Cost-effectiveness of bariatric surgery and non-surgical weight management programmes for adults with severe obesity: a decision analysis model.

OBJECTIVES: To determine the most cost-effective weight management programmes (WMPs) for adults, in England with severe obesity (BMI ≥ 35 kg/m2), who are more at risk of obesity related diseases. METHODS: An economic evaluation of five different WMPs: 1) low intensity (WMP1); 2) very low calorie diets (VLCD) added to WMP1; 3) moderate intensity (WMP2); 4) high intensity (Look AHEAD); and 5) Roux-en-Y gastric bypass (RYGB) surgery, all compared to a baseline scenario representing no WMP. We also compare a VLCD added to WMP1 vs. WMP1 alone. A microsimulation decision analysis model was used to extrapolate the impact of changes in BMI, obtained from a systematic review and meta-analysis of randomised controlled trials (RCTs) of WMPs and bariatric surgery, on long-term risks of obesity related disease, costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) measured as incremental cost per QALY gained over a 30-year time horizon from a UK National Health Service (NHS) perspective. Sensitivity analyses explored the impact of long-term weight regain assumptions on results. RESULTS: RYGB was the most costly intervention but also generated the lowest incidence of obesity related disease and hence the highest QALY gains. Base case ICERs for WMP1, a VLCD added to WMP1, WMP2, Look AHEAD, and RYGB compared to no WMP were £557, £6628, £1540, £23,725 and £10,126 per QALY gained respectively. Adding a VLCD to WMP1 generated an ICER of over £121,000 per QALY compared to WMP1 alone. Sensitivity analysis found that all ICERs were sensitive to the modelled base case, five year post intervention cessation, weight regain assumption. CONCLUSIONS: RYGB surgery was the most effective and cost-effective use of scarce NHS funding resources. However, where fixed healthcare budgets or patient preferences exclude surgery as an option, a standard 12 week behavioural WMP (WMP1) was the next most cost-effective intervention.

A systematic review of UK-based long-term nonsurgical interventions for people with severe obesity (BMI ≥35 kg m-2 ).

INTRODUCTION: The aim of this project was to systematically review UK evidence on the effectiveness of long-term (≥12 months) weight management services (WMSs) for weight loss and weight maintenance for adults (≥16 years) with severe obesity (body mass index ≥35 kg m-2 ), who would generally be eligible for Tier 3 services. METHODS: Four data sources were searched from 1999 to October 2018. RESULTS: Our searches identified 20 studies, mostly noncomparative studies: 10 primary care interventions, nine in secondary care specialist weight management clinics and one commercial setting intervention. A programme including a phase of low energy formula diet (810-833 kcal day-1 ) showed the largest mean (SD) weight change at 12 months of -12.4 (11.4) kg for complete cases, with 25.3% dropout. Limitations or differences in evaluation and reporting (particularly for denominators), unclear dropout rates, and differences between participant groups in terms of comorbidities and psychological characteristics, made comparisons between WMSs and inferences challenging. CONCLUSIONS: There is a persistent and clear need for guidance on long-term weight data collection and reporting methods to allow comparisons across studies and services for participants with severe obesity. Data could also include quality of life, clinical outcomes, adverse events, costs and economic outcomes. A randomised trial comparison of National Health Service Tier 3 services with commercial WMSs would be of value.

Cardiovascular effects of calcium supplementation.

Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27-31% increase in risk of myocardial infarction and a 12-20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and show consistent risk across the trials. The fact that cardiovascular events were not primary endpoints of any of these studies will introduce noise but not bias into the data. A recent re-analysis of the Women's Health Initiative suggests that co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, on the function of vascular cells, and on blood coagulation. Calcium-sensing receptors might mediate some of these effects. Because calcium supplements produce small reductions in fracture risk and a small increase in cardiovascular risk, there may be no net benefit from their use. Food sources of calcium appear to produce similar benefits on bone density, although their effects on fracture are unclear. Since food sources have not been associated with adverse cardiovascular effects, they may be preferable. Available evidence suggests that other osteoporosis treatments are still effective without calcium co-administration.

A qualitative study comparing commercial and health service weight loss groups, classes and clubs.

BACKGROUND: Group-based interventions for weight loss are popular; however, little is known about how health service groups compare with the commercial sector, from either the participant or the group leader perspective. Currently, health professionals have little guidance on how to deliver effective group interventions. The present study aimed to compare and contrast leaders' and attendees' experiences of health service and commercial weight loss groups, through in-depth interviews and group observations. METHODS: Purposive sampling, guided by a sampling frame, was employed to identify diverse groups operating in Scotland with differing content, structures and style. Data collection and analysis took place concurrently in accordance with a grounded theory approach. Thirteen semi-structured group observations and in-depth audio-recorded interviews with 11 leaders and 22 attendees were conducted. Identification of themes and the construction of matrices to identify data patterns were guided by the Framework Method for qualitative analysis. RESULTS: Compared to commercial groups, health service 'groups' or 'classes' tended to offer smaller periodic fixed term groups, involving gatekeeper referral systems. Commercial organisations provide a fixed branded package, for 'club' or 'class' members, and most commercial leaders share personal experiences of losing weight. Health service leaders had less opportunity for supervision, peer support or specific training in how to run their groups compared to commercial leaders. CONCLUSIONS: Commercial and health service groups differ in access; attendee and leader autonomy; engagement in group processes; and approaches to leadership and training, which could influence weight loss outcomes. Health service groups can provide different group content and experiences, particularly for those with chronic diseases and for populations less likely to attend commercial groups, such as men.

Does taking vitamin, mineral and fatty acid supplements prevent cognitive decline? A systematic review of randomized controlled trials.

BACKGROUND: Observational studies have shown associations between nutritional status and cognition in later life but evidence from intervention studies is unclear. The present study systematically reviewed the evidence on the effect of nutrient supplementation on cognitive function in people aged >or=65 years. METHODS: Databases including MEDLINE and EMBASE were searched up to 1 September 2006. Randomized controlled trials using at least one kind of vitamin, mineral or omega-3 fatty acid, evaluating standardized neuropsychological test(s), were included. There were no restrictions on participants' baseline nutritional status or cognitive function. Quality assessment and data abstraction were conducted by one author and checked by another. RESULTS: Of 4229 articles retrieved, 22 trials (3442 participants) were identified. Many were small, short duration and of poor methodology. Only 16 out of 122 cognitive tests were significantly different between groups. A meta-analysis showed no significant effect of taking B vitamins or antioxidant vitamins on global cognitive function. There was insufficient evidence to evaluate the effect of omega-3 fatty acids on any cognitive domains. CONCLUSION: There was little evidence of a beneficial effect from taking B vitamins or antioxidant supplements on global cognitive function in later life. Larger-scale randomized controlled trials of longer duration in selected age groups are needed.

Long-term weight loss effects on all cause mortality in overweight/obese populations.

This systematic review assesses the long-term effectiveness of weight loss on all cause mortality in overweight/obese people. Medline, Embase and Cinahl were searched (1966-2005). Cohort studies and trials on participants with body mass index > or =25 kg m(-2), with weight change and mortality with > or =2-year follow-up, were included finally identifying 11 papers based on eight studies. There may be gender differences in the benefits for all cause mortality. The impact of weight loss in men on mortality was not clear with some studies indicating weight loss to be detrimental, while a recent cohort study showed benefits, if it were a personal decision. Other studies with no gender separation had similarly mixed results. However, one study indicated that overweight/obese women with obesity-related illness, who lost weight intentionally within 1 year, had significantly reduced mortality rates of 19-25%. In contrast, studies of overweight/obese diabetics irrespective of gender showed significant benefit of intentional weight loss on mortality in a meta-analysis, hazard ratios = 0.75 (0.67-0.83). There is some evidence that intentional weight loss has long-term benefits on all cause mortality for women and more so for diabetics. Long-term effects especially for men are not clear and need further investigation.

Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial.

BACKGROUND: Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures. METHODS: In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures. FINDINGS: 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups. INTERPRETATION: The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.

Nutritional supplementation for hip fracture aftercare in older people.

BACKGROUND: Older people with hip fractures are often malnourished at the time of fracture, and have poor food intake subsequently. OBJECTIVES: To review the effects of nutritional interventions in older people recovering from hip fracture. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 1), MEDLINE, six other databases and reference lists. We contacted investigators and handsearched journals. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of nutritional interventions for people aged over 65 years with hip fracture. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, extracted data and assessed trial quality. We sought additional information from trialists, and pooled data for primary outcomes. MAIN RESULTS: Twenty-one randomised trials involving 1727 participants were included. Overall trial quality was poor, specifically regarding allocation concealment, assessor blinding and intention-to-treat analysis, and limited availability of outcome data. Eight trials evaluated oral multinutrient feeds: providing non-protein energy, protein, some vitamins and minerals. Oral feeds had no statistically significant effect on mortality (15/161 versus 17/176; relative risk (RR) 0.89, 95% confidence interval (CI) 0.47 to 1.68) but may reduce 'unfavourable outcome' (combined outcome of mortality and survivors with medical complications) (14/66 versus 26/73; RR 0.52, 95% CI 0.32 to 0.84). Four trials examining nasogastric multinutrient feeding showed no evidence of an effect on mortality (RR 0.99, 95% CI 0.50 to 1.97) but the studies were heterogeneous regarding case mix. Nasogastric feeding was poorly tolerated. There was insufficient information for other outcomes. Increasing protein intake in an oral feed was tested in four trials. There was no evidence for an effect on mortality (RR 1.42, 95% CI 0.85 to 2.37). Protein supplementation may have reduced the number of long term medical complications. Two trials, testing intravenous vitamin B1 and other water soluble vitamins, or 1-alpha-hydroxycholecalciferol (an active form of vitamin D) respectively, produced no evidence of effect for either supplement. One trial, evaluating dietetic assistants to help with feeding, showed a trend for a reduction in mortality (RR 0.57, 99% CI 0.29 to 1.11). AUTHORS' CONCLUSIONS: Some evidence exists for the effectiveness of oral protein and energy feeds, but overall the evidence for the effectiveness of nutritional supplementation remains weak. Adequately sized trials are required which overcome the methodological defects of the reviewed studies. In particular, the role of dietetic assistants requires further evaluation.

Nutritional supplementation for hip fracture aftercare in older people.

BACKGROUND: Fractures of the hip are an important cause of later ill health and mortality in older people. People with hip fractures are often malnourished at the time of fracture, and have poor food intake in hospital. OBJECTIVES: This review assesses the effects of nutritional interventions in older people recovering from hip fracture. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 3, 2004), MEDLINE (1966 to October week 1 2004), Nutrition Abstracts and Reviews, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, the National Research Register and reference lists. We contacted investigators and handsearched four nutrition journals. SELECTION CRITERIA: Randomised and quasi-randomised trials of nutritional interventions for mainly older people (aged over 65 years) with hip fracture. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, extracted data and assessed trial quality. We sought additional information from all trialists, and pooled data for primary outcomes. MAIN RESULTS: Eighteen randomised trials involving 1306 participants were included. Overall trial quality was poor; specifically in terms of allocation concealment, assessor blinding and intention-to-treat analysis. This, and the limited availability of outcome data, mean that the following results must be interpreted with caution. Eight trials evaluated oral multinutrient feeds: these provided non-protein energy, protein, some vitamins and minerals. Oral feeds had no statistically significant effect on mortality (15/161 versus 17/176; relative risk (RR) 0.89, 95% confidence interval (CI) 0.47 to 1.68) but may reduce 'unfavourable outcome' (combined outcome of mortality and survivors with complications) (14/66 versus 26/73; RR 0.52, 95% CI 0.32 to 0.84). Four trials examining nasogastric multinutrient feeding showed no evidence of an effect on mortality (RR 0.99, 95% CI 0.50 to 1.97), but the studies were heterogeneous regarding case mix. There was insufficient information for other outcomes. The specific effect of protein given in an oral feed was tested in three trials. There was no evidence for an effect on mortality (RR 1.38, 95% CI 0.82 to 2.34). Protein supplementation may have reduced the number of long term complications and days spent in rehabilitation wards. Two trials, testing intravenous thiamin (vitamin B1) and other water soluble vitamins, or 1-alpha-hydroxycholecalciferol (an active form of vitamin D) respectively, produced no evidence of effect for either vitamin supplement. AUTHORS' CONCLUSIONS: While some evidence exists for the effectiveness of oral protein and energy feeds, overall the evidence for the effectiveness of nutritional supplementation remains weak. Future trials are required which overcome the defects of the reviewed studies, particularly inadequate size, methodology and outcome assessment.

Protein and energy supplementation in elderly people at risk from malnutrition.

BACKGROUND: Evidence for the effectiveness of nutritional supplements containing protein and energy, which are often prescribed for older people, is limited. Furthermore malnutrition is more common in this age group and deterioration of nutritional status can occur during illness. It is important to establish whether supplementing the diet is an effective way of improving outcomes for older people at risk from malnutrition. OBJECTIVES: This review examined the evidence from trials for improvement in nutritional status and clinical outcomes when extra protein and energy were provided, usually in the form of commercial 'sip-feeds'. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Healthstar, CINAHL, BIOSIS, CAB abstracts. We also hand searched nutrition journals and reference lists and contacted 'sip-feed' manufacturers. Date of most recent search: March 2004. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials of oral protein and energy supplementation in older people with the exception of groups recovering from cancer treatment or in critical care. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials prior to inclusion and independently extracted data and assessed trial quality. Authors of trials were contacted for further information as necessary. MAIN RESULTS: Forty-nine trials with 4790 randomised participants have been included in the review. Most included trials had poor study quality. The pooled weighted mean difference [WMD] for percentage weight change showed a benefit of supplementation of 2.3% (95% confidence interval (CI) 1.9 to 2.7) from 34 trials. There was a reduced mortality in the supplemented compared with control groups (relative risk (RR) 0.74, CI 0.59 to 0.92) from 32 trials. The risk of complications from 14 trials showed no significant difference (RR 0.95, 95% CI 0.81 to 1.11). Few trials were able to suggest any functional benefit from supplementation. The pooled weighted mean difference (WMD) for length of stay from 10 trials also showed no statistically significant effect (WMD -1.98 days, 95% CI -5.20 to 1.24). AUTHORS' CONCLUSIONS: Supplementation produces a small but consistent weight gain in older people. There may also be a beneficial effect on mortality. However, there was no evidence of improvement in clinical outcome, functional benefit or reduction in length of hospital stay with supplements. Additional data from large-scale multi-centre trials are still required.

Medical versus surgical interventions for open angle glaucoma.

BACKGROUND: Open angle glaucoma (OAG) is the commonest cause of irreversible blindness worldwide. OBJECTIVES: To study the relative effects of medical and surgical treatment of OAG. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to February 2005), EMBASE (1988 to February 2005), and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials comparing medications to surgery in adults. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted trial investigators for missing information. MAIN RESULTS: Four trials involving 888 participants with previously untreated OAG were included. Surgery was Scheie's procedure in one trial and trabeculectomy in three trials. In three trials, primary medication was usually pilocarpine, in one trial a beta-blocker. In the most recent trial, participants with mild OAG, progressive visual field (VF) loss, after adjustment for cataract surgery, was not significantly different for medications compared to trabeculectomy (Odds ratio (OR) 0.74; 95% CI 0.54 to 1.01). Reduction of vision, with a higher risk of developing cataract (OR 2.69, 95%% CI 1.64 to 4.42), and more patient discomfort was more likely with trabeculectomy than medication. There is some evidence, from three trials, for people with moderately advanced glaucoma that medication is associated with more progressive VF loss and 6 to 8 mmHg less intraocular pressure (IOP) lowering than surgery, either by a Scheie's procedure or trabeculectomy. There was a trend towards an increased risk of failed IOP control over time for initial pilocarpine treatment compared to trabeculectomy. In the longer-term (two trials) the risk of failure was significantly greater with medication than trabeculectomy (OR 3.90, 95% CI 1.60 to 9.53; HR 7.27, 95% CI 2.23 to 25.71). Medicine and surgery have evolved since these trials were undertaken, and additionally the evidence is potentially subject to detection and attrition bias. AUTHORS' CONCLUSIONS: Evidence from one trial suggests, for mild OAG, that VF deterioration up to five-years is not significantly different whether treatment is initiated with medication or trabeculectomy. Reduced vision, cataract and eye discomfort are more likely with trabeculectomy. There is some evidence, for more severe OAG, that initial medication (pilocarpine, now rarely used as first line medication) is associated with greater VF deterioration than surgery. In general, surgery lowers IOP more than medication. There was no evidence to determine the effectiveness of contemporary medication (prostaglandin analogues, alpha2-agonists and topical carbonic anhydrase inhibitors) compared to surgery in severe OAG, and in people of black African ethnic origin who have a greater risk of more severe open angle glaucoma. More research is required.

Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus.

BACKGROUND: Obesity is closely related to type 2 diabetes and long-term weight reduction is an important part of the care delivered to obese persons with diabetes. OBJECTIVES: To assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes. SEARCH STRATEGY: Computerized searches were performed of MEDLINE (January 1966 to May 2004), EMBASE (January 1974 to May 2004, Web of Science (January 1981 to May 2004, and other electronic bibliographic databases, supplemented with hand searches of reference lists and selected journals. SELECTION CRITERIA: Randomized, controlled trials were included where pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished literature in any language and with any study design was included. DATA COLLECTION AND ANALYSIS: Two reviewers abstracted data and the quality of included studies was evaluated by assessing potential attrition, as well as selection and measurement bias, and a Jadad score was obtained. Effects were combined using a random effects model. MAIN RESULTS: A sufficient number of studies were available for a quantitative synthesis for fluoxetine, orlistat, and sibutramine. Twenty two randomized controlled trials were included in the review, with a total of 296 participants for fluoxitine, 2036 for orlistat, and 1047 for sibutramine. Pharmacotherapy produced modest reductions in weight for fluoxetine (5.1 kg (95% confidence interval [CI], 3.3 - 6.9) at 24 to 26 weeks follow up; orlistat 2.0 kg (CI, 1.3 - 2.8) at 12 to 57 weeks follow-up, and sibutramine 5.1 kg (CI, 3.2 - 7.0) at 12 to 52 weeks follow-up. Glycated hemoglobin also modestly and significantly reduced for fluoxetine and orlistat. Gastrointestinal side effects were common with orlistat; tremor, somnolence and sweating with fluoxetine; and palpitations with sibutramine. Some studies, using a variety of study designs, were available on other drugs and a significant decrease in weight was noted in three studies of mazindol, one of phenmetrazine, two of phentermine. No studies were identified that fit inclusion criteria for pseudophedrine, ephedra, sertraline, yohimbine, amphetamine or its derivatives, bupropion, topiramate, benzocaine, threachlorocitric acid, sertraline, and bromocriptine. AUTHORS' CONCLUSIONS: Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes.

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: July 2004. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Twenty-three randomised trials involving 3115 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% versus 58%) than six month therapy (Odds ratio (OR) 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR 0.75, 95% CI 0.39 to 1.43). Twelve trials examined the effect of Block-Replace versus Titration regimen. The relapse rates were similar in both groups at 51% in the Block-Replace group and 54% in the Titration group (Peto OR 0.86, 95% CI 0.68 to 1.08). Participants reporting rashes (10% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine with continued low dose antithyroid therapy after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio 0.58, 95% CI 0.05 to 6.21). Four studies considered the addition of thyroxine alone after initial therapy with antithyroid drugs. There was no significant difference in the relapse rates between the groups after 12 months follow-up with relapse rates being 31% (88/282) with thyroxine and 29% (82/284) with placebo (Peto OR 1.15, 95% CI 0.79 to 1.67). AUTHORS' CONCLUSIONS: The evidence (based on four studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 12 trials) of equal duration. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. The incidence of hypothyroidism was not reported and there were no deaths reported in the study populations.

Long-term non-pharmacological weight loss interventions for adults with prediabetes.

BACKGROUND: Most persons with prediabetes (impaired glucose tolerance or impaired fasting glucose) are overweight, and obesity worsens the metabolic and physiologic abnormalities associated with this condition. Prediabetes is an important risk factor for the development of type 2 diabetes. OBJECTIVES: The objective of this review was to assess the effectiveness of dietary, physical activity, and behavioral weight loss, and weight control interventions for adults with prediabetes. SEARCH STRATEGY: Studies were obtained from computerized searches of multiple electronic bibliographic databases, supplemented by hand searches of selected journals, and consultation with experts in obesity research. The last search was conducted May, 2004. SELECTION CRITERIA: Studies were included if they were published or unpublished randomized controlled trials in any language and examined weight loss or weight control strategies using one or more dietary, physical activity, or behavioral interventions, with a follow-up interval of at least 12 months. DATA COLLECTION AND ANALYSIS: Effects were combined using a random-effects model. MAIN RESULTS: Nine studies were identified, with a total of 5,168 participants. Follow-up ranged from 1 to 10 years. Quantitative synthesis was limited by the heterogeneity of populations, settings, and interventions and by the small number of studies that examined outcomes other than weight. Overall, in comparisons with usual care, four studies with a follow-up of one year reduced weight by 2.8 kg (95 % confidence interval (CI) 1.0 to 4.7) (3.3% of baseline body weight) and decreased body mass index by 1.3 kg/m(2) (95% CI 0.8 to 1.9). Weight loss at two years was 2.6 kg (95% CI 1.9 to 3.3) (three studies). Modest improvements were noted in the few studies that examined glycemic control, blood pressure, or lipid concentrations (P > 0.05). No data on quality of life or mortality were found. The incidence of diabetes was significantly lower in the intervention groups versus the controls in three of five studies examining this outcome at 3 to 6 years follow-up. AUTHORS' CONCLUSIONS: Overall, weight loss strategies using dietary, physical activity, or behavioral interventions produced significant improvements in weight among persons with prediabetes and a significant decrease in diabetes incidence. Further work is needed on the long-term effects of these interventions on morbidity and mortality and on how to implement these interventions in diverse community settings.