Prevalence and impact of obesity in people with haemophilia: Review of literature and expert discussion around implementing weight management guidelines.

Obesity affects more than 35% of Americans, increasing the risk of more than 200 comorbid conditions, impaired quality of life and premature mortality. This review aimed to summarize literature published over the past 15 years regarding the prevalence and impact of obesity in people with haemophilia (PWH) and to discuss implementing general guidelines for weight management in the context of the haemophilia comprehensive care team. Although few studies have assessed the effects of obesity on haemophilia-specific outcomes, existing evidence indicates an important impact of weight status on lower extremity joint range of motion and functional disability, with potentially important effects on overall quality of life. Data regarding bleeding tendency in PWH with coexisting obesity are largely inconclusive; however, some individuals may experience reduced joint bleeds following moderate weight loss. Additionally, conventional weight-based dosing of factor replacement therapy leads to increased treatment costs for PWH with obesity or overweight, suggesting pharmacoeconomic benefits of weight loss. Evidence-based recommendations for weight loss include behavioural strategies to reduce caloric intake and increase physical activity, pharmacotherapy and surgical therapy in appropriate patients. Unique considerations in PWH include bleed-related risks with physical activity; thus, healthcare professionals should advise patients on types and intensities of, and approaches to, physical activity, how to adjust treatment to accommodate exercise and how to manage potential activity-related bleeding. Increasing awareness of these issues may improve identification of PWH with coexisting obesity and referral to appropriate specialists, with potentially wide-ranging benefits in overall health and well-being.

A proposed clinical staging system for obesity.

Current classifications of obesity based on body mass index, waist circumference and other anthropometric measures, although useful for population studies, have important limitations when applied to individuals in clinical practice. Thus, these measures do not provide information on presence or extent of comorbidities or functional limitations that would guide decision making in individuals. In this paper we review historical and current classification systems for obesity and propose a new simple clinical and functional staging system that allows clinicians to describe the morbidity and functional limitations associated with excess weight. It is anticipated that this system, when used together with the present anthropometric classification, will provide a simple framework to aid decision making in clinical practice.

Effect of histaminergic manipulation on weight in obese adults: a randomized placebo controlled trial.

OBJECTIVE: To determine the magnitude and determinants of weight loss in humans exposed to betahistine, a centrally acting histamine-1 (H-1) agonist and partial histamine-3 (H-3) antagonist. DESIGN: A multicenter randomized, placebo-controlled dose-ranging weight loss trial with a 12-week treatment period. SUBJECTS: Two hundred and eighty-one obese but otherwise healthy participants. MEASUREMENTS: Weight and obesity-related comorbidities at baseline and at the end of the intervention. RESULTS: Betahistine, at the doses tested, did not induce significant weight loss. With the exception of headache, no difference in adverse effect profile was noted between placebo and treatment groups. Subgroup analysis revealed that age below 50 years, ethnicity (non-Hispanics) and gender (women) were the strongest predictors of weight loss in this population. When these three factors were combined together, the betahistine 48 mg group (n=23) lost -4.24+/-3.87 kg, whereas the placebo group (n=25) lost -1.65+/-2.96 kg during this time period (P=0.005). CONCLUSION: Betahistine, at the doses tested, induced significant weight loss with minimal adverse events only in women below 50 years.

Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat.

OBJECTIVE: The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST). METHODS: Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry. RESULTS: Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group. CONCLUSIONS: NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons.

One Health Solutions to Obesity in People and Their Pets.

Despite the high prevalence of overweight and obesity in the human and companion animal populations, and the global trends for increasing numbers of affected people and pets, there are few successful interventions that are proven to combat this complex multifactorial problem. One key strategy involves effective communication between human and veterinary healthcare professionals with patients and clients about obesity. In human healthcare, the focus of communication should be on physical activity as part of overall health and wellbeing, rather than assessment of the body mass index; clinical examination of patients should record levels of physical activity as a key 'vital sign' as part of their assessment. Successful weight loss programmes for companion animals also involves strategic communication with the entire healthcare team leading clients through the 'stages of change'. There is great potential in employing a 'One Health' framework to provide novel solutions for the prevention and treatment of this condition in people and their pets. Comparative clinical research into the biology of obesity and its comorbidities in dogs and cats is likely to lead to knowledge relevant to the equivalent human conditions. The advantages of companion animal clinical research over traditional rodent models include the outbred genetic background and relatively long lifespan of pets and the fact that they share the human domestic environment. The human-companion animal bond can be leveraged to create successful programmes that promote physical activity in people and their pets with obesity. Dog walking is a proven motivator for human physical activity, with health benefits to both the owner and the dog. Realizing the potential of a One Health approach will require the efforts and leadership of a committed group of like-minded individuals representing a range of scientific and medical disciplines. Interested parties will need the means and opportunities to communicate and to collaborate, including having the resources and funding for research. One Health proponents must have a role in forming public policy related to the prevention and management of overweight and obesity.

Metabolic acidosis. Development in two patients receiving a potassium-sparing diuretic and total parenteral nutrition.

Two patients developed a metabolic acidosis associated with a normal undetermined anion concentration while receiving a potassium-sparing diuretic and total parenteral nutrition. In both cases the metabolic acidosis resolved within one week after discontinuing administration of the diuretic. The use of potassium-sparing diuretics in a patient receiving total parenteral nutrition requires caution and continued monitoring for this potential drug-nutrient interaction.

Resting and total energy expenditure in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease often present with weight loss. Among possible causes, an elevated energy expenditure has frequently been suggested but is the least documented. In this study resting metabolic rate (RMR) and total daily energy expenditure (TDEE) were measured in 15 outpatients with inflammatory bowel diseases and in eight healthy control subjects. Measured RMR as a percentage of that predicted from fat-free mass was not significantly different for control subjects (102 +/- 9.8%, mean +/- SD) and patients (100 +/- 13.3%). TDEE, expressed as a multiple of RMR, was 1.70 +/- 0.31 for control subjects and 1.78 +/- 0.24 for patients. When patients were subgrouped as greater than or equal to 90% or less than 90% desirable body weight, a mean increase over RMR predicted from fat-free mass was seen in the underweight patients (106 +/- 9.3%) but not in normal-weight patients (99.0 +/- 15.6%). Mean TDEE/RMR values for the patient subgroups were 1.70 +/- 0.30 and 1.88 +/- 0.08, respectively. We conclude that stable outpatients with inflammatory bowel disease have only a minimal increase in energy needs.

Estimation of total body water by bioelectrical impedance analysis.

Total body water (TBW) measured by bioelectrical impedance analysis (BIA) was directly compared with deuterium-isotope dilution in a total of 58 subjects. First, sex-specific and group equations were developed by multiple regression analysis in (10 each) obese and nonobese men and women. Height/resistive impedance was the most significant variable used to predict deuterium-dilution space (D2O-TBW) and, combined with weight, yielded R = 0.99 and SE of estimate = 1.75 L. Equations predicted D2O-TBW equally well for obese and nonobese subjects. Second, the equations were prospectively tested in a heterogeneous group of 6 males and 12 females. Sex-specific equations predicted D2O-TBW with good correlation coefficients (0.96 and 0.93), total error (2.34 and 2.89 L), and a small difference between mean predicted and measured D2O-TBW (-1.4 +/- 2.05 and -0.48 +/- 2.83 L). BIA predicts D2O-TBW more accurately than weight, height, and/or age. A larger population is required to validate the applicability of our equations.

Clinical characteristics influencing bioelectrical impedance analysis measurements.

Standardization of measurement conditions is essential for obtaining accurate, precise, and reproducible bioelectrical impedance analysis (BIA) data. Errors due to lack of measurement control are propagated in subsequent calculations of body composition and contribute to differences in predictive equations among investigators. Various individual and environmental factors have been shown to influence BIA. We review the factors that have been identified from the literature as being conditions requiring standardization both for healthy subjects and for those in a medical setting.

How much physical activity is needed to minimize weight gain in previously obese women?

Exercise is frequently identified as a predictor of weight maintenance after elective weight loss in retrospective studies of treatments for obesity. We conducted a prospective study to test whether physical activity measured soon after weight loss predicted weight maintenance and to determine how much physical activity was required to optimize maintenance. Thirty-two women [mean (+/- SD) age, 38 +/- 7 y; body mass index (in kg/m2), 24 +/- 3] were recruited through local advertising within 3 mo of reaching their target for weight loss (23 +/- 9 kg). Total energy expenditure (TEE) was measured by the doubly labeled water method. Postabsorptive resting metabolic rate (RMR) and postprandial RMR [expressed as thermic effect of a meal (TEM)] were measured by respiratory gas exchange. Women in the physically active group (ratio of TEE to RMR = 1.89 +/- 0.08) gained 2.5 +/- 3.1 kg during the 12 mo after reaching their target for weight loss, moderately active women (TEE:RMR = 1.64 +/- 0.05) gained 9.9 +/- 10.5 kg, and sedentary women (TEE:RMR = 1.44 +/- 0.08) gained 7.0 +/- 5.9 kg (P < 0.01). Retrospective analyses of weight regain as a function of energy expended in physical activity indicated a threshold for weight maintenance of 47 kJ x kg body wt(-1) x d(-1). This corresponds to an average of 80 min/d of moderate activity or 35 min/d of vigorous activity added to a sedentary lifestyle.

Is the impedance index (ht2/R) significant in predicting total body water?

We investigated the general utility of bioelectrical impedance analysis (BIA) and the implications of BIA theory in populations of various ages from infancy to adulthood by developing a single impedance equation. Four subject data sets representing 62 adults, 37 prepubertal children, 44 preschool children, and 32 premature low-birth-weight neonates were combined. Subjects were randomly divided into a development group (n = 116) and a cross-validation group (n = 59). The single best predictor of total body water (TBW) was height2/resistance (ht2/R), which explained 99% of the variation in TBW (SEE = 1.67 kg). The addition of weight reduced the SEE to 1.41 kg. A significant bias was only seen in the preschool children. These results were confirmed in the cross-validation group and the best prediction formula was TBW = 0.59 ht2/R + 0.065 wt + 0.04. We conclude that the impedance index (ht2/R) is a significant predictor of TBW and that there is some improvement in prediction of TBW by inclusion of a weight term.

Use of bioelectrical impedance analysis measurements in the clinical management of patients undergoing dialysis.

The use of bioelectrical impedance analysis (BIA) in patients with end-stage renal disease who are receiving dialysis provides researchers with two important applications: 1) a biological model in which the underlying assumptions of BIA can be tested, and 2) if valid, a tool that can be used to improve the clinical management of patients receiving dialysis. We review the rationale of and purpose for using BIA in the dialysis population, the physiologic changes that occur during dialysis that influence BIA measurements, and last, conclusions reached from the current scientific literature.

Validation of doubly labeled water for measuring energy expenditure during parenteral nutrition.

The doubly labeled water method was compared with intake-balance for measuring energy expenditure in five patients receiving total parenteral nutrition (TPN). Because parenteral solutions were isotopically different from local water, patients had to be placed on TPN at least 10 days before the metabolic period. Approximately 0.1 g 2H2O and 0.25 g H2(18)O per kg total body water were given orally. We collected saliva before, 3 h, and 4 h after the dose for measurement of total body water and urine before, 1 day, and 14 days after the dose for measurement of isotope eliminations. On day 14, total body weight was remeasured and change in body energy stores was calculated, assuming constant hydration. Intake was assessed from weights of TPN fluids plus dietary record for any oral intake. Energy expenditure from doubly labeled water (+/- SD) averaged 3 +/- 6% greater than intake-balance. Doubly labeled water method is a noninvasive, nonrestrictive method for measuring energy expenditure in patients receiving TPN.

Effects of aerobic exercise and dietary carbohydrate on energy expenditure and body composition during weight reduction in obese women.

To test the benefits of aerobic exercise and dietary carbohydrate during reduced-energy feeding, 23 obese women (44 +/- 4% fat) were randomly assigned to either aerobic exercise (Ex) or no exercise (Nx), and to a low-fat (LF) or low-carbohydrate (LC) reducing diet (5.00 +/- 0.56 MJ/d) for 12 wk. Changes in body composition, postabsorptive resting metabolic rate (RMR), thermic effect of a meal (TEM), and total daily energy expenditure (TDEE) were measured by respiratory gas exchange and doubly labeled water. Significant effects of Ex included a greater loss of fat mass (Ex: -8.8 +/- 2.1 vs Nx: -6.1 +/- 2.3 kg, P = 0.008) and maintenance of TDEE (Ex: +0.07 +/- 1.23 vs Nx: -1.46 +/- 1.04 MJ/d, P = 0.004), due to a difference in physical activity (Ex: +0.75 +/- 1.06 vs Nx: -0.61 +/- 1.03 MJ/d, P = 0.006), which was not attributable solely to the Ex sessions. RMR in both groups decreased comparably (-0.54 MJ/d), and TEM (% of meal) did not change. Diet composition did not significantly influence body composition or energy expenditure changes, but a greater weight loss was observed after the LC than after the LF (-10.6 +/- 2.0 vs -8.1 +/- 3.0 kg, P = 0.037) diet. The addition of aerobic exercise to a low-energy diet was beneficial in the treatment of moderate obesity because of its favorable effects on body composition, physical activity, and TDEE.

Total daily energy expenditure and activity level in anorexia nervosa.

Clinical reports consistently comment on high physical activity for anorexia nervosa patients but provide few quantitative measurements. To assess activity, total daily energy expenditure (TDEE) by doubly labeled water, basal metabolic rate (BMR), and thermic effect of meals (TEM) were measured in six female outpatients with anorexia nervosa (67% of ideal body weight) and age-, sex-, and height-matched to six control subjects. Anorexia nervosa patients expended more energy as physical activity than did control subjects [0.084 +/- 0.012 vs 0.044 +/- 0.008 MJ/kg body wt, respectively (20.1 +/- 3.0 vs 10.5 +/- 1.9 kcal/kg body wt, respectively), P less than 0.04], although they had a lower BMR [4.17 +/- 0.37 vs 5.52 +/- 0.15 MJ/d, respectively (997 +/- 89 vs 1319 +/- 37 kcal/d, respectively), P less than 0.01]. TDEE and TEM were similar in both groups. There was a reduction in serum triiodothyronine (T3; 1.20 +/- 0.15 vs 2.04 +/- 0.13 nmol/L, respectively; P less than 0.003) and a slight reduction in serum thyroxine (T4); reverse T3, thyrotropin, free T4, serum cortisol, and adrenocorticotropin values were normal. BMR correlated with total body weight and fat-free mass. These results provide quantitative evidence for increased physical activity in anorexia nervosa despite profound underweight and hypometabolism.

Exercise enhances dietary compliance during moderate energy restriction in obese women.

The effect of aerobic exercise on dietary compliance was assessed in 13 obese women (44 +/- 3% fat) during a 12-wk weight-reduction program (EX group). Seventeen obese women (45 +/- 5% fat) not engaged in aerobic exercise (NX group) served as control subjects. The reducing diets were designed to promote a weight loss of 1 kg/wk, with energy intakes individually prescribed (mean +/- SD: 4.9 +/- 0.6 MJ/d) to approximate 75% of each subject's measured basal metabolic rate. The EX group completed of three 45-min sessions/wk of supervised aerobic exercise at 65% of maximal oxygen consumption (VO2max). Daily energy intakes were calculated by summing changes in body stores, measured by total body water isotope dilution, and total daily energy expenditure, measured by doubly labeled water (DLW). Dietary compliance was assessed by comparing calculated intakes with prescribed intakes. Both the EX and NX groups reported consuming close to their prescribed daily intakes, with differences of -0.08 +/- 0.28 (EX group) and +0.03 +/- 0.57 (NX group) MJ/d, respectively. However, expenditure/balance data determined by the DLW method indicated that the EX subjects exhibited better dietary compliance than the NX subjects, with intakes exceeding those prescribed by only 0.7 +/- 1.5 compared with 2.3 +/- 1.6 MJ/d for the NX subjects (P = 0.01). Therefore, an additional benefit of aerobic exercise during energy restriction is enhanced dietary compliance, which has important implications for the treatment of moderate obesity.

Validation of bioelectrical-impedance analysis as a measurement of change in body composition in obesity.

The bioelectrical-impedance-analysis (BIA) method accurately measures body composition in weight-stable subjects. This study validates the use of BIA to measure change in body composition. Twelve obese females underwent weight loss at a mean rate of 1.16 kg/wk. Body composition was measured by deuterium oxide dilution (D2O), BIA, and skinfold anthropometry (SFA) at baseline and at 5% decrements in weight. Highly significant correlations were obtained between D2O and BIA (r = 0.971) and between D2O and SFA (r = 0.932). Overall, BIA predicted change in fat-free mass with greater accuracy (to 0.4 kg) and precision (+/- 1.28 kg) than did anthropometry (to 0.8 kg and +/- 2.58 kg, respectively). We conclude that BIA is a useful clinical method for measuring change in body composition.

Implementing nutrition into the medical curriculum: a user's guide.

The medical profession is facing the challenges of the 1990s with a shift to outpatient care and preventive services. Medical schools will need to respond to these forces by reevaluating their curricula and setting new objectives. Nutrition is an essential element in the process of curriculum change. The nutrition educator will be expected to take a leading role in integrating nutrition into the medical school curriculum. This report presents steps and strategies to initiate the process.

Nutrition coverage on medical licensing examinations in the United States.

The 1985 National Academy of Sciences report Nutrition Education in US Medical Schools recommended that the National Board of Medical Examiners (NBME), who develops the US Medical Licensing Examination (USMLE), cover basic nutrition knowledge. According to the NBME, the USMLE includes nutrition on their Step 1 and 2 exams; however, this coverage has been questioned. To document whether the NBME adequately addresses nutrition, the 1986 Part I and Part II and the 1993 Step 1 and step 2 exams, which replaced the Part I and II exams, were reviewed by five nutrition professionals. This review identified the nutrition-related areas of the two-part exams and how the extent of nutrition coverage changed from 1986 to 1993. Nutrition items were coded on four dimensions: 1) specific nutrition-related topic area, 2) normal or abnormal scenario, 3) related organ system, and 4) importance in clinical medicine. The percentage of nutrition-related items, as identified by the nutrition professionals, increased from 9% on the 1986 Part I exam to 11% on the 1993 Step 1 exam and from 6% on the 1986 Part II exam to 12% on the 1993 Step 2 exam. The percentage of nutrition items related to vitamin deficiencies increased from 1986 to 1993 on both halves of the exam. Nutrition coverage on the USMLE Step 1 and Step 2 seems adequate in amount, however, the content and appropriateness of the items were not evaluated. The observed increased focus on vitamin deficiencies should be further considered.

Nutrition training in graduate medical (residency) education: a survey of selected training programs.

Because limited information exists about nutrition training of residents, we studied the teaching practices of nationally recognized nutrition programs. Two hundred thirty-eight nutrition educators and 787 residency-program directors identified 160 institutions with strong nutrition training. The 23 highest-ranked programs were surveyed and 7 were visited. The results showed that 1) clinically active physician-nutritionist role models are the key elements in teaching residents clinical nutrition; 2) multidisciplinary nutrition support teams are valuable learning resources unless they function primarily as technical support services; 3) nutrition elective rotations, although highly effective, are taken by a minority of residents; 4) the nutrition curriculum should include practical learning materials and conferences; and 5) a research environment is important to attract qualified physician-nutritionist role models. A major deficit is teaching nutritionally based approaches to disease prevention in the ambulatory setting. Finally, a shortage of nutrition-oriented physician role models is probably the major constraint in teaching nutrition to residents.