Baseline Predictors of Success When Comparing Two Treatments

Since few medications are equally effective in all patients, physicians can maximize the risk/benefit ratio of therapy for their patients by limiting exposure based on baseline predictors of success. Traditional procedures typically evaluate the response of patients receiving the same treatment regimen without evaluating a comparator. However, when treatments are compared, such as in clinical trials, traditional procedures of identifying predictors must be modified to analyze the treatment effect on the primary outcome variable. We focus on clinical and statistical considerations that arise when developing baseline predictors through models which consider treatment differences. To illustrate an application of this method, we used data from 1,026 patients completing at least 6 months of double-blind therapy in clinical trials comparing fluoxetine (N=522) with placebo (N=504) for weight loss. Stepwise regression procedures were used to identify baseline variables which were predictive of a beneficial fluoxetine treatment effect on last-visit-carried-forward (LVCF) weight change. In this example, age, smoking activity, and uric acid concentration were the best baseline predictors of long-term treatment effect relative to LVCF weight change. Patients were more likely to achieve long-term benefit with fluoxetine if they were older, and/or were nonsmokers, and/or had high concentrations of uric acid at baseline. These predictors, developed through models keying on treatment effect, can be used to identify patients who are more likely to accrue benefits with active therapy beyond those expected with placebo therapy, thus enriching the treatment population so that a higher proportion of treated patients are successful.     

Physical Activity and Long-Term Maintenance of Weight Loss

To examine the effect of exercise on the long-term maintenance of weight loss, two types of literature were reviewed - correlational studies of predictors of long-term weight loss, and randomized trials comparing diet, exercise, and the combination of diet plus exercise. Both literatures were striking in the consistency with which activity emerged as a determinant of long-term maintenance of weight loss. The benefits of exercise for long-term weight maintenance were observed with different types of populations, diets, and exercise interventions. Several possible explanations for these positive effects of diet plus exercise are presented, and suggestions made for future research on ways to maximize the benefit of this approach to weight control. Since adherence to exercise may ultimately prove to be the cornerstone for long-term weight maintenance, studying ways to improve exercise adherence is recommended.     

What Is the Role of Cognitive-Behavior Therapy in Patient Management?

This review summarizes the role of cognitive-behavior therapy (CBT) in obesity treatment. Although not a specific intervention per se, CBT is the systematic application of principles of social cognitive theory to modify behaviors that are thought to contribute to or maintain obesity. Most forms of CBT include the use of five strategies: self-monitoring and goal setting; stimulus control for the modification of eating style, activity, and related habits; cognitive restructuring techniques that focus on challenging and modifying unrealistic or maladaptive thoughts or expectations; stress management; and social support. The use of these strategies in comprehensive obesity programs has been helpful in improving short-term weight losses, but long-term success remains elusive, even though these strategies are predictors of long-term weight loss maintenance. Given that obesity is a chronic condition, not unlike hypertension or diabetes, CBT interventions will need to focus on broader treatment outcomes, such as improved metabolic profiles, quality of life, psychological functioning, and physical fitness. In addition, new methods for delivering CBT interventions should be explored, including home-based programs and combination with adjunctive pharmacotherapy delivered in primary care centers.     

The Addition of Dexfenfluramine to Fluoxetine in the Treatment of Obesity: A Randomized Clinical Trial

Current evidence demonstrates that pharmacologic agents, alone or in combination produce short-term weight-loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty-three patients were randomly assigned in a double-blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n=13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n=20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean ± SEM 6.2 ± 2.8 kg and Group II 13.4 ± 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m². However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL-cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.     

Obesity in Older Adults: Technical Review and Position Statement of the American Society for Nutrition and NAASO,The Obesity Society

Obesity causes serious medical complications and impairs quality of life. Moreover, in older persons, obesity can exacerbate the age‐related decline in physical function and lead to frailty. However, appropriate treatment for obesity in older persons is controversial because of the reduction in relative health risks associated with increasing body mass index and the concern that weight loss could have potential harmful effects in the older population. This joint position statement from the American Society for Nutrition and NAASO, The Obesity Society reviews the clinical issues related to obesity in older persons and provides health professionals with appropriate weight‐management guidelines for obese older patients. The current data show that weight‐loss therapy improves physical function, quality of life, and the medical complications associated with obesity in older persons. Therefore, weight‐loss therapy that minimizes muscle and bone losses is recommended for older persons who are obese and who have functional impairments or medical complications that can benefit from weight loss.     

Fluoxetine: A Randomized Clinical Trial in the Maintenance of Weight Loss

Because current weight-reduction treatments have considerable recidivism, a therapy that could help patients maintain weight loss would be of benefit. A six-center, randomized, double-blind trial compared the effects of the specific serotonin uptake inhibitor, fluoxetine hydrochloride, and placebo on maintenance of weight loss. Obese outpatients who had lost ≤3.6 kg after 8 weeks of single-blind fluoxetine 60 mg/day in the qualification phase (N=317 [70.4% of patients entered]; mean ± standard deviation [SD] weight loss, 6.8 ± 2.8 kg) were randomly assigned to fluoxetine 20 mg/day (N=104), fluoxetine 60 mg/day (N=106), or placebo (N=107) for 40 weeks (maintenance phase). Patients received minimal nutrition/dietary counseling. Qualification phase clinic visits were biweekly; maintenance phase visits were monthly for 4 months, then bimonthly for 6 months. Patients treated with fluoxetine 60 mg/day continued to lose weight for 8 additional weeks (16 weeks total; maximum mean ± SD weight loss, 7.2 ± 4.6 kg); those treated with fluoxetine 20 mg/day or placebo began to regain weight. Mean weights remained below baseline values at week 48 (all groups); treatment differences were not statistically significant. Study completion rates were comparable (fluoxetine 20 mg/day, 67.3%; fluoxetine 60 mg/day, 56.6%; placebo, 67.3%; p = 0.175). Among commonly reported adverse events (>10% incidence), only asthenia was reported statistically significantly (p< 0.050) more frequently with fluoxetine than with placebo. Few patients discontinued for any single adverse event. Fluoxetine 60 mg/day was effective for a longer period than fluoxetine 20 mg/day or placebo in maintaining weight loss. Overall, fluoxetine was safe and well tolerated.     

Patient characteristics as predictors of weight loss after an obesity treatment for children

Objective: To examine pretreatment patient characteristics as predictors of treatment outcome 2 years after completion of an inpatient treatment for children with obesity. Research Methods and Procedures: Children (N = 122) ranging in age from 7 to 17 years [mean, 12.7 ± 2.3 (SD) years] with a mean adjusted BMI of 179.5 ± 28.6% participated in an inpatient obesity treatment program. Children (90.2% response rate) participated in the 2‐year follow‐up. Eight predictors, administered at baseline, were entered in separate regression analyses, with weight loss and changes on three psychological health measures as the outcome measures. Results: Analyses revealed that baseline degree of overweight, age, and initial weight loss were significant positive predictors of weight loss 2 years after treatment, whereas eating disorder characteristics were a negative predictor. Sex, socioeconomic status, global self‐esteem, and symptoms of psychopathology did not predict weight loss. With regard to the psychological outcome measures, baseline symptomatology emerged as the most important predictor of treatment changes. Discussion: Long‐lasting weight loss is associated with severity of pretreatment characteristics. Identification of the clinical markers for long‐term response to treatment is useful to set realistic weight loss goals for clients and to tailor treatment programs to patient characteristics.     

Addressing the Unmet Medical Need for Safe and Effective Weight Loss Therapies

Obesity is a significant healthcare problem worldwide and increases the risk of developing debilitating diseases including type 2 diabetes, cardiovascular disease, and cancer. Although the health benefits of weight reduction are well‐recognized, weight loss by diet and exercise fail in most patients, and the current marketed drugs have had limited success. It is clear that there is a significant unmet medical need for safe and effective weight‐reducing agents. In this review, the current status of potential weight loss approaches that are in development by the pharmaceutical and biotechnology industry are discussed. This should lead to novel treatments that can be used long‐term to effectively treat this serious metabolic disorder.     

Overweight,Obesity, and Blood Pressure: The Effects of Modest Weight Reduction

Several large epidemiological studies have shown an association between body mass index and blood pressure in normal weight and overweight patients. Weight gain in adult life especially seems to be an important risk factor for the development of hypertension. Weight loss has been recommended for the obese hypertensive patient and has been shown to be the most effective nonpharmacological treatment approach. However, long‐term results of weight loss programs are disappointing with people often regaining most of the weight initially lost. In recent years, a modest weight loss, defined as a weight loss of 5% to 10% of baseline weight, has received increasing attention as a new treatment strategy for overweight and obese patients. A more gradual and moderate weight loss is more likely to be maintained over a longer period of time. Several studies have confirmed the blood pressure‐lowering effect of a modest weight loss in both hypertensive and nonhypertensive patients. A modest weight loss can normalize blood pressure levels even without reaching ideal weight. In patients taking antihypertensive medication, a modest weight loss has been shown to lower or even discontinue the need for antihypertensive medication. In patients with high normal blood pressure, a modest weight loss can prevent the onset of frank hypertension. The blood pressure‐lowering effect of weight loss is most likely a result of an improvement in insulin sensitivity and a decrease in sympathetic nervous system activity and occurs independent of salt restriction. In conclusion, a modest weight loss that can be maintained over a longer period of time is a valuable treatment goal in hypertensive patients.     

The Case for Medical Management of Obesity: A Call for Increased Physician Involvement

The United States is in the midst of an escalating epidemic of obesity. Over one-third of the adult population in the United States is currently obese and the prevalence of obesity is growing rapidly. By any criteria, obesity represents a chronic disease which is associated with a wide range of comorbidities, including coronary heart disease (CHD), Type 2 diabetes, hypertension and dyslipidemias. The comorbidities of obesity are common, occurring in over 70% of individuals with a BMI of ≥ 27. In addition to obesity itself, excessive accumulation of visceral abdominal fat and significant adult weight gain also represent health risks. Physicians have an important role to play in the treatment of obesity. Unfortunately, the medical community has not been involved actively enough to help stem the major epidemic of obesity occurring in the United States. This article puts forth a proposed model for the treatment of obesity in clinical practice, including obtaining the “vital signs” of obesity, recommending lifestyle measures, and instituting pharmacologic therapy when appropriate. By utilizing a chronic disease treatment model, physicians can join other health care professionals to effectively treat the chronic disease of obesity. Relatively modest weight loss, on the order of 510% of initial body weight can result in significant health improvements for many patients and represent an achievable goal for most obese patients.     

Capacity for physical activity predicts weight loss after Roux-en-Y gastric bypass

Despite its overall excellent outcomes, weight loss after Roux-en-Y gastric bypass (RYGB) is highly variable. We conducted this study to identify clinical predictors of weight loss after RYGB. We reviewed charts from 300 consecutive patients who underwent RYGB from August 1999 to November 2002. Data collected included patient demographics, medical comorbidities, and diet history. Of the 20 variables selected for univariate analysis, 9 with univariate P values 相似文献   

Correlations with Self-Reported Weight Loss in Overweight U.S. Adults

The authors investigated two issues among overweight men and women in the U.S.: 1) what is the influence of the self-expressed intention to lose weight in the presence of other potential predictors of loss and 2) what are easily identifiable predictors of intentional weight loss during a 1-year recall period. The sample consisted of 1996 overweight men (body mass index (BMI ≥ 27.8 kg/m²) and 2586 overweight women (BMI ≥ 27.3 kg/m²) who answered questions regarding 1-year weight change in a Current Health Topic supplement of the population-based 1989 National Health Interview Survey. Of these overweight persons, 56.8% of men and 72.1% of women attempted to lose weight during the previous year. The most important characteristic associated with weight loss was the expressed intention itself. For any weight loss, the odds ratios (95% confidence intervals) for intention were 4.6 (3.6?5.9) for men and 3.8 (2.8?5.0) for women. Controlling for other factors reduced the odds only slightly, to 4.3 for men and 3.5 for women. Among women, older age, having a greater frequency of blood pressure checks, and being in poorer health reduced the influence of intent as a predictor of loss. To address the second objective, the identification of predictors of intentional 1-year weight loss, analysis was restricted to overweight persons who attempted to lose weight. For both sexes, statistically significant predictors (p<0.05) included never being married, smoking, higher BMI, being diabetic, and having a higher number of blood pressure checks. Being divorced or separated was predictive of weight loss in men only. Also, men were more likely to achieve weight loss than women. In conclusion, 1-year weight loss among the overweight was primarily a function of the intention to lose weight, although other factors contributed to determine whether weight loss was achieved.     

Lipophilic Environmental Chemical Mixtures Released During Weight-Loss: The Need to Consider Dynamics

Intentional weight loss can increase health risk in the long-term, despite short-term benefits, because human adipose tissue is widely contaminated with various lipophilic environmental contaminants, especially persistent organic pollutants (POPs). Recently, chronic exposure to low POPs has emerged as a new risk factor for common metabolic diseases and cardiovascular diseases. The amount of POPs released from adipocytes to the circulation increases during weight loss, thereby increasing POPs exposure of other critical organs. Possible harmful effects due to release of POPs during weight loss are opposite to those usually expected from losing weight. It is speculated that this tradeoff can explain recent puzzling findings on intensive weight loss. The presence of POPs in adipose tissue adds a challenge to weight management and an optimal strategy of weight management needs to consider both fat mass and dynamics of POPs.     

Clinical Studies with Dexfenfluramine: From Past to Future

d Fenfluramine (dF) (15 mg twice daily) has been studied in controlled trials in human obesity. It has been shown to increase adherence to weight lowering programs, to double the number of patients losing 10 kg or more when compared with a fairly efficient placebo plus dietary counselling, and to prevent weight regain when continued over a 1 year period. Weight loss after 1 month and 4 months is likely to predict subsequent outcome. Also, significant improvement in metabolic risk factors and blood pressure were clearly demonstrated, even more markedly in some obesity-associated diseases, when body weight is maintained at a lower level. Even moderate but sustained weight loss of some 10 % of starting weight or less has been confirmed to be of medical value. Tolerance and safety of dF can be considered acceptable, even if longer term follow-up is clearly needed. These studies support the concept that long-term pharmacotherapy with this serotoninergic drug might help achieve better outcome in the management of many obese patients, particularly in preventing relapse. The long-term managerial strategies to be developed for each patient might thus include dF together with dietary advice, behavioral modification and physical exercise, either simultaneously or sequentially.     

Is weight loss an effective treatment for hypertension? The evidence against

Although there are many studies reporting correlations between relative body weight and blood pressure, the correlations are generally of low order. Furthermore, these observational studies provide, at best, circumstantial evidence concerning the effect of weight reduction on elevated blood pressure. After outlining key methodologic criteria for testing the hypothesis that weight loss lowers blood pressure among hypertensive obese subjects, this article reviews the best intervention studies that are available. Despite the demonstration in these randomized trials that weight reduction programs can lower weight successfully, the results for blood pressure lowering are in considerable disagreement. Two studies reported significant lowering of both systolic and diastolic blood pressure, one found significant lowering of systolic pressure only, and two failed to find significant differences in either. The definitive study of substantial weight loss among patients receiving no other antihypertensive treatment or standardized medical treatment with long-term follow-up has yet to be done. At best, weight loss offers very limited benefit for overweight hypertensives. At worst, weight loss programs are expensive to run, cause considerable patient discomfort and may delay the implementation of more effective therapy.     

The Fen-Phen Finale: A Study of Weight Loss and Valvular Heart Disease

Objective : To assess weight loss, as well as the prevalence of valvular heart disease, in 21 obese women who completed 2 years of treatment by fenfluramine and phentermine (fen-phen) in June 1997. Research Methods and Procedures : Patients were 21 of 22 women who had completed a 1-year, open-label trial of fen-phen combined with lifestyle modification. This study describes the results of a second year of treatment. The presence of valvular heart disease, defined as aortic regurgitation of mild or greater severity and/or mitral regurgitation of moderate or greater severity, was assessed using two-dimensional, color Doppler and pulsed- and continuouswave Doppler examinations. Results : At 2 years, the 21 patients had a mean reduction in initial weight of 13.9 ±10.1%, which was significantly (p<<0.001) smaller than their 1-year loss of 17.1 ±8.7%. Nine of 21 patients reported that they took fen-phen irregularly during the last 4 months of the study because of fears of developing health complications. These nine patients had a 2-year weight loss of 8.7 ± 7.5%, compared with a significantly (p<0.04) larger loss of 17.6 ± 10.5% for participants who reported taking medication regularly. Six of 20 (30%) patients met criteria for valvular heart disease. None of the six had signs or symptoms of this condition. Discussion : Fenfluramine was withdrawn from the market on September 15, 1997 because of concerns that it was associated with valvular heart disease. The present findings are discussed in terms of the potentially favorable long-term benefits of combining lifestyle modification with weight loss medications that are both safe and effective.     

Management of Obesity: A Challenge for Medical Training and Practice

Health‐care providers are in a unique position to encourage people to make healthy lifestyle choices. However, lifestyle modification counseling is a complex task, made even more so by the cultural and socioeconomic diversity of patient populations. The objective of this study is to evaluate the prevalence and predictors of attending and physician‐in‐training weight control counseling in an urban academic internal medicine clinic serving a unique low‐income multiethnic high‐risk population. In 2006, patients (n = 256) from the Associates in Internal Medicine clinic (Division of General Medicine at the New York Presbyterian Hospital, Columbia University Medical Center, New York, NY) were recruited and completed a questionnaire, which assessed demographic variables, health conditions, access to health‐care services, physician weight control counseling, and weight loss attempts. Seventy‐nine percent of subjects were either overweight or obese. Only 65% of obese subjects were advised to lose weight. Attending physicians were more likely than physicians‐in‐training to counsel subjects on weight control (P < 0.01). Factors that were significantly (P < 0.05) associated with different types of weight control counseling included obesity, cardiovascular disease (CVD) risk factors, female gender, nonblack race, college education, married status, and attending physician. Subjects advised to lose weight were more likely to report an attempt to lose weight (P < 0.01). Rates of weight control counseling among physicians are suboptimal, particularly among physicians‐in‐training. Training programs need to promote effective clinical obesity prevention and treatment strategies that address socioeconomic, linguistic, and cultural factors.     

Metformin Decreases Food Consumption and Induces Weight Loss in Subjects with Obesity with Type II Non-Insulin-Dependent Diabetes

Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased food intake. This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss. Twelve diet-treated NIDDM women with obesity were randomly given two dose levels (850 mg or 1700 mg) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3times3 Latin square design. The number of sandwich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake, and the level of subjective hunger was rated just before the sandwich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast. The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment. The 1700-mg metformin dose had the most marked appetite suppressant action. Similarly, hunger ratings were significantly lowered after metformin, and the effect was most pronounced after the administration of 1700 mg of metformin. To assess the efficacy of metformin in reducing bodyweight, 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA (American Diabetes Association) diet before being randomized to receive either metformin (850 mg) or placebo twice daily in a double-blind fashion for 24 weeks. A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period. Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment; their mean maximum weight loss was 8 kg greater than that of the placebo group, with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period. These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity.     

Barriers and Facilitators to Engagement With a Weight Management Intervention in Asian Patients With Overweight or Obesity: A Systematic Review

ObjectiveThe obesity epidemic is a global health concern with Asian countries facing one of the most rapid rises in obesity rates. However, given the underwhelming long-term efficacy of weight loss strategies, especially in Asia, this review aimed to explore barriers and facilitators to weight management of patients with overweight and obesity in Asia.MethodsMedline, CINAHL, PsycINFO, and Web of Science were searched for articles discussing barriers and facilitators of treatment to obesity from the perspectives of both health care professionals (HCPs) and patients. Qualitative and mixed method studies from Asia were included. Key quotes were extracted, coded, and thematically analyzed according to the methodology of Thomas and Harden.ResultsA total of 26 articles were included in this review. From patient perspectives, 3 main themes were identified: factors influencing poor eating behavior, inhibiting lifestyle modifications, and facilitating lifestyle modifications. Patients highlighted several barriers including the lack of social support, physiologic limitations to exercise, and low health literacy. Rigid sociocultural norms and lack of accessible health care services, exercise facilities, and healthy food exacerbated the barriers. Facilitators to lifestyle modifications consisted of strong support systems and high health literacy. HCPs agreed that low health literacy, lack of social support, and patient motivation impeded patients’ weight loss attempts but were unaware of the other barriers they faced.ConclusionThere are discrepancies between ideas of barriers and facilitators of HCPs and patients. A mixture of population level, primary care, and personal interventions are required to address this disparity, and enhanced health literacy can improve weight loss outcomes.     

Treatment of Morbid Obesity in Low‐income Adolescents: Effects of Parental Self‐monitoring

Objective: This study examined the extent to which consistency of self‐monitoring by participants and their parents was related to weight control over an initial period of 3 months within the context of a treatment program for morbidly obese low‐income minority adolescents. Research Methods and Procedures: Eighty‐three obese adolescents (mean age, 13.0 years; 51% boys; 92% African American; mean BMI, 43.0 kg/m²; mean BMI z‐score, 6.0) and at least one parent participated in a long‐term treatment program that included a very‐low‐fat dietary focus, weekly group cognitive‐behavior therapy, monthly nutrition education classes, a 12‐week physical therapy class, and medical monitoring. Results: Participants who self‐monitored on the majority of days compared with those who did not self‐monitor at all or who self‐monitored infrequently attended more sessions and generally lost more weight over the first 3 months. Although parents signed behavioral contracts committing to self‐monitor their own eating and exercising over the first month, only 12% did so. Nonetheless, participants whose parents self‐monitored were much more likely to self‐monitor consistently and lose weight during the first 3 months. Discussion: These results indicate that self‐monitoring is a cornerstone of successful weight control even for morbidly obese low‐income minority adolescents; targeting consistency of self‐monitoring among these high‐risk weight controllers and their parents should be just as important as it is for more affluent and less overweight adolescents.