Acupuncture and other physical treatments for the relief of pain due to osteoarthritis of the knee: network meta-analysis.

OBJECTIVE: To compare the effectiveness of acupuncture with other relevant physical treatments for alleviating pain due to knee osteoarthritis. DESIGN: Systematic review with network meta-analysis, to allow comparison of treatments within a coherent framework. Comprehensive searches were undertaken up to January 2013 to identify randomised controlled trials in patients with osteoarthritis of the knee, which reported pain. RESULTS: Of 156 eligible studies, 114 trials (covering 22 treatments and 9,709 patients) provided data suitable for analysis. Most trials studied short-term effects and many were classed as being of poor quality with high risk of bias, commonly associated with lack of blinding (which was sometimes impossible to achieve). End of treatment results showed that eight interventions: interferential therapy, acupuncture, TENS, pulsed electrical stimulation, balneotherapy, aerobic exercise, sham acupuncture, and muscle-strengthening exercise produced a statistically significant reduction in pain when compared with standard care. In a sensitivity analysis of satisfactory and good quality studies, most studies were of acupuncture (11 trials) or muscle-strengthening exercise (9 trials); both interventions were statistically significantly better than standard care, with acupuncture being statistically significantly better than muscle-strengthening exercise (standardised mean difference: 0.49, 95% credible interval 0.00-0.98). CONCLUSIONS: As a summary of the current available research, the network meta-analysis results indicate that acupuncture can be considered as one of the more effective physical treatments for alleviating osteoarthritis knee pain in the short-term. However, much of the evidence in this area of research is of poor quality, meaning there is uncertainty about the efficacy of many physical treatments.

Growth monitoring for short stature: update of a systematic review and economic model.

OBJECTIVES: The aim of the project was to compare different screening rules and/or referral cut-offs for the identification of children with disorders of short stature. We undertook an update of a previous systematic review and economic model that addressed the same question. DATA SOURCES: Sources searched included MEDLINE, EMBASE, Science Citation Index, Social Science Citation Index, Conference Proceedings Citation Index - Science/Social Science & Humanities, Cochrane Library 2009 Issue 4, Office of Health Economics Health Economic Evaluations Database, and the NHS Economic Evaluation Database. REVIEW METHODS: The review was conducted as an update to our previous assessment in 2007. Searching covered January 2005 to November 2009 with no language or publication restrictions. Two reviewers examined full papers for relevance. Data extraction was conducted by one reviewer and independently checked by a second. In addition, searches were conducted to identify quality of life or utility papers to inform the economic evaluation. We developed a probabilistic decision analytic model to estimate the costs and quality-adjusted life-year (QALY) gains from the perspective of the UK NHS and personal social services. The model was a cohort model, assuming a homogeneous population of 5-year-olds at baseline. RESULTS: One study was included in the systematic review. The study was not UK based, but had been identified in the brief as relevant to the UK setting. The study's authors examined the performance of a number of rules to determine sensitivity and specificity of referral for short stature in four patient groups and three reference groups in the Netherlands. They derived an algorithm for referral based on the optimal rules. No new studies were located that provided appropriate quality of life or utilities data for the economic model. The model was based on the previous assessment which was updated to better reflect current UK clinical practice. We compared two alternative monitoring strategies, one of which was based on the study identified in our systematic review (Grote strategy); the other was based on UK consensus (UK strategy). We identified that the UK strategy was the least effective and least costly, with a mean gain of 0.001 QALYs at a mean cost of £21. The Grote strategy was both more expensive and more effective, with a mean cost of £68 and a mean QALY gain of 0.042. The incremental cost-effectiveness ratio was £1144 per QALY gained. CONCLUSIONS: This assessment contributes further knowledge, but does not provide definitive answers on how to deliver growth monitoring. In particular, we were unable to ascertain current practice in the UK for growth screening. Further, we were unable to evaluate through the use of identified studies and modelling an optimal referral cut-off and age at which to screen. We identified a number of research questions that would further inform referral strategies, which in summary would involve further primary and secondary data collection. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A systematic review of photodynamic therapy in the treatment of pre-cancerous skin conditions, Barrett's oesophagus and cancers of the biliary tract, brain, head and neck, lung, oesophagus and skin.

BACKGROUND: Photodynamic therapy (PDT) is the use of a light-sensitive drug, in combination with light of a visible wavelength, to destroy target cells. PDT is used either as a primary treatment or as an adjunctive treatment. It is fairly well accepted in clinical practice for some types of skin cancer but has yet to be fully explored as a treatment for other forms of cancer. OBJECTIVE: To systematically review the clinical effectiveness and safety of PDT in the treatment of Barrett's oesophagus, pre-cancerous skin conditions and the following cancers: biliary tract, brain, head and neck, lung, oesophageal and skin. DATA SOURCES: The search strategy included searching electronic databases (between August and October 2008), followed by update searches in May 2009, along with relevant bibliographies, existing reviews, conference abstracts and contact with experts in the field. STUDY DESIGNS: Randomised controlled trials (RCTs) in skin conditions and Barrett's oesophagus, non-randomised trials for all other sites. PARTICIPANTS: People with Barrett's oesophagus, pre-cancerous skin conditions or primary cancer in the following sites: biliary tract, brain, head and neck, lung, oesophageal and skin. INTERVENTION: Any type of PDT for either curative or palliative treatment. COMPARATORS: Any comparator including differing applications of PDT treatments (relevant comparators varied according to the condition). MAIN OUTCOMES: The outcomes measured were mortality, morbidity, quality of life, adverse events and resource use. REVIEW METHODS: A standardised data extraction form was used. The quality of RCTs and non-randomised controlled studies was assessed using standard checklists. Data extracted from the studies were tabulated and discussed in a narrative synthesis, and the influence of study quality on results was discussed. Meta-analysis was used to estimate a summary measure of effect on relevant outcomes, with assessment of both clinical and statistical heterogeneity. Two reviewers independently screened all titles and abstracts, and data extracted and quality assessed the trials, with discrepancies resolved by discussion or referral to a third reviewer. A scoping review was also undertaken. RESULTS: Overall, 88 trials reported in 141 publications were included, with some trials covering more than one condition. For actinic keratosis (AK), the only clear evidence of effectiveness was that PDT appeared to be superior to placebo. For Bowen's disease, better outcomes with PDT were suggested when compared with cryotherapy or fluorouracil. For basal cell carcinoma (BCC), PDT may result in similar lesion response rates to surgery or cryotherapy but with better cosmetic outcomes. For nodular lesions, PDT appeared to be superior to placebo and less effective than surgery but suggestive of better cosmetic outcome. For Barrett's oesophagus, PDT in addition to omeprazole appeared to be more effective than omeprazole alone at long-term ablation of high-grade dysplasia and slowing/preventing progression to cancer. No firm conclusions could be drawn for PDT in oesophageal cancer. Further research into the role of PDT in lung cancer is needed. For cholangiocarcinoma, PDT may improve survival when compared with stenting alone. There was limited evidence on PDT for brain cancer and cancers of the head and neck. A wide variety of photosensitisers were used and, overall, no serious adverse effects were linked to PDT. LIMITATIONS: There were few well-conducted, adequately powered RCTs, and quality of life (QoL) and resource outcomes were under-reported. Problems were identified with reporting of key study features and quality parameters, making the reliability of some studies uncertain. Methodological limitations and gaps in the evidence base made it difficult to draw firm conclusions. CONCLUSIONS: Evidence of effectiveness was found for PDT in the treatment of AK and nodular BCC in relation to placebo, and possibly for treating Barrett's oesophagus. However, the effectiveness of PDT in relation to other treatments is not yet apparent. High-quality trials are needed to compare PDT with relevant comparators for all meaningful outcomes, including QoL and adverse effects. Further research is also needed on patient experience of PDT, as well as on the cost-effectiveness of PDT.

Use of non-randomised evidence alongside randomised trials in a systematic review of endovascular aneurysm repair: strengths and limitations.

OBJECTIVE: To assess whether limitations of randomised controlled trials (RCTs) of endovascular aneurysm repair (EVAR) can be addressed by evidence from non-randomised studies. DESIGN: Analysis of data from a systematic review. METHODS: We conducted a review of EVAR versus open repair or non-surgical management of abdominal aortic aneurysms. In addition to RCTs, we included pre-specified registries of EVAR and open repair. RESULTS: The six included RCTs randomised patients in 2003 and earlier. Of the three registries included, one contributed data on a large (>8000) sample of patients treated with newer generation EVAR devices and followed up for up to 8 years. However, treatment dates of these patients overlapped with those of the RCTs. The other registries were of limited usefulness. A large (>45,000) controlled observational study published while the review was in progress broadly supported the findings of RCTs comparing EVAR with open surgery. A comparison of outcomes across all studies did not support the hypothesis that the findings of the RCTs are no longer representative of clinical practice. CONCLUSIONS: Both randomised and non-randomised sources of evidence have strengths and weaknesses for assessing the effectiveness of EVAR. Further research should explore the optimum use of registry data, including patient-level analyses.

Endovascular stents for abdominal aortic aneurysms: a systematic review and economic model.

OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms (AAAs) in patients at varying levels of risk. DATA SOURCES: The following bibliographic databases were searched (2005-February 2007): BIOSIS Previews, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ISI Proceedings, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Science Citation Index and Zetoc Conferences. REVIEW METHODS: A systematic review of the clinical effectiveness of EVAR was performed using standard methods. Meta-analysis was employed to estimate a summary measure of treatment effect on relevant outcomes based on intention to treat analyses. A second systematic review was undertaken to identify existing cost-effectiveness analyses of EVAR compared with open surgery and non-surgical interventions. Two new decision models were developed to inform the review. RESULTS: Six RCTs were included in the clinical effectiveness review. Thirty-four studies evaluated the role of patients' baseline characteristics in predicting risks of particular outcomes after EVAR. The majority were based on data relating to devices in current use from the EUROSTAR registry. Compared with open repair EVAR reduces operative mortality (odds ratio 0.35, 95% CI 0.19 to 0.63) and medium-term aneurysm-related mortality (hazard ratio 0.49, 95% CI 0.29 to 0.83) but offers no significant difference in all-cause mortality. EVAR is associated with increased rates of complications and reinterventions, which are not offset by any increase in health-related quality of life. EVAR trial 2 comparing EVAR with non-surgical management in patients unfit for open repair found no differences in mortality between groups; however, substantial numbers of patients randomised to non-surgical management crossed over to receive surgical repair of their aneurysm. The cost-effectiveness systematic review identified six published decision models. Both models considered relevant for the decision in the UK concluded that EVAR was not cost-effective on average compared with open repair at a threshold of 20,000 pounds per quality-adjusted life-year (QALY). Another model concluded that EVAR would be on average more cost-effective than no surgical intervention in unfit patients at this threshold. The Medtronic model concluded that EVAR was more cost-effective than open repair for fit patients at this threshold. The York economic evaluations found that EVAR is not cost-effective compared with open repair on average at a threshold of 30,000 pounds per QALY, with the results very sensitive to model assumptions and the baseline risk of operative mortality. Exploratory analysis to evaluate management options in patients unsuitable for open surgery suggested that the cost-effectiveness of EVAR may be sensitive to aneurysm size and patient's age at operation. Indicative modelling suggests that EVAR may be cost-effective for small aneurysms in some patient groups. Ongoing RCTs will provide further evidence relating to these patients. CONCLUSION: Open repair is more likely to be cost-effective than EVAR on average in patients considered fit for open surgery. EVAR is likely to be more cost-effective than open repair for a subgroup of patients at higher risk of operative mortality. These results are based on extrapolation of mid-term results of clinical trials. Evidence does not currently support EVAR for the treatment of ruptured aneurysms. Further follow-up of the existing UK trials should be undertaken and the relative costs of procedures and devices should be investigated further.

Population tobacco control interventions and their effects on social inequalities in smoking: systematic review.

OBJECTIVE: To assess the effects of population tobacco control interventions on social inequalities in smoking. DATA SOURCES: Medical, nursing, psychological, social science and grey literature databases, bibliographies, hand-searches and contact with authors. STUDY SELECTION: Studies were included (n = 84) if they reported the effects of any population-level tobacco control intervention on smoking behaviour or attitudes in individuals or groups with different demographic or socioeconomic characteristics. DATA EXTRACTION: Data extraction and quality assessment for each study were conducted by one reviewer and checked by a second. DATA SYNTHESIS: Data were synthesised using graphical ("harvest plot") and narrative methods. No strong evidence of differential effects was found for smoking restrictions in workplaces and public places, although those in higher occupational groups may be more likely to change their attitudes or behaviour. Smoking restrictions in schools may be more effective in girls. Restrictions on sales to minors may be more effective in girls and younger children. Increasing the price of tobacco products may be more effective in reducing smoking among lower-income adults and those in manual occupations, although there was also some evidence to suggest that adults with higher levels of education may be more price-sensitive. Young people aged under 25 are also affected by price increases, with some evidence that boys and non-white young people may be more sensitive to price. CONCLUSIONS: Population-level tobacco control interventions have the potential to benefit more disadvantaged groups and thereby contribute to reducing health inequalities.

Effectiveness and cost-effectiveness of height-screening programmes during the primary school years: a systematic review.

OBJECTIVE: To determine the effectiveness and cost-effectiveness of height screening (of children aged 4 to 11) to identify height-related conditions. DESIGN: Systematic review and economic modelling. SETTING AND INTERVENTION: We included published and unpublished screening studies of any design, except case reports, conducted in any setting that measured children's height as part of a population-level assessment. Studies were identified by electronic database searches, contact with experts and from bibliographies of retrieved studies. PARTICIPANTS: Children aged between 4 and 11 years. OUTCOME MEASURES: Diagnostic yield of height-related conditions and change in quality of life, as measured by quality-adjusted life years (QALYs), for early versus late treatment of underlying conditions. RESULTS: Twelve studies described a height-screening programme and provided data on the diagnostic yield of newly diagnosed height-related conditions. Where reported, yield for growth-hormone deficiency (per 1000 children screened) ranged from 0.05 (1 in 20,000) to 0.62 (approximately 1 in 1500) and for Turner syndrome (per 1000 children screened) was between 0.02 (1 in 50,000) and 0.07 (approximately 1 in 14,000). As a secondary gain, children with other potentially treatable conditions were identified; diagnostic yields ranged from 0.22 to 1.84 per 1000 children screened. Three studies did not detect any new cases, but all of these studies had methodological limitations. Economic modelling suggested that height screening is associated with health improvements and is cost effective for a willingness to pay threshold of pound 30,000 per QALY. CONCLUSIONS: This review indicates the utility and acceptable cost-effectiveness of height screening arising from increased detection of height-related disorders and secondary pick-up of other undiagnosed conditions. Further research is needed to obtain more reliable data on quality of life gains and costs associated with early interventions for height-related conditions. The exact role of height-screening programmes in improving child health remains to be determined.

A systematic review of the routine monitoring of growth in children of primary school age to identify growth-related conditions.

OBJECTIVES: To clarify the role of growth monitoring in primary school children, including obesity, and to examine issues that might impact on the effectiveness and cost-effectiveness of such programmes. DATA SOURCES: Electronic databases were searched up to July 2005. Experts in the field were also consulted. REVIEW METHODS: Data extraction and quality assessment were performed on studies meeting the review's inclusion criteria. The performance of growth monitoring to detect disorders of stature and obesity was evaluated against National Screening Committee (NSC) criteria. RESULTS: In the 31 studies that were included in the review, there were no controlled trials of the impact of growth monitoring and no studies of the diagnostic accuracy of different methods for growth monitoring. Analysis of the studies that presented a 'diagnostic yield' of growth monitoring suggested that one-off screening might identify between 1:545 and 1:1793 new cases of potentially treatable conditions. Economic modelling suggested that growth monitoring is associated with health improvements [incremental cost per quality-adjusted life-year (QALY) of 9500 pounds] and indicated that monitoring was cost-effective 100% of the time over the given probability distributions for a willingness to pay threshold of 30,000 pounds per QALY. Studies of obesity focused on the performance of body mass index against measures of body fat. A number of issues relating to human resources required for growth monitoring were identified, but data on attitudes to growth monitoring were extremely sparse. Preliminary findings from economic modelling suggested that primary prevention may be the most cost-effective approach to obesity management, but the model incorporated a great deal of uncertainty. CONCLUSIONS: This review has indicated the potential utility and cost-effectiveness of growth monitoring in terms of increased detection of stature-related disorders. It has also pointed strongly to the need for further research. Growth monitoring does not currently meet all NSC criteria. However, it is questionable whether some of these criteria can be meaningfully applied to growth monitoring given that short stature is not a disease in itself, but is used as a marker for a range of pathologies and as an indicator of general health status. Identification of effective interventions for the treatment of obesity is likely to be considered a prerequisite to any move from monitoring to a screening programme designed to identify individual overweight and obese children. Similarly, further long-term studies of the predictors of obesity-related co-morbidities in adulthood are warranted. A cluster randomised trial comparing growth monitoring strategies with no growth monitoring in the general population would most reliably determine the clinical effectiveness of growth monitoring. Studies of diagnostic accuracy, alongside evidence of effective treatment strategies, could provide an alternative approach. In this context, careful consideration would need to be given to target conditions and intervention thresholds. Diagnostic accuracy studies would require long-term follow-up of both short and normal children to determine sensitivity and specificity of growth monitoring.