Patient-reported outcomes and measures are under-utilised in advanced therapy medicinal products trials for orphan conditions.

Objectives: Advanced therapy medicinal products (ATMPs) are medicines based on genes, tissues, or cells and can include gene therapy, somatic-cell therapy, and tissue-engineered medicines. Patient-reported outcomes (PROs) are reports on health and well-being that come directly from the individual without external interpretation. Patient-reported outcome measures (PROMs) are questionnaires aimed at assessing the individual and subjective experience with health and other psychosocial aspects.

Post-operative periprosthetic femoral fractures in England: Patient profiles and short-term outcomes.

Background And Objective: Post-operative periprosthetic femoral fractures (POPFF) present a growing challenge for healthcare services, but there are limited national data on patient profiles, short-term outcomes, and post-discharge follow-up. We aimed to fill these gaps.

Methods: Using Hospital Episode Statistics (HES), we identified POPFF discharges from hospitals in England for patients aged 18 and above between April 2016 and December 2022.

Fragment-Specific Fixation for Trimalleolar Fractures: Functional and Radiological Outcomes.

Introduction A trimalleolar fracture is a complex unstable fracture that usually occurs as the result of rotational injuries of the ankle. Management and understanding of these fractures have evolved greatly over the last decade. Our study aimed to assess the postoperative outcomes following the fixation of these fractures using fragment-specific low profile anatomical fixation implants.

Insights into durability against resistance from the antibiotic nitrofurantoin.

Nitrofurantoin has shown exceptional durability against resistance over 70 years of use. This longevity stems from factors such as rapid achievement of therapeutic concentrations, multiple physiological targets against bacteria, low risk of horizontal gene transfer, and the need to acquire multiple mutations to achieve resistance. These combined features limit resistance emergence and spread of nitrofurantoin resistance.

Safety and Efficacy of Deucravacitinib in Moderate to Severe Plaque Psoriasis For Up to 3 Years: An Open-Label Extension of Randomized Clinical Trials.

Importance: Safe and effective long-term treatments for moderate to severe plaque psoriasis are needed.

Objective: To evaluate the long-term safety and efficacy of deucravacitinib through 3 years (week 148) in the randomized POETYK PSO-1, PSO-2, and nonrandomized long-term extension (LTE) trials.

Design, Setting, And Participants: PSO-1/PSO-2 were global, 52-week, randomized, double-blinded phase 3 trials in patients with moderate to severe plaque psoriasis.

Update on cancer screening in children with syndromes of bone lesions, hereditary leiomyoma and renal cell carcinoma syndrome, and other rare syndromes.

The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for healthcare professionals. The 2023 AACR Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection, intervention, and reduce morbidity associated with such neoplasms. In this paper, we review several of the rare conditions discussed in this workshop.

Leptomeningeal Disease Secondary to Invasive Ductal Carcinoma of the Breast: A Rapidly Progressive and Fatal Complication.

Leptomeningeal disease (LMD) is a rare yet serious complication of advanced malignancy, often seen in breast cancer and associated with a poor prognosis.  This case report highlights the rapid progression and diagnostic challenges encountered in a woman in her 40s with advanced breast cancer who presented with severe headaches, absence seizures, and diplopia. The patient's complex past history included invasive ductal carcinoma, prior brain metastasis, and recent craniotomy, which added significant challenges to diagnosis and management.

Molecular diagnoses and candidate gene identification in the congenital heart disease cohorts of the 100,000 genomes project.

Congenital heart disease (CHD) describes a structural cardiac defect present from birth. A cohort of participants recruited to the 100,000 Genomes Project (100 kGP) with syndromic CHD (286 probands) and familial CHD (262 probands) were identified. "Tiering" following genome sequencing data analysis prioritised variants in gene panels linked to participant phenotype.

Experiences of a Digital Behavior Change Intervention to Prevent Weight Gain and Promote Risk-Reducing Health Behaviors for Women Aged 18 to 35 Years at Increased Risk of Breast Cancer: Qualitative Interview Study.

Background: Breast cancer is the most common form of cancer in women. Adult weight gain and modifiable health behaviors, including smoking, alcohol intake, and lack of physical activity, are well-known risk factors. Most weight gain in women occurs between the ages of 18 and 35 years.

Regional anaesthesia research priorities: a Regional Anaesthesia UK (RA-UK) priority setting partnership involving patients, carers and healthcare professionals.

Introduction: Regional anaesthesia provides important clinical benefits to patients but is underutilised. A barrier to widespread adoption may be the focus of regional anaesthesia research on novel techniques rather than evaluating and optimising existing approaches. Research priorities in regional anaesthesia identified by anaesthetists have been published, but the views of patients, carers and other healthcare professionals have not been considered previously.

Bimekizumab Efficacy in High-Impact Areas: Pooled 2-Year Analysis in Scalp, Nail, and Palmoplantar Psoriasis from Phase 3/3b Randomized Controlled Trials.

Introduction: Psoriasis in high-impact areas, including the scalp, nails, palms, and soles, can disproportionately impair patient quality of life. Here, we evaluate the 2-year efficacy of bimekizumab treatment in patients with moderate to severe plaque psoriasis in post hoc analyses of five phase 3/3b trials.

Methods: High-impact area efficacy data were pooled through 2 years across five phase 3/3b trials: BE VIVID, BE READY, BE SURE, their ongoing open-label extension (OLE) BE BRIGHT, and BE RADIANT (including its double-blinded treatment period and the first year of its OLE).

Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses.

Objective: Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages.

Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping.

Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate.

Displaced Pediatric Supracondylar Fracture (Gartland Type II and III): The Impact of Wire Fixation Type.

Introduction Supracondylar fractures are common in children. Percutaneous K-wire fixation is an accepted standard treatment for displaced supracondylar fractures in children, but the ideal wire configuration remains controversial. This study aimed to review the radiographic outcome and complications of Gartland type II and type III supracondylar fractures treated by the crossed and lateral K-wire fixation.

Association between Accelerometer-Measured Irregular Sleep Duration and Longitudinal Changes in Body Mass Index in Older Adults.

Irregular sleep duration may disrupt circadian rhythms and contribute to metabolic, behavioral, and mood changes, potentially increasing the risk for obesity. However, quantitative data on the relationship between sleep duration irregularity and weight change are lacking. In this prospective study, we analyzed data from 10,572 participants (mean age: 63 years) in the UK Biobank who wore accelerometers for a week between 2013-2015 and had two body mass index (BMI; kg/m) measurements on average 2.

Loss of DOT1L function disrupts neuronal transcription, animal behavior, and leads to a novel neurodevelopmental disorder.

Individuals with monoallelic pathogenic variants in the histone lysine methyltransferase DOT1L display global developmental delay and varying congenital anomalies. However, the impact of monoallelic loss of remains unclear. Here, we present a largely female cohort of 11 individuals with variants with developmental delays and dysmorphic facial features.

Triple inhaled therapy in asthma: Beliefs, behaviours and doubts.

Long-acting muscarinic antagonists (LAMA) in association with inhaled corticosteroids (ICS) plus long-acting beta-2 agonists (LABA) are recommended by the GINA report as further option in step 4 and first choice in step 5 treatment. Despite consistent evidence of its efficacy and safety, inhaled triple therapy (ITT) is still not largely used in patients with asthma. With the aim to explore belief and behaviours of asthma specialists, an ad hoc survey has been developed by a panel of Interasma Scientific Network (INESnet) experts and subsequently defined by two Delphi rounds among an international group of physicians.

Invasive Fungal Diseases of Combat Wounds: Burden, Epidemiology, and Mycology.

During the last two decades, wound invasive fungal diseases (WIFDs) have reemerged as important causes of mortality and morbidity in military personnel and civilian casualties in war areas. Historically, mycotic infections acquired in combat operations during Vietnam War and were associated with burn wounds. Modern combat related WIFDs are almost exclusively associated with severe traumatic events which encompass blast exposure as the primary mechanism of injury and subsequent extremity amputation and extensive blood loss.

UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.

Introduction: 2022 was a landmark year with two adeno-associated viral vectors (AAVs) receiving conditional marketing authorization from EMA for the treatment of persons with severe haemophilia A and severe to moderately severe haemophilia B and a third in 2024. Gene therapy is a transformative, irreversible treatment with long-lasting effects, necessitating development of new clinical pathways to ensure optimal outcomes.

Aim: To develop a consensus framework and service specification for delivery of AAV gene therapy for haemophilia in adults within the UK using the hub-and-spoke model proposed by the European Association of Haemophilia and Allied Disorders and the European Haemophilia Consortium.