Obstructive sleep apnoea and sexual function in men

Obstructive sleep apnoea (OSA) is associated with sexual dysfunction. Untreated OSA and erectile dysfunction (ED) have both been identified as being indicative of a high risk of developing cardiovascular disease. Treatments for ED, such as testosterone supplementation or PDE-5 inhibitors, and for OSA, such as Continuous Positive Airways Pressure (CPAP) are both readily available. The effects of these treatments on the other associated conditions have not been fully assessed. The efficacy of testosterone supplementation, in untreated OSA, on sexual function and quality of life has not been investigated. PDE-5 inhibitors are an established treatment for erectile dysfunction, however, there is a paucity of information regarding their efficacy in OSA, and there is a theoretical risk of worsening of OSA with their use. CPAP, in some observational and non-treatment or alternative treatment controlled studies, has been shown to improve erection function in men with OSA, however the majority of these studies have been in men with OSA, with and without ED. Two randomised controlled trials investigating the effects of testosterone in untreated OSA (n=67), and the effects of CPAP and a PDE-5 inhibitor in men with OSA and ED using a factorial design (n=61) were performed. Sleep, sexual function and quality of life was assessed. CPAP increased the quantity of nocturnal erections and a PDE-5 inhibitor improved their quality. However, neither CPAP use, exogenous testosterone nor a PDE-5 inhibitor improved subjective erectile function in men with OSA. Post-hoc analysis showed that adherent CPAP use (>4hours per night) increased subjective erectile function and sexual desire, as well as several parameters of quality of life in men with OSA and ED. Testosterone also increased sexual desire in men with OSA

Citizenship Status and Pressure Group Action

This thesis investigates the intersection between citizenship status and pressure group action. It asks a two-pronged question. First, does variation in citizenship status (to be citizen or noncitizen) produce variation in pressure group action? Second, where there is variation, how is it that citizenship status matters; where there is no variation, how is it that citizenship status (a decidedly political status) does not matter? In response to this two-part question, a two-part theoretical framework has been developed. To answer the question of whether citizenship status matters, an interactive model of action has been developed. This provides a common measure through which similarities and differences in action-paths between citizen and non-citizen pressure groups can be uncovered. It is found that citizenship status does have an effect on pressure group action, notably in a pressure group’s interaction with a) their constituency; b) potential allies; c) other-state political institutions; and d) other-state media. To answer the question of how citizenship matters and does not matter, the idea of the capability mechanism has been developed. This asserts that variation in citizenship status - understood through either a rights or identity framework - produces, reduces, or removes capabilities. This, in turn, shapes action. This model is also used to explain similarities. Both the empirical findings and the theoretical frameworks developed within this thesis are useful for further analysis of the significance of citizen or non-citizen status on one’s relationship to political systems

Bibliography

Regular use of beta2-agonists might result in increased bronchial hyper-responsiveness (BHR) and decreased forced expiratory volume in 1 sec (FEV1). It has been suggested that these possible detrimental effects are not a real deterioration of the disease, but that it might be only a transient (rebound) effect shortly after discontinuing this regular use. Moreover, these effects are thought to occur especially during short-acting and not during long-acting beta2-agonists use. The aim of this study was to invest gate whether a rebound effect (a pharmacological deterioration effect diminishing after several hours) in FEV1 and PC20 (concentration of histamine causing a 20% fall in FEV1 with regard to baseline) occurred after cessation of regular use of beta2-agonists, and whether this occurred both after short-acting and long-acting beta2-agonists. Allergic asthmatic patients (n = 134) were randomly allocated to the use of a short-acting (salbutamol), a long-acting beta2-agonist (formoterol) or placebo for 12 weeks (double-blind, double-dummy). No other asthma medication was allowed, including inhaled corticosteroids. At the start and every 4 weeks later FEV and PC20 were measured, each time at least 12 h after the last doses of study medication, which is in the possible rebound period. To investigate whether a (transient) rebound effect occurred, parameters were additionally measured at least 72 h later after discontinuation of the study medication. After 12 weeks of short-acting beta2-agonist use, a drop was seen in FEV1 from 85.6 (+/- 2.21)% predicted to 78.8 (+/- 2.9)% predicted, measured 15 h (median) after the last doses of medication. This was significantly different compared to placebo. When measured 168 h (median) later FEV1 recovered to 85.5 (+/- 2.4)% predicted, comparable to baseline. PC20 decreased with -1.17 (+/- 0.44) doubling dose after 12 weeks of short-acting beta2-agonist use, measured 15 h after the last doses of medication, which was significantly different compared to placebo. However, 168 h later PC20 recovered slightly with +0.55 (+/- 0.34) doubling dose, but this value was still lower compared to placebo. In contrast, during long-acting beta2-agonist and placebo use no significant changes were seen. In conclusion, the use of short-acting beta2-agonists resulted in a transient (rebound) effect in FEV while the effects on PC20 may point to a real deterioration of the disease. Long-acting beta2-agonist and placebo use showed no changes.We conclude that a mono-therapy of short-acting and not of long-acting beta2-agonists might have deleterious effects in asthma

Combining intensive practice nurse counselling or brief general practitioner advice with varenicline for smoking cessation in primary care: study protocol of a pragmatic randomized controlled trial

Introduction: Combining behavioural support and pharmacotherapy is most effective for smoking cessation and recommended in clinical guidelines. Despite that smoking cessation assistance from the general practitioner can be effective, dissemination of clinical practice guidelines and efforts on upskilling has not lead to the routine provision of smoking cessation advice among general practitioners. Intensive counselling from the practice nurse could contribute to better smoking cessation rates in primary care. However, the effectiveness of intensive counselling from a practice nurse versus usual care from a general practitioner in combination with varenicline is still unknown. Materials and methods: A pragmatic randomized controlled trial was conducted comparing: (a) intensive individual counselling delivered by a practice nurse and (b) brief advice delivered by a general practitioner; both groups received 12-weeks of open-label varenicline. A minimum of 272 adult daily smoking participants were recruited and treated in their routine primary care setting. The primary outcome was defined as prolonged abstinence from weeks 9 to 26, biochemically validated by exhaled carbon monoxide. Data was analysed blinded according to the intention-to-treat principle and participants with missing data on their smoking status at follow-up were counted as smokers. Secondary outcomes included: one-year prolonged abstinence, short-term incremental cost-effectiveness, medication adherence, and baseline predictors of successful smoking cessation. Discussion: This trial is the first to provide scientific evidence on the effectiveness, cost-effectiveness, and potential mechanisms of action of intensive practice nurse counselling combined with varenicline under real-life conditions. This paper explains the methodology of the trial and discusses the pragmatic and/or explanatory design aspects

Identity and Interests: Understanding the Meltdown in Israeli-Turkish Relations 2002-2012

The recent deterioration of the strong bilateral alliance between Israel and Turkey has significant affects on the balance of power within the Middle East. As such, it is important that scholars determine why this meltdown has occurred. This thesis sought to explain the deterioration of relations between Israel and Turkey and overcome gaps in the existing literature concerned with this meltdown of bilateral relations by taking a fresh look into the role of identity and the interests it creates. Hence, the framework of Wendtian constructivism was applied in order to examine the social origins and impacts of identity and interests on alliance formation and deterioration. In this thesis, I suggested that Israel’s identity has changed slowly over the past decade and as such, should be perceived as ‘relatively’ stable. Conversely, however, Turkey’s national identity changed sharply, drifting away from the Ataturk agenda of Westernisation and secularism towards an Islamic heritage. In order to strengthen my argument that this shift in Turkish identity has primarily accounted for the deterioration of its relations with Israel, I analysed Turkish attitudes towards foreign policies other than its bilateral relationship with Israel, as well as its newly defined interests. Thus, whereas Israel’s relatively stable national identity and domestic policies were matched by its relatively stable foreign interests over the past decade, deep changes to Turkey’s national identity redirected its domestic policies under Recep Tayyip Erdoğan’s government. Consequently, Turkey has employed a number of political tensions and events as pretexts in order to unilaterally disengage from its relations with Israel so that it can further new foreign policies and interests. Identity matters, and for better or worse, identity changes precede foreign policy change, a lesson we must not forget

Cardiovascular and neuropsychiatric risks of varenicline and bupropion in smokers with chronic obstructive pulmonary disease

BACKGROUND: Varenicline and bupropion are effective smoking cessation treatments, but there are concerns about their safety in smokers with COPD. OBJECTIVE: To investigate whether varenicline and bupropion are associated with serious adverse cardiovascular and neuropsychiatric events in smokers with COPD. METHODS: In a retrospective cohort study, we used data from 14 350 patients with COPD included in the QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients with COPD who received a prescription of nicotine replacement therapy (NRT; N=10 426; reference group), bupropion (N=350) or varenicline (N=3574) in the period between January 2007 and June 2012. Patients were followed up for 6 months to compare incident cardiovascular (ie, ischaemic heart disease, stroke, heart failure, peripheral vascular disease and cardiac arrhythmias) and neuropsychiatric (ie, depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders. Propensity score analysis was used as an additional approach to account for potential confounding by indication. We also modelled the effects of possible unmeasured confounders. RESULTS: Neither bupropion nor varenicline showed an increased risk of adverse events compared with NRT. Varenicline was associated with a significantly reduced risk of heart failure (HR=0.56, 95% CI 0.34 to 0.92) and depression (HR=0.73, 95% CI 0.61 to 0.86). Similar results were obtained from the propensity score analysis. Modelling of unmeasured confounding provided additional evidence that an increased risk of these adverse events was very unlikely. CONCLUSION: In smokers with COPD, varenicline and bupropion do not appear to be associated with an increased risk of cardiovascular events, depression or self-harm in comparison with NRT

Effect of a workplace-based group training programme combined with financial incentives on smoking cessation:a cluster-randomised controlled trial

Prevention, Population and Disease management (PrePoD)Public Health and primary car

One year cost effectiveness of sirolimus eluting stents compared with bare metal stents in the treatment of single native de novo coronary lesions: an analysis from the RAVEL trial

OBJECTIVE: To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study. DESIGN: Multicentre, double blind, randomised trial. SETTING: Percutaneous coronary intervention for single de novo coronary lesions. PATIENTS: 238 patients with stable or unstable angina. INTERVENTIONS: Randomisation to sirolimus eluting stent or bare stent implantation. MAIN OUTCOME MEASURES: Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs. RESULTS: At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of 1286. At one year, however, the estimated additional cost difference had decreased to 54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the addit

Exacerbations and associated healthcare cost in patients with COPD in general practice

Background. Acute exacerbations are a characteristic clinical expression of chronic obstructive pulmonary disease (COPD). The objective of this study was to investigate the occurrence rate, management, and healthcare costs of exacerbations in patients with COPD in Dutch general practice. Methods. Baseline data set from the COPD on Primary Care Treatment (COOPT) trial was used. Details on the occurrence and management of exacerbations were collected by systematic medical record review for the 2-year period preceding trial inclusion. Results. The mean age of the 286 study subjects involved was 59.2 (SD 9.6) years, postbronchodilator FEV1 67.1% (SD 16.2) of predicted. Following ERS criteria, subjects suffered from: no (26%); mild (19%); moderate (40%); or severe (15%) airflow obstruction. The overall mean and median annual exacerbation rates were 0.88 (SD 0.79) and 0.5 (IQR 1.0), respectively. Exacerbation rate was not related to severity of airflow obstruction (p=0.628). Mean annual exacerbation costs per subject were € 40, € 53, € 61 and € 92 for the respective severity subgroups (p=0.012). The increase of costs in the more severe subgroups was mainly attributable to more physician consultations, diagnostic procedures, and prescription of reliever medication (e.g., bronchodilators, cough preparations). Conclusions. Occurrence of exacerbations did not depend on the severity of airflow obstruction, whereas the healthcare cost associated with exacerbations increased along with the severity of the disease