Exploring what is important to patients with regards to quality of life after experiencing a lower limb reconstructive procedure: a qualitative evidence synthesis.

BACKGROUND: Patient reported outcome measures (PROMs) are used to understand the impact of lower limb reconstruction surgery on patients' quality of life (QOL). Existing measures have not been developed to specifically capture patient experiences amongst adults with lower limb conditions that require reconstruction surgery. This review aimed to synthesise qualitative evidence to identify what is important to patients requiring, undergoing, or following reconstructive surgery for lower limb conditions. METHODS: MEDLINE, Embase, PsychINFO and Cinahl were searched from inception until November 2020. Studies were included if they employed qualitative research methods, involved patients requiring, undergoing or following lower limb reconstruction and explored patients' experiences of care, treatment, recovery and QOL. Mixed methods studies that did not separately report qualitative findings, mixed population studies that were not separately reported and studies in languages other than English were excluded. Included studies were analysed using thematic synthesis. The Critical Appraisal Skills Programme qualitative studies checklist was used to undertake quality assessment. RESULTS: Nine studies met the inclusion criteria. The thematic synthesis identified two overarching themes: (1) areas of living key to QOL for lower limb reconstruction patients and (2) moving towards a new normal. The way in which lower limb reconstruction affects an individual's QOL and their recovery is complex and is influenced by a range of inter-related factors, which will affect patients to varying degrees depending on their individual circumstances. We identified these factors as: pain, daily functioning and lifestyle, identity, income, emotional wellbeing, support, the ability to adapt and adjust and the ability to move forwards. CONCLUSIONS: The way patients' QOL is affected after a lower limb reconstruction is complex, may change over time and is strongly linked to their recovery. These findings will aid us in developing a conceptual framework which identifies the outcomes important to patients and those that should be included in a PROM. Further research is then required to establish whether the range of factors we identified are captured by existing PROMs. Depending on the outcome of this work, a new PROM for patients following lower limb reconstruction may be required.

Systematic review: height-adjustable workstations to reduce sedentary behaviour in office-based workers.

BACKGROUND: Time spent sitting in the workplace is an important contributor to overall sedentary risk. Installation of height-adjustable workstations has been proposed as a feasible approach for reducing occupational sitting time in office workers. AIMS: To provide an accurate overview of the controlled trials that have evaluated the effects of height-adjustable workstation interventions on workplace sitting time in office-based workers. METHODS: A comprehensive search was conducted up until March 2014 in the following databases: Medline, PsychINFO, CENTRAL, EMBASE and PEDro. To identify unpublished studies and grey literature, the reference lists of relevant official or scientific web pages were also checked. Studies assessing the effectiveness of height-adjustable workstations using a randomized or non-randomized controlled design were included. RESULTS: The initial search yielded a total of 8497 citations. After a thorough selection process, five studies were included with 172 participants. A formal quality assessment indicated that risk of bias was high in all studies and heterogeneity in interventions and outcomes prevented meta-analysis. Nevertheless, all studies reported that height-adjustable workstation interventions reduced occupational sitting time in office workers. There was insufficient evidence to determine effects on other relevant health outcomes (e.g. body composition, musculoskeletal symptoms, mental health). CONCLUSIONS: There is insufficient evidence to make firm conclusions regarding the effects of installing height-adjustable workstations on sedentary behaviour and associated health outcomes in office workers. Larger and longer term controlled studies are needed, which include more representative populations.

Systematic review of the limited evidence base for treatments of Eustachian tube dysfunction: a health technology assessment.

BACKGROUND: The Health Technology Assessment programme commissioned a wide-ranging review of treatments for adult Eustachian tube dysfunction. Treatments range from advice and observation and pharmacological treatments to surgical options. OBJECTIVE: (i) To assess the evidence for interventions for adults with a clinical diagnosis of Eustachian tube dysfunction and (ii) to identify priorities for future research. TYPE OF REVIEW: Systematic review (PROSPERO registration CRD42012003035) adhering to PRISMA guidance. SEARCH: An extensive search of 15 databases including MEDLINE, EMBASE and CENTRAL (up to October 2012). EVALUATION METHOD: Controlled and uncontrolled studies of interventions for adult Eustachian tube dysfunction were included. Because of insufficient data, the protocol was amended to also include controlled studies with mixed adult/child populations. Risk of bias was assessed. Narrative synthesis was employed due to high clinical heterogeneity. RESULTS: Interventions assessed were pharmacological treatments [two randomised controlled trials (RCTs), one controlled non-randomised trial (CCT), 159 patients]; mechanical pressure equalisation devices (one randomised controlled trial, one CCT, 48 patients); and surgery, including laser tuboplasty (seven case series, 192 patients), balloon dilatation (three case series, 103 patients), myringotomy without grommet insertion (two case series, 121 patients), transtubal steroids (one case series, 11 patients) and laser coagulation (one retrospective controlled study, 40 patients). All studies had high risk of bias except two pharmacological trials; one had low risk and one unclear risk. No evidence was found for many treatments. The single low risk of bias RCT (n = 91; 67% adults) showed no effect of nasal steroids and favoured placebo for improved middle ear function (RR 1.20, 95% CI 0.91-1.58) and symptoms (P = 0.07). Other studies showed improvements in middle ear function for mechanical devices, antihistamine/ephedrine and nasal decongestant, but they had significant methodological weaknesses including insufficient length of follow-up. None of the surgical studies were adequately controlled, and many reported high levels of co-intervention. Therefore, observed benefits for tuboplasty and balloon dilatation in symptoms, middle ear function or hearing could not be reliably attributed to the interventions assessed. There was variability in definitions of the condition. CONCLUSION: Eustachian tube dysfunction is a poorly defined condition. Due to the limited and poor-quality evidence, it is inappropriate to make conclusions on the effectiveness of any intervention; the evidence base is insufficient to guide recommendations for a trial of any particular intervention. Consensus on diagnostic criteria for Eustachian tube dysfunction is required to inform inclusion criteria of future trials.

Management of frozen shoulder: a systematic review and cost-effectiveness analysis.

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.

Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review.

Non-opioid analgesics, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), or cyclo-oxygenase 2 (COX-2) inhibitors are often given along with morphine as part of multimodal analgesia after major surgery. We have undertaken a systematic review and a mixed treatment comparison (MTC) analysis in order to determine explicitly which class of non-opioid analgesic, paracetamol, NSAIDs, or COX-2 inhibitors is the most effective in reducing morphine consumption and morphine-related adverse effects. Sixty relevant studies were identified. The MTC found that when paracetamol, NSAIDs, or COX-2 inhibitors were added to patient-controlled analgesia (PCA) morphine, there was a statistically significant reduction in morphine consumption: paracetamol [mean difference (MD) -6.34 mg; 95% credibility interval (CrI) -9.02, -3.65], NSAIDs (MD -10.18; 95% CrI -11.65, -8.72), and COX-2 inhibitors (MD -10.92; 95% CrI -12.77, -9.08). There was a significant reduction in nausea and postoperative nausea and vomiting with NSAIDs compared with placebo (odds ratio 0.70; 95% CrI 0.53, 0.88) but not for paracetamol or COX-2 inhibitors, nor for NSAIDs compared with paracetamol or COX-2 inhibitors. There was no statistically significant difference in sedation between any intervention and comparator. On the basis of six trials (n=695), 2.4% of participants receiving an NSAID experienced surgical-related bleeding compared with 0.4% with placebo. The MTC found that there is a decrease in 24 h morphine consumption when paracetamol, NSAID, or COX-2 inhibitors are given in addition to PCA morphine after surgery, with no clear difference between them. Similarly, the benefits in terms of reduction in morphine-related adverse effects do not strongly favour one of the three non-opioid analgesics.

The effectiveness of interventions in the management of patients with primary frozen shoulder.

There are many types of treatment used to manage the frozen shoulder, but there is no consensus on how best to manage patients with this painful and debilitating condition. We conducted a review of the evidence of the effectiveness of interventions used to manage primary frozen shoulder using the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Physiotherapy Evidence Database, MEDLINE and EMBASE without language or date restrictions up to April 2009. Two authors independently applied selection criteria and assessed the quality of systematic reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. Data were synthesised narratively, with emphasis placed on assessing the quality of evidence. In total, 758 titles and abstracts were identified and screened, which resulted in the inclusion of 11 systematic reviews. Although these met most of the AMSTAR quality criteria, there was insufficient evidence to draw firm conclusions about the effectiveness of treatments commonly used to manage a frozen shoulder. This was mostly due to poor methodological quality and small sample size in primary studies included in the reviews. We found no reviews evaluating surgical interventions. More rigorous randomised trials are needed to evaluate the treatments used for frozen shoulder.

Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the reduction of morphine-related side effects after major surgery: a systematic review.

OBJECTIVES: To determine which class of non-opioid analgesics - paracetamol (acetaminophen), NSAIDs or COX-2 inhibitors - is the most effective at reducing morphine consumption and associated adverse effects when used as part of multimodal analgesia following major surgery. DATA SOURCES: A systematic literature review was conducted using MEDLINE, EMBASE and CENTRAL databases, searched from January 2003 to February 2009 and updating an earlier review. REVIEW METHODS: Randomised controlled trials comparing paracetamol, NSAIDs or COX-2 inhibitors to each other or placebo, in adults receiving patient-controlled analgesia (PCA) with morphine following major surgery, were included. The COX-2 inhibitors rofecoxib and valdecoxib were excluded. Only trials that reported 24-hour morphine consumption were included. Other outcomes of interest were morphine-related adverse effects and adverse effects related to the non-opioids. Adequacy of randomisation, concealment of allocation, double blinding, and the flow of patients within the trial was assessed. The main analysis was a mixed treatment comparison (MTC) evaluating the relative effects of the four treatment classes. Four main outcomes were prioritised: 24-hour morphine consumption, sedation, nausea and vomiting, and surgical bleeding. Studies reporting nausea alone were pooled with studies reporting postoperative nausea and vomiting (PONV). Comparisons were described as statistically significant (at 5% level) when the credibility interval (CrI) did not cross 1 for odds ratio (OR) and zero for mean difference (MD). Trials making direct comparisons between the active interventions were also pooled in a meta-analysis using a random effects model. Sensitivity analyses were performed to assess the effects of study quality, individual drugs, and baseline morphine consumption. RESULTS: Sixty relevant studies were identified. When paracetamol, NSAIDs or COX-2 inhibitors were added to PCA morphine, there was a statistically significant reduction in morphine consumption: paracetamol (MD -6.34 mg; 95% CrI -9.02 to -3.65); NSAIDs (MD -10.18; 95% CrI -11.65 to -8.72); and COX-2 inhibitors (MD -10.92; 95% CrI -12.77 to -9.08). NSAIDs and COX-2 inhibitors were both significantly better than paracetamol, and there was no significant difference between NSAIDs and COX-2 inhibitors (MD -0.74; 95% CrI -3.03 to 1.56). There was a significant reduction in nausea and PONV with NSAIDs compared to placebo (OR 0.70; 95% CrI 0.53 to 0.88) but not for paracetamol or COX-2 inhibitors, nor for NSAIDs compared to paracetamol or COX-2 inhibitors. CONCLUSIONS: 24-hour morphine consumption decreased by 6.3 mg to 10.9 mg, compared to placebo, when paracetamol, NSAID or COX-2 inhibitors were added to PCA morphine following surgery. Differences in effect between the three drug classes were small and unlikely to be of clinical significance. There does not appear to be a strong case for recommending routine addition of any of the three non-opioids to PCA morphine in the 24 hours immediately after surgery, or for favouring one drug class above the others.

Are adverse effects incorporated in economic models? An initial review of current practice.

OBJECTIVES: To identify methodological research on the incorporation of adverse effects in economic models and to review current practice. DATA SOURCES: Major electronic databases (Cochrane Methodology Register, Health Economic Evaluations Database, NHS Economic Evaluation Database, EconLit, EMBASE, Health Management Information Consortium, IDEAS, MEDLINE and Science Citation Index) were searched from inception to September 2007. Health technology assessment (HTA) reports commissioned by the National Institute for Health Research (NIHR) HTA programme and published between 2004 and 2007 were also reviewed. REVIEW METHODS: The reviews of methodological research on the inclusion of adverse effects in decision models and of current practice were carried out according to standard methods. Data were summarised in a narrative synthesis. RESULTS: Of the 719 potentially relevant references in the methodological research review, five met the inclusion criteria; however, they contained little information of direct relevance to the incorporation of adverse effects in models. Of the 194 HTA monographs published from 2004 to 2007, 80 were reviewed, covering a range of research and therapeutic areas. In total, 85% of the reports included adverse effects in the clinical effectiveness review and 54% of the decision models included adverse effects in the model; 49% included adverse effects in the clinical review and model. The link between adverse effects in the clinical review and model was generally weak; only 3/80 (< 4%) used the results of a meta-analysis from the systematic review of clinical effectiveness and none used only data from the review without further manipulation. Of the models including adverse effects, 67% used a clinical adverse effects parameter, 79% used a cost of adverse effects parameter, 86% used one of these and 60% used both. Most models (83%) used utilities, but only two (2.5%) used solely utilities to incorporate adverse effects and were explicit that the utility captured relevant adverse effects; 53% of those models that included utilities derived them from patients on treatment and could therefore be interpreted as capturing adverse effects. In total, 30% of the models that included adverse effects used withdrawals related to drug toxicity and therefore might be interpreted as using withdrawals to capture adverse effects, but this was explicitly stated in only three reports. Of the 37 models that did not include adverse effects, 18 provided justification for this omission, most commonly lack of data; 19 appeared to make no explicit consideration of adverse effects in the model. CONCLUSIONS: There is an implicit assumption within modelling guidance that adverse effects are very important but there is a lack of clarity regarding how they should be dealt with and considered in modelling. In many cases a lack of clear reporting in the HTAs made it extremely difficult to ascertain what had actually been carried out in consideration of adverse effects. The main recommendation is for much clearer and explicit reporting of adverse effects, or their exclusion, in decision models and for explicit recognition in future guidelines that 'all relevant outcomes' should include some consideration of adverse events.

A systematic review of presumed consent systems for deceased organ donation.

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.

Enhanced external counterpulsation for the treatment of stable angina and heart failure: a systematic review and economic analysis.

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.

Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea-hypopnoea syndrome: a systematic review and economic analysis.

OBJECTIVES: To determine the clinical effectiveness, safety and cost-effectiveness of continuous positive airway pressure (CPAP) devices for the treatment of obstructive apnoea-hypopnoea syndrome (OSAHS), compared with the best supportive care, placebo and dental devices. DATA SOURCES: The main search was of fifteen electronic databases, including MEDLINE, EMBASE and the Cochrane Library, up to November 2006. REVIEW METHODS: Randomised controlled trials (RCTs) comparing CPAP with best supportive/usual care, placebo, and dental devices in adults with a diagnosis of OSAHS were included. The primary outcomes of interest were subjective daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS) and objective sleepiness assessed by the Maintenance of Wakefulness Test (MWT) and the Multiple Sleep Latency Test (MSLT). A new economic model was developed to assess incremental cost per quality-adjusted life-year (QALY). The cost-effectiveness of CPAP was compared with that of the use of dental devices and conservative management. The costs and QALYs were compared over a lifetime time horizon. Effectiveness was based on the RCT evidence on sleepiness symptoms (ESS), which was 'mapped' to utilities using individual patient data from a subset of studies. Utilities were expressed on the basis of generic HRQoL instruments [the EQ-5D (EuroQoL-5 Dimensions) in the base-case analysis]. The base-case analysis focused on a male aged 50. A series of subgroup and scenario analyses were also undertaken. RESULTS: The searches yielded 6325 citations, from which 48 relevant clinical effectiveness studies were identified, 29 of these providing data on daytime sleepiness. The majority of the included RCTs did not report using an adequate method of allocation concealment or use an intention-to-treat analysis. Only the studies using a sham CPAP comparator were double blinded. There was a statistically significant benefit with CPAP compared with control (placebo and conservative treatment/usual care) on the ESS [mean difference (MD) -2.7 points, 95% CI -3.45 to -1.96]. However, there was statistical heterogeneity, which was reduced when trials were subgrouped by severity of disease. There was also a significant benefit with CPAP compared with usual care on the MWT. There was a non-statistically significant difference between CPAP and dental devices (six trials) in the impact on daytime sleepiness (ESS) among a population with moderate symptom severity at baseline (MD -0.9, 95% CI -2.1 to 0.4). A review of five studies evaluating the cost-effectiveness of CPAP was undertaken. All existing cost-effectiveness studies had limitations; therefore a new economic model was developed, based on which it was found that, on average, CPAP was associated with higher costs and benefits than dental devices or conservative management. The incremental cost per QALY gained of CPAP was below 20,000 pounds in the base-case analysis and most alternative scenarios. There was a high probability of CPAP being more cost-effective than dental devices and conservative management for a cost-effectiveness threshold of 20,000 pounds per QALY gained. CONCLUSIONS: CPAP is an effective and cost-effective treatment for OSAHS compared with conservative/usual care and placebo in populations with moderate to severe daytime sleepiness, and there may be benefits when the disease is mild. Dental devices may be a treatment option in moderate disease but some uncertainty remains. Further research would be potentially valuable, particularly investigation of the effectiveness of CPAP for populations with mild sleepiness and further trials comparing CPAP with dental devices.

Systematic review of effectiveness of different treatments for childhood retinoblastoma.

OBJECTIVES: To assess the clinical effectiveness of treatments for childhood retinoblastoma. DATA SOURCES: Electronic databases were searched from inception to April 2004. REVIEW METHODS: Studies of participants diagnosed with childhood retinoblastoma, any interventions and all clinical outcomes were eligible for inclusion. Randomised and non-randomised controlled trials and cohort studies with clear comparisons between treatment groups were included. Methodological quality was assessed. A narrative synthesis was conducted. Where possible, studies assessing common interventions were grouped together, with prospective and retrospective studies grouped separately. Emphasis was placed on prospective studies. RESULTS: Thirty-one individual studies, from 42 publications, were included in the review. Apart from one non-randomised controlled trial, only comparative studies of observational design were available for any of the treatments. Four of the included studies were prospective and the remaining 27 were retrospective. Most of the studies were of radiotherapy or chemotherapy, with few studies available on enucleation or focal treatments such as brachytherapy, photocoagulation, cryotherapy and thermotherapy. The methodological quality was generally poor, with a high risk of bias in all included studies. The main problems were in relation to how treatment was allocated and lack of consideration of potentially confounding factors, such as initial disease severity, in the study design and data analysis. The evidence base for effectiveness of treatments for childhood retinoblastoma is extremely limited. Owing to the considerable limitations of the evidence identified, it was not possible to make meaningful and robust conclusions about the relative effectiveness of different treatment approaches for childhood retinoblastoma. CONCLUSIONS: In the authors' opinion, the evidence base for the effectiveness of treatments for childhood retinoblastoma is not sufficiently robust to provide clear guidance for clinical practice. Ideally, good-quality randomised controlled trials (RCTs) assessing the effectiveness of different treatment options for childhood retinoblastoma are required. Research is required on all the treatments currently used for this condition. Where RCTs are not feasible, for ethical or practical reasons, only high-quality, prospective, non-randomised studies should be given consideration, owing to the generally higher risk of bias in retrospective studies. To reduce the risk of confounding due to allocation by clinical indication, studies should compare patients with similar disease severity rather than compare patients of mixed disease severities. Standardised outcomes should be agreed for use in studies assessing the effectiveness of treatment. These outcomes should encompass potential important adverse effects of treatment such as loss of visual acuity and cosmetic outcome, as well as beneficial effects.

Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation.

OBJECTIVES: To examine the clinical effectiveness, tolerability and cost-effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for epilepsy in adults. DATA SOURCES: Electronic databases. Internet resources. Pharmaceutical company submissions. REVIEW METHODS: Selected studies were screened and quality assessed. Separate analyses assessed clinical effectiveness, serious, rare and long-term adverse events and cost-effectiveness. An integrated economic analysis incorporating information on costs and effects of newer and older antiepileptic drugs (AEDs) was performed to give direct comparisons of long-term costs and benefits. RESULTS: A total of 212 studies were included in the review. All included systematic reviews were Cochrane reviews and of good quality. The quality of randomised controlled trials (RCTs) was variable. Assessment was hampered by poor reporting of methods of randomisation, allocation concealment and blinding. Few of the non-randomised studies were of good quality. The main weakness of the economic evaluations was inappropriate use of the cost-minimisation design. The included systematic reviews reported that newer AEDs were effective as adjunctive therapy compared to placebo. For newer versus older drugs, data were available for all three monotherapy AEDs, although data for OXC and TPM were limited. There was limited, poor-quality evidence of a significant improvement in cognitive function with LTG and OXC compared with older AEDs. However, there were no consistent statistically significant differences in other clinical outcomes, including proportion of seizure-free patients. No studies assessed effectiveness of AEDs in people with intellectual disabilities or in pregnant women. There was very little evidence to assess the effectiveness of AEDs in the elderly; no significant differences were found between LTG and carbamazepine monotherapy. Sixty-seven RCTs compared adjunctive therapy with placebo, older AEDs or other newer AEDs. For newer AEDs versus placebo, a trend was observed in favour of newer drugs, and there was evidence of statistically significant differences in proportion of responders favouring newer drugs. However, it was not possible to assess long-term effectiveness. Most trials were conducted in patients with partial seizures. For newer AEDs versus older drugs, there was no evidence to assess the effectiveness of LEV, LTG or OXC, and evidence for other newer drugs was limited to single studies. Trials only included patients with partial seizures and follow-up was relatively short. There was no evidence to assess effectiveness of adjunctive LEV, OXC or TPM versus other newer drugs, and there were no time to event or cognitive data. No studies assessed the effectiveness of adjunctive AEDs in the elderly or pregnant women. There was some evidence from one study (GBP versus LTG) that both drugs have some beneficial effect on behaviour in people with learning disabilities. Eighty RCTs reported the incidence of adverse events. There was no consistent or convincing evidence to draw any conclusions concerning relative safety and tolerability of newer AEDs compared with each other, older AEDs or placebo. The integrated economic analysis for monotherapy for newly diagnosed patients with partial seizures showed that older AEDs were more likely to be cost-effective, although there was considerable uncertainty in these results. The integrated analysis suggested that newer AEDs used as adjunctive therapy for refractory patients with partial seizures were more effective and more costly than continuing with existing treatment alone. Combination therapy, involving new AEDs, may be cost-effective at a threshold willingness to pay per quality-adjusted life year (QALY) greater than 20,000 pounds, depending on patients' previous treatment history. There was, again, considerable uncertainty in these results. There were few data available to determine effectiveness of treatments for patients with generalised seizures. LTG and VPA showed similar health benefits when used as monotherapy. VPA was less costly and was likely to be cost-effective. The analysis indicated that TPM might be cost-effective when used as an adjunctive therapy, with an estimated incremental cost-effectiveness ratio of 34,500 pounds compared with continuing current treatment alone. CONCLUSIONS: There was little good-quality evidence from clinical trials to support the use of newer monotherapy or adjunctive therapy AEDs over older drugs, or to support the use of one newer AED in preference to another. In general, data relating to clinical effectiveness, safety and tolerability failed to demonstrate consistent and statistically significant differences between the drugs. The exception was comparisons between newer adjunctive AEDs and placebo, where significant differences favoured newer AEDs. However, trials often had relatively short-term treatment durations and often failed to limit recruitment to either partial or generalised onset seizures, thus limiting the applicability of the data. Newer AEDs, used as monotherapy, may be cost-effective for the treatment of patients who have experienced adverse events with older AEDs, who have failed to respond to the older drugs, or where such drugs are contraindicated. The integrated economic analysis also suggested that newer AEDs used as adjunctive therapy may be cost-effective compared with the continuing current treatment alone given a QALY of about 20,000 pounds. There is a need for more direct comparisons of the different AEDs within clinical trials, considering different treatment sequences within both monotherapy and adjunctive therapy. Length of follow-up also needs to be considered. Trials are needed that recruit patients with either partial or generalised seizures; that investigate effectiveness and cost-effectiveness in patients with generalised onset seizures and that investigate effectiveness in specific populations of epilepsy patients, as well as studies evaluating cognitive outcomes to use more stringent testing protocols and to adopt a more consistent approach in assessing outcomes. Further research is also required to assess the quality of life within trials of epilepsy therapy using preference-based measures of outcomes that generate cost-effectiveness data. Future RCTs should use CONSORT guidelines; and observational data to provide information on the use of AEDs in actual practice, including details of treatment sequences and doses.