Nerys Woolacott

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.

Predicting adult obesity from childhood obesity: a systematic review and meta-analysis

A systematic review and meta‐analysis was performed to investigate the ability of simple measures of childhood obesity such as body mass index (BMI) to predict future obesity in adolescence and adulthood. Large cohort studies, which measured obesity both in childhood and in later adolescence or adulthood, using any recognized measure of obesity were sought. Study quality was assessed. Studies were pooled using diagnostic meta‐analysis methods. Fifteen prospective cohort studies were included in the meta‐analysis. BMI was the only measure of obesity reported in any study, with 200,777 participants followed up. Obese children and adolescents were around five times more likely to be obese in adulthood than those who were not obese. Around 55% of obese children go on to be obese in adolescence, around 80% of obese adolescents will still be obese in adulthood and around 70% will be obese over age 30. Therefore, action to reduce and prevent obesity in these adolescents is needed. However, 70% of obese adults were not obese in childhood or adolescence, so targeting obesity reduction solely at obese or overweight children needs to be considered carefully as this may not substantially reduce the overall burden of adult obesity.

Psychosocial interventions for the prevention of relapse in bipolar disorder: systematic review of controlled trials.

BACKGROUND Pharmacological interventions alone do not provide sufficient benefit for some individuals with bipolar disorder. AIMS To determine the effectiveness of psychosocial interventions for the prevention of relapse in bipolar disorder. METHOD A systematic review and meta-analysis of randomised or quasi-randomised controlled trials were conducted. RESULTS Cognitive-behavioural therapy or group psychoeducation may be effective for relapse prevention in stable individuals. Family therapy was no more or less effective than individual psychosocial therapy or crisis management. There is no evidence that care management or integrated group therapy is effective in the prevention of relapse. CONCLUSIONS Cognitive-behavioural therapy, group psychoeducation and possibly family therapy may be beneficial as adjuncts to pharmacological maintenance treatments.

Ultrasonography in screening for developmental dysplasia of the hip in newborns: systematic review

Abstract Objective To assess the accuracy and effectiveness of the screening of all newborn infants for developmental dysplasia of the hip (DDH) using ultrasound imaging, as is standard practice in some European countries but not in the United Kingdom, the United States, or Scandinavia. Design Systematic review. Data sources Twenty three medical, economic, and grey literature databases (to March 2004), with no limitations of design or language; some references were provided by experts. Selection of studies Only diagnostic accuracy studies and comparative studies conducted in an unselected newborn population were eligible for the review. Two reviewers independently selected the studies and performed the quality assessment. Results The review identified one diagnostic accuracy study, and this was of limited quality. In this study the reference standard was treatment up to age of 8 months or an abnormal ultrasound finding at age 8 months. Ultrasound screening had a sensitivity of 88.5% (95% confidence interval 84.1% to 92.1%), specificity of 96.7% (96.4% to 97.4%), a positive predictive value of 61.6% and a negative predictive value of 99.4%. Ten studies evaluated the impact of ultrasound in screening, but these too had various methodological weaknesses, limiting the reliability of their findings. Compared with clinical screening, general ultrasound screening in newborns may increase overall treatment rates, but ultrasound screening seems to be associated with shorter and less intrusive treatment. Conclusions Clear evidence is lacking either for or against general ultrasound screening of newborn infants for DDH. Studies that investigate the natural course of the disorder, the optimal treatment for DDH, and the best strategy for ultrasound screening are needed.

Childhood obesity as a predictor of morbidity in adulthood: a systematic review and meta‐analysis

Obese children are at higher risk of being obese as adults, and adult obesity is associated with an increased risk of morbidity. This systematic review and meta‐analysis investigates the ability of childhood body mass index (BMI) to predict obesity‐related morbidities in adulthood. Thirty‐seven studies were included. High childhood BMI was associated with an increased incidence of adult diabetes (OR 1.70; 95% CI 1.30–2.22), coronary heart disease (CHD) (OR 1.20; 95% CI 1.10–1.31) and a range of cancers, but not stroke or breast cancer. The accuracy of childhood BMI when predicting any adult morbidity was low. Only 31% of future diabetes and 22% of future hypertension and CHD occurred in children aged 12 or over classified as being overweight or obese. Only 20% of all adult cancers occurred in children classified as being overweight or obese. Childhood obesity is associated with moderately increased risks of adult obesity‐related morbidity, but the increase in risk is not large enough for childhood BMI to be a good predictor of the incidence of adult morbidities. This is because the majority of adult obesity‐related morbidity occurs in adults who were of healthy weight in childhood. Therefore, targeting obesity reduction solely at obese or overweight children may not substantially reduce the overall burden of obesity‐related disease in adulthood.

Stapled haemorrhoidopexy for the treatment of haemorrhoids: a systematic review

Objective  This systematic review aimed to evaluate the short‐ and long‐term safety, efficacy and costs of stapled haemorrhoidopexy (SH) compared with conventional haemorrhoidectomy.

The use of measures of obesity in childhood for predicting obesity and the development of obesity-related diseases in adulthood: a systematic review and meta-analysis

BACKGROUND It is uncertain which simple measures of childhood obesity are best for predicting future obesity-related health problems and the persistence of obesity into adolescence and adulthood. OBJECTIVES To investigate the ability of simple measures, such as body mass index (BMI), to predict the persistence of obesity from childhood into adulthood and to predict obesity-related adult morbidities. To investigate how accurately simple measures diagnose obesity in children, and how acceptable these measures are to children, carers and health professionals. DATA SOURCES Multiple sources including MEDLINE, EMBASE and The Cochrane Library were searched from 2008 to 2013. METHODS Systematic reviews and a meta-analysis were carried out of large cohort studies on the association between childhood obesity and adult obesity; the association between childhood obesity and obesity-related morbidities in adulthood; and the diagnostic accuracy of simple childhood obesity measures. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and a modified version of the Quality in Prognosis Studies (QUIPS) tool. A systematic review and an elicitation exercise were conducted on the acceptability of the simple measures. RESULTS Thirty-seven studies (22 cohorts) were included in the review of prediction of adult morbidities. Twenty-three studies (16 cohorts) were included in the tracking review. All studies included BMI. There were very few studies of other measures. There was a strong positive association between high childhood BMI and adult obesity [odds ratio 5.21, 95% confidence interval (CI) 4.50 to 6.02]. A positive association was found between high childhood BMI and adult coronary heart disease, diabetes and a range of cancers, but not stroke or breast cancer. The predictive accuracy of childhood BMI to predict any adult morbidity was very low, with most morbidities occurring in adults who were of healthy weight in childhood. Predictive accuracy of childhood obesity was moderate for predicting adult obesity, with a sensitivity of 30% and a specificity of 98%. Persistence of obesity from adolescence to adulthood was high. Thirty-four studies were included in the diagnostic accuracy review. Most of the studies used the least reliable reference standard (dual-energy X-ray absorptiometry); only 24% of studies were of high quality. The sensitivity of BMI for diagnosing obesity and overweight varied considerably; specificity was less variable. Pooled sensitivity of BMI was 74% (95% CI 64.2% to 81.8%) and pooled specificity was 95% (95% CI 92.2% to 96.4%). The acceptability to children and their carers of BMI or other common simple measures was generally good. LIMITATIONS Little evidence was available regarding childhood measures other than BMI. No individual-level analysis could be performed. CONCLUSIONS Childhood BMI is not a good predictor of adult obesity or adult disease; the majority of obese adults were not obese as children and most obesity-related adult morbidity occurs in adults who had a healthy childhood weight. However, obesity (as measured using BMI) was found to persist from childhood to adulthood, with most obese adolescents also being obese in adulthood. BMI was found to be reasonably good for diagnosing obesity during childhood. There is no convincing evidence suggesting that any simple measure is better than BMI for diagnosing obesity in childhood or predicting adult obesity and morbidity. Further research on obesity measures other than BMI is needed to determine which is the best tool for diagnosing childhood obesity, and new cohort studies are needed to investigate the impact of contemporary childhood obesity on adult obesity and obesity-related morbidities. STUDY REGISTRATION This study is registered as PROSPERO CRD42013005711. FUNDING The National Institute for Health Research Health Technology Assessment programme.

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.

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

Summary 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.

EOS 2D/3D X-ray Imaging System: A Systematic Review and Economic Evaluation

BACKGROUND EOS is a biplane X-ray imaging system manufactured by EOS Imaging (formerly Biospace Med, Paris, France). It uses slot-scanning technology to produce a high-quality image with less irradiation than standard imaging techniques. OBJECTIVE To determine the clinical effectiveness and cost-effectiveness of EOS two-dimensional (2D)/three-dimensional (3D) X-ray imaging system for the evaluation and monitoring of scoliosis and other relevant orthopaedic conditions. DATA SOURCES For the systematic review of EOS, electronic databases (MEDLINE, Allied and Complementary Medicine Database, BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, EMBASE, Health Management Information Consortium, Inspec, ISI Science Citation Index and PASCAL), clinical trials registries and the manufacturers website were searched from 1993 to November 2010. REVIEW METHODS A systematic review of studies comparing EOS with standard X-ray [film, computed radiography (CR) or digital radiography] in any orthopaedic condition was performed. A narrative synthesis was undertaken. A decision-analytic model was developed to assess the cost-effectiveness of EOS in the relevant indications compared with standard X-ray and incorporated the clinical effectiveness of EOS and the adverse effects of radiation. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the perspective of the NHS. RESULTS Three studies met the inclusion criteria for the review. Two studies compared EOS with film X-ray and one study compared EOS with CR. The three included studies were small and of limited quality. One study used an earlier version of the technology, the Charpak system. Both studies comparing EOS with film X-ray found image quality to be comparable or better with EOS overall. Radiation dose was considerably lower with EOS: ratio of means for posteroanterior spine was 5.2 (13.1 for the study using the Charpak system); ratio of means for the lateral spine was 6.2 (15.1 for the study using the Charpak system). The study comparing EOS with CR found image quality to be comparable or better with EOS. Radiation dose was considerably lower with EOS than CR; ratio of means for the centre of the back was 5.9 and for the proximal lateral point 8.8. The lowest ratio of means was at the nape of the neck, which was 2.9. No other outcomes were assessed in the included studies, such as implications for patient management from the nature and quality of the image. Patient throughput is the major determinant of the cost-effectiveness of EOS. The average cost per procedure of EOS decreases with utilisation. Using estimates of patient throughput at national level from Hospital Episode Statistics data suggests that EOS is not cost-effective for the indications considered. Throughput in the region of 15,100 to 26,500 (corresponding to a workload of 60 to 106 patient appointments per working day) for EOS compared with a throughput of only 7530 for CR (30 patient appointments per working day) is needed to achieve an incremental cost-effectiveness ratio of £30,000 per QALY. EOS can be shown to be cost-effective only when compared with CR if the utilisation for EOS is about double the utilisation of CR. LIMITATIONS The main limitation of the systematic review of the clinical effectiveness of EOS was the limited number and quality of the data available. In particular, there were no studies assessing the potential health benefits arising from the quality and nature of the image, over and above those associated with reduced radiation exposure. Uncertainty in the model inputs was not fully explored owing to a lack of reporting of standard deviations or confidence intervals in the published literature for most of the parameters. As a result, uncertainty in the cost-effectiveness results was not presented. CONCLUSIONS Radiation dose is considerably lower with EOS than standard X-ray, whereas image quality remains comparable or better with EOS. However, the long-term health benefits from reduced radiation exposure with EOS are very small and there was a lack of data on other potential patient health benefits. The implications of any changes in the quality and nature of the EOS image compared with standard X-ray, for patient health outcomes, needs to be assessed. Given the higher cost of an EOS machine, utilisation is the major determinant of cost-effectiveness. Estimates of patient throughput at national level suggest that EOS is not cost-effective. FUNDING The National Institute for Health Research Health Technology Assessment programme.