Murray N. Ehrinpreis

Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis.

OBJECTIVES:Clostridium difficile-associated diarrhea (CDAD) is a major cause of morbidity and increasing health-care costs among hospitalized patients. Although exposure to antibiotics remains the most documented risk factor for CDAD, attention has recently been directed toward a plausible link with proton pump inhibitors (PPIs). However, the results of studies on the association between CDAD and PPIs remain controversial. We have conducted a meta-analysis to summarize the association between PPIs and CDAD among hospitalized patients.METHODS:A systematic search of published literature on studies that investigated the association between PPIs and CDAD from 1990 to 2010 was conducted on Medline and PubMed. The identified articles were reviewed for additional references. The most adjusted risk estimates were extracted by two authors and summarized using random effects meta-analysis. We also conducted a subgroup analysis by study design. Publication bias was evaluated using the Begg and Egger tests. A sensitivity analysis using the Duval and Tweedie “trim-and-fill” method has also been performed.RESULTS:Twenty-three studies including close to 300,000 patients met the inclusion criteria. There was a 65% (summary risk estimate 1.69 with a 95% confidence interval (CI) from 1.395 to 1.974; P<0.000) increase in the incidence of CDAD among patients on PPIs. By study design, whether case–control study (17) or cohort study (6), there was still a significant increase in the incidence of CDAD among PPI users. The risk estimates were 2.31 (95% CI from 1.72 to 3.10; P<0.001) and 1.48 (95% CI from 1.25 to 1.75; P<0.001) for cohort and case–control studies, respectively.CONCLUSIONS:There is sufficient evidence to suggest that PPIs increase the incidence of CDAD. Our meta-analysis shows a 65% increase in the incidence of CDAD among PPI users. We recommend that the routine use of PPIs for gastric ulcer prophylaxis should be more prudent. Establishing a guideline for the use of PPI may help in the future with the judicious use of PPIs. Further studies, preferably prospective, are needed to fully explore the association between PPIs and CDAD.

African Americans with genotype 1 treated with interferon for chronic hepatitis C have a lower end of treatment response than Caucasians

African Americans as a group have a higher incidence of chronic hepatitis C (CHC) than Caucasians but are often under‐represented in clinical trials used to define response rates to interferon therapy. The aim of this study was to compare African Americans with Caucasians with respect to end‐of‐treatment response to interferon. This retrospective study had 61 African Americans and 49 Caucasians with CHC. All patients were treated for at least 12 weeks with interferon‐α2b (Intron A) thrice weekly. End‐of‐treatment response was defined as three consecutive nondetectable HCV RNA measurements at least 1 month apart. Sustained response was defined as a negative serum HCV RNA 6 months after end of treatment. Of the 110 patients, 19 achieved an end‐of‐treatment response (17%) but only four achieved a sustained response (4/110=4%). Of the patients achieving a sustained response, one was genotype 1 (male Caucasian), three were genotype 2/3 with four patients having no follow‐up information. The end‐of‐treatment response was 7% for patients with genotype 1 and 71% for genotype non‐1 (P < 0.005 for genotype non‐1). The end‐of‐treatment response was significantly higher in Caucasians (14/49=31%) compared with African Americans (5/61=8%; P < 0.05). A lower response rate in African Americans with genotype 1 in contrast to Caucasians was the primary reason for the difference in end‐of‐treatment response (1/45=2% vs. 5/33=15%, P < 0.05). Hence, interferon treatment resulted in a poor sustained response rate in the group of patients representative of the urban populations with the highest prevalence of hepatitis C. A genotype other than type 1 was the strongest predictor of end‐of‐treatment response in patients treated but over 86% of patients in this urban clinic were genotype 1. Caucasians were more likely to respond than African Americans, especially in patients with genotype 1.

Fatal hyperphosphatemia from a phosphosoda bowel preparation.

Oral phosphosoda is increasingly being used as a bowel preparation for colonoscopy, as it requires that a much smaller volume be ingested and is equally effective and less costly than polyethylene glycol-based electrolyte solutions. Oral phosphosoda has a good safety record, but complications of its use may occur. We describe a patient who died as a result of severe hyperphosphatemia after an oral phosphosoda bowel preparation. A 55-year-old man was admitted with rectal bleeding, abdominal pain, and vomiting. He had a history of diabetes, hypertension, and end-stage renal disease and had successful renal transplant 3 years prior. His initial serum creatinine, calcium, phosphate, and electrolyte levels were normal. He vomited after polyethylene glycol-based electrolyte solution, and an alternate bowel preparation with oral phosphosoda was recommended. He received 90 mL of oral phosphosoda as a single dose. Six hours later, he had cardiorespiratory arrest and was found to have hyperphosphatemia (serum phosphate, 17.8 mg/dL), a high anion gap acidosis, hypoxia, and oliguric renal failure. Resuscitation was unsuccessful. Autopsy showed ischemic colitis. We conclude that bowel preparation with phosphosoda may be associated with severe complications and should be avoided if there is any suggestion of impaired renal function or poor gut motility.

Increased colonic mucosal angiotensin I and II concentrations in Crohn's colitis

To define a potential role for the angiotensin system in Crohns colitis, the colonic mucosal levels of angiotensin I and II were measured in endoscopic biopsy samples from patients with active Crohns colitis (n = 20), ulcerative colitis (n = 13), other forms of colitis (n = 3), and normal controls (n = 17). Colonic mucosal levels of angiotensin I and II were greater in patients with Crohns colitis than in normal subjects (p less than 0.001 and p less than 0.001, respectively). Mucosal levels of angiotensin I and II were also higher in Crohns colitis than in ulcerative colitis (p less than 0.001 and p less than 0.001, respectively), and levels of angiotensin II were higher in Crohns than in other forms of colitis (p = 0.014). Mucosal levels of angiotensin I and II correlated well with the degree of macroscopic inflammation in Crohns colitis (r = 0.86, p less than 0.001 and r = 0.68, p less than 0.001, respectively). Mucosal levels of angiotensin I correlated fairly well with the Crohns Disease Activity Index (r = 0.46, p less than 0.05) while angiotensin II levels correlated poorly. These studies suggest that angiotensin I and II may have a role in the inflammation associated with Crohns colitis.

Thymosin α1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double‐blind and placebo‐controlled study

Previous clinical trials have suggested that thymosin α1 (Tα1), an immunomodulatory peptide, may be effective in the treatment of chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of Tα1 in a multicentre, placebo‐controlled and double‐blind study of 97 patients with serum hepatitis B virus (HBV) DNA‐ and hepatitis B e antigen (HBeAg)‐positive CHB. Patients who had been hepatitis B surface antigen (HBsAg) positive for at least 12 months entered a 3‐month screening period prior to randomization. Forty‐nine patients received Tα1 (1.6 mg) and 48 patients received placebo, twice weekly for 6 months, and were followed‐up for an additional 6 months. At inclusion, both groups were comparable for age, gender, histological grading, and aminotransferase and HBV DNA levels. A complete response to treatment, defined as a sustained serum HBV DNA‐negative status (two negative results at least 3 months apart) during the 12‐month study, with negative HBV DNA and HBeAg values at month 12, was seen in seven (14%) patients given Tα1 and in two (4%) patients treated with placebo (P = 0.084). Five (10%) patients given Tα1 and four (8%) patients given placebo exhibited a delayed response (defined as sustained serum HBV DNA negativity achieved after the 12‐month study period with negative HBV DNA and HBeAg values at the last assessment). A total of 12 (25%) patients given Tα1 and six (13%) patients given placebo showed a sustained loss of HBV DNA with a negative HBeAg value during or following the 12‐month study period (P < 0.11). These results do not confirm observations of treatment efficacy reported in other clinical studies.

Prevalence of hepatitis A virus and hepatitis B virus immunity in patients with polymerase chain reaction-confirmed hepatitis C: Implications for vaccination strategy

OBJECTIVES:Administration of vaccine for hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic hepatitis C (CHC) because of the potential for increased severity of acute hepatitis superimposed on existing liver disease. The aim of this study is to determine the prevalence of antibodies directed against HAV and HBV in patients with CHC, analyze demographic and risk factors associated with this prevalence, and develop a cost-effective vaccination strategy.METHODS:We reviewed records from 1092 CHC patients. Demographics and information regarding risk factors were obtained by history and questionnaire administered to all patients. The costs of vaccination and antibody testing were determined, based on standard laboratory and clinic charges at our institution. HAV and HBV markers were correlated to race, age, and risk factors.RESULTS:Of the total population studied (n = 1092), 72% were African-Americans, 27% white, and 1% others. Of 671 CHC patients tested for anti-HAV IgG, 252 (38%) were positive. Of 743 CHC patients tested for HBV antibodies (anti-hepatitis B core IgG or anti-hepatitis B surface), 494 (67%) were positive. African-Americans are more likely to have antibodies to HAV and HBV (67% and 75%, respectively) compared to whites (27% and 20%). The prevalence of anti-HAV was 76% in patients >60 yr, 34% in the 40- to 60-yr-old age group, and 21% in patients <40 yr. The highest prevalence of HBV antibodies was found in patients between the ages of 40–60 yr. No HCV risk factors were associated with increased HAV risk. In CHC patients with HBV antibodies, however, illicit injection drug use was the predominant risk factor.CONCLUSIONS:The prevalence of anti-HAV in patients with CHC was found to be similar to that of the general population in the United States (33% according to recent Centers for Disease Control data), consistent with the hypothesis that the two infections do not share risk factors. Because the prevalence of HAV immunity is low in CHC patients <40 yr, empiric HAV vaccination is cost effective. If two doses of vaccine are to be given, however, antibody testing of all HCV patients is indicated. In the subset of patients >60 yr of age or who are African-American, where the prevalence of HAV exposure is considerably higher, it would be cost effective to check the antibody (

Effect of SQ 14225, an Inhibitor of Angiotensin I-converting Enzyme, on the Granulomatous Response to Schistosoma mansoni Eggs in Mice

36.00), before vaccination (

Ultrasound diagnosis of fatty liver in patients with chronic liver disease: A retrospective observational study

97.00). The prevalence of HBV antibodies, however, is significantly increased in patients with CHC compared with the general population (5.3% per the Centers for Disease Control), likely as a result of exposure to similar parenteral risk factors. HBV antibody testing (

An Unusual Case of Amoxicillin/Clavulanic Acid-Related Hepatotoxicity

26.00 per test) should, therefore, be undertaken in all CHC patients who are hepatitis B surface antigen negative, as this approach is cost-effective compared to empiric HBV vaccination (

Prospectives on the treatment of chronic hepatitis B and chronic hepatitis C with thymic peptides and antiviral agents

438.00 for a three injection course).