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Add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: a randomized phase 3 study

Oncologist. 2026 May 21:oyag201. doi: 10.1093/oncolo/oyag201. Online ahead of print.

ABSTRACT

BACKGROUND: Ruxolitinib (JAK1/JAK2 inhibitor) is indicated for adults with intermediate or high-risk myelofibrosis; however, a subset of patients may exhibit a suboptimal response due to persistent PI3K/AKT activation. The phase 3, randomized, double-blind, placebo-controlled LIMBER-304 study (NCT04551053) investigated the efficacy and safety of add-on parsaclisib (highly selective PI3Kδ inhibitor) in patients with myelofibrosis and suboptimal or declining response to stable ruxolitinib monotherapy.

PATIENTS AND METHODS: Adults with primary or secondary myelofibrosis who received ruxolitinib with palpable spleen and Myelofibrosis Symptom Assessment Form (MFSAF) total symptom score (TSS) ≥10 were eligible. Primary end point was proportion of patients achieving ≥25% spleen volume reduction (SVR; baseline to Week 24); key secondary end point was proportion of.

PATIENT: s with ≥50% MFSAF-TSS reduction (baseline to Week 24).

RESULTS: In total, 90 patients received parsaclisib/ruxolitinib; 87 received placebo/ruxolitinib. At Week 24, 16.7% of patients receiving parsaclisib/ruxolitinib achieved ≥25% SVR versus 9.7% for placebo/ruxolitinib; this difference was not statistically significant. By Week 24, ≥50% reduction in MFSAF-TSS was observed in 17.1% of patients receiving parsaclisib/ruxolitinib versus 14.1% for placebo/ruxolitinib. Higher rates of infections (including cytomegalovirus) and gastrointestinal disorders were observed with parsaclisib/ruxolitinib. Grade ≥3 treatment-emergent adverse events occurred in 60.0% of patients receiving parsaclisib/ruxolitinib versus 42.5% with placebo/ruxolitinib. The study was terminated early based on efficacy findings.

CONCLUSIONS: Study results suggested adding parsaclisib to stable-dose ruxolitinib was unlikely to offer clinically meaningful benefits. Further research is needed on the potential of JAK and PI3K inhibitor-based combination therapy for patients with myelofibrosis.

PMID:42179186 | DOI:10.1093/oncolo/oyag201

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Improving mental health literacy of frontline community health workers in a rural district of Pakistan: mPareshan project

BJPsych Open. 2026 May 25;12(3):e144. doi: 10.1192/bjo.2026.11051.

ABSTRACT

BACKGROUND: In low- and middle-income countries, four out of five people with mental illness do not receive specialised treatment. Utilising non-specialist frontline workers to deliver basic mental health services at the community level therefore warrants exploration.

AIMS: This study assessed improvement in the knowledge and skills of frontline community workers in identifying symptoms of anxiety and depression, making appropriate referrals and providing psychosocial counselling, in a rural district of Pakistan.

METHOD: Project mPareshan developed a training manual to enhance the mental health literacy of government-employed lady health workers (LHWs) and lady health supervisors (LHSs). Content was adapted from the World Health Organization’s Mental Health Gap Action Programme 2.0 intervention guide to suit the local context. A total of 72 participants (36 LHSs and 36 LHWs) from the Badin District, Sindh, Pakistan, received the training. Pre- and post-tests were conducted to assess changes in knowledge and skills, using the Wilcoxon signed-rank test.

RESULTS: There was a statistically significant improvement in both knowledge (p < 0.01, r = 0.85) and competency (p < 0.01, r = 0.81) median scores following the mPareshan training. LHSs demonstrated higher percentage increase in knowledge and competencies in domains requiring practical application, such as coping mechanisms, psychosocial support and referral pathways, compared with LHWs, highlighting the importance of their supervisory role and support in mental health service delivery.

CONCLUSIONS: The mPareshan mental health training has the potential to improve the knowledge and competencies of community health workers. Such initiatives can be scaled up to enable frontline workers to function as an effective workforce in the absence of specialist mental health services.

PMID:42179177 | DOI:10.1192/bjo.2026.11051

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The Effect of Kinesio Taping on Handgrip Strength and Functional Outcomes in Elderly Patients After Lower Extremity Surgery: A Retrospective Cohort Study

Physiother Res Int. 2026 Jul;31(3):e70243. doi: 10.1002/pri.70243.

ABSTRACT

BACKGROUND AND PURPOSE: This study aims to investigate the effects of increasing handgrip strength by applying Kinesio taping to the wrist extensors on the functional level in patients undergoing lower extremity surgery who ambulate with a walker.

METHODS: This retrospective study analyzed data from 100 patients aged 65 years and older who underwent lower extremity surgery and ambulated with a walker. The patients were divided into two groups: a control group (CG) that was kept under the standard rehabilitation program and a Kinesio taping group (KT) in which Kinesio taping was applied to the forearm extensor muscles in addition to the group being under standard rehabilitation program. The patients’ handgrip strength (HGS), pain, and functional levels (Functional Independence Measurements (FIM), Iowa Level of Assistance Scale (ILAS), and Iowa Walking Speed Scale (IWSS)) were retrospectively assessed before treatment and at discharge.

RESULTS: Compared to the CG group, the right and left HGS, functional levels, and IWSS of the patients increased significantly in the KT group, and their activity-related pain levels decreased significantly (p < 0.005). A significant positive correlation was observed between the change in HGS and the change in ILAS and FIM scores, and a statistically significant negative correlation was found between the change in HGS and the change in activity-related pain and IWSS (p < 0.05).

DISCUSSION: Our findings suggest that Kinesio taping application is a simple and cost-effective method that increases HGS in patients and is an effective method in controlling pain, improving walking speed, and enhancing functionality in patients undergoing lower extremity surgery.

TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT06072261.

PMID:42179169 | DOI:10.1002/pri.70243

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Performance of Non-Dental Professional Caregivers in Oral Health Assessment Using the Oral Health Screener: Caregiver-Dentist Agreement and Inter-Rater Reliability

Gerodontology. 2026 May 25. doi: 10.1111/ger.70093. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate caregiver-dentist agreement and inter-rater reliability of the Oral Health Screener (OHS) following its optimisation for use in long-term care and to examine the effect of different caregiver OHS training modalities.

METHODS: This prospective reliability and agreement study was nested within a 2-year cluster-randomised controlled trial in Flemish nursing homes (Belgium). Professional caregivers and dentists independently assessed residents’ oral health using the OHS every 6 months across five timepoints, blinded to each other’s assessments. Caregivers received either e-learning only (IG1) or e-learning combined with on-site training (IG2). Agreement was analysed using percent agreement, Cohen’s kappa, prevalence-adjusted bias-adjusted kappa (PABAK) and logistic generalised linear mixed models (GLMM).

RESULTS: Fifty-one caregivers from six facilities and eight dentists assessed 193 residents. Within groups, IG1 showed higher agreement with dentists for self-reported items (GLMM 0.46-0.58) than for inspection-based OHS items (GLMM 0.10-0.48), whereas this difference was less pronounced in IG2 (self-reported items: GLMM 0.45-0.95, inspection-based items: GLMM 0.35-0.92). Comparing groups, GLMM analyses indicated overall higher reliability in IG2 for most items, except for chewing difficulty. Exploratory analyses suggested that longitudinal patterns varied across items. Inter-caregiver reliability analyses were exploratory due to the limited number of paired assessments.

CONCLUSION: Non-dental professional caregivers showed acceptable agreement with dentists when assessing residents’ oral health using the OHS. Although agreement varied across items due to prevalence and marginal imbalances, the findings suggest the potential added value of training and support when using the OHS as a first-line screening tool in care-dependent older adults.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06536322 (July 23, 2024).

PMID:42179168 | DOI:10.1111/ger.70093

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Spatially fractionated radiotherapy using straight and bending virtual rods as an alternative for cervical cancer brachytherapy-results from preclinical in-silico dose comparison and quality assurance

Br J Radiol. 2026 May 21:tqag075. doi: 10.1093/bjr/tqag075. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare virtual straight and bending rods Spatially Fractionated Radiation Therapy (SFRT) for cervical cancer brachytherapy delivery.

METHODS: CT scan datasets from ten patients with locally advanced cervical cancer who received brachytherapy were included. For each patient, two distinct plans were generated: one using straight virtual rods and the other using bending virtual rods. The total prescribed dose was 30 Gy in 5 fractions. All plans were created with 10XFFF beam. Dosimetric parameters, including D90, V100, V150, and V200 for high risk-clinical target volume (HRCTV), were evaluated. Additionally, dose constraints for OARs (bladder, rectum, sigmoid, and bowel D2cc) were compared. Plan delivery quality assurance was performed for using Mobius verification phantom, and gamma passing rate was analyzed.

RESULTS: Comparable CTV coverage was observed between the two configurations. D90 values showing no statistically significant difference (p > 0.05). In both plans, the D2cc ofbladder, rectum, sigmoid, and bowel were observed to be ≤ 23.75 Gy, ≤ 17.00 Gy, ≤ 19.50 Gy, and ≤ 17.00 Gy, respectively. The average hotspot in HRCTV was evaluated at 18.4% (±10.4) and 20.8% (±7.8) for V200%, respectively. The gamma passing rate was found to be greater than 90% for the 2%/2 mm criteria.

CONCLUSION: This in-silico study concludes that both virtual rod configurations provide comparable target coverage while effectively minimizing OAR exposure. Further clinical validation is recommended to confirm these findings.

ADVANCES IN KNOWLEDGE: This study demonstrates the feasibility of SFRT and the potential for future testing in patients who are unable to undergo brachytherapy.

PMID:42179164 | DOI:10.1093/bjr/tqag075

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Gender-Based Predictors of Sepsis in Patients Undergoing Urinary Decompression for Obstructive Uropathy

J Endourol. 2026 May 25:8927790261454506. doi: 10.1177/08927790261454506. Online ahead of print.

ABSTRACT

AIM OF THE STUDY: Epidemiological studies have shown that female patients are at higher risk of developing stone-related infectious complications and urosepsis than their male counterparts. However, this gender-based difference in outcomes has not been specifically explored in the context of obstructive uropathy. This study aimed to investigate gender-related predictors of sepsis in patients treated for obstructive uropathy for ureteral stones.

MATERIALS AND METHODS: We retrospectively analyzed clinical, laboratory, and radiological data from 291 consecutive patients presenting to the emergency department for obstructive uropathy because of ureteral stones and submitted to stent or nephrostomy tube decompression between 01/2016 and 10/2024. Comorbidities were assessed using the Charlson Comorbidity Index. Sepsis was defined as an acute increase in ≥2 sequenctial organ failure assesment points and documented blood or urine cultures. All patients underwent preoperative computed tomography. Clinical and stone characteristics were collected in each case. Descriptive statistics and logistic regression models were used to identify gender-specific factors associated with sepsis.

RESULTS: In males, sepsis is linked to older age, larger stones, higher white blood cells, and C-reactive protein (CRP). In females, sepsis is linked to older age, higher Charlson Index, creatinine, and CRP. Septic females had smaller stones and lower CRP and creatinine than males. CRP and age were strongest sepsis predictors, with lower thresholds in females. Limitations include single-center, retrospective design, missing data (e.g., antibiotic timing, hormonal status), and reduced power for sex-specific analyses. Larger, prospective studies needed.

CONCLUSIONS: Female patients with obstructive uropathy had a higher risk of sepsis than men. Clinical and laboratory predictors of sepsis are different according to gender. Female developed sepsis at lower inflammatory scores and smaller stone diameter than males, highlighting that a gender-based management strategy should be performed in patients with obstructive uropathy.

PMID:42179155 | DOI:10.1177/08927790261454506

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Wheelchair user spatial clustering in Wales is associated with socioeconomic deprivation: a multi-domain analysis using the Welsh index of multiple deprivation

Disabil Rehabil Assist Technol. 2026 May 25:1-13. doi: 10.1080/17483107.2026.2678549. Online ahead of print.

ABSTRACT

PURPOSE: Wheelchair users represent a population with significant and often permanent mobility impairment. Despite well-established links between disability and socioeconomic deprivation, the geographic relationship between wheelchair user concentration and area-level deprivation has not previously been examined at national scale. This study aimed to identify spatial clusters of wheelchair users across Wales and characterise their association with socioeconomic deprivation across domains of the Welsh Index of Multiple Deprivation (WIMD).

METHODS: This cross-sectional ecological study used 43,790 NHS-registered wheelchair users across all 1,917 Lower Layer Super Output Areas (LSOAs) in Wales. Local Moran’s I identified statistically significant High-High (HH) spatial clusters of wheelchair user counts. Chi-square goodness of fit tests, chi-square tests of association, and binary logistic regression quantified the association between WIMD deprivation quintile (Q1-5) and HH clustering across WIMD domain, with Benjamini-Hochberg false discovery rate correction applied throughout.

RESULTS: One-hundred-and-ten HH clusters were identified, with 41% in the most deprived WIMD Overall quintile. Significant deprivation gradients were observed across six domains; Health and Employment showed the strongest associations, with Q1:Q5 wheelchair user ratios of 1.747 and 1.738 and up to 20-fold greater odds of HH cluster membership in the most deprived quintile. Housing and Access to Services showed divergent patterns, with clusters concentrated in areas of moderate rather than extreme deprivation.

CONCLUSIONS: Wheelchair user spatial clustering in Wales is strongly associated with socioeconomic deprivation, but the association varies by WIMD domain. These findings provide actionable spatial evidence to support equitable NHS wheelchair service commissioning aligned with true geographic need.

PMID:42179143 | DOI:10.1080/17483107.2026.2678549

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Nalmefene Mitigates Opioid-Induced Nausea and Vomiting in Postoperative Analgesia but Not Resting Pain

Pain Res Manag. 2026;2026(1):e5531157. doi: 10.1155/prm/5531157.

ABSTRACT

BACKGROUND: Patient-controlled analgesia (PCA) pumps have emerged as the prevalent modality for managing postoperative pain. Opioids, although widely utilized as analgesic agents in these pumps, are often accompanied by undesirable side effects that can compromise patient comfort and hinder the widespread adoption of PCA therapy.

METHODS: We conducted a retrospective study involving 392 patients undergoing lumbar spine surgery who were prescribed PCA pumps for pain relief. Over the initial 1-3 days postsurgery, comprehensive data encompassing resting and activity-related pain levels, Ramsay sedation scores, activity status, and flatus passage were carefully recorded and analyzed.

RESULTS: Interestingly, patients who received a supplemental dose of nalmefene in their PCA pumps exhibited a notable increase in resting pain intensity on the second postoperative day. However, the incidence of postoperative nausea and vomiting (PONV) was notably reduced (15.5% in the sufentanil + nalmefene group vs 25.5% in the sufentanil group). Notably, no statistically significant variations were discerned between the two groups in Ramsay sedation scores, postoperative activity capabilities, flatus passage, or inflammatory biomarker levels.

CONCLUSION: The integration of nalmefene into PCA pumps presents a promising strategy for mitigating the occurrence of PONV, albeit with the caveat of potentially compromising opioid-mediated analgesia, necessitating further research and exploration. The delicate balance between enhancing patient comfort and preserving effective pain control remains a critical area of investigation in the field of postoperative pain management.

PMID:42179138 | DOI:10.1155/prm/5531157

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Associations of Life’s Essential 8 With Mortality Among Individuals With Diabetes and/or Hypertension: Statistical Mediation by Inflammation and Biological Aging

Mediators Inflamm. 2026;2026(1):e3674573. doi: 10.1155/mi/3674573.

ABSTRACT

BACKGROUND: Despite extensive evidence supporting the American Heart Association (AHA)’s life’s essential 8 (LE8) framework for cardiovascular health (CVH) assessment, the underlying biological mechanisms linking LE8 to mortality outcomes in high-risk populations remain unexplored. This study aimed to investigate the association between LE8 scores and mortality risk among individuals with diabetes, hypertension, and their coexistence, and explored whether inflammation and biological aging statistically mediate these relationships.

METHODS: We conducted a large-scale longitudinal analysis using National Health and Nutrition Examination Survey (NHANES) data (2005-2018), including 4939 individuals with diabetes, 13,298 with hypertension, and 3303 with both conditions. LE8 scores were calculated from eight CVH metrics, with mortality ascertained through the National Death Index (NDI). Mediation analyses examined the roles of inflammation markers (neutrophil-to-lymphocyte ratio [NLR] and pan-immune-inflammation value [PIV]) and phenotypic age acceleration (PhenoAgeAccel).

RESULTS: Higher LE8 scores were significantly associated with reduced all-cause mortality and heart disease mortality across all groups (p < 0.001). Stratified analyses showed stronger associations among younger individuals (≤60 years) and those with higher socioeconomic status. In mediation analyses, inflammatory markers and PhenoAgeAccel statistically explained a meaningful proportion of the LE8-mortality associations, with different patterns across disease groups. For all-cause mortality, in diabetes, NLR and PIV accounted for larger proportions of the association (NLR: 31.6%; PIV: 26.9%), whereas in hypertension, PhenoAgeAccel accounted for a larger proportion (56.3%). Among individuals with both conditions, PhenoAgeAccel (26.1%) and NLR (5.3%) contributed to the association. Similar patterns were observed for heart disease mortality.

CONCLUSION: Higher LE8 scores are associated with reduced mortality risk in individuals with diabetes and/or hypertension, with inflammation and biological aging statistically mediating these associations in an exploratory manner. These findings suggest potential statistical mediators that may inform future mechanistic research and therapeutic targets, but causal interpretation requires further longitudinal studies.

PMID:42179110 | DOI:10.1155/mi/3674573

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School Type and Disaster Preparedness: Evaluation of Disaster Safe Educational Unit Program Implementation in DKI Jakarta, Indonesia

Public Health Nurs. 2026 May 25. doi: 10.1111/phn.70135. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the Disaster Safe Educational Unit (SPAB), internationally known as the Comprehensive School Safety (CSS) program, in DKI Jakarta, Indonesia focusing on disaster preparedness across different types of educational units.

METHODS: This study employed an evaluative mixed-methods design combining quantitative and qualitative approaches. Quantitative data were analyzed using cross-tabulation and Chi-Square tests in IBM SPSS Statistics version 22. Semi-structured qualitative interviews with experts were conducted to support data triangulation.

SAMPLE: The study included 3672 schools in DKI Jakarta Province, Indonesia surveyed using an online instrument adapted from the National Disaster Management Agency (BNPB) monitoring framework, covering three implementation pillars: disaster-safe facilities, disaster management in schools, and disaster risk reduction education.

RESULTS: The findings indicate that while progress has been made in providing disaster-safe facilities, preparedness in disaster management and disaster risk reduction education remains limited. Notably, preschools were identified as a high-priority risk group due to regulatory exclusions and resource constraints. Key challenges include a lack of teaching materials, limited resources, and insufficient expertise.

CONCLUSION: Although institutional support for the SPAB is high, implementation capacity across schools remains insufficient. This study highlights the need for inclusive regulatory reinforcement, targeted capacity building for early childhood education, and the formal integration of SPAB into school budgeting to ensure resilient learning environments.

PMID:42179070 | DOI:10.1111/phn.70135