Alexis Llewellyn

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.

A checklist designed to aid consistency and reproducibility of GRADE assessments: development and pilot validation

BackgroundThe grading of recommendation, assessment, development and evaluation (GRADE) approach is widely implemented in health technology assessment and guideline development organisations throughout the world. GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention, but is complex and therefore challenging to apply in a consistent manner.MethodsWe developed a checklist to guide the researcher to extract the data required to make a GRADE assessment. We applied the checklist to 29 meta-analyses of randomised controlled trials on the effectiveness of health care interventions. Two reviewers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome.ResultsFor most (70%) checklist items, there was good agreement between reviewers. The main problems were for items relating to indirectness where considerable judgement is required.ConclusionsThere was consistent agreement between reviewers on most items in the checklist. The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessments, particularly for inexperienced users or in rapid reviews without the resources to conduct assessments by two researchers independently.

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.

HIV testing among men who have sex with men (MSM): systematic review of qualitative evidence

We conducted a systematic review of qualitative evidence relating to the views and attitudes of men who have sex with men (MSM) concerning testing for HIV. Studies conducted in high-income countries (Organisation for Economic Co-operation and Development members) since 1996 were included. Seventeen studies were identified, most of gay or bisexual men. Data were analysed using a thematic analysis methodology. The uncertainty of unknown HIV status is an important motive for testing; however, denial is also a common response to uncertainty. Fear of the consequences of a positive HIV test is widespread and may take several forms. A sense of responsibility towards oneself or ones partner may be a motive for testing. The perception of stigma, from other gay men or from the wider culture, is a barrier to testing. Gay and other MSM have clear preferences regarding testing services, particularly for those that are community based, include non-judgemental and gay-positive service providers, and offer a high degree of confidentiality.

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.

Screening for poststroke major depression: a meta-analysis of diagnostic validity studies

Background Major depression is common in stroke patients and associated with increased rates of disability and mortality. Identifying depression may improve mental and physical health. The aim of this review was to determine the most accurate tool for detecting poststroke depression. Methods Seven databases were searched up to November 2012. Two authors selected studies using International Classification of Disease or Diagnostic and Statistical Manual diagnosis of depression as the reference standard. Two authors extracted data and assessed methodological quality. Included studies were synthesised using meta-analyses. Results A total of 24 included studies provided data on 2907 participants. The Center of Epidemiological Studies-Depression Scale (CESD) (sensitivity: 0.75; 95% CI 0.60 to 0.85; specificity: 0.88; 95% CI 0.71 to 0.95), the Hamilton Depression Rating Scale (HDRS) (sensitivity: 0.84; 95% CI 0.75 to 0.90; specificity:0.83; 95% CI 0.72 to 0.90) and the Patient Health Questionnaire (PHQ)-9 (sensitivity: 0.86; 95% CI 0.70 to 0.94; specificity: 0.79; 95% CI 0.60 to 0.90) appeared to be the optimal measures for screening measures. However, the clinical utility of all tools was modest for case-finding. Interpretation There are a number of possible instruments that may help in screening for poststroke depression but none are satisfactory for case-finding. Preliminary data suggests the CESD, HDRS or the PHQ-9 as the most promising options. Although it should be noted such scales should not be used in isolation but followed up with a more detailed clinical assessment. While there is promising data for the PHQ-2 in other populations, it performed less well than other measures.

Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation

BACKGROUND Allergic asthma is a long-term disorder of the airways resulting from overexpression of immunoglobulin E (IgE) in response to environmental allergens. Patients with poorly controlled asthma are at high risk of exacerbations requiring additional treatment, including hospitalisations. Severe exacerbations are potentially life threatening. Guidelines identify five treatment steps for both adults and children. Omalizumab (Xolair(®)) is a recombinant DNA-derived humanised monoclonal antibody indicated as an add-on therapy in patients aged ≥ 6 years with severe persistent allergic asthma uncontrolled at treatment step 4 or 5. OBJECTIVE To determine the clinical effectiveness, safety and cost-effectiveness of omalizumab, as an add-on therapy to standard care, within its licensed indication, compared with standard therapy alone for the treatment of severe persistent allergic asthma in adults and adolescents aged ≥ 12 years and children aged 6-11 years. DATA SOURCES Eleven electronic databases (including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials) and additional sources including regulatory agency reports were searched from inception to October 2011. Additional data sources include: the manufacturers submission (MS); two previous National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) submissions; and existing reviews on the safety of omalizumab and oral corticosteroids (OCSs). REVIEW METHODS Systematic reviews of the clinical effectiveness and cost-effectiveness evidence for omalizumab were performed. The primary outcome was number of clinically significant (CS) exacerbations. Other outcomes included asthma symptoms, unscheduled health-care use, asthma-related mortality, OCS use and health-related quality of life (HRQoL). Because of methodological and clinical heterogeneity between trials, a narrative synthesis was applied. Pragmatic reviews with best evidence syntheses were used to assess adverse events of omalizumab and OCSs. The cost-effectiveness of omalizumab was assessed from the perspective of the UK NHS in the two separate populations: adults and adolescents, and children, using a cohort Markov model. Costs and outcomes were discounted at 3.5% per annum. Results are presented for additional subgroup populations: (1) hospitalised for asthma in the previous year, (2) adults and adolescents on maintenance OCSs and (3) three or more exacerbations in the previous year. RESULTS Eleven randomised controlled trials (RCTs) and 13 observational studies were identified, including four RCTs/subgroups in the adult licensed population and one subgroup in children. A minority of patients were on maintenance OCSs. No evidence comparing omalizumab with OCSs was identified. Omalizumab significantly reduced the incidence of CS exacerbations in both adults and children [adults: INvestigatioN of Omalizumab in seVere Asthma Trial (INNOVATE): rate ratio 0.74; 95% CI 0.55 to 1.00; children IA-05 EUP (the a priori subgroup of patients who met the European Medicines Agency license criteria) 0.66; 95% CI 0.44 to 1.00]. Significant benefits were observed for a range of other outcomes in adults. Subgroup evidence showed benefits in adults on maintenance OCSs. Evidence for an OCS-sparing effect of omalizumab was limited but consistent. Omalizumab is available as 75 mg and 150 mg prefilled syringes at prices of £128.07 and £256.15 respectively. The incremental cost-effectiveness ratio (ICER) for adults and adolescents is £83,822 per quality-adjusted life-year (QALY) gained, whereas the ICER for children is £78,009 per QALY gained. The results are similar for the subgroup population of ≥ 3 exacerbations in the previous year, whereas the ICER for the other subgroup populations are lower; £46,431 for the hospitalisation subgroup in adults and adolescents, £44,142 for the hospitalisation subgroup in children and £50,181 for the maintenance OCS subgroup. CONCLUSION Omalizumab reduces the incidence of CS exacerbations in adults and children, with benefits on other outcomes in adults. Limited, underpowered subgroup evidence exists that omalizumab reduces exacerbations and OCS requirements in adults on OCSs. Evidence in children is weaker and more uncertain. The ICERs are above conventional NHS thresholds of cost-effectiveness. The key drivers of cost-effectiveness are asthma-related mortality risk and, to a lesser extent, HRQoL improvement and OCS-related adverse effects. An adequately powered double-blind RCT in both adults and children on maintenance OCSs and an individual patient data meta-analysis of existing trials should be considered. A registry of all patients on omalizumab should be established. STUDY REGISTRATION The study was registered as PROSPERO CRD42011001625. FUNDING This report was commissioned by the National Institute for Health Research Health Technology Assessment programme on behalf of NICE as project number HTA 10/128/01.

Interventions for adult Eustachian tube dysfunction: a systematic review.

BACKGROUND Eustachian tube dysfunction (ETD) is the inability of the Eustachian tube (ET) to adequately perform at least one of its functions: to protect the middle ear from sources of disease, to ventilate the middle ear, and to help drain secretions away from the middle ear. There are a number of treatment options for ETD, but there is little consensus about management. OBJECTIVES To determine the clinical effectiveness of interventions for adult ETD and to identify gaps in the evidence to inform future research. DATA SOURCES Twelve databases were searched up to October 2012 for published and unpublished studies in English (e.g. MEDLINE from 1946, EMBASE from 1974, Biosis Previews from 1969 and Cumulative Index to Nursing and Allied Health Literature from inception). References of included studies, relevant systematic reviews and regulatory agency websites were checked. REVIEW METHODS A systematic review was undertaken. Controlled studies evaluating prespecified treatments for adult patients diagnosed with ETD were eligible. Uncontrolled studies with at least 10 participants were included for interventions where no controlled studies were found. Outcomes included change in symptoms severity/frequency (primary outcome), quality of life, middle ear function, hearing, clearance of middle ear effusion, early ventilation tube extrusion, additional treatment, adverse events and complications. All aspects of the review process were performed using methods to reduce reviewer error and bias. Owing to heterogeneous data, a quantitative synthesis could not be performed, and results were reported in a narrative synthesis. RESULTS Nineteen studies were included: three randomised controlled trials (RCTs) and two non-RCTs evaluating pharmacological interventions or mechanical devices for middle ear pressure equalisation; and 13 case series and one retrospective controlled before-and-after study evaluating surgical interventions. None was conducted in the UK. All studies were small (11 to 108 participants). Most non-surgical studies reported including mixed populations of adults and children. All except two studies were at high risk of bias, and subject to multiple limitations. Based on a single RCT, nasal steroids showed no improvement in symptoms or middle ear function for patients with otitis media with effusion and/or negative middle ear pressure. Very short-term improvements in middle ear function were observed in patients receiving directly applied topical decongestants or a combination of antihistamine and ephedrine. Single trials found two pressure equalisation devices were each associated with significant short-term improvements in symptoms, middle ear function and/or hearing. Eustachian tuboplasty (seven case series) and balloon dilatation (three case series) were associated with improved outcomes. Positive results were also reported for myringotomy (two case series), directly applied topical steroids (one case series) and laser point coagulation (one controlled before-and-after study). High rates of co-interventions were documented. Minor complications of surgery and pharmacological treatments but no serious adverse effects were reported. LIMITATIONS The evidence was limited in quantity and overall was of poor quality. No data were identified on several interventions despite extensive searches. CONCLUSIONS It is not possible to draw conclusions regarding the effectiveness of any of the interventions for the treatment of adults with an ETD diagnosis, and there is insufficient evidence to recommend a trial of any particular intervention. Further research is needed to address lack of consensus on several issues, including the definition of ETD in adults, its relation to broader middle ear ventilation problems and clear diagnostic criteria. STUDY REGISTRATION This study is registered as PROSPERO CRD42012003035. FUNDING The National Institute for Health Research Health Technology Assessment programme.

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

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.

Simple tests for the diagnosis of childhood obesity: a systematic review and meta‐analysis

There is a need to accurately quantify levels of adiposity in order to identify overweight and obesity in children. This systematic review aimed to identify all diagnostic accuracy studies evaluating simple tests for obesity and adiposity, including body mass index (BMI), skin‐fold thickness and waist circumference, compared against high‐quality reference tests. Twenty‐four cohort studies including 25,807 children were included. BMI had good performance when diagnosing obesity: a sensitivity of 81.9% (95% confidence interval [CI]: 73.0 to 93.8) for a specificity of 96.0% (95% CI: 93.8 to 98.1). It was less effective at diagnosing overweight (sensitivity: 76.3%, 95% CI: 70.2 to 82.4; specificity: 92.1% 95% CI: 90.0 to 94.3). When diagnosing obesity, waist circumference had similar performance (sensitivity: 83.8%; specificity: 96.5%). Skin‐fold thickness had slightly poorer performance (sensitivity: 72.5%; specificity: 93.7%). Few studies considered any other tests. There was no conclusive evidence that any test was generally superior to the others. BMI is a good simple diagnostic test for identifying childhood adiposity. It identifies most genuinely obese and adipose children while misclassifying only a small number as obese. There was no conclusive evidence that any test should be preferred to BMI, and the extra complexity of skin‐fold thickness tests does not appear to improve diagnostic accuracy.