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Prospective evaluation of real-world safety, symptoms improvement and adherence to mavacamten among Iranian patients with hypertrophic obstructive cardiomyopathy (PERSIA-HOCM): protocol of a multicentre observational study

Por: Ghaseminejad-Raeini · A. · Karimi · M. A. · Shirinezhad · A. · Aslani · M. · Soheili · A. · Ghaderi · A. · Haghjoo · M. · Bakhshandeh · H. · Naderi · N.
Introduction

Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disorder affecting approximately 1 in 200 to 1 in 500 adults, with nearly 70% exhibiting the obstructive phenotype Hypertrophic Obstructive Cardiomyopathy (HOCM). Randomised trials have demonstrated the efficacy of mavacamten, a first-in-class cardiac myosin inhibitor which significantly reduced outflow tract gradients and improved symptoms, exercise capacity and quality of life in the HOCM cases. Despite these findings, prospective real-world data on its safety and effectiveness remain limited, particularly in non-Western populations and further evidence from routine clinical practice is needed.

Methods and analysis

PERSIA-HOCM is a prospective, multicentre, observational study to be conducted at 19 cardiovascular referral centres in Iran. Adults aged 18 years or older with symptomatic obstructive HCM, defined as New York Heart Association (NYHA) class II to IV and a left ventricular outflow tract (LVOT) gradient of at least 50 mm Hg at rest or with provocation, who are prescribed mavacamten, will be enrolled. Key exclusions include left ventricular ejection fraction below 55%, non-obstructive phenotype and lack of consent. Participants will be followed for 1 year at 4-week intervals. Data collection will include symptoms, NYHA class, vital signs, echocardiographic parameters (including outflow gradients and ejection fraction), mavacamten dosing and adjustments and concomitant therapies. Echocardiography will be performed at weeks 4, 8, 12 and 24. Safety will be assessed using a predefined adverse event framework that includes mortality, hospitalisations and major clinical events. At weeks 12 and 48, cardiac troponin, N-terminal pro B-type natriuretic peptide and quality of life will be assessed. Primary endpoints will be safety, change in the NYHA class, resting and provoked LVOT gradient, quality of life, cardiac biomarkers and left ventricular ejection fraction. Secondary endpoints will include cardiac magnetic resonance imaging parameters for cardiac fibrosis, peak oxygen intake and genotype-based outcome. Analyses will be performed using R V.4.5.1, employing descriptive statistics, paired sample t tests and McNemar’s test.

Ethics and dissemination

Ethical approval was obtained from the Research Ethics Committee of Rajaie Cardiovascular, Medical and Research Institute/Iran National Committee for Ethics in Biomedical Research (Code: IR.RHC.REC.1404.210). Written informed consent will be required and filled by the patients. Considering full data confidentiality, analysis reports will be public every 6 months. Findings will be disseminated through peer-reviewed publications and scientific conferences.

Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatment

Por: Hikida · S. · Nomoto · H. · Uemura · Y. · Suzuki · T. · Izumikawa · K. · Ohge · H. · Yamato · M. · Kato · Y. · Hase · R. · Aoyagi · T. · Hagiya · H. · Nukui · Y. · Yamamoto · K. · Takesue · Y. · Sawada · K. · Shimizu · Y. · Miyamoto · S. · Tamura · N. · Takahashi · K. · Saito · S. · Miyazaki
Introduction

Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.

Methods and analysis

This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ≥65 years. Both T-705IV and oseltamivir phosphate will be administered for 5 days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group).

Ethics and dissemination

Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences.

Trial registration number

jRCT2031240586,

Prognostic value of different biomarkers in bladder cancer: protocol for an umbrella review of systematic reviews and meta-analyses

Por: Aghamir · S. M. K. · Rahimnia · R. · Taheri · D. · Ebrahimi · M. · Talebian · M. T. · Keshtkar · A. · Ghasemi · M. · Mohammadi · S. D. · Menbari Oskouie · I. · Nikoofar · P. · Khatami · F.
Introduction

Bladder cancer (BC), the second most common urinary cancer, is classified as either non-muscle-invasive BC or muscle-invasive BC. Although numerous studies have identified potential prognostic biomarkers, none have yet been implemented in clinical practice. A comprehensive umbrella review comparing all prognostic biomarkers in BC remains absent. Thus, we aim to synthesise evidence from systematic reviews and meta-analyses on prognostic factors in patients with BC.

Methods and analysis

We will search PubMed/MEDLINE, Scopus, Web of Science (WOS), EMBASE, Cochrane Database of Systematic Reviews (CDSR), Google Scholar and EPISTEMONIKOS for systematic reviews of BC prognostic biomarkers from the inception date to 1 November 2025. Title and abstract will be screened for potentially relevant studies. Then two reviewers will independently select eligible reviews based on eligibility criteria. A data extraction sheet will be used to extract relevant information. The risk of bias in the included reviews will be assessed with the Risk of Bias in systematic reviews tool. Using the random-effects model for each prognostic biomarker, we will estimate the pooled HR and its 95% CI as well as the prediction interval and its 95% CI. To quantify heterogeneity between studies, we will use the I2 metric. We will use contour funnel plots, doi plots, the Egger test and the Copas method to evaluate evidence of small-study effects. The credibility assessment will be assessed using the following items: level of statistical significance, number of cases, degree of statistical heterogeneity, significance of the PI, evidence of small-study effects and excess significance bias. We will perform sensitivity analyses with multiple approaches.

Ethics and dissemination

Formal ethical approval is not required, as primary data will not be collected in this study. The findings of this study will be disseminated through peer-reviewed publications.

PROSPERO registration number

CRD42024602432.

The In Vitro Wound‐Scratch Assay: Applications, Technical Advances, and Limitations in Wound Healing Research

ABSTRACT

The wound-scratch assay is a widely used in vitro model for studying collective cell migration, a fundamental process contributing to wound closure and re-epithelialisation. Owing to its simplicity, low cost, and adaptability, it has become a foundational tool for early-stage wound-healing research and therapeutic screening. The assay involves generating a defined gap in a confluent cell monolayer and monitoring gap closure over time as a surrogate readout of repair. This narrative review examined 199 published studies, identifying 73 relevant to wound healing. A technical hierarchy of wound creation methods was identified across three main categories: mechanical approaches (e.g., pipette tips and cell scrapers), accessible but prone to operator-dependent variability; semi-automated systems (e.g., inserts and wound maker devices), which improve reproducibility; and fully-automated robotic platforms offering high precision and high-throughput capability. While these advances enhance technical consistency, they do not overcome the assay's fundamental biological constraints. Importantly, gap closure in the wound-scratch assay primarily reflects planar collective cell migration and does not recapitulate the integrated inflammatory, vascular, metabolic, and extracellular matrix-dependent processes that govern wound repair in vivo. Consequently, bioactive compounds acting through antioxidant, anti-inflammatory, angiogenic, or matrix-modulating pathways may have their therapeutic potential underestimated or misclassified when assessed using migration-only readouts. Preliminary in-house (unpublished) data are presented to illustrate this limitation, demonstrating modest migration effects for compounds with established wound-healing activity in vivo. Despite these limitations, the wound-scratch assay remains a valuable first-line, hypothesis-generating tool when interpreted appropriately, with future utility dependent on integration with adapted models and complementary assays for translation.

Nursing‐Sensitive Process Indicators Predicting 30‐Day Readmission in Chronic Heart Failure

ABSTRACT

Aim(s)

To identify nursing-sensitive process indicators documented during hospitalization and at discharge that predict 30-day hospital readmission among adults with chronic heart failure (CHF).

Design

A retrospective case–control study.

Methods

This study included 640 adults hospitalized with CHF at two cardiac referral centres in Sabzevar, Iran, between February 2020 and April 2024. Cases were patients readmitted within 30 days of discharge (n = 320), and controls were patients without readmission during this period (n = 320). Data were extracted from medical records on nursing-sensitive process indicators, including in-hospital falls, fall-risk identification at admission, structured nursing education at discharge, nursing-led post-discharge follow-up, patient knowledge of prescribed medications, polypharmacy (≥ 4 medications at discharge), and medication dosing frequency. Sociodemographic and clinical characteristics were also collected.

Results

In-hospital falls, identification of fall risk at admission, poor knowledge of prescribed medications, polypharmacy, and complex medication dosing schedules were associated with higher odds of 30-day readmission. In contrast, receipt of structured nursing education at discharge was associated with a significantly lower likelihood of 30-day readmission.

Conclusion

Nursing-sensitive process indicators are significant and independent predictors of 30-day hospital readmission among adults with CHF. Strengthening fall prevention strategies, improving medication-related education, and enhancing discharge preparation represent actionable nursing interventions to reduce avoidable 30-day readmission.

Implications for the Profession and/or Patient Care

Targeted nursing interventions focused on fall prevention, medication management, and structured discharge education may improve discharge readiness, enhance continuity of care, and reduce preventable 30-day readmission in patients with CHF.

Problem Addressed

Unplanned 30-day readmission following hospitalization for chronic heart failure remains a persistent challenge for healthcare quality and patient safety.

Main Findings

Several nursing-sensitive process indicators, particularly fall-related indicators and discharge education, independently predicted readmission risk.

Research Impact

The findings support the integration of targeted nursing-led interventions in cardiac and medical units to reduce readmission risk.

Reporting Method

This study was reported in accordance with the STROBE guidelines for observational studies.

Patient or Public Contribution

No patient or public involvement was included in the design, conduct, or reporting of this study.

Determinants of collaborative reasoning in physician-to-physician teleconsultations: a qualitative study

Por: Ghasemi · S. · Changiz · T. · Omid · A.
Objective

Teleconsultation has become a vital component of modern healthcare delivery, within which clinical reasoning is a critical determinant of care quality, directly impacting patient outcomes. This qualitative study aimed to explore and validate the key components that constitute effective (accurate, timely and safe) physician-physician clinical reasoning in teleconsultations.

Design and setting

We employed a qualitative design using directed content analysis. The study was conducted within Iran’s national ‘Moein Program’, a structured teleconsultation service providing specialist support for obstetrics and gynaecology. Data collection was conducted between 2023 and 2024.

Participants

Semistructured interviews were conducted with 16 purposively sampled obstetrician-gynaecologists (both specialists and residents) who had direct teleconsultation experience. Data collection continued until theoretical saturation was achieved.

Analysis

The data analysis process was guided by an initial conceptual framework derived from a literature review, and the study’s rigour was ensured through Lincoln and Guba’s trustworthiness criteria, including triangulation and member checking.

Results

The analysis validated and refined the initial framework, culminating in five key components influencing clinical reasoning in teleconsultations: (1) Data collection and sharing, (2) Situation analysis, (3) Ethical and emotional factors, (4) Collaborative decision-making and (5) Resource-related factors.

Conclusions

The study concludes that successful teleconsultation relies not merely on technological infrastructure but critically on a complex interplay of human, cognitive and ethical factors. These findings underscore the necessity for developing integrated teleconsultation systems that are explicitly designed to support both the technical and the collaborative cognitive dimensions of clinical reasoning.

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