Search

We showed previously that supplementation for 30 d with 800 IU (727 mg) vitamin E/d did not adversely affect healthy elderly persons. We have now assessed the effects of 4 mo of supplementation with 60, 200, or 800 IU (55, 182, or 727 mg) all-rac-[Alpha]-tocopherol/d on general health, nutrient status, liver enzyme function, thyroid hormone concentrations, creatinine concentrations, serum autoantibodies, killing of Candida albicans by neutrophils, and bleeding time in 88 healthy subjects aged [is greater than] 65 y participating in a double-blind, placebo-controlled trial. No side effects were reported by the subjects. Vitamin E supplementation had no effect on body weight, plasma total proteins, albumin, glucose, plasma lipids or the lipoprotein profile, total bilirubin, alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase, lactate dehydrogenase, serum urea nitrogen, total red blood cells, white blood cells or white blood cell differential counts, platelet number, bleeding time, hemoglobin, hematocrit, thyroid hormones, or urinary or serum creatinine concentrations. Values from all supplemented groups were within normal ranges for older adults and were not significantly different from values in the placebo group. Vitamin E supplementation had no significant effects on plasma concentrations of other antioxidant vitamins and minerals, glutathione peroxidase, superoxide dismutase, or total homocysteine. There was no significant effect of vitamin E on serum nonspecific immunoglobulin concentrations or anti-DNA and anti-thyrogiobulin antibodies. The cytotoxic ability of neutrophils against Candida albicans was not compromised. Thus, 4 mo of supplementation with 60-800 IU vitamin E/d had no adverse effects. These results are relevant for determining risk-to-benefit ratios for vitamin E supplementation. Am J Clin Nutr 1998; 68:311-8.

Background: Chest pain is a common clinical problem, but up to 30% of patients who present with chest pain lack coronary disease. Subsequent investigation often reveals an esophageal source for the pain, with gastroesophageal reflux disease identified most frequently. Controversy exists regarding whether to establish the cause or to empirically treat as reflux. Objective: To assess the cost-effectiveness of empirical treatment in patients with noncardiac chest pain. Methods: Decision analysis was used to compare a strategy of empirical treatment as reflux using an H-blocker or proton pump inhibitor with initial investigation for gastrointestinal causes over a period of up to 16 weeks and over a period of more than a year. The prototype patient was an outpatient with chest pain and a normal coronary angiogram. Gastrointestinal investigations included an upper gastrointestinal tract series, endoscopy, manometry, 24-hour pH monitoring, and provocation tests. The main outcome measure was direct medical costs per case treated from a third-party payer perspective. Results: Total medical costs were $2187 per case treated for the initial investigation arm and $849 for the empirical treatment arm in the 8- to 16-week model. One-way sensitivity analyses revealed that the model was robust; the treatment arm was less expensive in all cases. At just over a year empirical treatment remained dominant. Conclusions: An initial therapeutic trial with antisecretory agents for patients with noncardiac chest pain is cost-effective compared with investigation for gastrointestinal causes in the short term of weeks, with cost savings persisting beyond a year. Arch Intern Med. 2000;160:844-852

OBJECTIVES:Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs.METHODS:Treatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs.RESULTS:Among 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5–97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3–97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1–97.0%) and 96.4% (95% CI 95.5–97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role.CONCLUSIONS:In phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high regardless of ARA/PPI use or PPI dose. These data support the co-administration of this regimen with ARAs including PPIs.

Background/Aims:Bacterial overgrowth of the small intestine commonly occurs in association with hypochlorhydria caused by atrophic gastritis or during treatment with omeprazole. The purpose of this study was to determine the clinical significance of bacterial overgrowth on small intestinal absorption and permeability and to evaluate the reliability of noninvasive breath tests to detect bacterial overgrowth in subjects with hypochlorhydria. Methods:Seventeen healthy, elderly subjects with atrophic gastritis or omeprazole treatment (40 mg/day) and documented bacterial overgrowth were studied. Results:There was no evidence of fat malabsorption (72-hour fecal fat) or clinically significant carbohydrate malabsorption (25 g d-xylose and fecal pH) in any subject. The ratio of lactulose to mannitol excreted was normal in both atrophic gastritis and omeprazole-treated groups. Three subjects in each group had abnormally high α1-antitrypsin clearances. Lactulose (10 g) and glucose (80 g) hydrogen breath tests were only abnormal in 1 out of 17 subjects, whereas the 1 g [14C]d-xylose test was abnormal in 6 out of 17 subjects. Conclusions:Bacterial overgrowth caused by atrophic gastritis or omeprazole treatment is typically not associated with clinically significant fat or carbohydrate malabsorption. Noninvasive breath tests for bacterial overgrowth are not reliable in subjects with hypochlorhydria.

•There is a wide variation across studies in the reported prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).•This targeted literature review was conducted to understand the prevalence of NALFD and NASH in the general population and specific sub-populations as well as identify risk factors associated with NASH.•Prevalence of NAFLD among general population ranged from 11.2% to 37.2% in the reviewed studies.•Wide ranges were shown in the frequency of biopsy-confirmed NASH among NAFLD patients ranging from 15.9% to 68.3%.•The prevalence of NAFLD and NASH among type 2 diabetes mellitus patients was 54% and 65.26%, respectively.•Frequency of NASH ranged from 12.6% to 30.4% among the obese patients.•The rate of disease progression was associated with age, ethnicity, genetics, and presence of comorbidities (e.g. obesity, T2DM, and hypertension).•There is significant variability in the reported prevalence globally, further emphasizing the need to achieve consensus in terminology, disease definition, and diagnostic methods to determine the actual prevalence of NAFLD and NASH.

Thrombocytopenia [TCP] is a complication of advanced chronic liver disease [CLD]. We examined clinical factors related to the development of severe TCP among patients with initially normal platelet counts using laboratory, clinical, and administrative data from the Veterans Administration Healthcare System, New England region.All patients with a diagnosis of CLD or hepatitis C who were seen in a VA hospital or in a VA outpatient clinic between 10/2002 and 9/2008 were included in this analysis. CLD diagnosis definitions included: 1) ICD9-CM code of 51.0 – 571.9, excluding 571.1at a clinic visit or hospital discharge 2) positive hepatitis C [Hep-C] antibody, and 3) elevated ALT (> 84 IU/dL) on two occasions at least 60 days. Subjects were required to have normal platelet counts (platelet count >150,000/µL) at baseline. Subjects were excluded if they had the following: 1) hepatorenal syndrome, coagulation disorders, immune TCP purpura, lupus erythematosis, rheumatoid arthritis, pernicious anemia, aplastic anemia or septicemia. Severe TCP was defined as a platelet count < 50,000/µL. Risk factors evaluated for the development of TCP included age, comorbidities (diabetes, alcoholic and/or drug dependence, chronic kidney disease, Hepatitis-C [Hep-C] status, hepatorenal syndrome, congestive heart failure [CHF], coronary artery disease, hypertension), resource utilization (infectious disease, gastrointestinal [GI] nephrology and/or hematology clinic visit), and current laboratory values (hemoglobin, ALT and MELD Score). All potential predictors were treated as time-varying exposures over the follow-up and updated at each interval. Relative risk was estimated using logistic regression with pooled repeated observations, using 3-month periods where risk factors at the beginning of a 3-month interval were used to predict severe TCP in that interval.6,102 subjects with Hep-C contributed a median follow-up of 1,414 days and had 82 events (1.34%) during the study. 5,358 Non Hep-C subjects contributed a median follow-up of 1,238 days and had 97 events (1.81%) during the study. The median platelet count among CLD patients at baseline was 238,000/µL (IQR 203,000/µL- 282,000/µL) and among Hep-C patients at baseline was 240,000 (IQR 205,000/µL- 285,000/µL). After multivariate adjustment, alcohol dependence [Odds ratio = 2.24, 95% confidence interval: (1.14, 4.39)], CHF [2.6 (1.05,6.43)], 5 unit change in MELD [1.13 (1.05,1.21)], GI clinic visits [1.89 (0.93,3.87)] and anti retroviral therapy [3.84 (1.60, 7.61)] increased the odds of severe TCP; while drug dependence [0.62 (0.34, 1.13)] and increasing hemoglobin [0.74 (0.65,0.84)] reduced the odds of severe TCP. In non Hep-C subjects, alcohol dependence [2.88 (1.58,5.25)], CHF [1.81 (0.9, 3.65)], 5 unit change in MELD [1.12 (1.03, 1.23)], hematology clinic [3.64 (1.91, 6.93)] current anti-retroviral therapy [6.65 (1.96, 22.6)] and ALT 42-84g/dL vs. ALT < 42g/dL [1.55 (0.78, 3.06)] increased the odds of severe TCP; while drug dependence [0.46 (0.17, 1.22)], increasing hemoglobin [0.68 (0.60, 0.78)] and ALT > 84g/dL vs. ALT < 42 reduced the odds of severe TCP.In a population of veterans with chronic liver disease or hepatitis C infection with normal platelet counts > 150,000/µL at baseline, we estimate the incidence of development of severe thrombocytopenia to be between 1 and 2% over an average of 3 years of follow-up. Key clinical predictors of development of severe TCP included prevalent CHF diagnosis and changing MELD score. Specialist care referrals to hematologists and gastroenterologists, also identified patients likely to become severe TCP cases. As expected, antiretroviral therapies were associated with an increased risk of severe TCP over the follow-up.GlaxoSmithKline provided research support for this project, with no restrictions on publication. The study was conducted using resources of the VA Cooperative Studies Program and VA Boston Healthcare System.Lawler: GlaxoSmithKline: Research Funding. Horblyuk:GlaxoSmithKline: Employment. Grotzinger:GlaxoSmithKline: Employment, Research Funding.

Background:Preliminary studies with qualitative detection methods suggest that 5-aminolevulinic acid-induced protoporphyrin IX fluorescence might improve the detection of dysplastic Barrett's epithelium. This study used quantitative methods to determine whether aminolevulinic acid-induced protoporphyrin IX fluorescence can differentiate between Barrett's mucosa with and without dysplasia. Methods:Patients were given 10 mg/kg of aminolevulinic acid orally 3 hours before endoscopy. Quantitative fluorescence spectra were acquired by using a nitrogen-pumped dye laser (l 400 nm) spectrograph system. The protoporphyrin IX fluorescence intensity at 635 nm was compared with the histopathologic diagnosis for mucosal biopsy specimens taken immediately after the fluorescence measurements. Results:Ninety-seven spectra were obtained from 20 patients. The mean (± standard error) standardized protoporphyrin IX fluorescence intensity was significantly greater (p< 0.05) for high-grade dysplastic Barrett's epithelium (0.29 ± 0.07, n = 13) than for nondysplastic Barrett's epithelium (0.11 ± 0.02, n = 43). By using protoporphyrin IX fluorescence alone, high-grade dysplasia was distinguished from nondysplastic tissue types with 77% sensitivity and 71% specificity. Decreased autofluorescence was particularly found in nodular high-grade dysplasia. By using the fluorescence intensity ratio of 635 nm/480 nm, nodular high-grade dysplasia could be differentiated from nondysplastic tissue with 100% sensitivity and 100% specificity. Conclusion:Protoporphyrin IX fluorescence may be useful for identifying areas of high-grade dysplasia in Barrett's esophagus and for targeting of biopsies. (Gastrointest Endosc 2002;56:479-87.)