Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

Background Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. Methods We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indicate statistical significance. Results Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P=0.001), but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant (34% and 19%, respectively; P=0.04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pioglitazone, as compared with placebo (P Conclusions Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some of the secondary outcomes. (ClinicalTrials.gov number, NCT00063622.

Psychosocial Characteristics and Pain Burden of Patients With Suspected Sphincter of Oddi Dysfunction in the EPISOD Multicenter Trial

Patients with several painful functional gastrointestinal disorders (FGIDs) are reported to have a high prevalence of psychosocial disturbance. These aspects have not been studied extensively in patients with suspected Sphincter of Oddi dysfunction (SOD)

Challenges in planning and initiating a randomized clinical study of sphincter of Oddi dysfunction

Sphincter of Oddi dysfunction (SOD) is a controversial topic, especially in patients with no objective findings on laboratory or imaging studies (SOD type III). The value of ERCP manometry with sphincterotomy is unproven and carries significant risks

Acute Cardiovascular and Metabolic Responses to Three Modes of Treadmill Exercise in Older Adults with Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative condition characterized by muscle tremors, rigidity and dyskinesis leading to balance and gait abnormalities that could alter physiologic responses during exercise. Locomotion on an aquatic treadmill (ATM) or anti-gravity treadmill (AGTM) may be a safe alternative to exercise on a traditional land treadmill (LTM) in those with PD. PUPROSE: To determine the acute cardiovascular and metabolic responses to three different modes of treadmill exercise in older adults diagnosed with Parkinson’s disease. METHODS: Eight adults diagnosed with PD (68 ± 3 years of age) completed one exercise session on an LTM, one session on an ATM, and one session on an AGTM at 50% body weight. Participants walked from 1 to 3 mph in 0.5 mph increments at 0% grade during each exercise session. Heart rate (HR), energy expenditure (EE), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured at rest and during steady-state exercise at each speed on each treadmill. Rate of perceived exertion was also measured during steady-state exercise. Rate pressure product (RPP) was calculated. RESULTS: All variables, with the exception of DBP, increased as speed increased across all treadmill modes (p \u3c 0.001). Between treadmill modes across all speeds, EE was statistically different (p = 0.025). There was a significant interaction effect for mode and speed for HR (p \u3c 0.001) and RPP (p = 0.003). At all speeds except 1.5 mph, HR was higher on the LTM versus the AGTM (p \u3c 0.05). CONCLUSION: Exercising on an ATM or an AGTM elicits similar physiologic responses to exercise on an LTM in adults with P

Changes in Balance, Gait and Motor Skills Following Treadmill Exercise in Adults with Parkinson’s Disease

Locomotion on an aquatic treadmill or anti-gravity treadmill may be a safe and effective alternative to exercise on a traditional land treadmill in those with Parkinson’s disease as the removal of body weight in these environments may allow the participant to exercise with less concern of falling at higher speeds before reaching volitional fatigue. PURPOSE: To determine the training effects of three different treadmill modalities on dynamic balance, gait, and fine motor control in older adults diagnosed with Parkinson’s disease. METHODS: Ten adults diagnosed with Parkinson’s disease (70 ± 5 years of age) completed 8 exercise sessions (4 weeks, 2x/week) each separately on a land treadmill, aquatic treadmill, and anti-gravity treadmill at 50% body weight. Two weeks separated each intervention and the order was randomized. A 4-week control period occurred at the start of the study in which no treadmill exercise was performed. Each exercise session included a 2-minute warm-up and 30 minutes at a moderate intensity. Before and after each intervention, balance, gait and fine motor control were measured. Dynamic balance and gait were assessed using a Timed-Up-and-Go test and Performance Oriented Mobility Assessment (POMA). Fine motor control was assessed with the Purdue Pegboard Test. RESULTS: The gait assessment of the POMA was significant across all time points (p = 0.028). All other variables were statistically similar (p \u3e 0.05) across all time points. CONCLUSION: Exercising on a traditional land treadmill, aquatic treadmill, or anti-gravity treadmill for 60 min/week for 4 weeks at a moderate intensity did not alter balance, gait or fine motor control in adults with Parkinson’s disease

Effect of Endoscopic Sphincterotomy for Suspected Sphincter of Oddi Dysfunction on Pain-Related Disability Following Cholecystectomy: The EPISOD Randomized Clinical Trial

Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy

Portal Hypertension in Children and Young Adults With Biliary Atresia

ObjectiveBiliary atresia (BA) frequently results in portal hypertension (PHT), complications of which lead to significant morbidity and mortality. The Childhood Liver Disease Research and Education Network was used to perform a cross-sectional multicentered analysis of PHT in children with BA.MethodsSubjects with BA receiving medical management at a Childhood Liver Disease Research and Education Network site were enrolled. A priori, clinically evident PHT was defined as "definite" when there was either history of a complication of PHT or clinical findings consistent with PHT (both splenomegaly and thrombocytopenia). PHT was denoted as "possible" if one of the findings was present in the absence of a complication, whereas PHT was "absent" if none of the criteria were met.ResultsA total of 163 subjects were enrolled between May 2006 and December 2009. At baseline, definite PHT was present in 49%, possible in 17%, and absent in 34% of subjects. Demographics, growth, and anthropometrics were similar amongst the 3 PHT categories. Alanine aminotransferase, γ-glutamyl transpeptidase, and sodium levels were similar, whereas there were significant differences in aspartate aminotransferase (AST), AST/alanine aminotransferase, albumin, total bilirubin, prothrombin time, white blood cell count, platelet count, and AST/platelet count between definite and absent PHT. Thirty-four percent of those with definite PHT had either prothrombin time >15 seconds or albumin <3 g/dL.ConclusionsClinically definable PHT is present in two-thirds of North American long-term BA survivors with their native livers. The presence of PHT is associated with measures of hepatic injury and dysfunction, although in this selected cohort, the degree of hepatic dysfunction is relatively mild and growth is preserved

Efficacy of Fat-Soluble Vitamin Supplementation in Infants With Biliary Atresia

ObjectiveCholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation.MethodsInfants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE.ResultsNinety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%-36% of patients), vitamin D (21%-37%), vitamin K (10%-22%), and vitamin E (16%-18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%-100% for the different vitamins) in infants whose TB was ≥2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV.ConclusionsBiochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL

Impact of Hepatitis C Virus Infection on Children and Their Caregivers : Quality of Life, Cognitive, and Emotional Outcomes

OBJECTIVE: HCV infection is associated with decreased quality of life (QOL) and neurocognitive dysfunction in adults, but little is known about its impact on children and their caregivers. DESIGN AND PATIENTS: We studied the QOL, behavioral, emotional, and cognitive functioning of 114 treatment-naïve children with HCV enrolled in a placebo-controlled, randomized, multi-site clinical trial evaluating peginterferon alpa-2a alone or with ribavirin. OUTCOME MEASURES: Baseline assessment included measures of children’s QOL, cognitive functioning, behavioral adaptation, and depression. Caregivers’ QOL was also assessed. RESULTS: Relative to published normative data, caregivers were more likely to believe that their children’s health was poor and would likely worsen (t = 3.93, p < 0.0001), reported higher concern about their children’s health status (t = 6.63, p < 0.0001) and that this concern limited family activities (t = 2.45, p < 0.01); they also viewed their children as having more internalizing behavioral problems (t = 1.98, p < 0.05). Only 2 (2%) children had a score in the clinically depressed range. Children with HCV had worse cognitive functioning than the normative sample, but significantly better functioning than children with attention deficit hyperactivity disorder. Caregivers’ QOL scores did not differ significantly from the normative sample, but infected mothers had lower QOL than non-infected caregivers. Caregivers were highly distressed about their children’s medical circumstances. CONCLUSION: While HCV infection, in its early stages, does not lead to global impairment in QOL, cognitive, behavioral, or emotional functioning in children, it is associated with higher caregiver stress and strain on the family system, and it may be associated with some cognitive changes in children