Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. METHODS: We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). RESULTS: Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. CONCLUSIONS: In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.

Algorithm based smartphone apps to assess risk of skin cancer in adults: systematic review of diagnostic accuracy studies.

OBJECTIVE: To examine the validity and findings of studies that examine the accuracy of algorithm based smartphone applications ("apps") to assess risk of skin cancer in suspicious skin lesions. DESIGN: Systematic review of diagnostic accuracy studies. DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, CPCI, Zetoc, Science Citation Index, and online trial registers (from database inception to 10 April 2019). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies of any design that evaluated algorithm based smartphone apps to assess images of skin lesions suspicious for skin cancer. Reference standards included histological diagnosis or follow-up, and expert recommendation for further investigation or intervention. Two authors independently extracted data and assessed validity using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2 tool). Estimates of sensitivity and specificity were reported for each app. RESULTS: Nine studies that evaluated six different identifiable smartphone apps were included. Six verified results by using histology or follow-up (n=725 lesions), and three verified results by using expert recommendations (n=407 lesions). Studies were small and of poor methodological quality, with selective recruitment, high rates of unevaluable images, and differential verification. Lesion selection and image acquisition were performed by clinicians rather than smartphone users. Two CE (Conformit Europenne) marked apps are available for download. SkinScan was evaluated in a single study (n=15, five melanomas) with 0% sensitivity and 100% specificity for the detection of melanoma. SkinVision was evaluated in two studies (n=252, 61 malignant or premalignant lesions) and achieved a sensitivity of 80% (95% confidence interval 63% to 92%) and a specificity of 78% (67% to 87%) for the detection of malignant or premalignant lesions. Accuracy of the SkinVision app verified against expert recommendations was poor (three studies). CONCLUSIONS: Current algorithm based smartphone apps cannot be relied on to detect all cases of melanoma or other skin cancers. Test performance is likely to be poorer than reported here when used in clinically relevant populations and by the intended users of the apps. The current regulatory process for awarding the CE marking for algorithm based apps does not provide adequate protection to the public. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033595.

Effects of physical activity calorie equivalent food labelling to reduce food selection and consumption: systematic review and meta-analysis of randomised controlled studies.

BACKGROUND: There is limited evidence that nutritional labelling on food/drinks is changing eating behaviours. Physical activity calorie equivalent (PACE) food labelling aims to provide the public with information about the amount of physical activity required to expend the number of kilocalories in food/drinks (eg, calories in this pizza requires 45 min of running to burn), to encourage healthier food choices and reduce disease. OBJECTIVE: We aimed to systematically search for randomised controlled trials and experimental studies of the effects of PACE food labelling on the selection, purchase or consumption of food/drinks. METHODS: PACE food labelling was compared with any other type of food labelling or no labelling (comparator). Reports were identified by searching electronic databases, websites and social media platforms. Inverse variance meta-analysis was used to summarise evidence. Weighted mean differences (WMD) and 95% CIs were used to describe between-group differences using a random effects model. RESULTS: 15 studies were eligible for inclusion. When PACE labelling was displayed on food/drinks and menus, significantly fewer calories were selected, relative to comparator labelling (WMD=-64.9 kcal, 95% CI -103.2 to -26.6, p=0.009, n=4606). Presenting participants with PACE food labelling results in the consumption of significantly fewer calories (WMD=-80.4 kcal, 95% CI-136.7 to -24.2, p=0.005, n=486) relative to comparator food labelling. CONCLUSION: Based on current evidence PACE food labelling may reduce the number of kilocalories selected from menus and decrease the number of kilocalories/grams of food consumed by the public, compared with other types of food labelling/no labelling. TRIAL REGISTRATION NUMBER: CRD42018088567.

Cost-Effectiveness of Treatments for the Management of Bone Metastases: A Systematic Literature Review.

BACKGROUND: Metastatic cancers occur when cancer cells break away from the primary tumour. One of the most common sites of metastasis is the bone, with several therapeutic options currently available for managing bone metastases. In a resource-constrained environment, policy makers and practitioners need to know which options are cost effective. OBJECTIVE: The aim of this systematic review was to review and appraise published economic evaluations on treatments for the management of bone metastases. METHODS: We searched eight bibliographic databases (MEDLINE, MEDLINE in Process, EMBASE, CSDR, DARE, HTA, EED and CPCI) for relevant economic evaluations published from each database's inception date until March 2017. Study selection, quality assessment and data extraction were carried out according to published guidelines. RESULTS: Twenty-four relevant economic analyses were identified. Seventeen of these studies focused on bone metastases resulting from a particular type of cancer, i.e. prostate (n = 8), breast (n = 7), lung (n = 1) or renal (n = 1), while seven report results for various primary tumours. Across types of cancer, evidence suggests that bisphosphonates result in lower morbidity and improved quality of life, for an additional cost, which is typically below conventional cost-effectiveness thresholds. While denosumab leads to health gains compared with zoledronic acid, it also results in substantial additional costs and is unlikely to represent value for money. The limited literature on the radiopharmaceutical strontium-89 (Sr89) and external beam radiotherapy (EBR) suggest that these treatments are cost effective compared with no treatment. CONCLUSIONS: The reviewed evidence suggests that bisphosphonate treatments are cost-effective options for bone metastases, while denosumab is unlikely to represent value for money. Evidence on EBR and Sr89 is limited and less conclusive.

The effect of domiciliary noninvasive ventilation on clinical outcomes in stable and recently hospitalized patients with COPD: a systematic review and meta-analysis.

INTRODUCTION: Noninvasive ventilation (NIV) improves survival among patients with hypercapnic respiratory failure in hospital, but evidence for its use in domiciliary settings is limited. A patient's underlying risk of having an exacerbation may affect any potential benefit that can be gained from domiciliary NIV. This is the first comprehensive systematic review to stratify patients based on a proxy for exacerbation risk: patients in a stable state and those immediately post-exacerbation hospitalization. METHODS: A systematic review of nonrandomized and randomized controlled trials (RCTs) was undertaken in order to compare the relative effectiveness of different types of domiciliary NIV and usual care on hospital admissions, mortality, and health-related quality of life. Standard systematic review methods were used for identifying studies (until September 2014), quality appraisal, and synthesis. Data were presented in forest plots and pooled where appropriate using random-effects meta-analysis. RESULTS: Thirty-one studies were included. For stable patients, there was no evidence of a survival benefit from NIV (relative risk [RR] 0.88 [0.55, 1.43], I2=60.4%, n=7 RCTs), but there was a possible trend toward fewer hospitalizations (weighted mean difference -0.46 [-1.02, 0.09], I2=59.2%, n=5 RCTs) and improved health-related quality of life. For posthospital patients, survival benefit could not be demonstrated within the three RCTs (RR 0.89 [0.53, 1.49], I2=25.1%), although there was evidence of benefit from four non-RCTs (RR 0.45 [0.32, 0.65], I2=0%). Effects on hospitalizations were inconsistent. Post hoc analyses suggested that NIV-related improvements in hypercapnia were associated with reduced hospital admissions across both populations. Little data were available comparing different types of NIV. CONCLUSION: The effectiveness of domiciliary NIV remains uncertain; however, some patients may benefit. Further research is required to identify these patients and to explore the relevance of improvements in hypercapnia in influencing clinical outcomes. Optimum time points for commencing domiciliary NIV and equipment settings need to be established.

Adverse effects of extracorporeal carbon dioxide removal (ECCO2R) for acute respiratory failure: a systematic review protocol.

BACKGROUND: The extracorporeal membrane carbon dioxide removal (ECCO2R) system is primarily designed for the purpose of removing CO2 from the body for patients with potentially reversible severe acute hypercapnic respiratory failure or being considered for lung transplantation. Systematic reviews have focused on the effectiveness of ECCO2R. To the author's best knowledge, this is the first systematic review to focus on the adverse effects of this procedure. METHODS: We will conduct a systematic review of procedure-related adverse effects of ECCO2R systems. A high sensitivity search strategy will be employed in Cochrane Library, MEDLINE, EMBASE, Web of Science and product regulatory databases and ongoing trial registers to identify citations. Reference lists of relevant studies and grey literature will also be searched. Screening of the results will be performed by two reviewers independently using pre-defined inclusion and exclusion criteria. Clinical trials and observational studies will be included. Data will be extracted using a purposefully developed extraction form. Appropriateness for statistical pooling of the results will be determined and carried out if heterogeneity is low to moderate. The GRADE framework will be employed to grade the overall quality of the evidence. DISCUSSION: In the UK, the current access to the use of ECCO2R is possible only with special arrangements for clinical governance, consent and for audit or research. Current evidence on ECCO2R suggests that there are a number of well-recognised complications which vary greatly across studies. This systematic review will consolidate the existing knowledge on adverse effects resulting from the use of ECCO2R. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023503 .

The cost-effectiveness of domiciliary non-invasive ventilation in patients with end-stage chronic obstructive pulmonary disease: a systematic review and economic evaluation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the U.K., domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation. DATA SOURCES: Bibliographic databases, conference proceedings and ongoing trial registries up to September 2014. METHODS: Standard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately. RESULTS: Thirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective. LIMITATIONS: Evidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data. CONCLUSIONS: The cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings. FUTURE WORK RECOMMENDATIONS: The results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003286. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Investigating the effectiveness of different aspirin dosing regimens and the timing of aspirin intake in primary and secondary prevention of cardiovascular disease: protocol for a systematic review.

BACKGROUND: Once-daily low-dose aspirin is routinely used for the prevention of secondary events in cardiovascular disease (CVD). The routine use of aspirin in primary prevention of CVD is less clear due to a finer balance between benefits and harms. In addition, the variability in benefit achievable from the prescription of aspirin has led to a growing interest in considering whether there are more effective aspirin regimens than once-daily dosing or whether effectiveness is influenced by the time of day aspirin is taken (chronotherapy). The proposed systematic review will evaluate the evidence on the effects of different aspirin regimens used in terms of number of doses (e.g. split or alternate dosing) or dosing time of aspirin (e.g. morning versus evening) in primary and secondary prevention of CVD. METHODS/DESIGN: Standard systematic review methodology will be employed for study identification, selection and data extraction. Electronic databases will be searched incorporating terms relating to population and the intervention. No date or language limitations will apply. Systematic reviews and controlled studies comparing different aspirin regimens-in terms of frequency or timing-for primary and/or secondary prevention of CVD will be included. No restrictions on outcome will apply. Quality assessment will be appropriate for each study design. The data will be tabulated and narratively synthesised. Meta-analysis may be undertaken where clinical and methodological homogeneity exists. DISCUSSION: There are a number of published and ongoing primary studies that investigate the cardiovascular protective effect of different aspirin regimens. However, no systematic review to date has attempted to review the evidence pertaining to aspirin dosing regimens differing in frequency and/or in timing. The proposed systematic review will cover both the above questions and could potentially be beneficial for reconsidering the current practice of managing patients with aspirin in primary care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014010596.

Occipital nerve stimulation for chronic migraine--a systematic review and meta-analysis.

BACKGROUND: Chronic migraine is a debilitating headache disorder that has significant impact on quality of life. Stimulation of peripheral nerves is increasingly being used to treat chronic refractory pain including headache disorders. This systematic review examines the effectiveness and adverse effects of occipital nerve stimulation (ONS) for chronic migraine. METHODS: Databases, including the Cochrane Library, MEDLINE, EMBASE, CINAHL and clinical trial registers were searched to September 2014. Randomized controlled trials (RCTs), other controlled and uncontrolled observational studies and case series (n≥ 10) were eligible. RCTs were assessed using the Cochrane risk of bias tool. Meta-analysis was carried out using a random-effects model. Findings are presented in summary tables and forest plots. RESULTS: Five RCTs (total n=402) and seven case series (total n=115) met the inclusion criteria. Pooled results from three multicenter RCTs show that ONS was associated with a mean reduction of 2.59 days (95% CI 0.91 to 4.27, I2=0%) of prolonged, moderate to severe headache per month at 3 months compared with a sham control. Results for other outcomes generally favour ONS over sham controls but quantitative analysis was hampered by incomplete publication and reporting of trial data. Lead migration and infections are common and often require revision surgery. Open-label follow-up of RCTs and case series suggest long-term effectiveness can be maintained in some patients but evidence is limited. CONCLUSIONS: While the effectiveness of ONS compared to sham control has been shown in multiple RCTs, the average effect size is modest and may be exaggerated by bias as achieving effective blinding remains a methodological challenge. Further measures to reduce the risk of adverse events and revision surgery are needed. SYSTEMATIC REVIEW REGISTRATION: this systematic review is an update and expanded work of part of a broader review registered with PROSPERO. Registration No. CRD42012002633.

Methodological issues and recommendations for systematic reviews of prognostic studies: an example from cardiovascular disease.

BACKGROUND: Prognostic factors are associated with the risk of future health outcomes in individuals with a particular health condition. The prognostic ability of such factors is increasingly being assessed in both primary research and systematic reviews. Systematic review methodology in this area is continuing to evolve, reflected in variable approaches to key methodological aspects. The aim of this article was to (i) explore and compare the methodology of systematic reviews of prognostic factors undertaken for the same clinical question, (ii) to discuss implications for review findings, and (iii) to present recommendations on what might be considered to be 'good practice' approaches. METHODS: The sample was comprised of eight systematic reviews addressing the same clinical question, namely whether 'aspirin resistance' (a potential prognostic factor) has prognostic utility relative to future vascular events in patients on aspirin therapy for secondary prevention. A detailed comparison of methods around study identification, study selection, quality assessment, approaches to analysis, and reporting of findings was undertaken and the implications discussed. These were summarised into key considerations that may be transferable to future systematic reviews of prognostic factors. RESULTS: Across systematic reviews addressing the same clinical question, there were considerable differences in the numbers of studies identified and overlap between included studies, which could only partially be explained by different study eligibility criteria. Incomplete reporting and differences in terminology within primary studies hampered study identification and selection process across reviews. Quality assessment was highly variable and only one systematic review considered a checklist for studies of prognostic questions. There was inconsistency between reviews in approaches towards analysis, synthesis, addressing heterogeneity and reporting of results. CONCLUSIONS: Different methodological approaches may ultimately affect the findings and interpretation of systematic reviews of prognostic research, with implications for clinical decision-making.

Protocol for a systematic review and economic evaluation of the clinical and cost-effectiveness of non-hospital-based non-invasive ventilation (NIV) in patients with stable end-stage COPD with hypercapnic respiratory failure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a significant public health burden. Non-invasive ventilation (NIV) is a method of supported breathing used as standard care for acutely unwell patients in hospital with COPD, but there is uncertainty around the potential benefits of using NIV in the treatment of stable patients in a non-hospital setting. This is a protocol for systematic reviews of the clinical and cost-effectiveness of NIV in this context, being undertaken in support of a model based economic evaluation. METHODS/DESIGN: Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction for both the clinical and economic systematic reviews. Bibliographic databases (for example MEDLINE, EMBASE) and ongoing trials registers will be searched from 1980 onwards. The search strategy will combine terms for the population with those for the intervention. Studies will be selected for review if the population includes adult patients with COPD and hypercapnic respiratory failure, however defined. Systematic reviews, randomised controlled trials and observational studies (with n >1) will be included, and quality assessment will be tailored to the different study designs. The primary outcome measures of interest are survival, quality of life, and healthcare utilisations (hospitalisation and Accident and Emergency attendances). Meta-analyses will be undertaken where clinical and methodological homogeneity exists, supported by predefined subgroup analyses where appropriate. A systematic review of the evidence on the cost-effectiveness of non-hospital NIV will be completed, and a model-based cost-utility analysis undertaken to determine the cost-effectiveness of non-hospital-based NIV compared with standard care. DISCUSSION: These reviews will attempt to clarify the clinical effectiveness of non-hospital NIV in COPD patients as well as the cost-effectiveness. The findings may indicate whether NIV in a non-hospital setting should be considered more routinely in this patient group, and what the likely cost implications will be. PROSPERO REGISTRATION: 2012:CRD42012003286.

Systematic review of the effectiveness of continuing dental professional development on learning, behavior, or patient outcomes.

This study is based on a systematic review of studies using a randomized controlled trial or quasi-experimental design in order to synthesize existing evidence evaluating the effectiveness of continuing professional development (CPD) interventions in dentistry on learning gains, behavior change, or patient outcomes. The authors searched a range of electronic databases from 1986 to the present and screened all potentially relevant studies for inclusion, using pre-established inclusion/exclusion criteria. Following data extraction and quality appraisal of all included studies, a narrative synthesis of the studies was undertaken. Ten studies (in fourteen articles) were included. All were evaluation studies of CPD interventions targeted exclusively at dentists. The ten included studies evaluated a range of interventions: courses/workshops, written information, CAL, audit/self-reflection, face-to-face support, and black box combinations of these interventions. Two high- and moderately high-quality studies evaluated CAL CPD for dentists and found equivocal impact of CAL for dentists. A black box combination of interventions was rigorously evaluated and showed moderate impact on patient care. This finding suggests that multimethod and multiphased CPD has potential for the greatest impact. There is a need for more high-quality randomized controlled trials evaluating CPD interventions in dentistry. It is important that future evaluations of CPD interventions clarify the nature of the interventions such that they are explicit and replicable and that appropriate outcomes are selected (health of patients and change in practice or behavior as well as knowledge and understanding) in order to move the evidence base of effective practice forward in this area of dental education.

Protocol for a systematic review of the diagnostic and prognostic utility of tests currently available for the detection of aspirin resistance in patients with established cardiovascular or cerebrovascular disease.

BACKGROUND: The benefits of aspirin as an anti-platelet agent are well established; however, there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function. In some patients, aspirin fails to inhibit platelets even where compliance has been verified, a phenomenon which has been termed "aspirin resistance". These patients may in turn be at a higher risk of future vascular events. The proportion of "resistant" patients identified depends on the type of platelet function test. Therefore, the aim of this systematic review is to determine which, if any, platelet function test has utility in terms of identifying patients with a high risk of vascular events. The review has been registered with PROSPERO (CRD42012002151). METHODS: Relevant studies will be sought from bibliographic databases. Trials registers will be searched for ongoing studies. Reference lists will be checked and subject experts contacted. There will be no date or language restrictions. Standard reviewing methodology to minimise bias will be employed. Any prospective studies in patients on aspirin therapy and assessing platelet function in relation to relevant clinical outcomes will be included, as will studies reporting prognostic models. Risk of bias assessment will be based on the Quality Assessment of Diagnostic Accuracy Studies guidelines, and suitable criteria for assessing quality of prognostic studies. Data on test accuracy measures, relative risks, odds or hazard ratios will be extracted and meta-analysed, where possible, using a random-effects model to account for between-study heterogeneity. Where appropriate, the causes of heterogeneity will be explored through meta-regression and sub-group or sensitivity analyses. If platelet function testing is demonstrated to have diagnostic/predictive utility in a specific population, the potential for a cost-effectiveness analysis will be considered and, if possible, an economic model constructed. This will be supported by a systematic review of existing economic evaluation studies. DISCUSSION: The results of the review could indicate if platelet function test(s) could lead to a reliable prediction of the risk of clinically important events in a defined population, and thus support investigations into adjustments to therapy in order to compensate for a predicted poor response to standard aspirin.

Oxygen therapy for acute myocardial infarction: a systematic review and meta-analysis.

Oxygen (O(2)) is widely recommended in international guidelines for treatment of acute myocardial infarction (AMI), but there is uncertainty about its safety and benefits. A systematic review and meta-analysis were performed to determine whether inhaled O(2) in AMI improves pain or the risk of death. Cochrane CENTRAL Register of Controlled Trials, MEDLINE, MEDLINE In-Process, EMBASE, CINAHL, LILACS and PASCAL were searched from start date to February 2010. Other sources included British Library ZETOC, Web of Science, ISI Proceedings, relevant conferences, expert contacts. Randomised controlled trials of inhaled O(2) versus air in patients with suspected or proven AMI of < 24 h onset were included. Two authors independently reviewed studies to confirm inclusion criteria met, and undertook data abstraction. Quality of studies and risk of bias was assessed according to Cochrane Collaboration guidance. Main outcomes were death, pain, and complications. Measure of effect used was the RR. Three trials (n=387 patients) were included. Pooled RR of death on O(2) compared to air was 2.88 (95%CI 0.88 to 9.39) on ITT analysis and 3.03 (95%CI 0.93 to 9.83) in confirmed AMI. While suggestive of harm, this could be a chance occurrence. Pain was measured by analgesic use. Pooled RR for the use of analgesics was 0.97 (95%CI 0.78 to 1.20). Evidence for O(2) in AMI is sparse, of poor quality and pre-dates advances in reperfusion and trial methods. Evidence is suggestive of harm but lacks power and excess deaths in the O(2) group could be due to chance. More research is required.

Community programs for the prevention of cardiovascular disease: a systematic review.

In this systematic review, the authors aimed to assess the effectiveness of community programs for prevention of cardiovascular disease (CVD). They searched numerous electronic databases (CDSR, DARE, HTA, EED, and CENTRAL via the Cochrane Library, MEDLINE, MEDLINE In Process, EMBASE, CINAHL, PsycINFO, HMIC, and ASSIA) and relevant Web sites from January 1970 to mid-July 2008. Controlled studies of community programs for the primary prevention of CVD were included. Net changes in CVD risk factors were used to generate an overall index for net change in 10-year CVD risk. The authors identified 36 relevant community programs that took place between 1970 and 2008. These programs were multifaceted interventions employing combinations of media, screening, and counseling activities and environmental changes and were primarily evaluated using controlled before-after studies. In 7 studies, investigators reported changes in CVD/total mortality rates, and in 5 they reported net changes. In all cases, these net changes were positive but were largely nonsignificant. In 22 studies, investigators reported changes in physiologic CVD risk factors, and there was a positive trend in the calculated CVD risk score. The average net reduction in 10-year CVD risk was 0.65%. Community programs for CVD prevention appear to have generally achieved favorable changes in overall CVD risk and, with adaptation to current circumstances, deserve continued consideration as possible approaches to preventing CVD.

Oxygen therapy for acute myocardial infarction.

BACKGROUND: Oxygen (O(2)) is widely recommended for patients with myocardial infarction yet a narrative review has suggested it may do more harm than good. Systematic reviews have concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on the heart ischaemia or infarct size. OBJECTIVES: To review the evidence from randomised controlled trials to establish whether routine use of inhaled oxygen in acute myocardial infarction (AMI) improves patient-centred outcomes, in particular pain and death. SEARCH STRATEGY: The following bibliographic databases were searched (to the end of February 2010): Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, MEDLINE In-Process, EMBASE, CINAHL, LILACS and PASCAL, British Library ZETOC, Web of Science ISI Proceedings. Experts were also contacted to identify any studies. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials of people with suspected or proven AMI, less than 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air and regardless of co-therapies provided these were the same in both arms of the trial. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the titles and abstracts of identified studies to see if they met the inclusion criteria and independently undertook the data extraction. The quality of studies and the risk of bias were assessed according to guidance in the Cochrane Handbook. The primary outcomes were death, pain and complications. The measure of effect used was the relative risk (RR). MAIN RESULTS: Three trials involving 387 patients were included and 14 deaths occurred. The pooled RR of death was 2.88 (95% CI 0.88 to 9.39) in an intention-to-treat analysis and 3.03 (95% CI 0.93 to 9.83) in patients with confirmed AMI. While suggestive of harm, the small number of deaths recorded meant that this could be a chance occurrence. Pain was measured by analgesic use. The pooled RR for the use of analgesics was 0.97 (95% CI 0.78 to 1.20). AUTHORS' CONCLUSIONS: There is no conclusive evidence from randomised controlled trials to support the routine use of inhaled oxygen in patients with acute AMI. A definitive randomised controlled trial is urgently required given the mismatch between trial evidence suggestive of possible harm from routine oxygen use and recommendations for its use in clinical practice guidelines.

Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation.

BACKGROUND: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. METHODS: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. RESULTS: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was pound81,000/QALY and pound212,000/LYG. To reduce this to pound30K/QALY would require a reduction in drug cost by about one third. CONCLUSION: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money.

The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials.

BACKGROUND: Conduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders. There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals. The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems. METHODS: Standard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006. Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies. RESULTS: 57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes. CONCLUSION: Parenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research.

So many filters, so little time: the development of a search filter appraisal checklist.

OBJECTIVES: The authors developed a tool to assess the quality of search filters designed to retrieve records for studies with specific research designs (e.g., diagnostic studies). METHODS: The UK InterTASC Information Specialists' Sub-Group (ISSG), a group of experienced health care information specialists, reviewed the literature to evaluate existing search filter appraisal tools and determined that existing tools were inadequate for their needs. The group held consensus meetings to develop a new filter appraisal tool consisting of a search filter appraisal checklist and a structured abstract. ISSG members tested the final checklist using three published search filters. RESULTS: The detailed ISSG Search Filter Appraisal Checklist captures relevance criteria and methods used to develop and test search filters. The checklist includes categorical and descriptive responses and is accompanied by a structured abstract that provides a summary of key quality features of a filter. DISCUSSION: The checklist is a comprehensive appraisal tool that can assist health sciences librarians and others in choosing search filters. The checklist reports filter design methods and search performance measures, such as sensitivity and precision. The checklist can also aid filter developers by indicating information on core methods that should be reported to help assess filter suitability. The generalizability of the checklist for non-methods filters remains to be explored.

Locating systematic reviews of test accuracy studies: how five specialist review databases measure up.

OBJECTIVES: The aim of this study was to examine location of systematic reviews of test accuracy in five specialist review databases: York CRD's DARE and HTA databases, Medion (University of Maastricht), C-EBLM (International Federation of Clinical Chemistry), and the ARIF in-house database (University of Birmingham). METHODS: Searches were limited to the period 1996-2006. Test accuracy reviews were located using in-house diagnostic search filters and with help from database producers where databases were not confined to test accuracy reviews. References were coded according to disease area, review purpose, and test application. Ease of use, volume, overlap, and content of databases was noted. RESULTS: A large degree of overlap existed between databases. Medion contained the largest number (n = 672) and the largest number of unique (n = 328) test accuracy references. A combination of three databases identified only 76% of test reviews. All databases were rated as easy to search but varied with respect to timeliness and compatibility with reference management software. Most reviews evaluated test accuracy (85%) but the HTA database had a larger proportion of cost-effectiveness and screening reviews and C-EBLM more reviews addressing early test development. Most reviews were conducted in secondary care settings. CONCLUSIONS: Specialist review databases offer an essential addition to general bibliographic databases where application of diagnostic method filters can compromise search sensitivity. Important differences exist between databases in terms of ease of use and content. Our findings raise the question whether the current balance of research setting, in particular the predominance of research on tests used in secondary care, matches the needs of decision makers.