Association between central blood pressure, arterial stiffness, and mild cognitive impairment.

BACKGROUND: To determine the relationship between central blood pressure (CBP) indices and mild cognitive impairment (MCI) in adults over the age of 50. METHODS: A cross-sectional study conducted using a non-invasive SphygmoCor XCEL device. CBP indices and brachial blood pressure were measured in 50 inpatients and outpatients. MCI was assessed using the Montreal Cognitive Assessment (MoCA) instrument and by the European Consortium Criteria (ECC). RESULTS: Seventy-six percent of subjects had hypertension, and 52% were diagnosed as having MCI using the ECC. No significant association was found between any of the measured blood pressure variables and global cognition. A significant relationship was observed between augmentation index (AI) and abnormal clock-drawing (p = 0.04) and language (p = 0.02), and between pulse pressure amplification (PPA) and language (p = 0.03). CONCLUSION: CBP indices like AI and PPA, which are markers of vascular stiffness, are associated with poor executive function and language cognitive domain deficits.

Intraclass differences among antihypertensive drugs.

The four major classes of antihypertensive drugs­diuretics, ß-blockers, calcium channel blockers, and renin-angiotensin system inhibitors (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers)­have significant qualitative and quantitative differences in the adverse effects they cause. Structural and chemical differences have been identified within these classes, especially among the calcium channel blockers and, to a lesser extent, among the thiazide/thiazide-like diuretics. However, it has been more difficult to demonstrate that these differences translate into differential effects with respect to either the surrogate endpoint of blood pressure reduction or, more importantly, hypertension-related cardiovascular complications. Based on a hierarchy-of-evidence approach, differences are apparent between hydrochlorothiazide and chlorthalidone based on evidence of moderate quality. Low-quality evidence suggests atenolol is less effective than other ß-blockers. However, no significant intraclass differences have been established among the other classes of antihypertensive drugs.

Women with severe obesity and relatively low bone mineral density have increased fracture risk.

UNLABELLED: Among women with obesity, those with the lowest bone density have the highest fracture risk. The types of fractures include any fracture, fragility-type fractures (vertebra, hip, upper arm, forearm, and lower leg), hand and foot fractures, osteoporotic, and other fracture types. INTRODUCTION: Recent reports have contradicted the traditional view that obesity is protective against fracture. In this study, we have evaluated the relationship between fracture history and bone mineral density (BMD) in subjects with obesity. METHODS: Fracture risk was assessed in 400 obese women in relation to body mass index (BMI), BMD, and clinical and laboratory variables. RESULTS: Subjects (mean age, 43.8 years; SD, 11.1 years) had a mean BMI of 46.0 kg/m(2) (SD, 7.4 kg/m(2)). There were a total of 178 self-reported fractures in 87 individuals (21.8% of subjects); fragility-type fractures (hip, vertebra, proximal humerus, distal forearm, and ankle/lower leg) were present in 58 (14.5%). There were higher proportions of women in the lowest femoral neck BMD quintile who had any fracture history (41.3 vs. 17.2%, p < 0.0001), any fragility-type fractures (26.7 vs. 11.7%, p = 0.0009), hand and foot fractures (16.0 vs. 5.5%, p = 0.002), other fracture types (5.3 vs. 1.2%, p = 0.02), and osteoporotic fractures (8.0 vs. 1.2%, p < 0.0001) compared to the remaining population. The odds ratio for any fracture was 0.63 (95% CI, 0.49-0.89; p = 0.0003) per SD increase in BMD and was 4.3 (95% CI, 1.9-9.4; p = 0.003) in the lowest BMD quintile compared to the highest quintile. No clinical or biochemical predictors of fracture risk were identified apart from BMD. CONCLUSIONS: Women with obesity who have the lowest BMD values, despite these being almost normal, have an elevated risk of fracture compared to those with higher BMD.

The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data.

BACKGROUND: In heart failure (HF), obesity, defined as body mass index (BMI) ≥30 kg m(-2), is paradoxically associated with higher survival rates compared with normal-weight patients (the 'obesity paradox'). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)). PATIENTS AND METHODS: A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5-24.9 (referent), 25-29.9, 30-34.9 and ≥35 kg m(-2). Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups. RESULTS: BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m(-2), the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15-1.50) for BMI <22.5, 0.85 (0.76-0.96) for BMI 25.0-29.9, 0.64 (0.55-0.74) for BMI 30.0-34.9 and 0.95 (0.78-1.15) for BMI ≥35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80-1.57) for BMI <22.5, 0.74 (0.56-0.97) for BMI 25.0-29.9, 0.64 (0.46-0.88) for BMI 30.0-34.9 and 0.71 (0.49-1.05) for BMI ≥35. CONCLUSIONS: In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0-34.9 kg m(-2).

The effect of weight loss on health-related quality of life: systematic review and meta-analysis of randomized trials.

The aim of this study was to examine the effect of weight loss on health-related quality of life (HRQL) in randomized controlled intervention trials (RCTs). MEDLINE, HealthStar and PsycINFO were searched. RCTs of any weight loss intervention and 20 HRQL instruments were examined. Contingency tables were constructed to examine the association between statistically significant weight loss and statistically significant HRQL improvement within five HRQL categories. In addition, Short Form-36 (SF-36) outcomes were pooled using random-effects models. Fifty-three trials were included. Seventeen studies reported statistically significant weight loss and HRQL improvement. No statistically significant associations between weight loss and HRQL improvement were found in any contingency table. Because of suboptimal endpoint reporting, quantitative data pooling could only be performed using 25% of SF-36 trials in any one model. Significant improvements in physical health were found: mean difference 2.83 points, 95% CI 0.55-5.1, for the physical component score, and mean difference 6.81 points, 95% CI 2.99-10.63, for the physical functioning domain score. Conversely, no significant improvements in mental health were found. No significant association was found between weight loss and overall HRQL improvement. Weight loss may be associated with modest improvements in physical, but not mental, health.

Obesity and outcomes in patients hospitalized with pneumonia.

Studies suggest obesity is paradoxically associated with better outcomes for patients with pneumonia. Therefore, we examined the impact of obesity on short-term mortality in patients hospitalized with pneumonia. For 2 years clinical and radiographic data were prospectively collected on all consecutive adults admitted with pneumonia to six hospitals in Edmonton, Alberta, Canada. We identified 907 patients who also had body mass index (BMI, kg/m(2)) collected and categorized them as underweight (BMI < 18.5), normal (18.5 to <25), overweight (25 to <30) and obese (>30). Overall, 65% were >65 years, 52% were female, and 15% reported recent weight loss. Eighty-four (9%) were underweight, 358 (39%) normal, 228 (25%) overweight, and 237 (26%) obese. Two-thirds had severe pneumonia (63% PSI Class IV/V) and 79 (9%) patients died. In-hospital mortality was greatest among those that were underweight (12 [14%]) compared with normal (36 [10%]), overweight (21 [9%]) or obese (10 [4%], p <0.001 for trend). Compared with those of normal weight, obese patients had significantly lower rates of in-hospital mortality in multivariable logistic regression analyses: adjusted odds ratio (OR), 0.46; 95% CI, 0.22-0.97; p 0.04. However, compared with patients with normal weight, neither underweight (adjusted OR, 1.13; 95% CI, 0.54-2.4; p 0.7) nor overweight (adjusted OR, 0.94; 95% CI, 0.52-1.69; p 0.8) were associated with in-hospital mortality. In conclusion, in patients hospitalized with pneumonia, obesity was independently associated with lower short-term mortality, while neither being underweight nor overweight were. This suggests a protective influence of BMIs > 30 kg/m(2) that requires better mechanistic understanding.

Bariatric surgery: a systematic review and network meta-analysis of randomized trials.

The clinical efficacy and safety of bariatric surgery trials were systematically reviewed. MEDLINE, EMBASE, CENTRAL were searched to February 2009. A basic PubCrawler alert was run until March 2010. Trial registries, HTA websites and systematic reviews were searched. Manufacturers were contacted. Randomized trials comparing bariatric surgeries and/or standard care were selected. Evidence-based items potentially indicating risk of bias were assessed. Network meta-analysis was performed using Bayesian techniques. Of 1838 citations, 31 RCTs involving 2619 patients (mean age 30-48 y; mean BMI levels 42-58 kg/m(2) ) met eligibility criteria. As compared with standard care, differences in BMI levels from baseline at year 1 (15 trials; 1103 participants) were as follows: jejunoileal bypass [MD: -11.4 kg/m(2) ], mini-gastric bypass [-11.3 kg/m(2) ], biliopancreatic diversion [-11.2 kg/m(2) ], sleeve gastrectomy [-10.1 kg/m(2) ], Roux-en-Y gastric bypass [-9.0 kg/m(2) ], horizontal gastroplasty [-5.0 kg/m(2) ], vertical banded gastroplasty [-6.4 kg/m(2) ], and adjustable gastric banding [-2.4 kg/m(2) ]. Bariatric surgery appears efficacious compared to standard care in reducing BMI. Weight losses are greatest with diversionary procedures, intermediate with diversionary/restrictive procedures, and lowest with those that are purely restrictive. Compared with Roux-en-Y gastric bypass, adjustable gastric banding has lower weight loss efficacy, but also leads to fewer serious adverse effects.

Canadian Physicians' Use of Antiobesity Drugs and Their Referral Patterns to Weight Management Programs or Providers: The SOCCER Study.

Antiobesity pharmacotherapy and programs/providers that possess weight management expertise are not commonly used by physicians. The underlying reasons for this are not known. We performed a cross-sectional study in 33 Canadian medical practices (36 physicians) examining 1788 overweight/obese adult patients. The frequency of pharmacotherapy use and referral for further diet, exercise, behavioral management and/or bariatric surgery was documented. If drug treatment or referral was not made, reasons were documented by choosing amongst preselected categories. Logistic regression models were used to identify predictors of antiobesity drug use. No single antiobesity management strategy was recommended by physicians in more than 50% of patients. Referral was most common for exercise (49% of cases) followed by dietary advice (46%), and only 5% of eligible patients were referred for bariatric surgery. Significant predictors of initiating/continuing pharmacotherapy were male sex (OR 0.70; 95% CI 0.52-0.94), increasing BMI (1.02; 95% CI 1.01-1.03), and private drug coverage (1.78; 95% CI 1.39-2.29). "Not considered" and "patient refusal" were the main reasons for not initiating further weight management. We conclude that both physician and patient factors act as barriers to the use of weight management strategies and both need to be addressed to increase uptake of these interventions.

Multicomponent, home-based resistance training for obese adults with type 2 diabetes: a randomized controlled trial.

PURPOSE: To investigate whether a home-based resistance training (RT) program that supplied high-quality equipment and qualified exercise specialists could provide benefits to obese patients with type 2 diabetes. METHODS: A total of 48 obese individuals with type 2 diabetes were randomly assigned to either an RT (n=27) or a control group (n=21). Those in the RT group received a multigym and dumbbells and performed RT 3 days per week for 16 weeks at home. A qualified exercise specialist supervised training, with supervision being gradually decreased throughout the study. Primary outcome measures included strength and hemoglobin-A1C, whereas secondary outcome measures included other cardiovascular risk markers, key social-cognitive constructs and health-related quality of life. RESULTS: Intention-to-treat analyses indicated a significant increase in upper and lower body strength for the RT group compared with controls (20-37% mean increases in the RT group). No significant reduction in A1C levels was observed. The RT group had unchanged high-density lipoprotein cholesterol levels in comparison to declines in the control group. Significant reductions in fasting insulin, and increases in RT-related self-efficacy and intentions, were also observed in the RT group. CONCLUSIONS: Supervised home-based RT with high-quality equipment was effective for improving strength, along with other secondary outcomes in obese patients with type 2 diabetes.

Association between obesity and health-related quality of life in patients with coronary artery disease.

BACKGROUND AND OBJECTIVE: In patients with coronary artery disease (CAD), obesity is paradoxically associated with better survival (the 'obesity paradox'). Our objective was to determine whether this counterintuitive relationship extends to health-related quality of life (HRQOL) outcomes. DESIGN: Cross-sectional observational study. SUBJECTS: All adults undergoing coronary angiography residing in Alberta, Canada between January 2003 and March 2006 in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry. METHODS: Patients completed self-reported questionnaires 1 year after their index cardiac catheterization, including the Seattle Angina Questionnaire (SAQ) and the EuroQol 5D (EQ-5D Index). Patients were grouped into six body mass index (BMI) categories (underweight, normal, overweight, mild obesity, moderate obesity and severe obesity). An analysis of covariance was used to create risk-adjusted scores. RESULTS: A total of 5362 patients were included in the analysis. Obese patients were younger than normal and overweight participants, and had a higher prevalence of depression and cardiovascular risk factors. In the adjusted models, SAQ physical function scores and the EQ Index (representing overall QOL) were significantly reduced in patients with mild, moderate and severe obesity compared with patients with a normal BMI. Patients with severe obesity had both statistically and clinically significant reductions in HRQOL scores. Depressive symptoms accounted for a large proportion in variability of all HRQOL scores. CONCLUSIONS: BMI is inversely associated with physical function and overall HRQOL in CAD patients, especially in patients with severe obesity. High body weight is a modifiable risk factor; however, given the apparent obesity paradox in patients with CAD, it is critical that future studies be conducted to fully clarify the relationships between HRQOL and body composition (body fat and lean mass), nutritional state and survival outcomes.

Obesity is a sign - over-eating is a symptom: an aetiological framework for the assessment and management of obesity.

Obesity is characterized by the accumulation of excess body fat and can be conceptualized as the physical manifestation of chronic energy excess. Using the analogy of oedema, the consequence of positive fluid balance or fluid retention, obesity can be seen as the consequence of positive energy balance or calorie 'retention'. Just as the assessment of oedema requires a comprehensive assessment of factors related to fluid balance, the assessment of obesity requires a systematic assessment of factors potentially affecting energy intake, metabolism and expenditure. Rather than just identifying and describing a behaviour ('this patient eats too much'), clinicians should seek to identify the determinants of this behaviour ('why, does this patient eat too much?'). This paper provides an aetiological framework for the systematic assessment of the socio-cultural, biomedical, psychological and iatrogenic factors that influence energy input, metabolism and expenditure. The paper discusses factors that affect metabolism (age, sex, genetics, neuroendocrine factors, sarcopenia, metabolically active fat, medications, prior weight loss), energy intake (socio-cultural factors, mindless eating, physical hunger, emotional eating, mental health, medications) and activity (socio-cultural factors, physical and emotional barriers, medications). It is expected that the clinical application of this framework can help clinicians systematically assess, identify and thereby address the aetiological determinants of positive energy balance resulting in more effective obesity prevention and management.

A systematic review of drug absorption following bariatric surgery and its theoretical implications.

Demand for bariatric surgery has risen exponentially and bariatric patients often have multiple indications for post-operative pharmacotherapy. The purpose of this study was to systematically review the published literature examining the effect of bariatric surgery on drug absorption. Studies were sought through searches of MEDLINE, EMBASE, the Cochrane Controlled Trials Registry and hand searches of reference lists. Two reviewers independently assessed studies for inclusion. Twenty-six studies (15 case reports/case series evaluating 12 different agents and 11 non-randomized controlled studies examining 15 different agents) were found. Evidence for diminished drug absorption was found in 15/22 studies involving jejunoileal bypass, 1/3 studies of gastric bypass/gastroplasty and 0/1 studies examining biliopancreatic diversion. The effect of bariatric surgery on drug absorption appears drug-specific. Drugs that are intrinsically poorly absorbed, highly lipophilic and/or undergo enterohepatic recirculation exhibited the greatest potential for malabsorption. The most consistent evidence for diminished absorption was found for cyclosporine, thyroxine, phenytoin and rifampin. Reduced drug absorption may occur post-bariatric surgery and this effect appears drug-specific. Individual dose-adjustment and therapeutic monitoring may be required. Rigorously conducted controlled studies are needed to evaluate the effect of modern bariatric procedures on drug absorption.

Long-term persistence with orlistat and sibutramine in a population-based cohort.

OBJECTIVE: Orlistat and sibutramine are widely prescribed antiobesity agents that are approved for 2 years of continuous use. Previous 1-4-year randomized, placebo-controlled trials of these drugs have reported average weight losses of <5 kg, significant adverse effects and attrition rates of up to 60%. The objective of this study was to determine the long-term persistence with orlistat and sibutramine therapy outside a clinical trial setting. DESIGN, SETTING AND PATIENTS: Population-based administrative data from British Columbia, Canada, were used to create an inception cohort of orlistat and sibutramine users and determine the 2-year persistence with therapy. MAIN OUTCOME MEASURE: Persistence with therapy at 2 years. Drug discontinuation was defined as the failure to refill a prescription within 120 days. Patients discontinuing therapy were censored at the 60-day mark. RESULTS: Nearly 17 000 users of orlistat and 3500 users of sibutramine were identified. For both orlistat and sibutramine, 1-year persistence rates were <10% and 2-year persistence rates were 2%. CONCLUSION: This population-based, retrospective cohort analysis demonstrated very poor long-term persistence rates with orlistat and sibutramine and discontinuation rates that were much higher than those reported in clinical trials.

Long-term pharmacotherapy for obesity and overweight.

BACKGROUND: Worldwide prevalence rates of obesity and overweight are rising and safe and effective treatment strategies are urgently needed. A number of anti-obesity agents have been studied in short-term clinical trials, but long-term efficacy and safety need to be established. OBJECTIVES: To assess/compare the effects and safety of approved anti-obesity medications in clinical trials of at least one-year duration. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Date of last search was December 2002. Drug manufacturers and two obesity experts were contacted in to detect unpublished trials. No language restrictions were imposed. SELECTION CRITERIA: Double-blind, randomised controlled weight loss and weight maintenance trials of approved anti-obesity agents that 1) enrolled adult overweight or obese patients, 2) included a placebo control group or compared two or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a minimum follow-up period of one year. Abstracts and pseudo-randomised trials were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measure was weight loss. MAIN RESULTS: Of the eight anti-obesity agents investigated, only orlistat and sibutramine trials met inclusion criteria. Eleven orlistat weight loss studies (four of which reported a second year weight maintenance phase) and five sibutramine studies (three weight loss and two weight maintenance trials) were included. Attrition rates averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies. All patients received lifestyle modification as a co-intervention. Compared to placebo, orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI: 2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95% CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The number of patients achieving ten percent or greater weight loss was 12% (95% CI: 8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with sibutramine therapy. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine was associated with small increases in blood pressure and pulse rate. REVIEWERS' CONCLUSIONS: Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.

The 2004 Canadian recommendations for the management of hypertension: Part III--Lifestyle modifications to prevent and control hypertension.

OBJECTIVE: To provide updated, evidence-based recommendations regarding the role of lifestyle modification in the treatment and prevention of hypertension. OUTCOMES: Lifestyle modification interventions including exercise, weight reduction, alcohol consumption, dietary modification, intake of dietary cations and stress management are reviewed. Antioxidants and fish oil supplements are also reviewed, although specific recommendations cannot be made at present. EVIDENCE: MEDLINE searches were conducted from January 2002 to September 2003 to update the 2001 recommendations for the management of hypertension. Supplemental searches in the Cochrane Collaboration databases were also performed. Reference lists were scanned, experts were contacted, and the personal files of the subgroup members and authors were used to identify additional published studies. All relevant articles were reviewed and appraised independently using prespecified levels of evidence by content and methodology experts. RECOMMENDATIONS: Key recommendations include the following: lifestyle modification should be extended to nonhypertensive individuals who are at risk for developing high blood pressure; 30 min to 45 min of aerobic exercise should be performed on most days (four to five days) of the week; an ideal body weight (body mass index 18.5 kg/m2 to 24.9 kg/m2) should be maintained and weight loss strategies should use a multidisciplinary approach; alcohol consumption should be limited to two drinks or fewer per day, and weekly intake should not exceed 14 standard drinks for men and nine standard drinks for women; a reduced fat, low cholesterol diet that emphasizes fruits, vegetables and low fat dairy products, and maintains an adequate intake of potassium, magnesium and calcium, should be followed; salt intake should be restricted to 65 mmol/day to 100 mmol/day in hypertensive individuals and less than 100 mmol/day in normotensive individuals at high risk for developing hypertension; and stress management should be considered as an intervention in selected individuals. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. Individuals with irreconcilable competing interests (declared by all members, compiled and circulated before the meeting) relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving at least 70% consensus are reported here. These guidelines will continue to be updated annually.

Long-term pharmacotherapy for obesity and overweight.

BACKGROUND: Worldwide prevalence rates of obesity and overweight are rising and safe and effective treatment strategies are urgently needed. A number of anti-obesity agents have been studied in short-term clinical trials, but long-term efficacy and safety need to be established. OBJECTIVES: To assess/compare the effects and safety of approved anti-obesity medications in clinical trials of at least one-year duration. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Date of last search was December 2002. Drug manufacturers and two obesity experts were contacted in to detect unpublished trials. No language restrictions were imposed. SELECTION CRITERIA: Double-blind, randomised controlled weight loss and weight maintenance trials of approved anti-obesity agents that 1) enrolled adult overweight or obese patients, 2) included a placebo control group or compared two or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a minimum follow-up period of one year. Abstracts and pseudo-randomised trials were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measure was weight loss. MAIN RESULTS: Of the eight anti-obesity agents investigated, only orlistat and sibutramine trials met inclusion criteria. Eleven orlistat weight loss studies (four of which reported a second year weight maintenance phase) and five sibutramine studies (three weight loss and two weight maintenance trials) were included. Attrition rates averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies. All patients received lifestyle modification as a co-intervention. Compared to placebo, orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI: 2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95% CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The number of patients achieving ten percent or greater weight loss was 12% (95% CI: 8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with sibutramine therapy. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine was associated with small increases in blood pressure and pulse rate. REVIEWER'S CONCLUSIONS: Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.

Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Safe and effective strategies to curb rising obesity prevalence rates are urgently needed and medications may play a more prominent role in future therapeutic regimens. OBJECTIVE: To review systematically the long-term efficacy and safety of approved antiobesity medications. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Drug manufacturers and two obesity experts were contacted. No language restrictions were imposed. STUDY SELECTION: Double-blind, randomized controlled studies of approved antiobesity medications with follow-up periods of 1 y or greater were eligible for inclusion. DATA EXTRACTION: Two reviewers independently assessed all potentially relevant studies for inclusion and methodological quality using standardized abstraction forms. RESULTS: A total of 11orlistat (n=6021) and three sibutramine (n=929) studies met inclusion criteria. Attrition rates averaged 33% in orlistat studies and 48% in sibutramine studies. A random effects model was used for meta-analysis. Compared to placebo, orlistat-treated patients displayed a 2.7 kg (95% CI: 2.3-3.1 kg) or 2.9% (95% CI: 2.3-3.4%) greater reduction in weight and patients on sibutramine displayed a 4.3 kg (95% CI: 3.6-4.9 kg) or 4.6% (95% CI: 3.8-5.4%) greater weight reduction after 1 y of follow-up. The number of patients achieving 10% or greater weight loss was 12% (95% CI: 8-16%) higher with orlistat and 15% (95% CI: 4-27%) higher with sibutramine compared to placebo. Orlistat caused gastrointestinal side effects and sibutramine increased blood pressure and pulse rate. CONCLUSION: There is a relative paucity of long-term studies of antiobesity agents. In weight loss trials of 1-y duration, orlistat and sibutramine appear modestly effective in promoting weight loss. Longer, more methodologically rigorous studies that are powered to examine end points such as mortality and cardiovascular morbidity are required.

Anterior cranial base morphology in mice with midfacial retrusion.

The role of the anterior cranial base in the morphogenesis of class III malocclusions remains uncertain. This study was conducted to determine whether morphologic deficiencies occur in the anterior cranial base in the Brachyrrhine (Br) mouse mutant showing severe midfacial retrusion, which is characteristic of a class III malocclusion. Crania from three groups of C3H/Hej, 3H1 Br/+, and 3H1+/+ mice, each consisting of 15 animals, were collected at 1, 3, and 5 days of age (total = 135). The anterior cranial base from each specimen was subjected to computerized reconstruction and ten landmarks were digitized from each model. The landmark configurations were compared using Procrustes analysis. Significant differences between models were determined at each age. In order to localize differences between forms, average landmark configurations derived from Procrustes analysis were subjected to finite-element analysis. Size-change values for the 3H1 Br/+ animals showed magnitudes that increased in an anteroposterior direction when compared to the 3H1 +/+ and C3H/Hej animals at all ages. The largest values were located posteriorly along the ossifying front of the presphenoid. In five of six comparisons, the size-change values separated into two distinct clusters. The posterior region of the anterior cranial base was divisible into two subclusters, one located superiorly and the other inferiorly. These data suggest that midfacial retrusion in the Br mouse may be caused, in part, by growth deficiencies in the posterior region of the anterior cranial base, particularly the presphenoidal and sphenoethmoidal regions.