Disability is an emerging field within public health; people with significant disabilities account for more than 12% of the US population. Disparity status for this group would allow federal and ...state governments to actively work to reduce inequities. We summarize the evidence and recommend that observed differences are sufficient to meet the criteria for health disparities: population-level differences in health outcomes that are related to a history of wide-ranging disadvantages, which are avoidable and not primarily caused by the underlying disability. We recommend future research and policy directions to address health inequities for individuals with disabilities; these include improved access to health care and human services, increased data to support decision-making, strengthened health and human services workforce capacity, explicit inclusion of disability in public health programs, and increased emergency preparedness.
To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.
Randomized trial.
Multicenter collaboration at US two sites, August 2014 to May 2017.
164 adults ...aged 18-65 years with a body mass index of 25 or more.
After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).
The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.
Total energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval -29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (-6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).
Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.
ClinicalTrials.gov NCT02068885.
Treatment of acute Kawasaki disease with intravenous immune globulin and aspirin reduces the risk of coronary-artery abnormalities and systemic inflammation, but despite intravenous immune globulin ...therapy, coronary-artery abnormalities develop in some children. Studies have suggested that primary corticosteroid therapy might be beneficial and that adverse events are infrequent with short-term use.
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to determine whether the addition of intravenous methylprednisolone to conventional primary therapy for Kawasaki disease reduces the risk of coronary-artery abnormalities. Patients with 10 or fewer days of fever were randomly assigned to receive intravenous methylprednisolone, 30 mg per kilogram of body weight (101 patients), or placebo (98 patients). All patients then received conventional therapy with intravenous immune globulin, 2 g per kilogram, as well as aspirin, 80 to 100 mg per kilogram per day until they were afebrile for 48 hours and 3 to 5 mg per kilogram per day thereafter.
At week 1 and week 5 after randomization, patients in the two study groups had similar coronary dimensions, expressed as z scores adjusted for body-surface area, absolute dimensions, and changes in dimensions. As compared with patients receiving placebo, patients receiving intravenous methylprednisolone had a somewhat shorter initial period of hospitalization (P=0.05) and, at week 1, a lower erythrocyte sedimentation rate (P=0.02) and a tendency toward a lower C-reactive protein level (P=0.07). However, the two groups had similar numbers of days spent in the hospital, numbers of days of fever, rates of retreatment with intravenous immune globulin, and numbers of adverse events.
Our data do not provide support for the addition of a single pulsed dose of intravenous methylprednisolone to conventional intravenous immune globulin therapy for the routine primary treatment of children with Kawasaki disease. (ClinicalTrials.gov number, NCT00132080 ClinicalTrials.gov.)
Objective To describe common associated symptoms within the 10 days before diagnosis in subjects enrolled in the Pediatric Heart Network's trial of steroid therapy in Kawasaki disease (KD). Study ...design Patients with acute KD were enrolled between days 4 and 10 of illness at 8 centers between 2002 and 2004. We defined common associated symptoms as those occurring in ≥10% of patients. Principal clinical criteria for KD were not included in this analysis. Results Among 198 patients, irritability was reported in 98 (50%), vomiting in 88 (44%), decreased food/fluid intake in 73 (37%), cough in 55 (28%), diarrhea in 52 (26%), rhinorrhea in 37 (19%), weakness in 37 (19%), abdominal pain in 35 (18%), and joint pain (arthralgia or arthritis) in 29 (15%). One or more gastrointestinal symptom (vomiting, diarrhea, or abdominal pain) was present in 120 patients (61%) and 69 patients (35%) had ≥ 1 respiratory symptom (rhinorrhea or cough). Conclusions Nonspecific symptoms occur commonly in children with KD. To reduce delays in diagnosis, clinicians should be educated that such symptoms may comprise a significant component in the chief complaint.
Because late diagnosis of Kawasaki disease increases the risk for coronary artery abnormalities, we explored the prevalence of and possible risk factors for delayed diagnosis by using the database of ...the Pediatric Heart Network trial of corticosteroid treatment for Kawasaki disease.
We collected sociodemographic and clinical data at presentation for all patients who were treated for presumed Kawasaki disease at 8 centers (7 in the United States, 1 in Canada). Delayed diagnosis was evaluated by total number of illness days to diagnosis and by the percentage of patients who were treated after day 10 of illness. Independent predictors of delayed diagnosis were identified by using multivariate linear and logistic regression.
Of the 589 patients who received intravenous immunoglobulin, 27 were treated before screening for the trial and excluded; 562 patients formed the cohort for analysis. Kawasaki disease was diagnosed at 7.9 +/- 3.9 days, 92 (16%) cases after day 10. Centers were similar with respect to patient age and gender. Centers differed in the patient percentage with incomplete Kawasaki disease; clinical criteria of cervical adenopathy, oral changes, and conjunctivitis; and distance of residence from the center. Independent predictors of greater number of illness days at diagnosis included center, age of <6 months, incomplete Kawasaki disease, and greater distance from the center. Independent predictors of diagnosis after day 10 were age of <6 months, incomplete Kawasaki disease, and greater distance). Socioeconomic variables had no association with delayed diagnosis.
Even after adjustment for patient factors, illness duration at diagnosis varies by center. These findings underscore the need to maintain a high index of suspicion of Kawasaki disease in the infant who is younger than 6 months and has prolonged fever even with incomplete criteria. Outreach educational programs may be useful in promoting earlier recognition and treatment of Kawasaki disease.
Background Cardiovascular disease, including aortic root dilation, dissection, and rupture, is the leading cause of mortality in patients with Marfan syndrome (MFS). The maximal aortic root diameter ...at the sinuses of Valsalva is considered the best predictor of adverse cardiovascular outcome. Although advances in therapy have improved life expectancy, affected individuals continue to suffer cardiovascular morbidity and mortality. Recent studies in an FBN1 -targeted mouse model of MFS with aortic disease similar to that seen in humans showed that treatment with losartan normalized aortic root growth and aortic wall architecture. Methods The Pediatric Heart Network designed a randomized clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in subjects with MFS receiving atenolol or losartan. Individuals 6 months to 25 years of age with a body surface area–adjusted aortic root z score >3.0 will be eligible for inclusion. The primary aim is to compare the effect of atenolol therapy with that of losartan therapy on the rate of aortic root growth over 3 years. Secondary end points include progression of aortic regurgitation; incidence of aortic dissection, aortic root surgery, and death; progression of mitral regurgitation; left ventricular size and function; echocardiographically derived measures of central aortic stiffness; skeletal and somatic growth; and incidence of adverse drug reactions. Conclusion This randomized trial should make a substantial contribution to the management of individuals with MFS and expand our understanding of the mechanisms responsible for the aortic manifestations of this disorder.
Longer-term feeding studies suggest that a low-carbohydrate diet increases energy expenditure, consistent with the carbohydrate-insulin model of obesity. However, the validity of methodology utilized ...in these studies, involving doubly labeled water (DLW), has been questioned.
The aim of this study was to determine whether dietary energy requirement for weight-loss maintenance is higher on a low-compared with high-carbohydrate diet.
The study reports secondary outcomes from a feeding study in which the primary outcome was total energy expenditure (TEE). After attaining a mean Run-in weight loss of 10.5%, 164 adults (BMI ≤25 kg/m2 ; 70.1% women) were randomly assigned to Low-Carbohydrate (percentage of total energy from carbohydrate, fat, protein: 20/60/20), Moderate-Carbohydrate (40/40/20), or High-Carbohydrate (60/20/20) Test diets for 20 wk. Calorie content was adjusted to maintain individual body weight within ± 2 kg of the postweight-loss value. In analyses by intention-to-treat (ITT, completers, n = 148) and per protocol (PP, completers also achieving weight-loss maintenance, n = 110), we compared the estimated energy requirement (EER) from 10 to 20 wk of the Test diets using ANCOVA.
Mean EER was higher in the Low-versus High-Carbohydrate group in models of varying covariate structure involving ITT ranging from 181 (95% CI: 8–353) to 246 (64–427) kcal/d; P e0.04 and PP ranging from 245 (43–446) to 323 (122–525) kcal/d; P ≤0.02. This difference remained significant in sensitivity analyses accounting for change in adiposity and possible nonadherence.
Energy requirement was higher on a low- versus high-carbohydrate diet during weight-loss maintenance in adults, commensurate with TEE. These data are consistent with the carbohydrate-insulin model and lend qualified support for the validity of the DLW method with diets varying in macronutrient composition. This trial was registered at clinicaltrials.gov as NCT02068885.
Background The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome ...randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. Methods and results Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area–adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. Conclusions Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome.
Abstract
Context
According to the carbohydrate-insulin model of obesity, an elevated insulin-to-glucagon ratio in response to a high-carbohydrate diet directs metabolic fuels toward storage, ...resulting in lower circulating energy.
Objective
To determine differences in total circulating energy post-meal related to dietary carbohydrate.
Design
Ancillary study within the Framingham State Food Study.
Setting
University community.
Participants
29 adults (aged 20 to 65 years) with overweight or obesity (body mass index ≥25 kg/m2)
Intervention
After achieving 10% to 14% weight loss on a run-in diet, participants were randomized to weight-loss-maintenance test diets varying in carbohydrate content (high-carbohydrate, 60% of total energy, n = 11; moderate-carbohydrate, 40%, n = 8; low-carbohydrate, 20%, n = 10) and controlled for protein (20%). During 24-hour metabolic ward admissions between 10 and 15 weeks on the test diets, metabolic fuels and hormones were measured.
Main Outcome Measure
Energy availability (EA) based on energy content of blood glucose, beta-hydroxybutyrate, and free fatty acids, in the late postprandial period (180 to 300 minutes). Insulin at 30 minutes into the test meal (Meal Insulin-30) was measured as an effect modifier.
Results
Insulin-to-glucagon ratio was 7-fold higher in participants on the high- vs low-carbohydrate diet (2.5 and 0.36, respectively). Late postprandial EA was 0.58 kcal/L lower on the high- vs low-carbohydrate diet (P < 0.0001), primarily related to suppression of free fatty acids. Early postprandial EA (30 to 180 minutes) declined fastest in the high-carbohydrate group, and Meal Insulin-30 modified this diet effect.
Conclusions
During weight-loss maintenance on a high-carbohydrate diet, late postprandial EA is reduced, consistent with the carbohydrate-insulin model.
Surgical and perioperative improvements permit earlier repair of partial and transitional atrioventricular septal defects (AVSD). We sought to describe contemporary outcomes in a multicenter cohort.
...We studied 87 patients undergoing primary biventricular repair of partial or transitional AVSD between June 2004 and February 2006 across seven North American centers. One-month and 6-month postoperative data included weight-for-age z-scores, left atrioventricular valve regurgitation (LAVVR) grade, residual shunts, and left ventricular ejection fraction. Paired methods were used to assess 6-month change.
Median age at surgery was 1.8 years; median weight z-score was -0.88. Median days for ventilation were 1, intensive care 2, and hospitalization 5, all independent of age, with 1 in-hospital death. At 1 month, 27% (16 of 73) had ejection fraction less than 55%; 20% (17 of 87) had significant LAVVR; 2 had residual shunts; 1 each had subaortic stenosis and LAVV stenosis. At 6 months (n = 60), there were no interim deaths, reinterventions, or new development of subaortic or LAVV stenosis. Weight z-score improved by a median 0.4 units (p < 0.001), especially for underweight children less than 18 months old. Left atrioventricular valve regurgitation occurred in 31% (change from baseline, p = 0.13), occurring more frequently in patients repaired at 4 to 7 years (p = 0.01). Three patients had ejection fraction less than 55%, and 1 had a residual atrial shunt.
Surgical repair for partial/transitional AVSD is associated with low morbidity and mortality, short hospital stays, and catch-up growth, particularly in underweight children repaired between 3 and 18 months of age. Left atrioventricular valve regurgitation remains the most common residual defect, occurring more frequently in children repaired after 4 years of age.