Tag: nevin manimala

Hepatol Commun. 2026 Mar 31;10(4):e0936. doi: 10.1097/HC9.0000000000000936. eCollection 2026 Apr 1.

ABSTRACT

BACKGROUND: Individuals with cirrhosis frequently require Emergency Department (ED) care, with some experiencing repeated ED use, yet little is known about the patient and caregiver perspectives driving decisions to visit the ED. We aimed to explore perspectives of including high ED utilizers with cirrhosis and their caregivers to identify drivers of ED use and opportunities to optimize care.

METHODS: Using human-centered design methods, we conducted an in-person group engagement session with 7 adults with cirrhosis and their caregivers, recruited from recent ED encounters. A custom board-game activity facilitated the discussion. Data were analyzed using snippet extraction, affinity mapping, and affinity concept modeling.

RESULTS: Seven major themes emerged: (1) Mindset around symptoms, which includes fear, uncertainty, and caregiver burden. (2) Informational needs, including reliance on variable-quality online resources and lack of trusted education. (3) Day-to-day cirrhosis management, particularly challenges related to medications and symptom monitoring. (4) Symptom-driven ED triggers, with some prompting, urgent visits. (5) Decision-making factors, including limited alternatives to ED care and prior experiences, and mismatched patient-caregiver thresholds for seeking care. (6) Expectations of ED care, focused on pain relief and return to baseline health. (7) Challenges during ED care, including long wait times, misdiagnosis concerns, and stigma related to pain treatment. Concept modeling revealed that ED decision-making is a dynamic journey shaped by symptom severity, emotional states, logistical considerations, and evolving patient-caregiver-provider roles.

CONCLUSIONS: Pain, uncertainty about symptom severity, and lack of accessible real-time clinical support were major drivers of ED utilization in cirrhosis. Interventions addressing these specific needs may reduce avoidable ED use. These findings provide a patient-informed foundation for care delivery redesign in cirrhosis.

PMID:41921201 | DOI:10.1097/HC9.0000000000000936

Brief Bioinform. 2026 Mar 1;27(2):bbag132. doi: 10.1093/bib/bbag132.

ABSTRACT

N6-methyladenosine (m6A) is the most prevalent internal modification in mRNA and plays a critical role in post-transcriptional regulation. Despite the development of various detection methods, accurate and quantitative detection of m6A modifications at single-molecule and single-nucleotide resolution remains challenging. Many existing approaches struggle with limited resolution, inaccurate quantification, or dependence on sequence motifs. Here, we present m6Astorm, a novel computational framework for stoichiometry-preserving and stochasticity-aware identification of m6A. m6Astorm encodes the signal features (signal intensity and maximum instantaneous amplitudes derived from raw signal) and sequence context via a hybrid architecture built from convolutional neural networks and bidirectional long short-term memory networks. Trained with quantitative labels from GLORI, m6Astorm could achieve motif-independent detection of m6A modifications at single-molecule resolution by a dual-objective optimization: (i) minimizing binary cross-entropy loss for methylation state classification at molecule level, regularized by a confidence-aware penalty term suppressing low-certainty predictions; (ii) minimizing the stoichiometry bias for accurate quantitative at the nucleotide level. m6Astorm resolves co-methylation events at single-molecule, revealing coordination in m6A regulatory patterning across transcriptomes. Systematic evaluation across Hela and mouse embryonic stem cell datasets demonstrates robust cross-sample generalizability, evidenced by high prediction power (Recall), low false positive rate, accurate stoichiometric, and high area under the receiver operating characteristic curve/area under the precision-recall curve in transcriptome-wide modification profiling.

PMID:41921196 | DOI:10.1093/bib/bbag132

Brief Bioinform. 2026 Mar 1;27(2):bbag141. doi: 10.1093/bib/bbag141.

ABSTRACT

Understanding the complex nature of multifunctional interactions among genes is crucial for interpreting omics data. We developed NetCrafter, an ontology-driven platform for constructing de novo gene networks that are specific to each input gene list and quantitatively defined by ontology-weighted similarity. By incorporating the probabilistic association of ontology or curated gene sets into a weighted Tanimoto similarity metric, NetCrafter transforms enrichment results into quantitative semantic similarity scores between genes, enabling the creation of context-specific statistical networks. These networks can be further decomposed into optimal sub-networks, facilitating multifunctional interpretation and the identification of gene interaction hotspots. NetCrafter also supports the integration of heterogeneous omics-derived gene lists through consensus ontology scoring. Importantly, this list-specific, quantitative framework reveals functional hotspots and target-biomarker relationships-even in cases where ontology terms alone are not predictive of node-level attributes such as clustered regularly interspaced short palindromic repeats (CRISPR) efficacy. NetCrafter provides an interactive platform for constructing and interpreting dynamic, context-specific gene networks, leveraging ontology-based functional associations to uncover underlying mechanisms and identify key nodes. It is freely available at https://netcrafter.sookmyung.ac.kr and integrated into Q-omics platform (https://qomics.ai) to enhance the utility of cancer omics data.

PMID:41921194 | DOI:10.1093/bib/bbag141

Hepatol Commun. 2026 Mar 31;10(4):e0905. doi: 10.1097/HC9.0000000000000905. eCollection 2026 Apr 1.

ABSTRACT

BACKGROUND: Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with high mortality in cirrhosis. Recent FDA approval of terlipressin and updated clinical guidance have expanded management options, but real-world practice patterns remain unknown.

METHODS: We conducted a nationwide survey of U.S. hepatology providers regarding HRS-AKI management practices. The 33-question survey assessed provider demographics, vasoconstrictor selection, treatment timing, and adherence to guideline recommendations.

RESULTS: Among 162 respondents, most were hepatologists (94%) at academic centers (83%). Only 11% obtained a nephrology consultation at AKI detection, with 44% waiting until worsening renal function. Terlipressin was available at 80% of institutions but more commonly at academic centers (84% vs. 53%, p=0.003). Consistent with guideline recommendations, 77% of providers initiate vasoconstrictors only after completing a trial of volume expansion (if no renal improvement), particularly in academic centers (80% vs. 60% non-academic, p=0.03). Terlipressin (49%) and midodrine/octreotide (44%) were preferred first-line treatments, with providers at academic centers more likely to use midodrine/octreotide (46% vs. 30%, p=0.008). Mean arterial pressure was used by 62% of providers to guide vasoconstrictor dosing. Most providers (73%) discontinued vasoconstrictor treatment after 4 days if no improvement.

CONCLUSIONS: Significant variations exist between guideline recommendations and real-world HRS-AKI management, especially first-line treatment choice, treatment monitoring, and nephrology consultation. These findings highlight opportunities to improve guideline implementation and identify areas where practice patterns might inform provider education and future guidance updates.

PMID:41921139 | DOI:10.1097/HC9.0000000000000905

JMIR Res Protoc. 2026 Apr 1;15:e83377. doi: 10.2196/83377.

ABSTRACT

BACKGROUND: Retention of specialists is critical for sustaining health system performance. In Malaysia, the Ministry of Health (MOH) has implemented multiple workforce retention strategies (WRSs) to enhance job satisfaction and reduce turnover among specialists. However, evidence on specialists’ awareness, participation, and perceived effectiveness of these strategies remains limited. To address this gap, we plan to administer a standardized survey among specialists in MOH health care facilities to guide evidence-based strategic planning toward specialist retention.

OBJECTIVE: This protocol describes a national-level online survey to assess MOH specialists’ perceptions of WRS and examine their associations with job satisfaction and turnover intention, using REDCap (Research Electronic Data Capture) to ensure real-time data collection within a robust and secure digital platform.

METHODS: A cross-sectional mixed methods study will be conducted among 1325 MOH specialists selected through systematic random sampling from the Human Resource Management Information System. Data collection will be implemented using a REDCap-based workflow to support secure and efficient survey administration. REDCap functionalities will be used, including automated survey invitations with nontransferable links to prevent duplicate responses, branching logic to tailor item relevance, auto-reminder scheduling, and real-time data validation to minimize entry errors. The self-administered questionnaire comprises measures of specialists’ awareness, participation, and perceived effectiveness of 12 MOH-implemented WRSs, job satisfaction assessed using the Job Satisfaction Survey, and turnover intention measured with the Turnover Intention Scale-6, as well as 2 optional open-ended questions for qualitative input to strengthen the quantitative results. A pilot study will be conducted to assess instrument reliability and REDCap platform usability. Quantitative data will be exported from REDCap for descriptive and inferential analyses, while qualitative responses will undergo thematic analysis using NVivo and be integrated with quantitative findings during interpretation.

RESULTS: This study will generate vital evidence of MOH specialists’ engagement with WRSs and how perceptions of these strategies related to their job satisfaction and turnover intention. Participant recruitment and data collection have been completed, and the study is in the data analysis phase. It is expected that the data analysis will be completed in March 2026 and that the results will be published in June 2026.

CONCLUSIONS: This protocol establishes a REDCap-based survey for conducting large-scale research focused on MOH specialists. Findings are expected to guide data-driven improvements to WRS implementation within the MOH Malaysia and may serve as a useful methodological model for similar research in public sector workforce studies.

PMID:41921120 | DOI:10.2196/83377

JCO Oncol Pract. 2026 Apr 1:OP2501270. doi: 10.1200/OP-25-01270. Online ahead of print.

ABSTRACT

PURPOSE: The objective of priority review is to expedite the review duration for drugs that provide significant improvements. We analyzed the duration of regulatory review of cancer drugs granted priority versus nonpriority review and differences in the proportion of cancer drugs with high therapeutic value granted priority versus nonpriority review in the United States, European Union, and Switzerland.

METHODS: In this cross-sectional study, we used US Food and Drug Administration’s (FDA), European Medicines Agency’s (EMA), and Swissmedic’s databases to identify all new cancer drugs approved in 2010-2024, their submission and approval dates, and approval pathways. European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) and ESMO-Magnitude of Clinical Benefit Scale for Haematological Malignancies scores were calculated to assess their therapeutic value. We applied summary statistics (medians and IQR) to describe differences in review duration for priority versus nonpriority review. Review duration was calculated from submission to approval date. For estimated differences in proportions of high therapeutic value scores for drugs granted priority versus nonpriority review, we calculated classical normal 95% CIs.

RESULTS: In all, 144 (86%) of 168 cancer drugs were granted priority review by the FDA, 37 (25%) of 147 by EMA, and 37 (28%) of 132 by Swissmedic. Of those, the FDA reviewed 30%, EMA 5%, and Swissmedic 49% within the required time period; review duration was similar for drugs with high and low therapeutic value. The difference in the proportion of high value scores between priority and nonpriority review was -4% (95% CI, -20 to 13) for the FDA, 22% (95% CI, 6 to 38) for EMA, and 17% (95% CI, <1 to 33]) for Swissmedic.

CONCLUSION: It could be beneficial for patients if agencies applied more scrutiny in the selection of which cancer drugs to grant priority review. Such drugs should have a high therapeutic value, and their review should be completed in a timely manner to enable quicker access to important cancer drugs for patients. Although the FDA would need to take the most substantial steps, EMA and Swissmedic could also improve their systems.

PMID:41921119 | DOI:10.1200/OP-25-01270

JCO Oncol Pract. 2026 Apr 1:OP2501182. doi: 10.1200/OP-25-01182. Online ahead of print.

ABSTRACT

PURPOSE: Contact days exceeding trial protocol-mandated care may represent adverse clinical events and portend worse outcomes. Identifying patients at risk of poor outcomes could enable clinical teams to intervene early and support patients’ needs.

MATERIALS AND METHODS: We linked data from 6 SWOG trials to Medicare claims. We calculated contact days (days with ambulatory, emergency department, inpatient, or facility-based care) and their composition using protocol calendars. Total contact days were delineated as protocol-mandated (planned) ambulatory or unplanned (including unplanned ambulatory v unplanned inpatient). Cox frailty landmark regression analysis was used in a random 60% training set to identify the optimal threshold (percentile) and landmark (months) for contact-day measures as the predictor based on the chi-square statistic. Candidate predictors were tested in the remaining 40% sample.

RESULTS: We included 1,429 patients (median age, 71 years, 7.6% Black, 21.4% female). In the first 3 months, among 15,301 contact days in the training set (6.4 contact days per person per month; 21.2% of total days), 4,102 (26.8%) were protocol-mandated ambulatory, and 11,199 (73.2%) were unplanned (including 7,328 [47.9%] ambulatory and 3,871 [25.3%] inpatient). The 2-month follow-up time at the 75th percentile threshold was the optimal model in the training set. In the test set, unplanned contact days, especially unplanned inpatient contact days, were associated with subsequent survival (≥1 unplanned inpatient contact days, adjusted hazard ratio, 1.25 [1.02-1.52], P = .014).

CONCLUSION: One in five trial follow-up days was a health care contact day, of which the majority were unplanned ambulatory contact days. Meaningfully decreasing contact-day burdens will require addressing uncoordinated unplanned ambulatory contact days. The low threshold (≥1 in the first 2 months) of unplanned inpatient days in predicting mortality highlights the adverse impact of any acute care use on survival.

PMID:41921118 | DOI:10.1200/OP-25-01182

JMIR Public Health Surveill. 2026 Apr 1;12:e85875. doi: 10.2196/85875.

ABSTRACT

BACKGROUND: Utilization of the maternal continuum of care (CoC)-comprising adequate antenatal care (ANC), skilled birth attendance, and postnatal care (PNC)-is critical for improving maternal and child health outcomes. However, dropout from the CoC remains substantial in Bangladesh, with women discontinuing services at different stages of pregnancy, delivery, and postpartum care.

OBJECTIVE: This study aimed to quantify maternal dropout at each stage of the CoC and identify socioeconomic and demographic factors associated with discontinuity, comparing two nationally representative survey rounds.

METHODS: Data were drawn from the Bangladesh Demographic and Health Surveys (BDHS) 2017-2018 and 2022. Women aged 15 to 49 years with a live birth in the preceding 2 to 3 years were included. Completion of full CoC was defined as receiving at least 4 ANC visits, delivering with a skilled birth attendant, and obtaining at least 1 PNC contact within 48 hours of delivery. Predisposing (age, education, parity, religion, and division), enabling (wealth index, media exposure, health care access, and residence), and need factors (terminated pregnancy and desired pregnancy status) were identified using the Andersen Behavioral Model. Survey-weighted multivariable logistic regression models were fitted for each CoC component and overall CoC completion, with interaction terms to assess whether associations differed between survey rounds.

RESULTS: Among 8424 mothers, 27.9% (n=2350) failed to complete all components of the maternal CoC. Dropout was highest at the ANC stage (n=4962, 55.7%), followed by PNC (n=3976, 47.2%) and skilled birth attendant-assisted delivery (n=3378, 40.1%). Between survey rounds, overall CoC dropout decreased significantly from 31.9% (BDHS 2017-2018) to 22.4% (BDHS 2022), reflecting modest improvements in service continuity. Factors significantly associated with higher odds of CoC dropout included lower maternal education (adjusted odds ratio [AOR] 2.70, 95% CI 1.94-3.77; P<.001), higher parity (AOR 2.73, 95% CI 2.12-3.50; P<.001), lower wealth quintiles (AOR 4.04, 95% CI 3.02-5.41; P<.001), and rural residence (AOR 1.40, 95% CI 1.18-1.67; P<.001). Protective factors included older maternal age at delivery (AOR 0.56, 95% CI 0.42-0.74; P<.001) and history of ever-terminated pregnancy (AOR 0.74, 95% CI 0.63-0.86; P<.001). Significant temporal interactions (all P<.05) indicated that the strength of associations for education, parity, religion, wealth, media exposure, health care access barriers, residence, and pregnancy desire differed between survey rounds, reflecting changing determinants of CoC engagement amid policy reforms and pandemic disruptions.

CONCLUSIONS: Maternal, socioeconomic, and geographic factors are strongly associated with discontinuity along the maternal health care continuum in Bangladesh. Statistically significant temporal variations underscore the impact of evolving health policies and system disruptions on maternal service utilization patterns. Targeted, area-specific interventions addressing these determinants across all CoC components are essential to improve maternal health care retention and achieve better maternal and child health outcomes.

PMID:41921113 | DOI:10.2196/85875

Acta Orthop. 2026 Apr 1;97:225-231. doi: 10.2340/17453674.2026.45693.

ABSTRACT

BACKGROUND AND PURPOSE: In elastic stable intramedullary nailing (ESIN) for forearm fractures, nail protrusion may cause irritation-related implant removal. The primary aim was to evaluate implant retention after nail impaction, and secondarily to assess secondary procedures, complications, and protrusion as a predictor of removal.

METHODS: We analyzed a retrospective cohort of children with diaphyseal forearm fractures treated with impacted ESIN between 2017 and 2024. Implant retention was defined as no nail removal at record review. Secondary procedures were unplanned operations, while complications were adverse events managed conservatively. Radiographic nail protrusion was measured as extraosseous nail length and evaluated using receiver operating characteristic analysis to predict irritation-related implant removal.

RESULTS: 160 children with diaphyseal forearm fractures were included. At a mean observation time of 5 years, 132/160 children retained their implants (83%, 95% confidence interval [CI] 76-88). Secondary procedures occurred in 30/160 patients (19%, CI 13-26), most commonly irritation-related implant removal (10%, CI 6-16) and refracture (6%, CI 3-10). Complications occurred in 19/160 patients (12%, CI 7-18), including superficial radial nerve symptoms (7/160; 4.4%) and irritation without implant removal (6/160; 3.8%). A protrusion threshold of 3.3 mm predicted irritation-related implant removal (AUC 0.79, CI 0.71-0.86; sensitivity 100%, CI 83-100; specificity 55%, CI 49-61). No irritation-related removals occurred below this threshold.

CONCLUSION: Impacted ESIN was associated with high long-term implant retention, although secondary procedures and complications occurred in about one-third of the patients. A protrusion threshold of 3 mm was linked to irritation-related removal and may guide implant retention.

PMID:41921102 | DOI:10.2340/17453674.2026.45693

Acta Orthop. 2026 Apr 1;97:217-224. doi: 10.2340/17453674.2026.45695.

ABSTRACT

BACKGROUND AND PURPOSE: Denosumab may preserve periprosthetic bone mineral density (pBMD) around uncemented total hip arthroplasty (THA) components. This exploratory analysis of a previously published randomized controlled trial (RCT) aimed to assess the effects of denosumab on BMD 5 years after treatment cessation.

METHODS: 64 non-osteoporotic patients undergoing uncemented THA were enrolled in a randomized, double-blind, placebo-controlled phase-2 trial and received either 2 doses of denosumab or placebo. The primary outcome was pBMD at 12 months, measured by dual-energy X-ray absorptiometry (DEXA). At a mean follow-up of 5.6 years (range 4.3-7.3), 54 patients remained for clinical assessment, DEXA, and plain radiography. The study was registered on ClinicalTrials.gov (NCT01630941).

RESULTS: No differences in pBMD in the acetabular Digas zones or femoral Gruen zones were found between the groups at 5 years. The estimated mean difference in the sum of all zones around the cup was 0.042 g/cm² (95% confidence interval [CI] -0.31 to 0.35; P = 0.8), and for the sum of all Gruen zones -0.06 g/cm² (CI -0.55 to 0.43; P = 0.8). No statistically significant differences were observed in patient-reported outcome measures or the incidence of heterotopic ossification. A gradual decline in pBMD was evident.

CONCLUSION: At 5 years, the adjusted between-group difference and its 95% confidence interval showed no statistically or clinically relevant effect of denosumab. Whether longer treatment duration or a sequential post-denosumab regimen could influence long-term periprosthetic bone preservation is unknown.

PMID:41921101 | DOI:10.2340/17453674.2026.45695