Tag: nevin manimala

Ther Innov Regul Sci. 2026 Jun 18. doi: 10.1007/s43441-026-00998-w. Online ahead of print.

ABSTRACT

BACKGROUND: The ICH E9 (R1) addendum establishes frameworks for efficacy estimands (using a hypothetical strategy to handle intercurrent events) and treatment regimen estimands (using a treatment policy strategy to handle intercurrent events) in clinical trials. While Phase 3 studies often adopt treatment regimen estimands for regulatory purposes, direct use of the results from Phase 2 treatment regimen estimands for Phase 3 planning may produce suboptimal results due to differences in population, study duration, treatment regimen itself, and treatment delivery methods that affect adherence rates.

METHODS: We developed a modeling framework that decomposes treatment regimen estimands into adherent (efficacy estimand) and non-adherent patient responses. Using historical Phase 3 study data from chronic weight management and type 2 diabetes populations, we first establish empirical linear relationships between efficacy and non-adherent responses through regression modeling without intercept. Then we estimate Phase 3 efficacy responses from Phase 2 data, project discontinuation rates for Phase 3 study, and apply the empirical relationship to predict treatment regimen responses.

RESULTS: Linear relationships were identified for change in absolute weight loss and glycated hemoglobin (HbA1c) endpoints using data from multiple Phase 3 studies. Model validation showed close agreement between predicted and observed treatment regimen responses in the training data. Application to the SURPASS-2 Phase 3 study demonstrated reasonable predictive accuracy, with estimates generally within expected ranges of observed results.

CONCLUSIONS: This approach provides a systematic method for translating Phase 2 efficacy estimand results into Phase 3 treatment regimen estimand predictions. It leverages empirical relationships between efficacy responses and non-adherent responses, and may complement direct Phase 2 data extrapolation, particularly for endpoints where treatment effects persist after discontinuation. Current applications focus on change in body weight (kg) and change in HbA1c (%).

PMID:42315826 | DOI:10.1007/s43441-026-00998-w

Clin Oral Investig. 2026 Jun 19;30(7):296. doi: 10.1007/s00784-026-06977-7.

ABSTRACT

OBJECTIVES: Xerostomia significantly affects oral health and quality of life, yet no validated Hebrew assessment exists. This study aimed to translate the Xerostomia Inventory (XI) into Hebrew (HXI) and evaluate its validity and reliability.

METHODS: The XI was translated into Hebrew using cross-cultural adaptation guidelines. The HXI was examined for internal consistency, using Cronbach’s alpha, as well as for construct validity (convergent and discriminant validity).

RESULTS: The HXI was completed by 102 xerostomia patients, 89.2% women, and the mean age was 63.5 ± 13.8 years with age range of 20-90 years. The mean HXI score was 39.9 ± 1.2, with score range 12-55. The HXI exhibited a high level of reliability with Cronbach’s α = 0.975. The convergent validity of the HXI, indicated by Spearman’s correlation between the HXI and the unstimulated salivary flow (USF) whole volume, demonstrated a strong, negative, and statistically significant correlation (r = -0.862). Strong negative correlations were also found between the total HXI score and other sialometry variables (ranging from r=-0.696 to r=-0.879). The absence of significant associations between the HXI scores and unrelated sociodemographic variables supports the discriminant validity of the HXI. Confirmatory factor analysis supported a robust unidimensional structure for the Hebrew 11-item HXI, with a single factor accounting for 80.3% of the total variance and all item loadings exceeding 0.82.

CONCLUSIONS: The HXI is a valid and reliable instrument for assessing xerostomia in Hebrew-speaking populations, demonstrating psychometric robustness consistent with international versions.

CLINICAL RELEVANCE: The HXI provides a valid and reliable tool for assessing patient-reported oral dryness, supporting diagnosis, treatment, and evaluation of interventions in Hebrew-speaking populations.

PMID:42315815 | DOI:10.1007/s00784-026-06977-7

Environ Monit Assess. 2026 Jun 19;198(7):747. doi: 10.1007/s10661-026-15566-w.

ABSTRACT

Since tropospheric ozone poses a significant threat to public health, this research aims to estimate urban daily ozone levels using 2004-2021 polluting and meteorological data of three major European capitals (Madrid, Stockholm, and Rome). The resulting expression showed a goodness-of-fit of 84.99% (range 2-120 µg O₃/m³), with an average accuracy of 0.01 µg O₃/m³ (equivalent to 0.86%). According to the European legislative requirements for short-term ozone modeling (associated uncertainty < 50%), the total number of 2004-2021 daily exceedances was 0.079% (21 cases). As a novelty, the current work evaluated the performance of the suggested approach at both temporal (using data not included in the original approach) and geographical scales (applied to an area different from those used in the original approach), differing from previous studies that did not address these features. Temporally, a global r value of 0.863 was observed, also complying with the current legislative requirements for short-term ozone modeling. The RMSE, MAE, and MAPE metrics were 1.05 μg/m³, 1.11 μg/m³, and 11.16%, respectively (range 7 to 139 µg/m³). Geographically, an r value of 0.921 was reached, meeting legislative requirements in 98.8% of data. RSME, MAE, and MAPE values of 1.79 µg/m³, 3.20 µg/m³, and 12.80% were observed. As a potential limitation, reanalysis datasets were used instead of independent observational data. Despite this, a validated, easy-to-implement approach for estimating daily urban ozone levels using satellite data is provided, reducing uncertainty due to limited information, which could complement European Legislative directives on short-term ambient air ozone modeling.

PMID:42315800 | DOI:10.1007/s10661-026-15566-w

Knee. 2026 Jun 18;62:104548. doi: 10.1016/j.knee.2026.104548. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to biomechanically evaluate and compare five different fixation techniques for isolated Letenneur Type I lateral Hoffa fractures using a fresh-frozen cadaveric model under both static and dynamic axial loading conditions.

METHODS: Twenty-five fresh-frozen distal femurs were homogeneously assigned to five groups based on fixation method: (A) two postero-anterior (PA) screws (6.5 mm), (B) two antero-posterior (AP) screws (6.5 mm), (C) two PA screws combined with a posterior 3.5-mm tubular plate, (D) one PA screw combined with a lateral 3.5-mm locking compression plate (LCP), and (E) two AP screws combined with a lateral horizontal 3.5-mm tubular plate. Specimens underwent dynamic loading (2500 cycles, five stages, 2 Hz) followed by static axial loading using a servo-hydraulic testing machine. The parameters evaluated included load at 3-mm displacement, ultimate load, stiffness, and photogrammetric displacement.

RESULTS: Plate-augmented constructs demonstrated significantly superior biomechanical stability. Ultimate load was highest in Group C (1761.8 ± 299.5 N), followed by Group D (1564.4 ± 162.1 N) and Group E (1571.2 ± 420.8 N), all significantly greater than Groups A (902.4 ± 522.8 N) and B (1088.2 ± 323.1 N) (P < 0.01). Photogrammetric displacement was significantly lower in plate-augmented groups (Group C: 0.32 ± 0.24 mm; Group E: 0.59 ± 0.58 mm) (P < 0.05). No statistically significant differences were observed between screw-only constructs.

CONCLUSIONS: Plate-augmented fixation provides superior biomechanical stability for isolated Letenneur Type I lateral Hoffa fractures. Lateral plating achieves comparable stability to posterior plating while avoiding the technical challenges. The comparable performance of screw configurations suggests that screw trajectory can be flexibly selected based on fracture morphology. These findings offer guidance for surgical planning and implant selection in the management of these complex fractures.

PMID:42314239 | DOI:10.1016/j.knee.2026.104548

Asian Pac Isl Nurs J. 2026 Jun 18;10:e85340. doi: 10.2196/85340.

ABSTRACT

BACKGROUND: Breast cancer (BC) symptom awareness through screening measures, such as breast self-examination practice (BSEP), is promoted in low-resource countries. The Muslim culture has a unique impact on family support for women’s health care decisions, especially from the mother. Given the proven effect of educational intervention on breast health through interactive sessions and mobile health, implementation according to Muslim cultural values through family support, especially from the mother, was lacking, and this study was planned.

OBJECTIVE: This study aimed to determine the effects of a culture-based breast health education program (CBBHEP) on BSEP in high-risk women.

METHODS: A single-site randomized controlled trial was conducted in a hospital on 72 high-risk women, aged 20-50 years, from August 19 to November 29, 2024. The trial was registered prospectively (ID: ISRCTN-39194106). The participants were matched in pairs by age and educational level, and randomly assigned to experimental and control groups. The intervention program was based on social cognitive theory and the cultural identity concept of the PEN-3 model. The program consisted of face-to-face interactive sessions and a health app called a Women’s Health app for promoting BSEP. The experimental group received CBBHEP, whereas the control group received the usual care. BSEP was measured at baseline and 12 weeks using a translated, valid, and reliable Toronto BSE frequency and proficiency of practice scale. Data analysis was performed using 1-way analysis of covariance and paired sample 1-tailedt test.

RESULTS: The participants in the experimental group who received CBBHEP for 12 weeks increased their BSEP much better than those in the control group (F1, 69=58.908, η2=0.46; P<.001). The results also revealed a statistically significant effect of a higher BSEP in the experimental group (t35=7.21, Cohen d=0.88; P<.001).

CONCLUSIONS: The findings suggest that health care practitioners can apply this program to increase BSEP among high-risk women through their family support, especially from mothers.

PMID:42314192 | DOI:10.2196/85340

J Occup Environ Hyg. 2026 Jun 18:1-13. doi: 10.1080/15459624.2026.2664464. Online ahead of print.

ABSTRACT

Exposure monitoring data available to industrial hygienists will eventually surpass the ability of a practitioner to effectively interpret without a consolidating computational approach. For large sets of time-series exposure data, the most important question that can be answered to determine if further exposure evaluation is required may be formulated as: Does this exposure data contain any period of time during which the identified occupational exposure limit value could be exceeded? Determining the answer to this question may be computationally intensive using current exposure decision methodology, better suited for small data sets consisting of single time-weighted average exposures. The authors instead proposed an algorithmic method for evaluating large sets of time-series exposure data without clearly defined exposure start and stop times, while also incorporating recommended data cleaning methods and an evaluation of statistical uncertainty. The outcome of this analysis was a binary “thumbs up,” indicating the time-series exposure data did not contain any time period that may have exceeded the limit value when considering confidence intervals, or “thumbs down,” indicating the opposite. Finally, the authors demonstrated the algorithmic heuristic using a proof-of-concept available to the public at no cost at https://athena-heuristic.streamlit.app/.

PMID:42314188 | DOI:10.1080/15459624.2026.2664464

Obstet Gynecol. 2026 Jun 18. doi: 10.1097/AOG.0000000000006354. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess adverse pregnancy and birth outcomes after bivalent prefusion F subunit-based respiratory syncytial virus vaccine (RSVpreF) vaccination during the first season of availability.

METHODS: This was a target trial emulation study including eight health systems across eight states (California, Oregon, Washington, Colorado, Maryland, Virginia, Minnesota, and Wisconsin) and Washington, DC, in the Vaccine Safety Datalink (VSD). We included pregnant patients aged 16-49 years who had enrolled at a VSD site between September 22, 2023, and February 29, 2024. Exposure was defined as receipt of RSVpreF vaccination between 32 and less than 37 weeks of gestation. Outcomes included preterm birth (PTB), stillbirth, small-for-gestational-age (SGA) birth weight, and hypertensive disorders of pregnancy (HDP) assessed with electronic health record data. Stillbirth cases were confirmed through chart review. Pregnant patients exposed to RSVpreF vaccines were matched 1:1 to unexposed pregnant patients at the gestational week of vaccination by propensity to be vaccinated and VSD site. Unexposed pregnant patients were assigned an index date equivalent to the gestational day of vaccination for their vaccinated match. If the unvaccinated match was subsequently vaccinated, the pair was censored. We report adverse event risks and adjusted risk ratios (aRRs) with corresponding 95% CIs adjusted for nulliparity using a log binomial model with robust variance.

RESULTS: We identified 13,966 pregnant patients who received the RSVpreF vaccine. A higher percentage of nulliparous patients were in the vaccinated group (46.4%) compared with the unvaccinated group (38.7%). Comparing RSVpreF vaccinated pregnant patients and their unvaccinated matches, rates of PTB (4.0% vs 4.5%, respectively; aRR 0.90, 95% CI, 0.80-1.00), stillbirth (0.79/1,000 and 0.72/1,000; aRR 0.99, 95% CI, 0.41-2.36), and SGA birth weight (6.8% and 6.5%; aRR 1.02, 95% CI, 0.92-1.12) did not significantly differ. The rate of any HDP among RSVpreF vaccinated patients was 17.3% vs 15.0% among their unvaccinated matches (aRR 1.13, 95% CI, 1.07-1.19).

CONCLUSION: Initial prenatal RSVpreF safety surveillance shows a largely favorable safety profile. Although we identified a small but statistically significant increased risk for HDP after RSVpreF vaccination, there was no increased risk for PTB, SGA birth weight, or stillbirth.

PMID:42314184 | DOI:10.1097/AOG.0000000000006354

J Urol. 2026 Jun 18:101097JU0000000000005151. doi: 10.1097/JU.0000000000005151. Online ahead of print.

NO ABSTRACT

PMID:42314173 | DOI:10.1097/JU.0000000000005151

Brain. 2026 Jun 18:awag213. doi: 10.1093/brain/awag213. Online ahead of print.

ABSTRACT

Despite improved survival in recent years, long-term outcomes in patients surviving progressive multifocal leukoencephalopathy beyond the first year remain poorly defined. This international multicenter retrospective study aimed to characterize the three-year prognosis of patients with progressive multifocal leukoencephalopathy who had survived at least one year, identify factors associated with favorable outcomes and late mortality, and determine recurrence rate. Data were collected through standardized questionnaires across forty-one centers in twelve countries. Patients were eligible if they met the 2013 diagnostic criteria for definite progressive multifocal leukoencephalopathy of the American Academy of Neurology, survived at least one year after diagnosis, and had documented follow-up three years after diagnosis. Demographic, clinical, virological, and radiological data were retrieved at diagnosis, one year, and three years. Functional status was assessed using the modified Rankin Scale, with scores of 0-2 defining a favorable outcome. Generalized linear mixed models identified independent predictors of three-year functional status and late mortality. Among 1877 screened cases, 245 patients met inclusion criteria. The most common underlying causes of immunosuppression were HIV infection (48%), autoimmune/inflammatory diseases (26%), and hematological malignancies (18%). At three years, 220 patients (89.8% of the cohort) were alive and 188 (85.5% of survivors) had neurological sequelae, most frequently motor or cognitive impairment. Overall, 112/245 (45.7%) achieved a favorable functional outcome. HIV-associated progressive multifocal leukoencephalopathy (OR 2.36, 95% CI 1.05-5.28) was associated with a favourable outcome, whereas higher modified Rankin Scale score at diagnosis (OR 0.48, 95% CI 0.35-0.66) and higher number of affected brain regions on baseline MRI (OR 0.78, 95% CI 0.64-0.95) were independently associated with poorer functional outcome. Among variables collected one year after diagnosis, good functional status at that time was significantly associated with long-term favorable outcome (OR 0.01, 95% CI <0.01-0.03). Twenty-five patients (10.2%) died after the first year, with mortality associated with higher lesion burden at diagnosis and primary immunodeficiency as underlying disease. Even beyond the first year, progressive multifocal leukoencephalopathy remained the leading cause of death (11/25). Recurrence occurred in seven patients (2.9%) and was almost always fatal (6/7). This study provides a comprehensive evaluation of long-term outcomes among survivors of progressive multifocal leukoencephalopathy. These findings present a nuanced picture: while most remain neurologically impaired, nearly half achieve functional independence at three years. The results emphasize the prognostic relevance of the initial clinical and radiological burden and early functional trajectory and highlight the need for research into mechanisms driving disease recurrence.

PMID:42314166 | DOI:10.1093/brain/awag213

JMIR Res Protoc. 2026 Jun 18;15:e92511. doi: 10.2196/92511.

ABSTRACT

BACKGROUND: Workplace violence against health care professionals has increased worldwide, leading to negative psychological, professional, and organizational outcomes. Despite existing prevention and reporting programs, underreporting and lack of accessible, confidential support persist. Digital health tools, including chatbots, may offer scalable support, guidance, and follow-up for affected professionals.

OBJECTIVE: This study aims to design, develop, and validate a chatbot (Sanidad Segura) to assist health care professionals who experience workplace aggression and evaluate its usability, readability, and exploratory indicators of perceived usefulness and support in a pilot study.

METHODS: This study will follow a mixed methods design conducted in two main phases: (1) design, development, and content validation of the chatbot based on literature review, institutional protocols, and expert consensus; and (2) pilot-testing, including usability and readability assessment using standardized instruments, as well as feasibility and acceptability evaluation among health care professionals working in emergency and critical care settings in Almería (Spain). The study is aligned with the Medical Research Council framework for complex interventions, incorporating development and feasibility stages. Quantitative data will be collected using the System Usability Scale and Inflesz readability scale. Qualitative data will be collected through semistructured interviews and analyzed using thematic analysis to explore user experience and identify barriers to and facilitators of use.

RESULTS: The study has been funded for a 2-year period starting on December 18, 2024. Quantitative outcomes will include usability scores (System Usability Scale), readability scores (Inflesz), and participants’ sociodemographic characteristics. Qualitative findings will identify themes related to usability, user experience, and suggestions for improvement. Integration of quantitative and qualitative findings will be conducted through triangulation to provide a comprehensive understanding of the usability, acceptability, and readability of the chatbot.

CONCLUSIONS: This study addresses the increasing incidence of workplace violence against health care professionals through the development of a new chatbot (Sanidad Segura). This intervention seeks to facilitate the identification, support, and follow-up of affected individuals while minimizing the adverse effects of such events on their physical and psychological well-being, social interaction, and professional performance. Sanidad Segura will enable confidential case reporting and provide access to tailored medical, psychological, and legal resources, as well as information about institutional support services. This project represents a crucial step toward implementing an integrated digital framework for the detection, management, and prevention of workplace violence in health care settings.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/92511.

PMID:42314161 | DOI:10.2196/92511