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Simoff M.J.,Ford Motor Company | Lally B.,University of Miami | Slade M.G.,Oxford Center for Respiratory Medicine | Goldberg W.G.,Ford Motor Company | And 4 more authors.
Chest | Year: 2013

Background: Many patients with lung cancer will develop symptoms related to their disease process or the treatment they are receiving. These symptoms can be as debilitating as the disease progression itself. To many physicians these problems can be the most difficult to manage. Methods: A detailed review of the literature using strict methodologic review of article quality was used in the development of this article. MEDLINE literature reviews, in addition to Cochrane reviews and other databases, were used for this review. The resulting article lists were then reviewed by experts in each area for quality and finally interpreted for content. Results: We have developed recommendations for the management of many of the symptom complexes that patients with lung cancer may experience: pain, dyspnea, airway obstruction, cough, bone metastasis, brain metastasis, spinal cord metastasis, superior vena cava syndrome, hemoptysis, tracheoesophageal fistula, pleural effusions, venous thromboembolic disease, depression, fatigue, anorexia, and insomnia. Some areas, such as dyspnea, are covered in considerable detail in previously created high-quality evidence-based guidelines and are identified as excellent sources of reference. The goal of this guideline is to provide the reader recommendations based on evidence supported by scientific study. Conclusions: Improved understanding and recognition of cancer-related symptoms can improve management strategies, patient compliance, and quality of life for all patients with lung cancer. Copyright © by the American College of Chest Physicians 2013. Source


Craig S.E.,Oxford Center for Respiratory Medicine | Kohler M.,University of Zurich | Nicoll D.,Oxford Center for Respiratory Medicine | Bratton D.J.,Medical Research Council Clinical Trials Unit | And 4 more authors.
Thorax | Year: 2012

Background: Continuous positive airway pressure (CPAP) for symptomatic obstructive sleep apnoea (OSA) improves sleepiness and reduces vascular risk, but such treatment for the more prevalent, minimally symptomatic disease is contentious. Methods: This multicentre, randomised controlled, parallel, hospital-based trial across the UK and Canada, recruited 391 patients with confirmed OSA (oxygen desaturation index >7.5/h) but insufficient symptoms to warrant CPAP therapy. Patients were randomised to 6 months of auto-adjusting CPAP therapy, or standard care. Coprimary endpoints were change in Epworth Sleepiness Score (ESS) and predicted 5-year mortality using a cardiovascular risk score (components: age, sex, height, systolic blood pressure, smoking, diabetes, cholesterol, creatinine, left ventricular hypertrophy, previous myocardial infarction or stroke). Secondary endpoints included some of the individual components of the vascular risk score, objectively measured sleepiness and self-assessed health status. Results: Of 391 patients randomised, 14 withdrew, 347 attended for their follow-up visit at 6 months within the predefined time window, of which 341 had complete ESS data (baseline mean 8.0, SD 4.3) and 310 had complete risk score data. 22% of patients in the CPAP group reported stopping treatment and overall median CPAP use was 2 : 39 h per night. CPAP significantly improved subjective daytime sleepiness (adjusted treatment effect on ESS -2.0 (95% CI -2.6 to -1.4), p<0.0001), objectively measured sleepiness and self-assessed health status. CPAP did not improve the 5-year calculated vascular risk or any of its components. Conclusions: In patients with minimally symptomatic OSA, CPAP can reduce subjective and objective daytime sleepiness, and improve self-assessed health status, but does not appear to improve calculated vascular risk. Source


Rossi V.A.,University of Zurich | Stoewhas A.-C.,University of Zurich | Camen G.,University of Zurich | Steffel J.,University of Zurich | And 3 more authors.
European Heart Journal | Year: 2012

Aims The preliminary evidence supports an association between obstructive sleep apnoea (OSA), disturbed cardiac repolarization, and consequent cardiac dysrhythmias. The aim of the current trial was to assess the effects of continuous positive airway pressure (CPAP) therapy withdrawal on the measures of cardiac repolarization in patients with OSA.Methods and resultsForty-one OSA patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Polysomnography was performed, and indices of cardiac repolarization (QTc, TpTec intervals) and dispersion of repolarization (TpTe/QT ratio) were derived from 12-lead electrocardiography (ECG) at baseline and 2 weeks. Continuous positive airway pressure withdrawal led to a recurrence of OSA. Compared with therapeutic CPAP, subtherapeutic CPAP for 2 weeks was associated with a significant increase in the length of the QTc and TpTec intervals (mean difference between groups 21.4 ms, 95 CI 11.31.6 ms, P < 0.001 and 14.4 ms, 95 CI 7.221.5 ms, P < 0.001, respectively) and in the TpTe/QT ratio (mean difference between groups 0.02, 95 CI 0.000.03, P = 0.020). There was a statistically significant correlation between the change in apnoea/hypopnoea index (AHI) from baseline, and both the change in the QTc interval and the TpTec interval (r 0.60, 95 CI 0.360.77, P < 0.001 and r 0.45, 95 CI 0.170.67, P = 0.003, n 41, respectively). Conclusion Continuous positive airway pressure withdrawal is associated with the prolongation of the QTc and TpTec intervals and TpTe/QT ratio, which may provide a possible mechanistic link between OSA, cardiac dysrhythmias, and thus sudden cardiac death. © 2012 The Author. Source


Kohler M.,University of Zurich | Stradling J.R.,Oxford Center for Respiratory Medicine
Expert Opinion on Investigational Drugs | Year: 2011

The standard treatment for obstructive sleep apnoea (OSA) is continuous positive airway pressure (CPAP). Depending on selection criteria and quality of care, up to 50% of patients with OSA do not tolerate CPAP. For patients who cannot tolerate CPAP despite good quality care, pharmacological treatment would be a desirable alternative. The mechanisms by which pharmacological treatment is supposed to improve OSA include, amongst others, an augmentation in pharyngeal dilator muscle tone, an increase in ventilatory drive, a reduction in airway resistance and alterations in pharyngeal surface tension forces. In humans, most recent pharmacological approaches to the treatment of OSA in clinical trials have focused on modulating serotoninergic and cholinergic activities, as both have been shown to augment pharyngeal dilator muscle tone. However, currently there is not enough evidence to recommend any particular drug treatment for OSA. Methodological issues of published clinical trials on pharmacological OSA treatment make it difficult to draw definitive conclusions and inform further drug developments in this area. In this article, the pitfalls of clinical trials on pharmacological OSA therapy are summarised and potential solutions and directions for future studies are given. © 2011 Informa UK, Ltd. Source


Smith T.G.,University of Oxford | Talbot N.P.,University of Oxford | Talbot N.P.,Oxford Center for Respiratory Medicine
Antioxidants and Redox Signaling | Year: 2010

Prolyl hydroxylases are members of the iron-and 2-oxoglutarate-dependent dioxygenase enzyme family. Collagen prolyl hydroxylase is well known for its involvement in scurvy, in which ascorbate deficiency inhibits the enzyme and results in characteristic signs of the disease. Several distinct prolyl hydroxylases that hydroxylate (and thereby regulate) the hypoxia-inducible factor (HIF) transcription factors were discovered in 2001. These HIF prolyl hydroxylases, termed prolyl hydroxylase domain enzymes (PHDs), are the subject of this forum. HIF coordinates the cellular response to hypoxia, and the PHDs have attracted widespread interest as potential therapeutic targets in a wide range of diseases including anemia, ischemic heart disease, stroke, cancer, and pulmonary hypertension. Novel PHD-based pharmaceutical agents are now undergoing clinical trials. As well as original data, this forum includes reviews discussing recent advances in the biochemistry and therapeutic manipulation of PHDs, the potential role of PHD inhibitors in neuroprotection, and the involvement of PHDs in the complex interaction between oxygen homeostasis and iron homeostasis. Antioxid. Redox Signal. 12, 431-433. © Mary Ann Liebert, Inc. Source

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