Noncoding variants are a rare cause of recessive developmental disorders in trans with coding variants.

Purpose: Identifying pathogenic noncoding variants is challenging. A single protein-altering variant is often identified in a recessive gene in individuals with developmental disorders (DD), but the prevalence of pathogenic noncoding "second hits" in trans with these is unknown.

Methods: In 4073 genetically undiagnosed rare-disease trio probands from the 100,000 Genomes project, we identified rare heterozygous protein-altering variants in recessive DD-associated genes.

Management and outcomes for older women with early breast cancer treated with primary endocrine therapy (PET).

Background: This study reports the detailed management and outcomes of women treated with Primary Endocrine Therapy (PET) in a large prospective UK cohort of older women (≥70) with breast cancer.

Methods: This was an unplanned secondary analysis of a prospective, multicentre, observational study (The Age Gap study). Data were collected at baseline and regular intervals on patient, tumour and treatment characteristics with tumour RECIST response category recorded.

Patient, supporter and primary healthcare professional perspectives on health risks in over 16s with attention deficit hyperactivity disorder (ADHD) in England: a national survey study.

Background: Current research suggests that people with attention deficit hyperactivity disorder (ADHD) are at higher risk of physical and mental health disorders. This study aimed to explore these health risks in ADHD from the perspectives of multiple stakeholders.

Methods: This study forms part of the 'Managing young people with ADHD in Primary care (MAP) study'.

Does the Addition of Point-of-Care Testing Alter Antibiotic Prescribing Decisions When Patients Present with Acute Sore Throat to Primary Care? A Prospective Test of Change.

Accurate clinical diagnosis of patients presenting to primary care settings with acute sore throat remains challenging, often resulting in the over-prescribing of antibiotics. Using point-of-care tests (POCTs) to differentiate between respiratory infections is well-accepted, yet evidence on the application within primary care is sparse. We assessed the application of testing patients ( = 160) from three family practices with suspected Streptococcal infections using rapid molecular tests (ID NOW Strep A2, Abbott).

Mental Imagery to Reduce Alcohol-related harm in patients with alcohol use disorder and alcohol-related liver damaGE: the MIRAGE randomised pilot trial results.

Objective: The healthcare burden of alcohol-related liver disease (ARLD) is increasing. ARLD and alcohol use disorder (AUD) is best managed by reduction or cessation of alcohol use, but effective treatments are lacking. We tested whether people with ARLD and AUD admitted to hospital could be recruited to and retained in a trial of Functional Imagery Training (FIT), a psychological therapy that uses mental imagery to reduce alcohol craving.

Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease.

Dysfunctional RNA processing caused by genetic defects in RNA processing enzymes has a profound impact on the nervous system, resulting in neurodevelopmental conditions. We characterized a recessive neurological disorder in 18 children and young adults from 10 independent families typified by intellectual disability, motor developmental delay and gait disturbance. In some patients peripheral neuropathy, corpus callosum abnormalities and progressive basal ganglia deposits were present.

Selection of patients with malignant melanoma for pelvic lymph node dissection (PLND) using CT-PET.

Objectives: In melanoma patients with positive pelvic nodes, pelvic lymph node dissection (PLND) to achieve fully resected disease status facilitates adjuvant-dose systemic therapy and avoids higher treatment doses with greater toxicity. This study aimed to test the accuracy of prediction of nodal involvement of the 2010 joint BAPRAS/BAD guidance compared with Positron Emission Tomography (CT-PET).

Methods: A retrospective review was undertaken of 26 melanoma patients undergoing PLND by a single surgeon between July 2012 and July 2020.

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.

Background: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP ) receptor type 1 (IP R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood.

Nitrofurantoin: what is the evidence for current UK guidance?

Three days of nitrofurantoin at 100 mg twice daily is recommended as first-line treatment for uncomplicated urinary tract infection (UTI) in evidence-based guidelines across the UK. A review of international guidelines shows that the evidence base has been interpreted in very different ways. UK guidelines are unusual in promoting short (3 day) courses, and we find little direct evidence to support this.

Standards of diabetes care and burden of hypoglycaemia in people with diabetes on peritoneal dialysis: Results from a real-world clinical audit.

There is limited data on the standards of diabetes care in people on peritoneal dialysis (PD). Our aim was to assess the standards of diabetes care and the burden of hypoglycaemia in people with diabetes on PD. We performed a retrospective study at three university hospitals from December 2021 to January 2022.

The Exeter-Trident THA with ceramic-on-ceramic-bearings: 10-year outcomes in 275 total hip arthroplasties.

Aims: This study reports on the Exeter-Trident total hip arthroplasty (THA) using an alumina ceramic-on-ceramic bearing with 10-year clinical and radiographic follow-up.

Patients And Methods: Between January 2001 and January 2006, 275 THAs were performed. Mean age at surgery was 52.

Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement.

Persistent symptoms in patients treated for hypothyroidism are common. Despite more than 20 years of debate, the use of liothyronine for this indication remains controversial, as numerous randomised trials have failed to show a benefit of treatment regimens that combine liothyronine (T3) with levothyroxine over levothyroxine monotherapy. This consensus statement attempts to provide practical guidance to clinicians faced with patients who have persistent symptoms during thyroid hormone replacement therapy.

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

Background: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time.

Methods: Prospective observational multicentre study.