A single-site randomized controlled trial of partner navigation to HCV treatment for people who inject drugs: a study protocol for the You're Empowered for Treatment Initiation (YETI) partner trial.

Background: Disparities persist in testing and treatment for hepatitis C virus (HCV), leaving socially marginalized populations, including people who inject drugs (PWID), less likely to benefit from curative treatment. Linkage services are often insufficient to overcome barriers to navigating the medical system and contextual factors.

Methods: The You're Empowered for Treatment Initiation (YETI) Partner trial is a single-site randomized controlled trial evaluating the efficacy of a two-session behavioral intervention that engages injecting partners as peer navigators for HCV treatment.

Disease-modifying strategies: Targeting protein kinases in multiple sclerosis and other autoimmune disorders.

A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced.

DISCOntinuation of disease-modifying therapies in MS: The DISCOMS extension trial.

Background: In the DISCOMS (DISCOntinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS)) randomized clinical trial, we could not demonstrate that discontinuing MS DMTs in older, stable adults was not inferior to continuing DMTs. Relapses were rare in both groups, and most new disease activity was one to two new brain magnetic resonance imaging (MRI) lesions unassociated with clinical changes.

Objective/aims: Describe results of the DISCOMS extension study.

Performance of the pooled cohort equations and D:A:D risk scores among individuals with HIV in a global cardiovascular disease prevention trial: a cohort study leveraging data from REPRIEVE.

Background: Risk estimation is an essential component of cardiovascular disease prevention among people with HIV. We aimed to characterise how well atherosclerotic cardiovascular disease (ASCVD) risk scores used in clinical guidelines perform among people with HIV globally.

Methods: In this prospective cohort study leveraging REPRIEVE data, we included participants aged 40-75 years, with low-to-moderate traditional cardiovascular risk, not taking statin therapy.

Histopathologic Progression and Metastatic Relapse Outcomes in Small Cell Neuroendocrine Carcinomas of the Urinary Tract.

Introduction: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

Materials And Methods: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021.

Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data.

As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Discordance, accuracy and reproducibility study of pathologists' diagnosis of melanoma and melanocytic tumors.

Accurate melanoma diagnosis is crucial for patient outcomes and reliability of AI diagnostic tools. We assess interrater variability among eight expert pathologists reviewing histopathological images and clinical metadata of 792 melanoma-suspicious lesions prospectively collected at eight German hospitals. Moreover, we provide access to the largest panel-validated dataset featuring dermoscopic and histopathological images with metadata.

Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial.

Background: Aspirin is a simple, globally available medication that has been shown to reduce the incidence of colorectal cancer. We aimed to evaluate the safety and efficacy of aspirin in the secondary prevention of colorectal cancer.

Methods: This phase 3, randomised, double-blind, placebo-controlled trial was conducted at 66 centres across 11 countries and territories (ten in Asia-Pacific; one in the Middle East).

The Efficacy of Lubiprostone in Patients of Constipation: An Updated Systematic Review and Meta-Analysis.

Background And Aim: Lubiprostone increases chloride and water secretion in the intestines, and several studies have demonstrated the efficacy of lubiprostone in treating functional constipation. Several new clinical trials have emerged since the previous meta-analysis conducted in 2020. We conducted this updated meta-analysis to assess clinical efficacy of lubiprostone in these patients.

Association of plasma biomarkers of Alzheimer's pathology and neurodegeneration with gait performance in older adults.

Background: Declining gait performance is seen in aging individuals, due to neural and systemic factors. Plasma biomarkers provide an accessible way to assess evolving brain changes; non-specific neurodegeneration (NfL, GFAP) or evolving Alzheimer's disease (Aβ 42/40 ratio, P-Tau181).

Methods: In a population-based cohort of older adults, we evaluate the hypothesis that plasma biomarkers of neurodegeneration and Alzheimer's Disease pathology are associated with worse gait performance.

A retrospective review of the common childhood illnesses and the indications for antibiotic prescription at community hospital in Malawi.

Background: Childhood remains a vulnerable period and a key determiner for adult health. Various illnesses experienced by children in their early years determine future performance and contribution to society. Acute and chronic infectious diseases, undernutrition, and early childhood non-communicable diseases have greatly been linked to intellectual disability, poor childhood development, increased morbidity, and household and healthcare economic costs.

The impact of highly effective modulator therapy on sinusitis and dysosmia in young children with cystic fibrosis: a prospective study protocol.

Background: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown.

Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.

Background: The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Methods: In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA).

Acute effect of a Mediterranean-style dietary pattern (MDP) on mood, anxiety and cognition in UK adults with mild to moderate anxiety and depression: the MediMood randomised controlled trial protocol.

Introduction: Psychological disorders including depression and anxiety are significant public health concerns. A Mediterranean-style dietary pattern (MDP) has been associated with improved mental well-being in observational studies. Evidence of the acute (defined as postprandial to 1 week) effects of an MDP on brain function, mood, cognition and important modulators, including sleep and the gut microbiota is limited.

Sexual health and healthy relationships for Further Education (SaFE) in Wales and England: results from a pilot cluster randomised controlled trial.

Objectives: To examine the acceptability of implementing, trialling and estimating the cost of the Sexual health and healthy relationships for Further Education (SaFE) intervention.

Design: Two-arm repeated cross-sectional pilot cluster randomised controlled trial (cRCT) of SaFE compared with usual practice, including a process evaluation and an economic assessment.

Setting: Eight further education (FE) settings in South Wales and the West of England, UK.

Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol.

Introduction: Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resource intensive. Globally, there is an unmet need for a non-invasive, cost-effective test.

Mailed smoking cessation support for Aboriginal and Torres Strait Islander people who smoke: protocol for a hybrid type 1 effectiveness - implementation trial.

Introduction: Smoking is the leading preventable cause of death and the single most significant risk behaviour contributing to adverse health conditions among Aboriginal and Torres Strait Islander people. There is an urgent need for innovative approaches to support reductions in smoking prevalence. This study will assess the implementation and effectiveness of a mailed smoking cessation support programme that includes nicotine replacement therapy (NRT) () for Aboriginal and Torres Strait Islander people.

A Comparative Study of Nalbuphine, Clonidine, and Dexmedetomidine as Adjuvants to Ropivacaine in Epidural Anesthesia for Lower Limb Surgery.

Background: In epidural anaesthesia, the addition of an adjuvant to local anaesthetics enhances the efficacy, thereby providing increased duration and intensity of blockade in lower limb surgeries. The aim was to compare the efficacy, onset, and duration of sensory and motor blockade; haemodynamic changes; and sedative and analgesic effects of nalbuphine, clonidine, and dexmedetomidine as an adjuvant to ropivacaine in epidural anaesthesia.

Methodology: A prospective, randomised, double-blind study among 90 patients after taking consent was divided into three groups (30 patients each; Group D received 15 ml of 0.

Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial.

Introduction: Patients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance genes from whole blood samples within hours of collection could enable earlier antibiotic optimisation for patients suspected to have bacterial infections. However, few randomised trials have evaluated the effect of using direct-from-blood bacterial testing on antibiotic administration and clinical outcomes.

First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer.

Background: SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion protein provided superior antitumor immunity in comparison to CD47- and CD40-targeted antibodies. A first-in-human phase I trial of SL-172154 was conducted in patients with platinum-resistant ovarian cancer.

Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.