Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation

Importance: Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective: To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants: A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions: There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures: Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results: A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. Conclusions and Relevance: Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. Trial Registration: clinicaltrials.gov Identifier: NCT00990132

A case study of local environmental policy-making in the United Kingdom

The contention posed by Rod Rhodes that policy is made and delivered by autonomous and self-organising policy networks is at the heart of many contemporary debates about the nature of policy and politics. However, while the concept has commanded considerable attention from policy theorists, case studies of how policy networks operate on the ground remain relatively rare. Further still, much of the empirical work has centred on testing relatively abstract claims about the nature of networks rather than thinking through their practical implications for governance. Here, we contrast the approaches taken by two English local authorities in seeking more participatory approaches to environmental policy-making. Building on the work of Kickert et al., we argue that - far from being self-organising - the form of policy networks can be strongly directed by the state through network activation strategies and, indeed, that strong state management of networks is required if policy-making is to proceed in a more inclusive manner. Indeed, we argue that when policy-making is viewed from a network governance perspective the most effective routes to participatory policy-making may rely heavily on manipulation strategies despite the fact that these are frequently described as weaker (or lower) forms of participation. This apparent compromise of participatory objectives may be required to ensure effective policy development

Clinical effectiveness and cost-effectiveness results from the randomised controlled Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea–hypopnoea (TOMADO) and long-term economic analysis of oral devices and continuous positive airway pressure

Background Obstructive sleep apnoea–hypopnoea (OSAH) causes excessive daytime sleepiness (EDS), impairs quality of life (QoL) and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment is clinically effective but undermined by intolerance, and its cost-effectiveness is borderline in milder cases. Mandibular advancement devices (MADs) are another option, but evidence is lacking regarding their clinical effectiveness and cost-effectiveness in milder disease. Objectives (1) Conduct a randomised controlled trial (RCT) examining the clinical effectiveness and cost-effectiveness of MADs against no treatment in mild to moderate OSAH. (2) Update systematic reviews and an existing health economic decision model with data from the Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea–hypopnoea (TOMADO) and newly published results to better inform long-term clinical effectiveness and cost-effectiveness of MADs and CPAP in mild to moderate OSAH. TOMADO A crossover RCT comparing clinical effectiveness and cost-effectiveness of three MADs: self-moulded [SleepPro 1™ (SP1); Meditas Ltd, Winchester, UK]; semibespoke [SleepPro 2™ (SP2); Meditas Ltd, Winchester, UK]; and fully bespoke [bespoke MAD (bMAD); NHS Oral-Maxillofacial Laboratory, Addenbrooke’s Hospital, Cambridge, UK] against no treatment, in 90 adults with mild to moderate OSAH. All devices improved primary outcome [apnoea–hypopnoea index (AHI)] compared with no treatment: relative risk 0.74 [95% confidence interval (CI) 0.62 to 0.89] for SP1; relative risk 0.67 (95% CI 0.59 to 0.76) for SP2; and relative risk 0.64 (95% CI 0.55 to 0.76) for bMAD (p ˂ 0.001). Differences between MADs were not significant. Sleepiness [as measured by the Epworth Sleepiness Scale (ESS)] was scored 1.51 [95% CI 0.73 to 2.29 (SP1)] to 2.37 [95% CI 1.53 to 3.22 (bMAD)] lower than no treatment (p ˂ 0.001), with SP2 and bMAD significantly better than SP1. All MADs improved disease-specific QoL. Compliance was lower for SP1, which was unpopular at trial exit. At 4 weeks, all devices were cost-effective at £20,000/quality-adjusted life-year (QALY), with SP2 the best value below £39,800/QALY. Meta-analysis A MEDLINE, EMBASE and Science Citation Index search updating two existing systematic reviews (one from November 2006 and the other from June 2008) to August 2013 identified 77 RCTs in adult OSAH patients comparing MAD with conservative management (CM), MADs with CPAP or CPAP with CM. MADs and CPAP significantly improved AHI [MAD −9.3/hour (p ˂ 0.001); CPAP −25.4/hour (p ˂ 0.001)]. Effect difference between CPAP and MADs was 7.0/hour (p ˂ 0.001), favouring CPAP. No trials compared CPAP with MADs in mild OSAH. MAD and CPAP reduced the ESS score similarly [MAD 1.6 (p ˂ 0.001); CPAP 1.6 (p ˂ 0.001)]. Long-term cost-effectiveness An existing model assessed lifetime cost–utility of MAD and CPAP in mild to moderate OSAH, using the revised meta-analysis to update input values. The TOMADO provided utility estimates, mapping ESS score to European Quality of Life-5 Dimensions three-level version for device cost–utility. Using SP2 as the standard device, MADs produced higher mean costs and mean QALYs than CM [incremental cost-effectiveness ratio (ICER) £6687/QALY]. From a willingness to pay (WTP) of £15,367/QALY, CPAP is cost-effective, although the likelihood of MADs (p = 0.48) and CPAP (p = 0.49) being cost-effective is very similar. Both were better than CM, but there was much uncertainty in the choice between CPAP and MAD (at a WTP £20,000/QALY, the probability of being the most cost-effective was 47% for MAD and 52% for CPAP). When SP2 lifespan increased to 18 months, the ICER for CPAP compared with MAD became £44,066. The ICER for SP1 compared with CM was £1552, and for bMAD compared with CM the ICER was £13,836. The ICER for CPAP compared with SP1 was £89,182, but CPAP produced lower mean costs and higher mean QALYs than bMAD. Differential compliance rates for CPAP reduces cost-effectiveness so MADs become less costly and more clinically effective with CPAP compliance 90% of SP2. Conclusions Mandibular advancement devices are clinically effective and cost-effective in mild to moderate OSAH. A semi-bespoke MAD is the appropriate first choice in most patients in the short term. Future work should explore whether or not adjustable MADs give additional clinical and cost benefits. Further data on longer-term cardiovascular risk and its risk factors would reduce uncertainty in the health economic model and improve precision of effectiveness estimates.</p

Clinical effectiveness and cost-effectiveness results from the randomised controlled Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea–hypopnoea (TOMADO) and long-term economic analysis of oral devices and continuous positive airway pressure

Background Obstructive sleep apnoea–hypopnoea (OSAH) causes excessive daytime sleepiness (EDS), impairs quality of life (QoL) and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment is clinically effective but undermined by intolerance, and its cost-effectiveness is borderline in milder cases. Mandibular advancement devices (MADs) are another option, but evidence is lacking regarding their clinical effectiveness and cost-effectiveness in milder disease. Objectives (1) Conduct a randomised controlled trial (RCT) examining the clinical effectiveness and cost-effectiveness of MADs against no treatment in mild to moderate OSAH. (2) Update systematic reviews and an existing health economic decision model with data from the Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea–hypopnoea (TOMADO) and newly published results to better inform long-term clinical effectiveness and cost-effectiveness of MADs and CPAP in mild to moderate OSAH. TOMADO A crossover RCT comparing clinical effectiveness and cost-effectiveness of three MADs: self-moulded [SleepPro 1™ (SP1); Meditas Ltd, Winchester, UK]; semibespoke [SleepPro 2™ (SP2); Meditas Ltd, Winchester, UK]; and fully bespoke [bespoke MAD (bMAD); NHS Oral-Maxillofacial Laboratory, Addenbrooke’s Hospital, Cambridge, UK] against no treatment, in 90 adults with mild to moderate OSAH. All devices improved primary outcome [apnoea–hypopnoea index (AHI)] compared with no treatment: relative risk 0.74 [95% confidence interval (CI) 0.62 to 0.89] for SP1; relative risk 0.67 (95% CI 0.59 to 0.76) for SP2; and relative risk 0.64 (95% CI 0.55 to 0.76) for bMAD (p ˂ 0.001). Differences between MADs were not significant. Sleepiness [as measured by the Epworth Sleepiness Scale (ESS)] was scored 1.51 [95% CI 0.73 to 2.29 (SP1)] to 2.37 [95% CI 1.53 to 3.22 (bMAD)] lower than no treatment (p ˂ 0.001), with SP2 and bMAD significantly better than SP1. All MADs improved disease-specific QoL. Compliance was lower for SP1, which was unpopular at trial exit. At 4 weeks, all devices were cost-effective at £20,000/quality-adjusted life-year (QALY), with SP2 the best value below £39,800/QALY. Meta-analysis A MEDLINE, EMBASE and Science Citation Index search updating two existing systematic reviews (one from November 2006 and the other from June 2008) to August 2013 identified 77 RCTs in adult OSAH patients comparing MAD with conservative management (CM), MADs with CPAP or CPAP with CM. MADs and CPAP significantly improved AHI [MAD −9.3/hour (p ˂ 0.001); CPAP −25.4/hour (p ˂ 0.001)]. Effect difference between CPAP and MADs was 7.0/hour (p ˂ 0.001), favouring CPAP. No trials compared CPAP with MADs in mild OSAH. MAD and CPAP reduced the ESS score similarly [MAD 1.6 (p ˂ 0.001); CPAP 1.6 (p ˂ 0.001)]. Long-term cost-effectiveness An existing model assessed lifetime cost–utility of MAD and CPAP in mild to moderate OSAH, using the revised meta-analysis to update input values. The TOMADO provided utility estimates, mapping ESS score to European Quality of Life-5 Dimensions three-level version for device cost–utility. Using SP2 as the standard device, MADs produced higher mean costs and mean QALYs than CM [incremental cost-effectiveness ratio (ICER) £6687/QALY]. From a willingness to pay (WTP) of £15,367/QALY, CPAP is cost-effective, although the likelihood of MADs (p = 0.48) and CPAP (p = 0.49) being cost-effective is very similar. Both were better than CM, but there was much uncertainty in the choice between CPAP and MAD (at a WTP £20,000/QALY, the probability of being the most cost-effective was 47% for MAD and 52% for CPAP). When SP2 lifespan increased to 18 months, the ICER for CPAP compared with MAD became £44,066. The ICER for SP1 compared with CM was £1552, and for bMAD compared with CM the ICER was £13,836. The ICER for CPAP compared with SP1 was £89,182, but CPAP produced lower mean costs and higher mean QALYs than bMAD. Differential compliance rates for CPAP reduces cost-effectiveness so MADs become less costly and more clinically effective with CPAP compliance 90% of SP2. Conclusions Mandibular advancement devices are clinically effective and cost-effective in mild to moderate OSAH. A semi-bespoke MAD is the appropriate first choice in most patients in the short term. Future work should explore whether or not adjustable MADs give additional clinical and cost benefits. Further data on longer-term cardiovascular risk and its risk factors would reduce uncertainty in the health economic model and improve precision of effectiveness estimates.</p

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–˂30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three non-adjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p˂0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p˂0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p˂0.001, bMAD) lower than no treatment (p˂0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective. Of those trialled, the semi-bespoke MAD is an appropriate first choice.</p