Mini-Stern Trial: A randomized trial comparing mini-sternotomy to full median sternotomy for aortic valve replacement.

OBJECTIVE: Aortic valve replacement (AVR) can be performed either through full median sternotomy (FS) or upper mini-sternotomy (MS). The Mini-Stern trial aimed to establish whether MS leads to quicker postoperative recovery and shorter hospital stay after first-time isolated AVR. METHODS: This pragmatic, open-label, parallel randomized controlled trial (RCT) compared MS with FS for first-time isolated AVR in 2 United Kingdom National Health Service hospitals. Primary endpoints were duration of postoperative hospital stay and the time to fitness for discharge from hospital after AVR, analyzed in the intent-to-treat population. RESULTS: In this RCT, 222 patients were recruited and randomized (n = 118 in the MS group; n = 104 in the FS group). Compared with the FS group, the MS group had a longer hospital length of stay (mean, 9.5 days vs 8.6 days) and took longer to achieve fitness for discharge home (mean, 8.5 days vs 7.5 days). Adjusting for valve type, sex, and surgeon, hazard ratios (HRs) from Cox models did not show a statistically significant effect of MS (relative to FS) on either hospital stay (HR, 0.874; 95% confidence interval [CI], 0.668-1.143; P = .3246) or time to fitness for discharge (HR, 0.907; 95% CI, 0.688-1.197; P value = .4914). During a mean follow-up of 760 days (745 days for the MS group and 777 days for the FS group), 12 patients (10%) in the MS group and 7 patients (7%) in the FS group died (HR, 1.871; 95% CI, 0.723-4.844; P = .1966). Average extra cost for MS was £1714 during the first 12 months after AVR. CONCLUSIONS: Compared with FS for AVR, MS did not result in shorter hospital stay, faster recovery, or improved survival and was not cost-effective. The MS approach is not superior to FS for performing AVR.

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. TRIAL REGISTRATION NUMBER: ISRCTN02309506.

Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial.

BACKGROUND: Malignant pleural mesothelioma incidence continues to rise, with few available evidence-based therapeutic options. Results of previous non-randomised studies suggested that video-assisted thoracoscopic partial pleurectomy (VAT-PP) might improve symptom control and survival. We aimed to compare efficacy in terms of overall survival, and cost, of VAT-PP and talc pleurodesis in patients with malignant pleural mesothelioma. METHODS: We undertook an open-label, parallel-group, randomised, controlled trial in patients aged 18 years or older with any subtype of confirmed or suspected mesothelioma with pleural effusion, recruited from 12 hospitals in the UK. Eligible patients were randomly assigned (1:1) to either VAT-PP or talc pleurodesis by computer-generated random numbers, stratified by European Organisation for Research and Treatment of Cancer risk category (high vs low). The primary outcome was overall survival at 1 year, analysed by intention to treat (all patients randomly assigned to a treatment group with a final diagnosis of mesothelioma). This trial is registered with ClinicalTrials.gov, number NCT00821860. FINDINGS: Between Oct 24, 2003, and Jan 24, 2012, we randomly assigned 196 patients, of whom 175 (88 assigned to talc pleurodesis, 87 assigned to VAT-PP) had confirmed mesothelioma. Overall survival at 1 year was 52% (95% CI 41-62) in the VAT-PP group and 57% (46-66) in the talc pleurodesis group (hazard ratio 1·04 [95% CI 0·76-1·42]; p=0·81). Surgical complications were significantly more common after VAT-PP than after talc pleurodesis, occurring in 24 (31%) of 78 patients who completed VAT-PP versus ten (14%) of 73 patients who completed talc pleurodesis (p=0·019), as were respiratory complications (19 [24%] vs 11 [15%]; p=0·22) and air-leak beyond 10 days (five [6%] vs one [1%]; p=0·21), although not significantly so. Median hospital stay was longer at 7 days (IQR 5-11) in patients who received VAT-PP compared with 3 days (2-5) for those who received talc pleurodesis (p<0·0001). INTERPRETATION: VAT-PP is not recommended to improve overall survival in patients with pleural effusion due to malignant pleural mesothelioma, and talc pleurodesis might be preferable considering the fewer complications and shorter hospital stay associated with this treatment. FUNDING: BUPA Foundation.

The characteristics and quality of randomized controlled trials in neuropathic pain: a descriptive study based on a systematic review.

BACKGROUND: Evidence from randomized controlled trials is regarded as the gold standard in clinical research and yet the quality of the conduct and reporting of trials is variable, even post-Consolidated Standards of Reporting Trials. This study arose from a systematic review and cost-effectiveness analysis of treatment for neuropathic pain. The aim was to provide a description of the included trials and investigate trends in study characteristics and measures of quality over time. METHODS: The review provided data regarding study characteristics (patients, place, time, drugs, outcomes), methodological factors (sample size calculations, randomization, reporting baseline patient data, withdrawals, intention-to-treat (ITT), and statistical analysis (completeness and correctness of reporting of results, methods of analysis). RESULTS: A total of 131 trials from 1969 to 2007 were included. Of these, 63% were parallel-group designs, the remainder were cross-over; 73% were placebo-controlled. Several trial features increased or improved over time: trial size, quality (using Jadad score), presentation of baseline data by group, reporting of power calculations, use of visual analogue score or numerical rating scale scales to assess pain, completeness of reporting of statistical results, use of modeling to allow for baseline pain scores. The proportion of withdrawals was constant over time with a mean of 14.3%. The proportion of studies stating the analysis as ITT, increased over time, but inspection of papers indicated that the proportion confirmed as ITT was unchanged. CONCLUSIONS: There have been a number of improvements regarding the quality and reporting of randomized controlled trials in neuropathic pain, but some failings remain that at best make some results difficult to interpret and at worst lead to bias.

The cost of changing physical activity behaviour: evidence from a "physical activity pathway" in the primary care setting.

BACKGROUND: The 'Physical Activity Care Pathway' (a Pilot for the 'Let's Get Moving' policy) is a systematic approach to integrating physical activity promotion into the primary care setting. It combines several methods reported to support behavioural change, including brief interventions, motivational interviewing, goal setting, providing written resources, and follow-up support. This paper compares costs falling on the UK National Health Service (NHS) of implementing the care pathway using two different recruitment strategies and provides initial insights into the cost of changing physical activity behaviour. METHODS: A combination of a time driven variant of activity based costing, audit data through EMIS and a survey of practice managers provided patient-level cost data for 411 screened individuals. Self reported physical activity data of 70 people completing the care pathway at three month was compared with baseline using a regression based 'difference in differences' approach. Deterministic and probabilistic sensitivity analyses in combination with hypothesis testing were used to judge how robust findings are to key assumptions and to assess the uncertainty around estimates of the cost of changing physical activity behaviour. RESULTS: It cost £53 (SD 7.8) per patient completing the PACP in opportunistic centres and £191 (SD 39) at disease register sites. The completer rate was higher in disease register centres (27.3% vs. 16.2%) and the difference in differences in time spent on physical activity was 81.32 (SE 17.16) minutes/week in patients completing the PACP; so that the incremental cost of converting one sedentary adult to an 'active state' of 150 minutes of moderate intensity physical activity per week amounts to £ 886.50 in disease register practices, compared to opportunistic screening. CONCLUSIONS: Disease register screening is more costly than opportunistic patient recruitment. However, additional costs come with a higher completion rate and better outcomes in terms of behavioural change in patients completing the care pathway. Further research is needed to rigorously evaluate intervention efficiency and to assess the link between behavioural change and changes in quality adjusted life years (QALYs).

The effects and costs of expanding the coverage of immunisation services in developing countries: a systematic literature review.

The range of potential effects and costs of interventions to expand the coverage of immunisation programs in developing countries was reviewed for the first time and demonstrated that increasing coverage is achievable. With the exception of a mass campaign, all interventions were reported to increase the proportion of fully vaccinated children. The findings are of particular value for policy debates about the introduction of new vaccines versus the need to vaccinate as many children as possible with the current ones. The review highlighted the need for: cost analyses to be undertaken alongside evaluations of interventions; and an improvement in the methodological quality of studies.

A systematic and critical review of the process of translation and adaptation of generic health-related quality of life measures in Africa, Asia, Eastern Europe, the Middle East, South America.

In recent years there has been a worldwide increase in demand for subjective measures of health-related quality of life (HRQL). Researchers have the choice of whether to develop a new measure or whether to adapt an existing measure in another language. This review evaluates the processes used in translating and adapting nine generic HRQL instruments (15D, Dartmouth COOP/WONCA Charts, EuroQol, HUI, NHP, SIP, SF-36, QWB, WHOQOL) for use in Africa, Asia, Eastern Europe, the Middle East, and South America. The review adopts a universalist model of equivalence, outlined by Herdman, Fox-Rushby, and Badia (Qual. Life Res. 7 (1998) 323), to judge the 58 papers reviewed. Research spans 23 countries and is dominated by research in the East Asia and Pacific region and the SF-36. Results are reported for conceptual, item, semantic, operational, measurement and functional equivalence. It is argued that currently there is a misguided pre-occupation with scales rather than the concepts being scaled and too much reliance on unsubstantiated claims of conceptual equivalence. However, researchers using the WHOQOL approach are more likely to establish reliable conclusions concerning the equivalence of their instrument across countries. It is a key conclusion of this review that research practice and translation guidelines still need to change to facilitate more effective and less biased assessments of equivalence of HRQL measures across countries.

Who buys insecticide-treated nets? Implications for increasing coverage in Nigeria.

OBJECTIVES: To investigate the determinants of purchase of insecticide-treated nets (ITNs) and explore the policy implications of the findings for ITN programmes. METHODS: Two surveys were conducted 1 month apart in three villages. The first survey was used to determine stated willingness to pay (WTP) and respondent practices regarding untreated nets and ITNs. The second survey was accompanied by actual sales of ITNs. Pre-tested interviewer-administered questionnaires using three contingent valuation method (CVM) question formats, namely the bidding game (BG), binary with follow up (BWFU) and a structured haggling technique (SH), were administered to different sub-samples of the respondents. The nets were sold at a price of 350 Naira (US dollars 1 = 110 Naira). Bivariate analysis and logistic regression were used to investigate the factors that explain actual WTP. FINDINGS: While 15/158 (9.5%), 21/166 (12.7%) and 35/144 (24.3%) of the respondents in the BG, BWFU and SH stated WTP amounts that were equal to or greater than the price of the net, 19.6%, 24.7% and 24.3% of respondents actually purchased the nets in the three groups respectively. Lower socioeconomic groups were less likely to purchase the nets, while households with a recent attack of malaria and those that stated higher WTP amounts were more likely to purchase nets. Stated WTP was positively associated with actual WTP (p < 0.01). Increased distance of the respondents to the ITNs sales point decreased net purchases (p < 0.05). CONCLUSIONS: Stated WTP was a good predictor of actual WTP. ITNs distribution strategies that will decrease time and travel costs to households are needed to increase net coverage. Also, ITNs financing mechanisms are needed that will ensure that lower socioeconomic groups and those at greater risk of malaria are protected. Governments and donors should take the lead to ensure that ITNs programmes are equitable.

Managing a household survey: a practical example from the KENQOL survey. Kenya Quality of Life.

It is vital that surveys are well managed for results to be reliable and meaningful. Poorly managed surveys can result in falsified, lost or incomplete data. Good management requires time to plan and think about all those involved in the process of the survey: the respondents, interviewers, supervisors, coders and the wider community. This paper draws on our experience of running a randomized household survey in three locations in the rural area of Makueni district, Eastern Kenya. The paper outlines the various strategies used to: gain access to the local community; recruit and train interviewers; supervise; plan day to day activities; and manage data.