Nevin Manimala

Pharm Res. 2025 Jul 18. doi: 10.1007/s11095-025-03892-6. Online ahead of print.

ABSTRACT

PURPOSE: In vitro dissolution testing is a critical quality attribute for solid dosage forms. Apart from similarity factor (f2), other alternatives namely model independent and dependent methods are suggested by regulatory agencies. Current manuscript attempts to compare various model independent approaches on dissolution similarity.

METHODS: Dissolution data with various degrees of variability (10-20%, 40-50%, 70-80%) are compared using similarity factor f2 (estimated, expected, bias corrected with percentile & BCa intervals) and novel approaches such as EDNE, SE, T2EQ, and MSD. Further, a flow chart is proposed to assist selection of suitable methodology.

RESULTS: The expected f2 was stringent as compared to other f2 types and the Bca confidence intervals approach increased chance of acceptance as compared to conventional f2 bootstrap. Further, EDNE results synchronized with f2 analysis. Outcome from SE, T2EQ approaches depends on value of equivalence margin. MSD approach was most stringent as compared to others. Finally, a decision tree has been proposed to facilitate the selection of appropriate methodology for similarity analysis with consideration of regulatory perspectives.

CONCLUSIONS: Overall, various model independent approaches are compared for dissolution similarity analysis. This comprehensive guidance will assist formulation and biopharmaceutics scientists to enhance the success rate of similarity while ensuring regulatory compliance and thus helps to achieve drug product with consistent performance.

PMID:40679781 | DOI:10.1007/s11095-025-03892-6

Int J Clin Pharm. 2025 Jul 18. doi: 10.1007/s11096-025-01964-6. Online ahead of print.

ABSTRACT

INTRODUCTION: The American Geriatrics Society (AGS) Beers Criteria and Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) criteria are extensively utilized in identifying potentially inappropriate medications (PIMs) among older adults. Older adults with heart failure (HF) confront the dual challenge of polypharmacy and inadequate adherence to evidence-based medications, which further complicates their medication management and clinical outcomes.

AIM: To assess the effectiveness of the AGS Beers (2023) Criteria and the STOPP (v3) criteria in identifying PIMs among older adults with HF and to analyze patterns of polypharmacy and evidence-based medications.

METHOD: This retrospective study was conducted at a tertiary academic medical center in China and involved 1578 outpatients aged ≥ 65 years with HF who received at least one outpatient prescription between January 1 and December 31, 2023. Data on demographics, comorbidities, and prescribed medications were extracted from the hospital’s electronic medical record (EMR) system. PIMs were identified with the AGS Beers (2023) Criteria and the STOPP (v3) criteria. The data were analyzed using descriptive statistics in Microsoft Excel.

RESULTS: Polypharmacy and hyperpolypharmacy were prevalent among the patients, affecting 65.3% and 15.7% of the cohort, respectively. PIMs were identified in 75.5% of patients (1192/1578), with a total of 2128 PIM cases observed according to the Beers Criteria, with the most common PIM being rivaroxaban (32.3%). The STOPP (v3) criteria identified PIMs in 28.9% of patients (n = 471), with the most frequent PIMs being statin use in frail patients aged ≥ 85 years (26.8%) and prolonged use of proton-pump inhibitors (16.6%). Among all patients in our study, 61.6% received either an angiotensin-converting enzyme inhibitor, angiotensin-II receptor blocker, or angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI); 57.0% were prescribed β-blockers; and 32.6% used a sodium-glucose cotransporter 2 inhibitor.

CONCLUSION: While the Beers Criteria identified a greater number of PIMs in this study, both tools have differing strengths in detecting medication-related risks. Their combined use may provide a more holistic assessment of prescribing appropriateness. The widespread use of PIMs in older adults with HF, coupled with the frequent underuse of beneficial therapies, calls for systematic interventions. Pharmacist-led interventions and electronic decision-support systems that integrate evidence-based prescribing, deprescribing, and regular medication reviews are crucial for optimizing therapeutic outcomes in older adults with HF.

PMID:40679772 | DOI:10.1007/s11096-025-01964-6

Sleep Breath. 2025 Jul 18;29(4):249. doi: 10.1007/s11325-025-03415-y.

ABSTRACT

PURPOSE: Evaluate patient phenotypes and longitudinal patterns of hypoglossal nerve stimulator (HGNS) use and identify predictors of long-term HGNS adherence.

METHODS: Patients who underwent HGNS implantation for obstructive sleep apnea (OSA) from 2017 to 2023 and had available data through 9 months post-device activation were included. Adherence rate was defined as percentage of patients using the device for at least 4 h for 70% of nights. Repeated measures ANOVA and Cochran’s Q tests were used to analyze changes in HGNS use over time. A k-means clustering analysis was used to identify HGNS user subgroups with shared characteristics and associations with HGNS use.

RESULTS: A total of 59 patients were included, with a mean (SD) age of 62.7 (11.2) years, mean (SD) body mass index of 28.5 kg/m2 (3.2), and an average pre-operative apnea-hypopnea index (AHI) of 38.7 events/hour; the majority were male (78%) and White (98.3%). Patients used their HGNS devices on average for 81.1% of nights (SD 23.5%) and 362 min/night (SD 115), with 0.96 (SD 1.4) pauses/night at 9 months post-activation. The mean percentage of nights and the time/night used decreased significantly over the first 9 months (p < 0.001 for both), while pauses/night increased (p = 0.008). The estimated adherence rate was 52.5% at 9 months. The cluster analysis revealed subgroups with shared characteristics; however, clusters were not associated with HGNS use.

CONCLUSIONS: HGNS use appears to decrease over the first nine months after activation. Additional research is warranted to investigate drivers of HGNS use decrement. Given lack of a standardized definition for adherence, future studies should report more granular HGNS use metrics to facilitate comparison across studies.

PMID:40679756 | DOI:10.1007/s11325-025-03415-y

Emerg Radiol. 2025 Jul 18. doi: 10.1007/s10140-025-02366-x. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to evaluate and compare the diagnostic performance and image quality of deep learning reconstruction (DLR) with hybrid iterative reconstruction (Hybrid IR) and filtered back projection (FBP) in contrast-enhanced CT venography for deep vein thrombosis (DVT).

METHODS: A retrospective analysis was conducted on 51 patients who underwent lower limb CT venography, including 20 with DVT lesions and 31 without DVT lesions. CT images were reconstructed using DLR, Hybrid IR, and FBP. Quantitative image quality metrics, such as contrast-to-noise ratio (CNR) and image noise, were measured. Three radiologists independently assessed DVT lesion detection, depiction of DVT lesions and normal structures, subjective image noise, artifacts, and overall image quality using scoring systems. Diagnostic performance was evaluated using sensitivity and area under the receiver operating characteristic curve (AUC). The paired t-test and Wilcoxon signed-rank test compared the results for continuous variables and ordinal scales, respectively, between DLR and Hybrid IR as well as between DLR and FBP.

RESULTS: DLR significantly improved CNR and reduced image noise compared to Hybrid IR and FBP (p < 0.001). AUC and sensitivity for DVT detection were not statistically different across reconstruction methods. Two readers reported improved lesion visualization with DLR. DLR was also rated superior in image quality, normal structure depiction, and noise suppression by all readers (p < 0.001).

CONCLUSIONS: DLR enhances image quality and anatomical clarity in CT venography. These findings support the utility of DLR in improving diagnostic confidence and image interpretability in DVT assessment.

PMID:40679754 | DOI:10.1007/s10140-025-02366-x

Infection. 2025 Jul 18. doi: 10.1007/s15010-025-02606-9. Online ahead of print.

ABSTRACT

PURPOSE: Sepsis survivors suffer from frequent rehospitalizations, of which a certain proportion is considered preventable by timely and adequate management in the outpatient setting (= ambulatory care sensitive conditions, ACSC). We aimed to assess the frequency of and risk factors for ACSC and infection-associated ACSC rehospitalization among sepsis survivors.

METHODS: Population-based, retrospective cohort study among using nationwide health claims data of the “AOK- die Gesundheitskasse”. Sepsis patients with inpatient treatment in 2016-2019 were identified using ICD-codes. Among sepsis hospital survivors, ACSC and infection-related ACSC were identified. Patient-related risk factors for ACSC were assessed by a multiple logistic regression analysis.

RESULTS: We included 347,826 sepsis patients and 234,874 sepsis hospital survivors. A total of 53.2% and 21.3% of sepsis survivors had at least one ACSC and infection-related ACSC rehospitalizations in the 12-months post-discharge, respectively. ACSC rehospitalizations often occurred closely after discharge and more frequently affected older, male, care dependent patients as well as those living in rural areas.

CONCLUSION: ACSC are common among sepsis survivors. This underlines to need for structured aftercare programs and interventions in these patients, particularly for ACSC risk groups which comprise older, male, care dependent patients in rural areas.

PMID:40679743 | DOI:10.1007/s15010-025-02606-9

Obes Surg. 2025 Jul 18. doi: 10.1007/s11695-025-08077-z. Online ahead of print.

ABSTRACT

Bariatric surgery is effective for treating obesity and its comorbidities, but the optimal technique remains debated. This meta-analysis compared one-anastomosis gastric bypass (OAGB) and Roux-en-Y gastric bypass (RYGB) in comorbidity remission and postoperative outcomes. We analyzed 12 trials, assessing T2DM, hypertension, and sleep apnea remission, as well as postoperative complications. Statistical analyses included risk differences (RD) and risk ratios (RR). OAGB was non-inferior to RYGB for T2DM remission (RD -1%; 95% CI -10% to 8%) but had higher risks of bile reflux (RR 7.62; 95% CI 1.97-29.46) and de novo GERD (RR 5.10; 95% CI 1.44-18.00). While OAGB is effective for T2DM remission, RYGB is superior in reducing bile reflux and GERD, highlighting the need for individualized surgical approaches.

PMID:40679731 | DOI:10.1007/s11695-025-08077-z

J Epidemiol Glob Health. 2025 Jul 18;15(1):99. doi: 10.1007/s44197-025-00445-3.

ABSTRACT

BACKGROUND: The pediatric intensive care unit (PICU) plays a crucial role in managing critically ill children requiring advanced airway, respiratory, and hemodynamic support. Reducing the mortality rate is one of the primary objectives in every ICU. However, data regarding mortality and associated risk factors from low-resource countries remain insufficient. The aim of our study was to describe the mortality pattern, and to evaluate risk factors associated with mortality in the PICU at Mukalla Maternity and Childhood Hospital.

METHODS: This retrospective study analyzed the admission records for children aged over 1 month to 15 years from the PICU over four years (1st January 2021 to 31st December 2024). The information retrieved included gender, age, place of residence, body weight, nutritional status, vaccination status, clinical presentations on admission, temperature, level of consciousness, presence of co-morbidities, the lag time between illness onset and hospital admission, date of admission, date of discharge, referring source, readmission frequency, diagnosis, need for mechanical ventilation, and condition at discharge (survived /deceased).

RESULTS: Out of the 790 patients admitted to the PICU, 716 were included in the study. The three most common disease categories among admissions were respiratory diseases (29.5%), central nervous system diseases (27.1%), and gastrointestinal diseases (11%). The overall mortality rate was 38.1%. Among deceased patients, 57.9% were severely undernourished, 38.5% were unvaccinated, and 63.4% had associated co-morbidities. The most common causes of death were pneumonia (26%), meningoencephalitis (17.2%), and sepsis/septic shock (9.2%). Independent risk factors of PICU mortality included length of PICU stay [AOR 0.129, p < 0.001], need for mechanical ventilation [AOR 68.6, p < 0.001], cardiovascular diseases [AOR 3.1, p = 0.003], hypothermia [AOR 7.1, p = 0.014], convulsions [AOR 0.375, p = 0.001], disturbance of consciousness [AOR 2.1, p = 0.002], and hepatosplenomegaly [AOR 15.7, p = 0.024].

CONCLUSION: The mortality in our PICU is high and is associated with several independent factors. Recognizing these risk factors will facilitate the identification of critical cases, enable the prioritization of resources, and support the implementation of essential modifications.

PMID:40679717 | DOI:10.1007/s44197-025-00445-3

Breast Cancer Res Treat. 2025 Jul 18. doi: 10.1007/s10549-025-07781-9. Online ahead of print.

ABSTRACT

PURPOSE: Previous studies have demonstrated that ductal carcinoma in situ (DCIS) component often exhibits higher HER2 expression than the invasive component when assessed by immunohistochemistry, while some other studies showed concordant HER2 expression between these two components. In this study, we used our high-sensitivity HER2 (HS-HER2) quantitative immunofluorescence assay to compare HER2 expression in IDC and co-existing DCIS and correlate with clinicopathologic characteristics.

METHODS: We included 36 IDC + DCIS cases from the Yale Pathology department. DCIS was classified according to the three-tier nuclear grading system: low (grade 1), intermediate (grade 2), and high (grade 3) nuclear grade. Invasive carcinoma was graded according to the modified Bloom-Richardson histologic grading system. Cases were divided into two groups: low to intermediate-grade DCIS (G1-2) with co-existing invasive carcinoma (n = 26) and high-grade DCIS (G3) with co-existing invasive carcinoma (n = 10). Separate regions of interest for IDC and DCIS were annotated by two board-certified pathologists. Serial sections of FFPE tumor specimens were used to accurately measure the HER2 protein expression by the HS-HER2 assay in attomole/mm² unit and the acquisition by QuPath v.04 with the Qymia extension.

RESULTS: Low to intermediate-grade DCIS expressed higher HER2 levels (4295 ± 449 amol/mm²) than co-existing invasive carcinoma (2880 ± 413 amol/mm²). Similarly, high-grade DCIS expressed higher HER2 levels (4953 ± 700 amol/mm²) than co-existing invasive carcinoma (3560 ± 688 amol/mm²). Neither of these trends toward lower expression levels in the IDC were statistically significant. Additionally, no significant statistic difference was noted between low to intermediate-grade DCIS versus high-grade DCIS or between their corresponding co-existing invasive carcinomas in this cohort.

CONCLUSION: Using the HS-HER2 assay, our results demonstrated comparable HER2 expression levels in DCIS and paired invasive carcinoma regardless of histopathological grade or HER2 immunohistochemical score. These findings contributed to a more nuanced understanding of HER2 biology in early breast carcinogenesis and may inform future biomarker-driven therapeutic strategies.

PMID:40679712 | DOI:10.1007/s10549-025-07781-9

Sleep Breath. 2025 Jul 18;29(4):248. doi: 10.1007/s11325-025-03389-x.

ABSTRACT

BACKGROUND: The increasing use of e-cigarettes and the decline in sleep duration among young people are growing public health concerns. While cigarette smoking has been linked to shorter sleep duration, less is known about the effects of e-cigarettes. This study explores the association between exclusive e-cigarette use and sleep duration among US young adults aged 18-24 who only use e-cigarettes.

METHODS: We analyzed data from 26,943 young adults in the 2022 Behavioral Risk Factor Surveillance System survey. Sleep duration was categorized as short (< 7 h/24 hours), normal (7-9 h), or long (> 9 h). We excluded participants using any tobacco/nicotine products other than e-cigarettes and restricted the sample to 4,553 young adults with complete data. Logistic regression models assessed e-cigarette use status (i.e., current use, past use, and non-use) in relation to sleep duration, adjusting for demographics, current substance use, lifestyle factors, and health conditions.

RESULTS: Overall, 31.9% of young adults experienced short sleep duration, 63.2% reported normal sleep, and 4.9% had long sleep. Current e-cigarette users had a higher prevalence of short sleep duration (44.6%) than past users (33.0%) and non-users (27.4%; p-value < 0.001). Weighted analyses indicated that current e-cigarette use was significantly associated with short sleep duration (adjusted OR = 1.82; 95%CI: 1.30-2.54), but no significant associations were found with long sleep duration (all p-values > 0.05).

CONCLUSIONS: Current exclusive e-cigarette use is associated with short sleep duration among US young adults. Efforts to reduce e-cigarette use in this population may contribute to improved sleep health.

PMID:40679707 | DOI:10.1007/s11325-025-03389-x

Trop Anim Health Prod. 2025 Jul 18;57(7):307. doi: 10.1007/s11250-025-04550-0.

ABSTRACT

This study investigated the effects of Lactobacillus plantarum (LAC) and its cell-free supernatant (CFS) on vaginal health and reproductive performance in ewes. The ewes were synchronized using fluorogestone acetate (FGA) or medroxyprogesterone acetate (MPA) impregnated intravaginal sponges. A total of 196 Merino ewes were randomly assigned to four groups in a 2 × 2 factorial design. Intravaginal sponges remained for 14 days, and vaginal discharge, sponge weight change, estrus response, and pregnancy rates were evaluated. No adverse health effects were observed following intravaginal probiotic treatment. There was a tendency (p = 0.07) for higher sponge loss in the FGA group (13.2%) compared to the MPA group (5.7%). On the day of sponge removal, 90.8% of ewes exhibited vaginal discharge. Although not statistically significant, mean vaginal discharge scores were lower in LAC-treated groups compared to CFS-treated groups. While L. plantarum had no significant effect on vaginal discharge scores in the MPA group (40.7% in MPA + LAC vs. 41.7% in MPA + CFS for score 2; p > 0.05), it significantly reduced purulent/hemorrhagic discharge in the FGA group (29.7% in FGA + LAC vs. 47.6% in FGA + CFS; p < 0.05). Estrus initiation occurred significantly earlier in the FGA group (36.8 ± 1.9 h) compared to the MPA group (49.1 ± 1.2 h; p < 0.01), although neither the probiotic treatment nor its interaction with progestagen type significantly influenced estrus timing. Pregnancy rates were significantly higher in the FGA + LAC (71.7%) and FGA + CFS (75.6%) groups compared to the MPA + LAC (49.0%) and MPA + CFS (50.0%) groups (p < 0.01). Our findings suggest that FGA-based synchronization improves pregnancy rates, while treatment with L. plantarum may enhance vaginal health, providing a potential non-antibiotic approach for reproductive management.

PMID:40679696 | DOI:10.1007/s11250-025-04550-0