A randomized controlled trial of a self-guided mobile app targeting repetitive negative thought to prevent depression in university students: study protocol of the Nurture-U Reducing Worry prevention trial.

Background: Tackling poor mental health in university students has been identified as a priority in higher education. However, there are few evidence-based prevention initiatives designed for students. Repetitive Negative Thought (RNT, e.

Application of a Human Factors and Systems Engineering Approach to Explore Care Transitions of Sepsis Survivors From Hospital to Home Health Care.

Study Aim: This study aims to describe the transition-in-care work process for sepsis survivors going from hospitals to home health care (HHC) and identify facilitators and barriers to enable practice change and safe care transitions using a human factors and systems engineering approach.

Background: Despite high readmission risk for sepsis survivors, the transition-in-care work process from hospitals to HHC has not been described.

Methods: We analyzed semi-structured needs assessment interviews with 24 stakeholders involved in transitioning sepsis survivors from two hospitals and one affiliated HHC agency participating in the parent implementation science study, I-TRANSFER.

Secondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure.

Purpose: The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, and costs.

Methods: An observational study in an area representing one-fifth of England.

The Role and Initiatives Led by the Sepsis Coordinator to Improve Sepsis Bundle Compliance and Care Across the Continuum.

A dedicated sepsis coordinator role at Penn Medicine Lancaster General Hospital led initiatives to improve sepsis core measure compliance by 40% during the course of 4 years with submission of all sepsis cases. Chart abstraction and analysis of noncompliant cases identified areas for improvement: early recognition education, order set revisions, documentation support, and the implementation of a nurse-driven 24/7 sepsis monitoring process. The cooperative work with Penn Medicine affiliates, sharing best practices, improves overall sepsis bundle compliance and transitions of care.

Evaluation of the prehospital use of a Valsalva assist device in the emergency treatment of supraventricular tachycardia (EVADE SVT): study protocol for a stepped wedge cluster randomised controlled trial.

Introduction: Patients with episodes of supraventricular tachycardia (SVT), a common heart arrhythmia, are often attended by ambulance services. International guidelines advocate treatment with the Valsalva manoeuvre (VM), but this simple physical treatment has a low success rate, with most patients requiring conveyance to hospital. The Valsalva Assist Device (VAD) is a simple device that might help practitioners and patients perform a more effective VM and reduce the need for patients to be taken to hospital.

GNA11 Variants Identified in Patients with Hypercalcemia or Hypocalcemia.

Familial hypocalciuric hypercalcemia type 2 (FHH2) and autosomal dominant hypocalcemia type 2 (ADH2) are due to loss- and gain-of-function mutations, respectively, of the GNA11 gene that encodes the G protein subunit Gα11, a signaling partner of the calcium-sensing receptor (CaSR). To date, four probands with FHH2-associated Gα11 mutations and eight probands with ADH2-associated Gα11 mutations have been reported. In a 10-year period, we identified 37 different germline GNA11 variants in >1200 probands referred for investigation of genetic causes for hypercalcemia or hypocalcemia, comprising 14 synonymous, 12 noncoding, and 11 nonsynonymous variants.

Spectrum of germline AIRE mutations causing APS-1 and familial hypoparathyroidism.

Objective: The autoimmune polyendocrine syndrome type 1 (APS-1) is an autosomal recessive disorder characterised by immune dysregulation and autoimmune endocrine gland destruction. APS-1 is caused by biallelic mutations affecting the autoimmune regulator (AIRE) gene on chromosome 21q22.3, which facilitates immunological self-tolerance.

UK recommendations for germline genetic testing and surveillance in clinical practice.

pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history.

The online version of an evidence-based hand exercise program for people with rheumatoid arthritis: A mixed-method, proof-of-concept study.

Introduction: The Strengthening And stretching for Rheumatoid Arthritis of the Hand (SARAH) program is a tailored, 12-week hand and arm exercise program recommended in the National Institute for Health and Care Excellence guidelines. It includes seven mobility exercises and four strength exercises against resistance. An online version of the SARAH program (mySARAH) has been developed to allow direct access for people with rheumatoid arthritis.

Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 73 () Variant.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid tumors, pituitary adenomas, and pancreatic neuroendocrine neoplasms (PNENs). MEN1 is caused by germline mutations in > 75% of patients, and the remaining 25% of patients may have mutations in unidentified genes or represent phenocopies with mutations in genes such as cell cycle division 73 (, the calcium sensing receptor (, and cyclin-dependent kinase inhibitor 1B (, which are associated with the hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric hypercalcemia type 1, and MEN4, respectively. Here, we report a heterozygous c.

Multiple Endocrine Neoplasia Type 1 (MEN1) 5'UTR Deletion, in MEN1 Family, Decreases Menin Expression.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic and pituitary tumors, and is due to mutations in the coding region of the MEN1 gene, which encodes menin. We investigated a family with identical twins that had MEN1, with different MEN1 tumors. DNA sequence analysis of the MEN1 coding region had not identified any abnormalities and we hypothesized that deletions and mutations involving the untranslated regions may be involved.

Cancer Variant Interpretation Group UK (CanVIG-UK): an exemplar national subspecialty multidisciplinary network.

Advances in technology have led to a massive expansion in the capacity for genomic analysis, with a commensurate fall in costs. The clinical indications for genomic testing have evolved markedly; the volume of clinical sequencing has increased dramatically; and the range of clinical professionals involved in the process has broadened. There is general acceptance that our early dichotomous paradigms of variants being pathogenic-high risk and benign-no risk are overly simplistic.

Neonatal Hypocalcemic Seizures in Offspring of a Mother With Familial Hypocalciuric Hypercalcemia Type 1 (FHH1).

Context: Familial hypocalciuric hypercalcemia type 1 (FHH1) is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR) and is considered a benign condition associated with mild-to-moderate hypercalcemia. However, the children of parents with FHH1 can develop a variety of disorders of calcium homeostasis in infancy.

Objective: The objective of this work is to characterize the range of calcitropic phenotypes in the children of a mother with FHH1.

Activating Mutations of the G-protein Subunit α 11 Interdomain Interface Cause Autosomal Dominant Hypocalcemia Type 2.

Context: Autosomal dominant hypocalcemia types 1 and 2 (ADH1 and ADH2) are caused by germline gain-of-function mutations of the calcium-sensing receptor (CaSR) and its signaling partner, the G-protein subunit α 11 (Gα 11), respectively. More than 70 different gain-of-function CaSR mutations, but only 6 different gain-of-function Gα 11 mutations are reported to date.

Methods: We ascertained 2 additional ADH families and investigated them for CaSR and Gα 11 mutations.

Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias.

The calcium-sensing receptor (CaSR) is a homodimeric G-protein-coupled receptor that signals via intracellular calcium (Ca2+i) mobilisation and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) to regulate extracellular calcium (Ca2+e) homeostasis. The central importance of the CaSR in Ca2+e homeostasis has been demonstrated by the identification of loss- or gain-of-function CaSR mutations that lead to familial hypocalciuric hypercalcaemia (FHH) or autosomal dominant hypocalcaemia (ADH), respectively. However, the mechanisms determining whether the CaSR signals via Ca2+i or ERK have not been established, and we hypothesised that some CaSR residues, which are the site of both loss- and gain-of-function mutations, may act as molecular switches to direct signalling through these pathways.

An Online Hand Exercise Intervention for Adults With Rheumatoid Arthritis (mySARAH): Design, Development, and Usability Testing.

Background: The Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH) program is a tailored, progressive 12-week exercise program for people with hand problems due to rheumatoid arthritis. The program was shown to be clinically and cost-effective in a large clinical trial and is recommended by the UK National Institute for Health and Care Excellence (NICE) guidelines for rheumatoid arthritis in adults.

Objective: We have developed an online version of the SARAH program (mySARAH) to make the SARAH program widely accessible to people with rheumatoid arthritis.

Pachydermoperiostosis Masquerading as Acromegaly.

Context: Acromegaly usually is suspected on clinical grounds. Biochemical confirmation is required to optimize therapy, but there are other differential diagnoses.

Case Description: We describe a 24-year-old Uzbek man who presented with many clinical symptoms and signs of apparent acromegaly.

A Web-Based Training Resource for Therapists to Deliver an Evidence-Based Exercise Program for Rheumatoid Arthritis of the Hand (iSARAH): Design, Development, and Usability Testing.

Background: The Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH) is a tailored, progressive exercise program for people having difficulties with wrist and hand function due to rheumatoid arthritis (RA). The program was evaluated in a large-scale clinical trial and was found to improve hand function, was safe to deliver, and was cost-effective. These findings led to the SARAH program being recommended in the UK National Institute for Health and Care Excellence guidelines for the management of adults with RA.

Cinacalcet Rectifies Hypercalcemia in a Patient With Familial Hypocalciuric Hypercalcemia Type 2 (FHH2) Caused by a Germline Loss-of-Function Gα Mutation.

G-protein subunit α-11 (Gα ) couples the calcium-sensing receptor (CaSR) to phospholipase C (PLC)-mediated intracellular calcium (Ca ) and mitogen-activated protein kinase (MAPK) signaling, which in the parathyroid glands and kidneys regulates parathyroid hormone release and urinary calcium excretion, respectively. Heterozygous germline loss-of-function Gα mutations cause familial hypocalciuric hypercalcemia type 2 (FHH2), for which effective therapies are currently not available. Here, we report a novel heterozygous Gα germline mutation, Phe220Ser, which was associated with hypercalcemia in a family with FHH2.

Technical Peer Review: Methods and Outcomes.

Peer review is routine among physicians, nurses, and pharmacy staff yet is uncommon in the field of nuclear medicine technology. Although not a requirement of regulatory agencies, nuclear medicine technical peer review can greatly enhance the quality of patient care in both hospital and outpatient settings. To date, detailed methods for accomplishing this task have not been published.

Routine genetic screening with a multi-gene panel in patients with pheochromocytomas.

Purpose: Several new gene mutations have been reported in recent years to be associated with a risk of familial pheochromocytoma. However, it is unclear as to whether extensive genetic testing is required in all patients.

Methods: The clinical data of consecutive patients operated for pheochromocytoma over a decade in a tertiary referral center were reviewed.