Mercaptopurine metabolite results in clinical gastroenterology practice.

BACKGROUND: Azathioprine (AZA) and its active metabolite mercaptopurine (MP) are frequently used in the management of inflammatory bowel disease. Measurement of the AZA/MP metabolites, thioguanine (TG) and methylmercaptopurine (MMP), has been suggested as a means to optimize therapy with AZA/MP in inflammatory bowel disease. AIM: To evaluate the results of initial AZA/MP metabolite panels sent by gastroenterologists during the first year of its widespread availability. METHODS: Initial AZA/MP metabolite panels sent by gastroenterologists to a single laboratory were reviewed and the metabolite panels were interpreted. RESULTS: Initial metabolite levels were reviewed for 9187 patients. Noncompliance was detected in 263 patients (3%) and under-dosing in 4260 patients (46%). 534 patients (6%) had levels that were consistent with preferential metabolism via the TPMT pathway. The therapeutic goal was achieved in 2444 patients (27%) and an additional 552 patients (6%) had appropriate TG levels but potential hepatotoxicity. 936 patients (10%) had potential TPMT deficiency, and 58 patients (1%) had potential TPMT absence and were at risk for leukopenia. 140 patients (2%) had too high a dose. CONCLUSIONS: Measurement of AZA/MP metabolites can be used by practising gastroenterologists to identify potential reasons for nonresponse to AZA or MP, and to identify patients at risk for certain drug-related toxicities.

Performing a cost-effectiveness analysis: surveillance of patients with ulcerative colitis.

OBJECTIVE: To illustrate the principles of cost-effectiveness analysis, this third article in the "Primer on Economic Analysis for the Gastroenterologist" applies published criteria for appraising an economic analysis to a study of the cost-effectiveness of surveillance of patients with ulcerative colitis. METHODS: We review and apply the 10 standard criteria for critical appraisal and evaluation of cost-effectiveness analyses. SUMMARY: We outlined the development and critique of a decision analytic model that examines the cost-effectiveness of surveillance of patients with ulcerative colitis, and we compared the cost-effectiveness of surveillance of patients with ulcerative colitis to other well-accepted medical practices.

ERCP and sphincterotomy in the context of laparoscopic cholecystectomy: academic and community practice patterns and results.

OBJECTIVE: To study the effect of practice setting and practitioner experience on the use and results of ERCP and sphincterotomy in the context of laparoscopic cholecystectomy. METHODS: Data were collected on 780 ERCPs performed before or after laparoscopic cholecystectomy. Biliary endoscopists at four academic centers and 33 community-based gastroenterologists of varying experience participated. RESULTS: Indications for perioperative ERCP were similar in academic centers and community practice, but academic experts performed a significantly higher proportion of postoperative procedures. Success rates were high for all participants, although the least experienced group of community-based gastroenterologists had a significantly lower rate of success with sphincterotomy. Complication rates did not vary significantly among participants. CONCLUSIONS: Experienced community-based gastroenterologists can perform ERCP and sphincterotomy in the context of laparoscopic cholecystectomy with results comparable to those of academic experts. Gastroenterologists with a life-time experience of fewer than 200 ERCPs have lower success rates for sphincterotomy than more experienced practitioners in either practice setting. ERCP performed in community or academic settings can provide safe and effective management of common bile duct stones and biliary leaks or strictures that occur after laparoscopic cholecystectomy.

Predicting the presence of choledocholithiasis in patients with symptomatic cholelithiasis.

OBJECTIVES: Accurate preoperative prediction of choledocholithiasis is essential in order to minimize patient risk and curtail health care expenditures. This study was designed to identify independent risk factors for choledocholithiasis in patients who had undergone cholecystectomy for symptomatic cholelithiasis and to develop a predictive model based on those factors. METHODS: The charts of 1264 consecutive patients who had undergone cholecystectomy at one of three North Carolina hospitals between January 1, 1989 and December 31, 1991 were reviewed; 465 of these patients had confirmed presence or absence of choledocholithiasis by cholangiography and/or common bile duct exploration and were eligible for analysis. Candidate predictor variables included age and maximum preoperative values for each of the following: temperature, alkaline phosphatase, bilirubin, AST, amylase, white blood cell count, and common bile duct diameter. Model development and validation were conducted using standard data-splitting (60% "training," 40% "test") and logistic regression techniques. RESULTS: Choledocholithiasis was confirmed in 115 (25%) of the 465 eligible patients. Univariate analysis identified bilirubin, common bile duct diameter, AST, temperature, alkaline phosphatase, and age as predictors. Multivariable analysis subsequently identified bilirubin, common bile duct diameter, AST, alkaline phosphatase, and age as independent predictors of choledocholithiasis. A final model containing these variables (except age, whose contribution to the model was small) accurately predicted choledocholithiasis (c-index = 0.76). CONCLUSIONS: Accurate estimates of choledocholithiasis risk can be made using maximum preoperative bilirubin, common bile duct diameter, AST, and alkaline phosphatase values. Use of the model may help physicians select those patients with symptomatic cholelithiasis who would most likely benefit from further investigation to exclude choledocholithiasis.

Effect of different coffees on esophageal acid contact time and symptoms in coffee-sensitive subjects.

The purpose of this study was to correlate the effects of different coffees on esophageal acid contact, heartburn, and regurgitation in patients with coffee-sensitivity. Twenty volunteers with coffee-sensitivity were studied in a double-blind, 3 period, crossover study examining the effect of three regular (caffeinated) coffees (a coffee from the USA--"A"; a "treated" coffee from Europe--"B"; and an "untreated" coffee from Europe--"C") before and after a high-fat test meal. The median acid contact times for coffees A, B, and C were 6.5%, 9%, and 10.5%, respectively (A vs. C, p = 0.005). Significantly fewer patients reported any symptoms with coffee A compared with coffee C (p < 0.05). Symptoms were usually more frequent and severe after the test meal. There was a trend toward fewer and less severe symptoms with the treated coffee (B) compared with its untreated counterpart (C). Our conclusions are as follows: (a) Different coffees induce variations in gastroesophageal reflux in coffee-sensitive individuals. (b) Coffee can be treated in a manner which decreases heartburn symptoms by 75% while decreasing acid contact by only 14%. (c) Gastroesophageal reflux and symptoms of coffee sensitivity increase with the concomitant ingestion of food. (d) Symptoms of dyspepsia appear to be influenced by variations in both the coffee itself and characteristics of susceptible individuals. (e) Although gastroesophageal reflux is important in the genesis of coffee-sensitivity, there must be other factors which act in concert with reflux to produce symptoms of coffee-sensitivity.

Clinical trials. How should they be designed?

The fundamental principles of clinical trial design include (1) a priori formulation of a specific research question, (2) precise description of the population to be studied, (3) limitation of the effects of chance by predetermining the study hypothesis and using methods that account for multiple statistical testing, (4) calculation of the sample size necessary to answer the research question, and (5) limitation of the potential bias whenever possible through blinding and random allocation of subjects to treatment and control groups (Table 2). Although the randomized controlled trial is regarded as the gold standard for determination of efficacy of therapy, cost and sample size are frequently rate-limiting. Other techniques have been developed to supplement clinical trials and include meta-analysis, data base (observational) research, and decision analysis. In the current climate of concern over staggering health care costs and variable practice patterns, research emphases are shifting from cost containment to maximizing value of health-related services and assessing patient outcomes.