Jennifer Leonard

CONTEXT: Proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RAs) have become the mainstay of therapy in acid-related upper gastrointestinal disorders. There have been concerns raised about the possible association of PPIs with enteric infections. OBJECTIVE: We conducted a systematic review to evaluate any association between acid suppression and enteric infection. We also assessed differences between types of enteric infections and the type of acid suppression. DATA SOURCES: Electronic searches of MEDLINE (1966-2005), EMBASE (1988-2005), and CINAHL (1982-2005) were undertaken using a combination of subject headings and text words related to PPI therapy, H(2)RAs, and enteric infections. STUDY SELECTION: All observational studies were eligible, including cross-sectional, case control, and cohort studies that evaluated risk of enteric infection associated with antisecretory therapy. Eligibility assessment was made by two independent researchers. DATA EXTRACTION: Information on study design, patient population, type of acid suppression, type of infection, and outcomes was collected. The odds ratio (OR) of taking acid suppression therapy in cases and controls was calculated and results were synthesized using a random effects model (DerSimonian and Laird, Stats direct version 2.4.4). DATA SYNTHESIS: A total of 12 papers evaluating 2,948 patients with Clostridium difficile were included in the review. There was an increased risk of taking antisecretory therapy in those infected with C. difficile (pooled OR 1.94, 95% CI 1.37-2.75). There was significant heterogeneity between the studies (P= 0.0006) that was not explained by planned subgroup analysis. The association was greater for PPI use (OR 1.96, 95% CI 1.28-3.00) compared with H(2)RA use (OR 1.40, 95% CI 0.85-2.29). A total of six studies evaluated Salmonella, Campylobacter, and other enteric infections in 11,280 patients. There was an increased risk of taking acid suppression in those with enteric infections (OR 2.55, 95% CI 1.53-4.26). There was significant heterogeneity between the studies (P < 0.0001) that was not explained by subgroup analysis. The association was greater for PPI use (OR 3.33, 95% CI 1.84-6.02) compared with H(2)RA use (OR 2.03, 95% CI 1.05-3.92). CONCLUSION: There is an association between acid suppression and an increased risk of enteric infection. Further prospective studies on patients taking long-term acid suppression are needed to establish whether this association is causal.

The impact of obesity on outcomes following liver transplantation has been difficult to determine, in part due to the confounding effects of ascites on BMI. We evaluated the impact of pretransplant recipient obesity on outcomes following liver transplantation using the NIDDK Liver Transplantation Database. Pretransplant BMI, corrected for ascites, was categorized as underweight (BMI <18 kg/m2), normal weight (BMI 18–25 kg/m2), overweight (BMI 25.1–30 kg/m2), Class I obese (BMI 30.1–35 kg/m2), Class II obese (BMI 35.1–40 kg/m2) and Class III obese (BMI >40 kg/m2). Primary outcomes were patient and graft survival. Secondary outcomes included days in hospital and days in ICU. Data from 704 adult liver transplant recipients from the NIDDK LTD and a further 609 patients from the Mayo Clinic were analyzed. Early and late patient and graft survival was similar across all BMI categories. Correcting for ascites volume resulted in 11–20% of patients moving into a lower BMI classification. The relative risk for mortality increased by 7% for each liter of ascites removed. We conclude that corrected BMI is not independently predictive of patient or graft survival. Obesity, within the ranges observed in this study, should not be considered to be a contraindication to liver transplantation in the absence of other relative contraindications. The impact of obesity on outcomes following liver transplantation has been difficult to determine, in part due to the confounding effects of ascites on BMI. We evaluated the impact of pretransplant recipient obesity on outcomes following liver transplantation using the NIDDK Liver Transplantation Database. Pretransplant BMI, corrected for ascites, was categorized as underweight (BMI <18 kg/m2), normal weight (BMI 18–25 kg/m2), overweight (BMI 25.1–30 kg/m2), Class I obese (BMI 30.1–35 kg/m2), Class II obese (BMI 35.1–40 kg/m2) and Class III obese (BMI >40 kg/m2). Primary outcomes were patient and graft survival. Secondary outcomes included days in hospital and days in ICU. Data from 704 adult liver transplant recipients from the NIDDK LTD and a further 609 patients from the Mayo Clinic were analyzed. Early and late patient and graft survival was similar across all BMI categories. Correcting for ascites volume resulted in 11–20% of patients moving into a lower BMI classification. The relative risk for mortality increased by 7% for each liter of ascites removed. We conclude that corrected BMI is not independently predictive of patient or graft survival. Obesity, within the ranges observed in this study, should not be considered to be a contraindication to liver transplantation in the absence of other relative contraindications.

This study aimed to examine variations in patient-physician communication by obesity status. We pooled data from the 2005-2007 Medical Expenditure Panel Survey (MEPS),_included only individuals who completed the self-administered questionnaire themselves, and restricted the sample to patients who received care from primary care physicians. We included a total of 6,628 unique individuals between the ages of 18 and 65 who had at least one office or hospital outpatient visit during the past 12 months. There are six outcomes of interest in this study. The patient-physician communication composite score is based on five questions that the MEPS adapted from the Consumer Assessment of Healthcare Providers and Systems Survey. The other five variables were: respect from providers, providers' listening skills, explanations from providers, time spent with patients, and patient involvement in treatment decisions. The key independent variable was obesity. Bivariate and multivariate models such as ordinary least squares (OLS) and logistic regression were used to examine the relationship between patient-physician communication and obesity status. Multivariate models showed that obese patients had a reduced physician-patient communication composite score of 0.19 (95% CI 0.03-0.34, p=0.02), physicians' show of respect OR 0.77 (95% CI 0.61-0.98, p=0.04), listening ability OR 0.82 (95% CI 0.65-1.02, p=0.07), and spending enough time OR 0.80 (95% CI 0.62-0.99, p=0.04) compared to non-obese patients. We found a negative association between physician-patient communication and patients' obesity status. These findings may inform public health practitioners in the design of effective initiatives that account for the needs and circumstances of obese individuals.

BACKGROUND: AGN 201904-Z is a new, slowly absorbed, acid-stable pro-proton pump inhibitor (pro-PPI) rapidly converted to omeprazole in the systemic circulation giving a prolonged residence time. AIM: To investigate pharmacodynamics and pharmacokinetics of AGN 201904-Z compared to esomeprazole. METHODS: A randomized, open-label, parallel group, investigator-blinded intragastric pH study was conducted in 24 healthy Helicobacter pylori negative male volunteers. AGN 201904-Z enteric-coated capsules (600 mg/day) or esomeprazole delayed-release tablets (40 mg/day) were administered for 5 days. Twenty-four-hour intragastric pH recordings were acquired at baseline, days 1, 3 and 5 with blood levels of omeprazole, AGN 201904-Z and gastrin. RESULTS: On day 1, median nocturnal pH and proportion of nocturnal time with pH >or=4 and 24-h and nocturnal time pH >or=5 were significantly higher with AGN 201904-Z than esomeprazole. At day 5, 24-h and median nocturnal pH were significantly higher for AGN 201904-Z than esomeprazole (P < 0.0001). There was also a marked reduction in periods of nocturnal pH <4.0. Area under curve of the AGN 201904-Z active metabolite (omeprazole) in the blood was twice that of esomeprazole at day 5. CONCLUSIONS: AGN 201904-Z produced a significantly greater and more prolonged acid suppression than esomeprazole, and nocturnal acid suppression was more prolonged over all 5 days. AGN 201904-Z should provide true once-a-day treatment and better clinical efficacy than current PPIs.

BACKGROUND: This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers. METHODS: One hundred twenty liver transplantation recipients from across Canada with HCV recurrence were started on SOF-based regimens (SOF + simeprevir ± ribavirin (RBV), n = 53; SOF + pegylated interferon + RBV, n = 25; SOF + RBV, n = 36; and SOF + ledipasvir, n = 6) between January and November 2014. Mean age 58 ± 6.85 years, majority (83%) were genotype 1, male (81%), and treatment experienced (82%). Twenty-seven percent had fibrosing cholestatic hepatitis/early aggressive HCV in the graft, and 48% had F3/4 fibrosis. The primary outcomes included patient and graft survival, on- and end-of-treatment response and sustained virological response at 12 weeks after treatment end (SVR12), and adverse events. RESULTS: One hundred thirteen of 120 (94%) patients were HCV RNA undetectable at end of treatment, and SVR12 was achieved in 102/120 (85%) patients, with 7 relapses, 1 nonresponder, and 10 deaths (liver-related complications). Sixty-three percent had HCV RNA levels below the lower limit of quantification at week 4. Serum creatinine levels remained stable throughout the treatment. Severe anemia occurred in 13% of patients, primarily in RBV-based regimens. CONCLUSIONS: Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.