DOI:10.1007/s12032-025-02759-5

Ann Hematol. 2025 May 28. doi: 10.1007/s00277-025-06431-w. Online ahead of print.

ABSTRACT

Nucleophosmin 1 (NPM1) mutation is commonly associated with a favorable prognosis in acute myeloid leukemia (AML). Conversely, secondary mutations such as those in ASXL1, RUNX1, EZH2, and SRSF2 are generally linked to poor outcomes. The combined prognostic impact of NPM1 and secondary mutations in AML patients remains unclear. This meta-analysis aimed to evaluate the prognostic significance of secondary mutations in AML patients harboring NPM1 mutation. A systematic literature search was conducted following PRISMA guidelines, identifying studies published up to June 2024 from databases such as PubMed, Web of Science, and the Cochrane Library. The inclusion criteria included adult AML patients with confirmed NPM1 mutation, detailed reporting of secondary mutations, and comparative prognostic outcomes. Fourteen high-quality studies from twelve publications were included, encompassing 4,022 patients who all carried NPM1 mutations; among these, 618 also harbored secondary mutations. Data extraction and quality assessment were performed independently by two researchers via the Newcastle-Ottawa Scale (NOS). Statistical analyses involved fixed-effects models due to low heterogeneity (I²=0% for OS and I²=35% for EFS/RFS). Publication bias and sensitivity analyses confirmed the robustness of the findings. Secondary mutations were not significantly associated with OS (HR = 1.16, 95% CI: 0.99-1.35, p = 0.07) or EFS/RFS (HR = 1.15, 95% CI: 0.96-1.38, p = 0.14) in the overall NPM1-mutated AML population. However, within the European LeukemiaNet (ELN) favorable prognosis group, the presence of secondary mutations was significantly associated with reduced OS (HR = 1.95, 95% CI: 1.39-2.73, p < 0.01). Subgroup analyses based on median age, geographical region, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) rates did not reveal significant modifiers of the prognostic impact of secondary mutations. Secondary mutations do not significantly adversely affect OS or EFS/RFS in the general population of AML patients with NPM1 mutation. Notably, within the ELN favorable prognosis group, secondary mutations are associated with markedly poorer OS, highlighting the need for careful prognostic assessment and potential treatment strategy adjustments in this subset of patients.

PMID:40434717 | DOI:10.1007/s00277-025-06431-w

Support Care Cancer. 2025 May 28;33(6):508. doi: 10.1007/s00520-025-09581-9.

ABSTRACT

PURPOSE: Diarrhea is a common complication that can lead to hospitalization in cancer patients. Few studies evaluated its impact on resource utilization and cost. Our objective was to evaluate the resource utilization and costs associated with hospital admission due to diarrhea in cancer patients.

METHODS: This was a retrospective study at a comprehensive cancer center in Jordan. We included adult cancer patients with primary admission diagnosis of diarrhea, between January 2022 and December 2023. Patients were identified using the International Classification of Diseases, Tenth Revision. Resources evaluated included hospital length of stay and admission to the intensive care unit (ICU). Costs in US$ were estimated based on reports from the finance department, reflecting the payers’ perspective, which provided total admission costs, as well as costs of medications, laboratory tests, and procedures. Descriptive analysis was used to report the results.

RESULTS: During the study period, 390 patients were admitted for diarrhea. Mean age was 56 ± 14 (SD) years and 57% were females. Median(IQR) hospital length of stay was 4 (2-7) days, and 34 (9%) patients required ICU admission. The median (IQR) total cost per admission was US$2636 (1441-6132), while median (IQR) cost for ICU admissions was US$10,628(5759-17,235). Laboratory tests had the highest cost, (US$975, 537-1813), followed by medications (US$552, 241-1621) and procedures (US$251, 139-576).

CONCLUSION: Diarrhea among cancer patients is associated with resource utilization and costs. Laboratory tests and medications accounted for the highest proportion of the cost. Future studies should identify strategies to prevent such complications and to reduce cost.

PMID:40434708 | DOI:10.1007/s00520-025-09581-9

Torture. 2025 May 16;35(1). doi: 10.7146/torture.v35i1.152344.

ABSTRACT

The 2024 student-led job quota reform protests in Bangladesh, initially peaceful, escalated into a nationwide uprising. The government responded with excessive force, leading to widespread violence, including severe eye injuries to hundreds of protesters. This study investigates the causes, consequences, and medical responses to these eye injuries, which resulted in lasting physical, psychological, and economic impacts on the victims using secondary data, including reports from human rights organizations, hospital records, and media sources. Victim testimonies were collected from published sources to assess the immediate and long-term effects. A total of 647 individuals sustained severe eye injuries during the protests. The use of pellet bullets by law enforcement was the primary cause. Hospitals reported over 1,300 eye injury cases, with more than 90% of those who underwent surgery and 550 lost vision in one or both eyes. This movement resulted in devastating eye injuries for hundreds of young men, with long-lasting physical and economic impacts. Victims, many of whom were breadwinners, faced significant challenges in receiving adequate medical treatment and long-term rehabilitation. Immediate governmental intervention is needed to ensure their inclusion in the rebuilding of post-uprising Bangladesh.

PMID:40434700 | DOI:10.7146/torture.v35i1.152344

Osteoporos Int. 2025 May 28. doi: 10.1007/s00198-025-07530-0. Online ahead of print.

ABSTRACT

The purpose of the study was to evaluate trabecular bone score (TBS) technology for orthopedic application (TBSortho) as a predictor of a screw pull-out strength in a cadaveric model. This study finds that TBSortho correlates more strongly with the screw pull-out strength compared to cortical density, computed tomography (CT) Hounsfield units (HU), and dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD).

INTRODUCTION: Patient bone quality impacts the mechanical strength of surgical fixation constructs. Preoperative assessments of bone quality and the potential for a screw pull-out are important for surgical planning as well as postoperative rehabilitation protocols. Previous work has correlated the screw pull-out strength with the screw insertional torque, cortical thickness, and CT HU. TBS is a gray-level textural metric that can be extracted from a two-dimensional DXA scan, improves fracture prediction, and may evaluate the mechanical competence of both the cortical and trabecular bones. The purpose of the study was to evaluate TBS technology for TBSortho as a predictor of the screw pull-out strength in a cadaveric model.

METHODS: Twenty paired, fresh-frozen cadaver femurs stripped of soft tissue were obtained (5 M, 5 F specimens, age range of 56-96 years). Standard clinical femur CT were performed to obtain HU, cortical thickness, and cortical density. DXA was also performed using a novel analysis technique as distal femur DXA is not routinely acquired clinically. DXA data were used to generate TBSortho values in two distal femur regions of interest. All femurs then underwent a screw pull-out testing with five lateral distal femoral 5-mm locking screws (n = 100 screws total). The correlation coefficient from Spearman tests and R-squared of the fixed effects from the linear mixed effects models were calculated.

RESULTS: TBSortho was found to correlate most strongly of CT and DXA measures with the screw pull-out strength, having marginal R² and standardized beta of 0.75 and 0.87 in the proximal screw cluster and 0.67 and 0.83 in the distal screw cluster, respectively. TBSortho accounted for 75% variance in the pull-out strength. CT HU and DXA bone mineral density (BMD) did not have a statistically significant correlation with the screw pull-out strength.

CONCLUSION: This study finds that TBSortho correlates more strongly with the screw pull out strength in a cadaveric distal femur model compared to cortical density, CT HU, and DXA BMD. These preliminary results suggest that TBSortho may be a valuable tool to model mechanical integrity of bone preoperatively.

PMID:40434688 | DOI:10.1007/s00198-025-07530-0

Osteoporos Int. 2025 May 28. doi: 10.1007/s00198-025-07526-w. Online ahead of print.

ABSTRACT

To address cultural relevance in assessing osteoporosis-related quality of life, we validated and assessed the psychometric properties of the Hebrew version of QUALEFFO-41. The tool showed moderate reliability and validity, with diagnostic performance comparable to EQ-5D. This supports its clinical utility in Hebrew-speaking women with postmenopausal osteoporosis and vertebral fractures.

BACKGROUND: Osteoporosis and its associated vertebral fractures significantly impact the quality of life among postmenopausal women. The Quality-of-Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) is widely used to assess the quality of life in patients with osteoporotic spinal fractures but requires proper cultural adaptation for different populations.

PURPOSE: To translate, culturally adapt, and validate the QUALEFFO-41 questionnaire for Hebrew-speaking Israeli women with osteoporotic vertebral fractures (OVFs) and to compare its validity with the previously validated EQ-5D questionnaire in Israel.

METHODS: The study included 155 postmenopausal women aged 50-90 years: 49 with osteoporotic vertebral fractures (OVF group) and 106 with osteoporosis but no fractures (OPC group). The QUALEFFO-41 was translated following international guidelines and tested for reliability, validity, and sensitivity. Statistical analysis included internal consistency (Cronbach’s alpha), test-retest reliability, discriminant and convergent validity, and ROC curve analysis.

RESULTS: The Hebrew QUALEFFO-41 demonstrated good internal consistency (Cronbach’s alpha = 0.88) and test-retest reliability. Most questions (90% in the OVF group and 97% in the OPC group) showed good to excellent correlations. Both QUALEFFO-41 and EQ-5D questionnaires showed sufficient sensitivity in diagnosing women with osteoporosis and fractures (AUC = 0.767 and 0.756, respectively).

CONCLUSION: The Hebrew version of QUALEFFO-41 demonstrates moderate reliability and validity properties for assessing quality of life in Israeli postmenopausal women with osteoporosis and vertebral fractures. The questionnaire shows satisfactory psychometric properties, though certain domains may benefit from further refinement.

PMID:40434687 | DOI:10.1007/s00198-025-07526-w