Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Life after Pelvic Exenteration for Rectal Cancer: The Patient and Carer Perspective on Long Term Consequences and Survivorship.

Objective: To explore the perspectives and experiences of patients and carers living with the long-term consequences of pelvic exenteration.

Summary Background Data: Pelvic exenteration is accepted as the standard of care for selected patients with locally advanced or recurrent rectal cancer. With contemporary 5-year survival reported at 40-60%, the number of long-term survivors is expected to increase.

Interventions for quitting vaping.

Rationale: There is limited guidance on the best ways to stop using nicotine-containing vapes (otherwise known as e-cigarettes) and ensure long-term abstinence, whilst minimising the risk of tobacco smoking and other unintended consequences. Treatments could include pharmacological interventions, behavioural interventions, or both.

Objectives: To conduct a living systematic review assessing the benefits and harms of interventions to help people stop vaping compared to each other or to placebo or no intervention.

The clinical and cost effectiveness of a STAndardised DIagnostic Assessment for children and adolescents with emotional difficulties: the STADIA multi-centre randomised controlled trial.

Background: Standardised Diagnostic Assessment tools, such as the Development and Well-Being Assessment (DAWBA), may aid detection and diagnosis of emotional disorders but there is limited real-world evidence of their clinical or cost effectiveness.

Methods: We conducted a multicentre, two-arm parallel group randomised controlled trial in eight large National Health Service Trusts in England providing multidisciplinary specialist Child and Adolescent Mental Health Services (CAMHS). Participants (5-17 year-olds with emotional difficulties referred to CAMHS) were randomly assigned (1:1), following referral receipt, to either receive the DAWBA and assessment-as-usual (intervention group) or assessment-as-usual (control group).

Outcomes of Hematopoietic Stem Cell Transplantation in 5 Patients with Autosomal Recessive RIPK1-Deficiency.

Receptor Interacting Serine/Threonine Kinase 1 (RIPK1) is widely expressed and integral to inflammatory and cell death responses. Autosomal recessive RIPK1-deficiency, due to biallelic loss of function mutations in RIPK1, is a rare inborn error of immunity (IEI) resulting in uncontrolled necroptosis, apoptosis and inflammation. Although hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy, the extent to which disease may be driven by extra-hematopoietic effects of RIPK1-deficiency, which are non-amenable to HSCT, is not clear.

"Central retinal artery occlusion following scleral buckling surgery with gas insertion in a patient with sickle cell disease".

Purpose: To describe a case of central retinal artery occlusion following scleral buckling procedure combined with pneumoretinopexy in a patient with sickle cell (HbSC) retinopathy (SCR).

Methods: Scleral buckling procedure, combined with injection of 0.3 ml of 100% perfluoropropane (C3F8) gas in the vitreous, was performed without intra-operative complications under general anaesthesia as treatment of two separate macula-sparing rhegmatogenous retinal detachments secondary to round holes, involving superior and inferior retina respectively, in the right eye of a 26-year-old Afro-Caribbean female with sickle cell disease.

Impact of the SARS-CoV-2/COVID-19 pandemic on the patient journeys of those with a newly diagnosed paediatric brain tumour in the UK: a qualitative study.

Objectives: To explore the impact of the SARS-CoV-2/COVID-19 pandemic on the diagnosis, management and patient journey for children and young people with a newly diagnosed brain tumour in the UK.

Design: Exploratory qualitative study focused on patient journeys from multiple perspectives, conducted as part of a wider mixed-methods study.

Setting: Three paediatric oncology tertiary centres in the UK.

An expert consensus statement on biomarkers of ageing for use in intervention studies.

Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.

Nonpharmacological Approaches to Chronic Cough.

Although cough is a protective reflex, it can occur in the absence of any physical need to clear the airway. In chronic cough, cough can be triggered by innocuous stimuli and persist despite medical treatment. Nonpharmacological interventions such as cough control therapy, provided by speech pathologists, have gained popularity in recent years.

Corrigendum to "Genetic Variants of Are Major Determinants of Kidney Failure in People of African Ancestry With HIV" [ Volume 7, Issue 4, April 2022, Pages 786-796].

[This corrects the article DOI: 10.1016/j.ekir.

Metabolomic heterogeneity of ageing with ethnic diversity: a step closer to healthy ageing.

Introduction: Outside of case-control settings, ethnicity specific changes in the human metabolome are understudied especially in community dwelling, ageing men. Characterising serum for age and ethnicity specific features can enable tailored therapeutics research and improve our understanding of the interplay between age, ethnicity, and metabolism in global populations.

Objective: A metabolomics approach was adopted to profile serum metabolomes in middle-aged and elderly men of different ethnicities from the Northwest of England, UK.

Global Insights from Patients, Providers, and Staff on Challenges and Solutions in Managing Neovascular Age-Related Macular Degeneration.

Introduction: Neovascular age-related macular degeneration is a global public-health concern, associated with a considerable burden to individuals, healthcare systems, and society. The objective of this study was to understand different perspectives on the challenges associated with the clinical management of neovascular age-related macular degeneration, which could elucidate measures to comprehensively improve clinical care and outcomes.

Methods: A survey was carried out of patients with neovascular age-related macular degeneration, their providers, and clinic staff in 77 clinics across 24 countries on six continents, from a diverse range of healthcare systems, settings, and reimbursement models.

Improving Clinical Management of Diabetic Macular Edema: Insights from a Global Survey of Patients, Healthcare Providers, and Clinic Staff.

Introduction: In contrast with patients receiving therapy for retinal disease during clinical trials, those treated in routine clinical practice experience various challenges (including administrative, clinic, social, and patient-related factors) that can often result in high patient and clinic burden, and contribute to suboptimal visual outcomes. The objective of this study was to understand the challenges associated with clinical management of diabetic macular edema from the perspectives of patients, healthcare providers, and clinic staff, and identify opportunities to improve eye care for people with diabetes.

Methods: We conducted a survey of patients with diabetic macular edema, providers, and clinic staff in 78 clinics across 24 countries on six continents, representing a diverse range of individuals, healthcare systems, settings, and reimbursement models.

Metastatic basal cell carcinomas in Gorlin syndrome-A case series and literature review.

Metastatic basal cell carcinomas (mBCCs) are exceedingly rare, with an estimated variable prevalence rate between 0.003 and 0.55% among all basal cell carcinomas.

A matter of survival-patients' and carers' perspectives on the decision to undergo pelvic exenteration surgery for locally advanced and recurrent rectal cancer.

Aim: Pelvic exenteration is the only potentially curative treatment for patients with locally advanced or recurrent rectal cancer. This study aimed to investigate how patients decide to undergo such radical surgery.

Method: This qualitative study employed an exploratory interpretive design informed by hermeneutic philosophy.

GOLD Science Committee recommendations for the use of pre- and post-bronchodilator spirometry for the diagnosis of COPD.

The Global initiative for chronic Obstructive Lung Disease (GOLD) report states that the diagnosis of chronic obstructive pulmonary disease (COPD) should be considered in individuals with chronic respiratory symptoms and / or exposure to risk factors. Forced spirometry demonstrating airflow obstruction after bronchodilation is required to confirm the diagnosis using a threshold of forced expiratory volume in 1 s (FEV) / forced vital capacity (FVC) ratio<0.7.

Brief imagery based metacognitive intervention for flashforwards in psychosis: a fixed baseline case series.

Background: Distressing mental images are common in people with psychosis. The central role of metacognitive difficulties in psychosis suggests that metacognitive interventions with imagery properties could play a central role in managing distressing mental imagery. A brief imagery-based metacognitive intervention was developed to target the control mechanism of distressing mental images in psychosis.

Exploring the current provision of pancreatic transplantations in low- and middle-income countries: Current landscape, challenges, future prospects.

This comprehensive review addresses the global health challenge of disparities in pancreas transplant access, particularly in low- and middle-income countries (LMICs) compared to high-income countries. Despite advancements in surgical techniques and immunosuppression for procedures like simultaneous pancreas-kidney, pancreas-after-kidney, and pancreas-transplant alone, LMICs face significant challenges, including limited infrastructure, financial constraints, and a shortage of skilled medical professionals. Donation after brain death remains constrained by sociocultural barriers.

Mortality in chronic pulmonary aspergillosis: a systematic review and individual patient data meta-analysis.

Background: Despite antifungal treatment, chronic pulmonary aspergillosis (CPA) is associated with substantial morbidity and mortality. We conducted a systematic review and meta-analysis to evaluate rates of mortality and its predictors in CPA.

Methods: A systematic literature search was conducted across MEDLINE (PubMed), Scopus, Embase, and Web of Science to identify studies in English, reporting mortality in CPA, from database inception to Aug 15, 2023.