RESUMEN
BACKGROUND: Frozen shoulder is condition in which movement of the shoulder becomes restricted. It can be described as either primary (idiopathic) whereby the aetiology is unknown, or secondary, when it can be attributed to another cause. It is commonly a self-limiting condition, of approximately 1 to 3 years' duration, though incomplete resolution can occur. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of treatments for primary frozen shoulder, identify the most appropriate intervention by stage of condition and highlight any gaps in the evidence. DATA SOURCES: A systematic review was conducted. Nineteen databases and other sources including the Cumulative Index to Nursing and Allied Health (CINAHL), Science Citation Index, BIOSIS Previews and Database of Abstracts of Reviews of Effects (DARE) were searched up to March 2010 and EMBASE and MEDLINE up to January 2011, without language restrictions. MEDLINE, CINAHL and PsycINFO were searched in June 2010 for studies of patients' views about treatment. REVIEW METHODS: Randomised controlled trials (RCTs) evaluating physical therapies, arthrographic distension, steroid injection, sodium hyaluronate injection, manipulation under anaesthesia, capsular release or watchful waiting, alone or in combination were eligible for inclusion. Patients with primary frozen shoulder (with or without diabetes) were included. Quasi-experimental studies were included in the absence of RCTs and case series for manipulation under anaesthesia (MUA) and capsular release only. Full economic evaluations meeting the intervention and population inclusion criteria of the clinical review were included. Two researchers independently screened studies for relevance based on the inclusion criteria. One reviewer extracted data and assessed study quality; this was checked by a second reviewer. The main outcomes of interest were pain, range of movement, function and disability, quality of life and adverse events. The analysis comprised a narrative synthesis and pair-wise meta-analysis. A mixed-treatment comparison (MTC) was also undertaken. An economic decision model was intended, but was found to be implausible because of a lack of available evidence. Resource use was estimated from clinical advisors and combined with quality-adjusted life-years obtained through mapping to present tentative cost-effectiveness results. RESULTS: Thirty-one clinical effectiveness studies and one economic evaluation were included. The clinical effectiveness studies evaluated steroid injection, sodium hyaluronate, supervised neglect, physical therapy (mainly physiotherapy), acupuncture, MUA, distension and capsular release. Many of the studies identified were at high risk of bias. Because of variation in the interventions and comparators few studies could be pooled in a meta-analysis. Based on single RCTs, and for some outcomes only, short-wave diathermy may be more effective than home exercise. High-grade mobilisation may be more effective than low-grade mobilisation in a population in which most patients have already had treatment. Data from two RCTs showed that there may be benefit from adding a single intra-articular steroid injection to home exercise in patients with frozen shoulder of < 6 months' duration. The same two trials showed that there may be benefit from adding physiotherapy (including mobilisation) to a single steroid injection. Based on a network of nine studies the MTC found that steroid combined with physiotherapy was the only treatment showing a statistically and clinically significant beneficial treatment effect compared with placebo for short-term pain (standardised mean difference -1.58, 95% credible interval -2.96 to -0.42). This analysis was based on only a subset of the evidence, which may explain why the findings are only partly supportive of the main analysis. No studies of patients' views about the treatments were identified. Average costs ranged from £36.16 for unguided steroid injections to £2204 for capsular release. The findings of the mapping suggest a positive relationship between outcome and European Quality of Life-5 Dimensions (EQ-5D) score: a decreasing visual analogue scale score (less pain) was accompanied by an increasing (better) EQ-5D score. The one published economic evaluation suggested that low-grade mobilisation may be more cost-effective than high-grade mobilisation. Our tentative cost-effectiveness analysis suggested that steroid alone may be more cost-effective than steroid plus physiotherapy or physiotherapy alone. These results are very uncertain. LIMITATIONS: The key limitation was the lack of data available. It was not possible to undertake the planned synthesis exploring the influence of stage of frozen shoulder or the presence of diabetes on treatment effect. As a result of study diversity and poor reporting of outcome data there were few instances where the planned quantitative synthesis was possible or appropriate. Most of the included studies had a small number of participants and may have been underpowered. The lack of available data made the development of a decision-analytic model implausible. We found little evidence on treatment related to stage of condition, treatment pathways, the impact on quality of life, associated resource use and no information on utilities. Without making a number of questionable assumptions modelling was not possible. CONCLUSIONS: There was limited clinical evidence on the effectiveness of treatments for primary frozen shoulder. The economic evidence was so limited that no conclusions can be made about the cost-effectiveness of the different treatments. High-quality primary research is required.
Asunto(s)
Bursitis/economía , Bursitis/terapia , Evaluación de Resultado en la Atención de Salud , Articulación del Hombro , Acupuntura/economía , Artrografía/economía , Análisis Costo-Beneficio , Diatermia/economía , Manejo de la Enfermedad , Humanos , Manejo del Dolor , Modalidades de Fisioterapia/economía , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Esteroides/economía , Espera VigilanteRESUMEN
BACKGROUND: Two aldosterone inhibitors are currently licensed for heart failure (HF) in the UK: spironolactone and eplerenone. Recent clinical guidelines recommend eplerenone after an acute myocardial infarction (MI) for patients with symptoms and/or signs of HF and left ventricular dysfunction. OBJECTIVES: The primary objective was to evaluate relative clinical effectiveness and cost-effectiveness of spironolactone and eplerenone in patients with postMI HF and explore the possibility of conducting an indirect comparison of spironolactone and eplerenone. A second objective was to undertake value-of-information (VOI) analyses to determine the need for further research to identify research questions critical to decision-making and to help inform the design of future studies. DATA SOURCES: Relevant databases including MEDLINE, EMBASE and CENTRAL were searched between September and December 2008. Randomised controlled trials (RCTs) of spironolactone, eplerenone, canrenone or potassium canrenoate were included if conducted in a postMI HF population. Trials of general HF patients with a subgroup of postMI HF patients were considered if they had at least 100 ischaemic participants per arm and the authors provided subgroup data when contacted. Adverse events summary data were sought from recognised reference sources and RCTs or observational studies in any population that recruited more than 100 participants. REVIEW METHODS: The comparative clinical effectiveness and cost-effectiveness of spironolactone and eplerenone was derived using Bayesian meta-regression drawing on a wider 'network' of aldosterone trials to those considered in the main clinical effectiveness review. An alternative scenario was also considered assuming a 'class effect' for the aldosterone antagonists in terms of major clinical events, but allowing for potential differences in side effect profiles. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs) where appropriate. Uncertainty in cost-effectiveness results was also presented and used to inform future research priorities using VOI analyses based on expected value of perfect information (EVPI). A probabilistic decision analytic model was developed to estimate cost-effectiveness of spironolactone, eplerenone and standard care for management of postMI HF, provide estimates relevant to the NHS and explore alternative approaches to an indirect comparison between spironolactone and eplerenone. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the NHS persepctive. In the base-case analysis, 2-year treatment duration was assumed, consistent with the follow-up in the main RCTs. Other scenarios were explored to examine the robustness of alternative assumptions including impact of different treatment durations. RESULTS: Searches yielded five RCTs: two spironolactone trials of poor methodological quality and three trials of which only one (of eplerenone) specifically examined postMI HF (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study, EPHESUS). One trial of spironolactone (Randomised Aldactone Evaluation Study, RALES) and one of canrenone (Antiremodelling Effect of Aldosterone receptors blockade with canrenone In mild Chronic Heart Failure, AREA IN-CHF) comprised general HF, but data were available for an ischaemic subgroup. Structural similarity of spironolactone and eplerenone suggests that they may be interchangeable, but formal indirect comparison between the three trials was severely limited by trial differences. Relative safety data were limited from RCTs and observational sources. Hyperkalaemia rates varied, but were generally higher than for placebo; data were insufficient to assess discontinuation because of hyperkalaemia.Gynaecomastia rates were higher with spironolactone. Adverse event data were sparse. Systematic review of economic evidence identified three main published studies but none used a UK perspective or attempted to compare cost-effectiveness in postMI HF. The new decision model indicated that eplerenone was the most cost-effective strategy for postMI HF (ICER of eplerenone compared with standard care was 4457 pounds per QALY, increasing to 7893 pounds per QALY if treatment continued over the patient's lifetime); in neither scenario did spironolactone appear cost-effective. The ICER of eplerenone was consistently under the 20,000-30,000 pounds per QALY threshold used to establish value for money in the NHS. Uncertainty resulted in EVPI estimates between 820M pounds (base-case) and 1265M pounds (lifetime treatment duration scenario). When class effect for mortality and hospitalisations was assumed spironolactone emerged as the most cost-effective treatment and EVPI estimates were negligible. If class effect is considered more plausible than the results of the evidence synthesis model then there would be limited value in additional research. LIMITATIONS: Exchangeability between trials was poor and there was a lack of robust data in RCTs. CONCLUSIONS: Only two good-quality trials of aldosterone inhibitors in the postMI HF population were found, but lack of exchangeability with respect to study populations, meant that a comparison between these drugs could not be done. It consistently emerged that, compared with usual care, use of an aldosterone antagonist appears to be a highly cost-effective strategy for the management of postMI HF patients in the NHS. An adequately powered, well-conducted RCT that directly compares spironolactone and eplerenone is required to provide more robust evidence on the optimal management of postMI HF patients.
Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Antagonistas de Receptores de Mineralocorticoides/economía , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Infarto del Miocardio/complicaciones , Teorema de Bayes , Ensayos Clínicos como Asunto , Análisis Costo-Beneficio , Eplerenona , Humanos , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Años de Vida Ajustados por Calidad de Vida , Espironolactona/análogos & derivados , Espironolactona/economía , Espironolactona/uso terapéutico , Medicina Estatal , Reino UnidoRESUMEN
OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of enhanced external counterpulsation (EECP) compared with usual care and placebo for refractory stable angina and heart failure, and to undertake analyses of the expected value of information to assess the potential value of future research on EECP. DATA SOURCES: Major electronic databases were searched between November 2007 and March 2008. REVIEW METHODS: A systematic review of the literature was undertaken and a decision model developed to compare EECP treatment with no treatment in adults with chronic stable angina. RESULTS: Five studies were included in the review. In the Multicenter Study of Enhanced External Counterpulsation (MUST-EECP), time to greater than or equal to 1-mm ST segment depression (exercise-induced ischaemia) was statistically significantly improved in the EECP group compared with the control group (sham EECP), mean difference (MD) 41 seconds [95% confidence interval (CI) 9.10-73.90]. However, there was no statistically significant difference between the EECP and control groups in the change in exercise duration from baseline to end of treatment, self-reported angina episodes or daily nitroglycerin use, and the clinical significance of the limited benefits was unclear. There was also a lack of data on long-term outcomes. There were more withdrawals due to adverse events in the EECP group than in the control group, as well as a greater proportion of patients with adverse events [relative risk (RR) 2.13, 95% CI 1.35-3.38]. The three non-randomised studies compared EECP with elective percutaneous coronary intervention (PCI) and usual care. There was a high risk of selection bias in all three studies and the results should be treated with considerable caution. The study comparing an EECP registry with a PCI registry reported similar 1-year all-cause mortality in both groups. In the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) trial, patients with heart failure were randomised to EECP or to usual care (pharmacotherapy only). At 6 months post treatment, the proportion of patients achieving at least a 60-second increase in exercise duration was higher in the EECP group (RR 1.39, 95% CI 0.89-2.16), but the proportion with an improvement in peak VO2 was similar in both groups. The clinical significance of this is unclear. The proportion of patients in the EECP group with an improvement in New York Heart Association classification was higher (RR 2.25, 95% CI 1.25-4.06) at 6 months, as was mean exercise duration, MD 34.6 (95% CI -4.86 to 74.06). There were more withdrawals in the EECP group than in the control group as a result of adverse events (RR 1.05, 95% CI 0.67-1.66). There were limitations in the generalisability of results of the trial and, again, a lack of data on long-term outcomes. The review of cost-effectiveness evidence found only one unpublished study but demonstrated that the long-term maintenance of quality of life benefits of EECP is central to the estimate of its cost-effectiveness. The incremental cost-effectiveness ratio of EECP was 18,643 pounds for each additional quality-adjusted life-year (QALY), with a probability of being cost-effective of 0.44 and 0.70 at cost-effectiveness thresholds of 20,000 pounds and 30,000 pounds per QALY gained respectively. Results were sensitive to the duration of health-related quality of life (HRQoL) benefits from treatment. CONCLUSIONS: The results from a single randomised controlled trial (MUST-EECP) do not provide firm evidence of the clinical effectiveness of EECP in refractory stable angina or in heart failure. High-quality studies are required to investigate the benefits of EECP, whether these outweigh the common adverse effects and its long-term cost-effectiveness in terms of quality of life benefits.
Asunto(s)
Angina de Pecho/terapia , Contrapulsación , Insuficiencia Cardíaca/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To examine the impact of presumed consent legislation on organ donation and to review data on attitudes to presumed consent among the public, professionals and any other stakeholders. DATA SOURCES: Eight electronic databases (MEDLINE, MEDLINE In-Process, EMBASE, CINAHL, PsycINFO, HMIC, PAIS International and OpenSIGLE) were searched from inception to January 2008. Supplementary internet searches were also performed. REVIEW METHODS: A systematic review of studies comparing donation rates in a single country before and after the introduction of a presumed consent law or in countries with and without presumed consent systems. The methodological quality of these studies was assessed and a narrative synthesis of results undertaken. Surveys of attitudes towards presumed consent legislation were also included. RESULTS: Over 2000 potentially relevant citations were identified, of which 13 studies met the inclusion criteria for the primary objective and 13 for the secondary objective. For the primary objective, eight studies were between-country comparisons and five were before-and-after studies. Four of the between-country comparisons were of sufficient methodological quality to provide reliable results. In all four studies presumed consent law or practice was associated with increased rates of organ donation, ranging from an increase of 2.7 donors per million population (pmp) in one study to 6.14 donors per million in another, and an increase of between 20% and 30% in two other studies. Factors other than presumed consent that had an impact on organ donation rates were mortality from road traffic accidents and cerebrovascular accident, the transplant capacity of a country, gross domestic product per capita and health expenditure per capita, religion, education, public access to information and a common law legal system. The five before-and-after studies represented three countries, all of which reported an increase in donation rates following the introduction of a presumed consent system (Austria, from 4.6 to 27.2 donors pmp over a 5-year period; Belgium, increase in kidney donation from 10.9 to 41.3 pmp during a 3-year period; Singapore, increase in kidney procurement from 4.7 to 31.3 per year in the 3 years after the change in legislation). There was very limited investigation of any other changes taking place concurrently with the changes in legislation across this set of studies. Of the 13 studies addressing the secondary objective, eight were surveys of the UK public, four were from other countries and one was an international survey of health professionals. There was variation among the UK surveys in the level of support for presumed consent, with surveys conducted before 2000 reporting the lowest levels of support (28-57%). The most recent survey by YouGov in 2007 reported that 64% of respondents supported a change to presumed consent. CONCLUSIONS: Presumed consent alone is unlikely to explain the variation in organ donation rates between different countries. A combination of legislation, availability of donors, transplantation system organisation and infrastructure, wealth and investment in health care, as well as underlying public attitudes to and awareness of organ donation and transplantation, may all play a role, although the relative importance of each is not clear. Further reviews could investigate the factors likely to modify donor rates, such as procedures for family involvement. The way in which families of any potential donor are approached is likely to be an important factor and a review of qualitative research examining the experience of relatives in this context would be useful.