Airway remodeling complicates longstanding asthma. It is characterized by an increase in the number of airway smooth muscle cells (SMCs) as well as an increase in and alteration of the type of extra-cellular matrix (ECM) in the airways. Although the number of SMCs in the airways depends on the balance of cell proliferation and cell death, studies to date have concentrated on factors affecting SMC proliferation. Here we report the first study on airway SMC survival factors: these cells receive a strong survival signal, which is not dependent on the known growth factor mitogens. We identified the ECM factors fibronectin, laminin, and collagens I and IV as important anti-apoptotic elements, and characterized the expression of the ECM receptors (integrins) on cultured SMC. Functionally blocking antibody and peptide studies revealed the alpha(5)beta(1) integrin to be an important transducer of the ECM-derived survival signal in these cells. Confocal microscopy confirmed the striking effects that discrete ECM factors have on SMC phenotype, notably the cytoskeleton. In summary, our data improves the understanding of the mechanisms underlying airway remodeling by outlining the key survival factors for airway SMC and by highlighting the impact of the cell-matrix interactions on cell death and phenotype.

BackgroundRelatively little is known about prescribing errors in general practice, or the factors associated with error.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Deliberate self-poisoning accounts for 170 000 presentations to UK hospitals each year with a profound impact on the health of individual patients. We have basic demographic information on self-poisoning but there is a relative paucity of contemporary, detailed information on the patterns of presentation, drugs taken in overdose and the current impact on services. WHAT THIS STUDY ADDS• This study provides detailed analyses of demographics, timing of presentation, patterns of overdose, drugs taken with special emphasis on paracetamol, the patient pathway through hospital and an estimation of the financial impact to the hospital of this patient group. This information is essential in planning the necessary service developments in emergency departments and medical admissions units that are required to optimize management of this patient group. AIMSThe primary aim of this paper is to provide comprehensive contemporaneous data on the demographics, patterns of presentation and management of all episodes of deliberate self-poisoning presenting to a large regional teaching hospital over a 12 month period. METHODSWe undertook detailed, retrospective analyses using information from electronic patient records and local patient-tracking, pathology and administrative databases. Statistical analyses were performed using Chi-squared tests, ANOVA and two-tailed t-tests (Graphpad Prism). RESULTSOne thousand five hundred and ninety-eight episodes of deliberate self-poisoning presented over the year. Demographic data and information on the month, day and time of admission are provided. 70.7% presented to the emergency department (ED) within 4 h of ingestion. 76.3% of patients had only one episode in an extended 29 month follow-up period. A mean of 1.72 drugs were taken per episode with just over half of all episodes involving a single drug only. Paracetamol and ibuprofen were the two most commonly ingested drugs involved in 42.5% and 17.3% of all overdoses respectively. 56.3% of patients taking paracetamol reported ingesting over 8 g (one over the counter packet). Detailed mapping of the patients' pathway through the hospital allowed an estimation of the hospital cost of caring for this patient group at £1.6 million pounds per year. CONCLUSIONSWe present comprehensive and contemporary data on presentations to hospital resulting from deliberate self-poisoning. We include demographic information, presentation patterns, drugs used, a detailed analysis of episodes involving paracetamol and an estimate of the financial burden to hospitals of overdose presentations.

Background: In the absence of research into therapies and care pathways for long covid, guidance based on “emerging experience” is needed. Aim: To provide a rapid expert guide for GPs and long covid clinical services. Design: Delphi study. Setting: Primary and secondary care doctors. Method: The authors generated recommendations pertaining to the investigation and management of long covid. These were distributed online to a panel of UK doctors (any specialty) with an interest in, lived experience of, and/or experience treating long covid. Over two rounds of Delphi testing, panellists indicated their agreement with each recommendation (5-point Likert scale) and gave comments. Recommendations eliciting a response of “strongly agree”, “agree”, or “neither agree nor disagree” from ≥90% of respondents were taken as showing consensus. Results: Thirty-three clinicians representing 14 specialties reached consensus on 35 recommendations. Chiefly: GPs should consider long covid in the presence of a wide range of presenting features (not limited to fatigue and breathlessness) and exclude differential diagnoses where appropriate. Detailed history and examination with baseline investigations should be conducted in primary care. Indications for further investigation and specific therapies (for myocarditis, PoTS, mast cell disorder) include hypoxia/desaturation, chest pain, palpitations, and histamine-related symptoms. Rehabilitation should be individualised, with careful activity pacing (to avoid relapse) and multidisciplinary support. Conclusions: Long covid clinics should operate as part of an integrated care system, with GPs playing a key role in the multidisciplinary team. Holistic care pathways, investigation of specific complications, management of potential symptom clusters, and tailored rehabilitation are needed.