H. Thomas Schneider

Incidence and costs of adverse drug reactions during hospitalisation: computerised monitoring versus stimulated spontaneous reporting.

AbstractObjective: To implement a computer-based adverse drug reaction monitoring system and compare its results with those of stimulated spontaneous reporting, and to assess the excess lengths of stay and costs of patients with verified adverse drug reactions. Design: A prospective cohort study was used to assess the efficacy of computer-based monitoring, and case-matching was used to assess excess length of stay and costs. Setting: This was a study of all patients admitted to a medical ward of a university hospital in Germany between June and December 1997. Patients and participants: 379 patients were included, most of whom had infectious, gastrointestinal or liver diseases, or sleep apnoea syndrome. Patients admitted because of adverse drug reactions were excluded. Methods: All automatically generated laboratory signals and reports were evaluated by a team consisting of a clinical pharmacologist, a clinician and a pharmacist for their likelihood of being an adverse drug reaction. They were classified by severity and causality. For verified adverse drug reactions, control patients with similar primary diagnosis, age, gender and time of admission but without adverse drug reactions were matched to the cases in order to assess the excess length of hospitalisation caused by an adverse drug reaction. Results: Adverse drug reactions were detected in 12% of patients by the computer-based monitoring system and stimulated spontaneous reporting together (46 adverse reactions in 45 patients) during 1718 treatment days. Computer-based monitoring identified adverse drug reactions in 34 cases, and stimulated spontaneous reporting in 17 cases. Only 5 adverse drug reactions were detected by both methods. The relative sensitivity of computer-based monitoring was 74% (relative specificity 75%), and that of stimulated spontaneous reporting was 37% (relative specificity 98%). All 3 serious adverse drug reactions were detected by computer-based monitoring, but only 2 out of the 3 were detected by stimulated spontaneous reporting. The percentage of automatically generated laboratory signals associated with an adverse drug reaction (positive predictive value) was 13%. The mean excess length of stay was 3.5 days per adverse drug reaction. 48% of adverse reactions were predictable and detected solely by computer-based monitoring. Therefore, the potential for savings on this ward from the introduction of computer-based monitoring can be calculated as EUR56 200/year (

Acute hepatitis induced by greater celandine (Chelidonium majus)

US59 600/year) [1999 values]. Conclusion: Computer monitoring is an effective method for improving the detection of adverse drug reactions in inpatients. The excess length of stay and costs caused by adverse drug reactions are substantial and might be considerably reduced by earlier detection.

Pancreatic duct stones in chronic pancreatitis: Criteria for treatment intensity and success☆

The hepatotoxic potential of conventional drugs is well known, but herbal medicines are often assumed to be harmless. In the last 2 years, we have observed 10 cases of acute hepatitis induced by preparations of greater celandine (Chelidonium majus), which are frequently prescribed to treat gastric and biliary disorders. The course of hepatitis was mild to severe. Marked cholestasis was observed in 5 patients, but liver failure did not occur. Other possible causes of liver disease (viral, autoimmune, hereditary, alcohol, and secondary biliary) were excluded by laboratory tests and imaging procedures, and liver biopsy specimens were consistent with drug-induced damage. After discontinuation of greater celandine, rapid recovery was observed in all patients and liver enzyme levels returned to normal in 2-6 months. Unintentional rechallenge led to a second flare of hepatic inflammation in 1 patient. Greater celandine has to be added to the list of herbs capable of inducing acute (cholestatic) hepatitis. A significant proportion of unexplained cases of hepatitis may be caused by greater celandine.

Benefits and risks of needle-knife papillotomy

BACKGROUND The aim of the study was to evaluate interventional endoscopic management of pancreatic duct stones in patients with chronic pancreatitis by describing therapeutic methods and defining factors that predict technical success. METHODS Records were retrospectively analyzed for 125 patients with symptoms caused by chronic pancreatitis with pancreatic duct stones (single 43, multiple 82) treated by interventional endoscopy, including extracorporeal shockwave lithotripsy. RESULTS Technical success was achieved in 85% of patients (11 patients by mechanical lithotripsy, 114 by piezoelectric extracorporeal shockwave lithotripsy). There were no serious complications from lithotripsy. Univariate analysis disclosed a statistically significant association between treatment success and patient age as well as prepapillary location of stones. A greater therapeutic effort was necessary in patients with stones located in the tail of the pancreas, 2 or more stones, a stone 12 mm or more in diameter, or who have had a longer duration (>8 years) of the disease. However, with exception of the last parameter, correction for multiple testing of data removed statistical significance. CONCLUSIONS Extracorporeal shockwave lithotripsy enhances endoscopic measures for treatment of pancreatic duct stones when mechanical lithotripsy fails. Middle-aged patients in the early stages of chronic pancreatitis with stones in a prepapillary location proved to be the best candidates for successful treatment. Unfavorable patient-related or morphologic factors can be compensated for through more intense efforts at therapy.

Impact of skill and experience of the endoscopist on the outcome of endoscopic sphincterotomy techniques

BACKGROUND The objective of the present investigation was to assess the risks and benefits of pre-cutting with the needle knife at the papilla of Vater and to compare the findings with the results of classic endoscopic sphincterotomy. METHODS From January 1973 to December 1993, 2752 endoscopic cutting procedures-biliary or pancreatic sphincterotomy (EST) or needle-knife papillotomy (NKP)-were performed. Since 1981 the pre-cut technique with the needle knife has been used alone or in combination with standard sphincterotomy. Indications, success, and complications of NKP and EST were analyzed retrospectively. To demonstrate changes in indications and technique, the study period was divided into two time periods: period A, 1981 to 1987; and period B, 1988 to 1993. RESULTS Between 1981 and 1993, diagnostic or therapeutic access to the biliary or pancreatic duct system was attempted in 2105 patients by means of EST or related procedures (period A 1093 patients; period B 1012 patients). The overall success rate was 95.1% (2001 of 2105). In 694 of 2105 cases (33.0%) an EST was not possible or not attempted and an NKP was performed (period A 31.9%; period B 34.1%). This was successful in 590 of 694 cases (85.2%). The rate of NKP in relation to EST varied depending on the different indications for EST: 22.8% NKP in classic indications like choledocholithiasis and over 40% in newer indications such as chronic pancreatitis. In these novel indications NKP alone was often sufficient, and EST to complete the procedure was not necessary (151 patients). In period B, NKP (63 patients) and EST (23 patients) were also used to achieve endoscopic retrograde imaging of the biliary or pancreatic duct system when primary cannulation was not possible. Visualization was achieved in 81.4% (70 of 86) and pathologic findings were noted in 68.6% (59 of 86). The total complication rate of primary EST was 6.8% (96 of 1411) and 7.3% (51 of 694) for all procedures in which NKP was involved (NS). In period B the complication rate was 4.6% for NKP without subsequent EST and 7.6% for NKP in combination with EST. Compared with the complication rate of primary standard EST (6.1%) there was no statistically significant difference. CONCLUSIONS Needle-knife papillotomy increases the success of diagnostic and therapeutic procedures at the papilla of Vater. This pre-cut technique is safe and does not increase the overall complication risk of sphincterotomy.

Piezoelectric lithotripsy: Stone disintegration and follow-up results in patients with symptomatic gallbladder stones

BACKGROUND Our aim was to assess the influence of the skill and experience of the endoscopist on the success and risk of endoscopic sphincterotomy techniques. METHODS The outcome of all endoscopic sphincterotomies (n = 1335) carried out between 1988 and 1995 were retrospectively analyzed with respect to the endoscopist performing the procedure. Endoscopists were differentiated according to whether they had previous experience with endoscopic sphincterotomy techniques (n > 100) and the frequency of endoscopic sphincterotomy during the study period (>40, 26 to 40, 10 to 25, <10 per year). RESULTS Indications for endoscopic sphincterotomy techniques and technical execution had only a minor influence on the results of endoscopic sphincterotomy and were comparable for the individual endoscopists. The overall success rate of endoscopic sphincterotomy was 94.4% and did not significantly differ among the endoscopists. The overall complication rate of endoscopic sphincterotomy was 7.3%. Endoscopists learning endoscopic sphincterotomy techniques with a case frequency of less than 10 procedures per year had a consistently high complication rate (10.5%). Those learning endoscopic sphincterotomy techniques with a case frequency of more than 25 procedures per year had an above-average complication rate for their first 40 endoscopic sphincterotomy procedures and a significant decrease in complication rate as the number of procedures increased. The complication rate for experienced endoscopists was 7.7%. There were distinct and, in one case, significant differences in complication rates between individual endoscopists (11.5% vs. 4.8%, p = 0.01). However, when corrected for multiple testing, there were no significant differences at the p < 0. 05 level. The endoscopic sphincterotomy frequency of the endoscopist was the only significant risk factor for complications. Endoscopists with a frequency of more than 40 procedures per year had a significantly lower complication rate (5.6%) than endoscopists with a lower case frequency (9.3%, p < 0.05). CONCLUSIONS A low endoscopic sphincterotomy frequency is, even for endoscopists with previous experience with the procedure, a risk factor for complications after endoscopic sphincterotomy. The learning of endoscopic sphincterotomy techniques requires a minimum of 40 procedures, but also after 100 procedures a further decrease of the complication rate can be expected.

Safety and efficacy of pancreatic sphincterotomy in chronic pancreatitis.

One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm).

Risperidone-induced cholestatic hepatitis.

BACKGROUND Endoscopic pancreatic sphincterotomy (EPS) is being performed with increasing frequency as a prerequisite to interventional measures in the pancreatic duct. The aim of this study was to evaluate EPS with regard to technique, success, complications, and mortality in patients with chronic pancreatitis. METHODS Between January 1989 and September 1996, the results of all consecutive EPSs in patients with chronic pancreatitis were documented in a standardized form. Patients were followed by clinical investigation and blood sample analysis at 4, 24, and 48 hours after EPS. Complications were classified according to commonly accepted criteria. RESULTS EPS was performed in 118 patients with chronic pancreatitis (men 75%, women 25%, 48+/-10 years). Ninety-four patients (80%) underwent guidewire-assisted EPS, and 24 patients (20%) underwent needle-knife EPS. Seventy-seven EPS procedures (65%) were primarily successful (guidewire EPS: 60 of 94, 64%; needle-knife EPS: 17 of 24, 71%). Additional endoscopic cutting techniques (needle-knife papillotomy, biliary endoscopic sphincterotomy) were required in 41 patients (35%). In total, EPS was successful in 116 patients (98%). The complication rate was 4.2% (4 cases of moderate pancreatitis, 1 severe bleeding, no deaths). All complications were managed nonoperatively. CONCLUSIONS In patients with chronic pancreatitis, EPS with a standard sphincterotome or with a needle-knife offers an effective and reliable approach to the pancreatic duct system. Additional cutting techniques may be necessary in approximately one third of cases before an EPS can be successfully performed. The complication rate of EPS in patients with chronic pancreatitis appears to be lower than the complication rate of biliary sphincterotomy for other indications.

Extracorporeal shockwave lithotripsy of gallstones in cystic duct remnants and Mirizzi syndrome

Risperidone, a widely used atypical and potent neuroleptic drug, is assumed to induce fewer hepatic side-effects than phenothiazine anti-psychotics. Recently, we observed a case of risperidone-induced cholestatic hepatotoxicity. A 37-year-old male developed a rapid increase in liver enzymes and cholestatic parameters after starting treatment with risperidone for paranoid psychosis. Work-up for other potential aetiologies was negative. The results of a percutaneous liver biopsy were consistent with drug-induced liver injury and cholestasis. Over the course of one month after the discontinuance of all anti-psychotic agents, the liver function test results returned to near-normal values. This observation supports the need to monitor cholestatic parameters in addition to liver function enzymes during initiation and the first weeks of risperidone intake.

Interventional endoscopic therapy in chronic pancreatitis including temporary stenting : A definitive treatment?

BACKGROUND Although the efficacy of extracorporeal shockwave lithotripsy for treatment of bile duct calculi is established, there are few studies of the value of extracorporeal shockwave lithotripsy for cystic duct remnant stones and for Mirizzi syndrome. METHODS Patients who required extracorporeal shockwave lithotripsy for cystic duct stones were identified in a cohort of 239 patients with bile duct stones treated by extracorporeal shockwave lithotripsy between January 1989 and December 2001 at a single institution. The medical records of these patients were reviewed. Follow-up information was obtained by telephone contact. OBSERVATIONS Six women (age range 19-85 years) underwent extracorporeal shockwave lithotripsy for cystic duct stones after failure of endoscopic treatment measures. Three of the patients presented with retained cystic duct remnant calculi (one also had Mirizzi syndrome type I), and 3 presented with Mirizzi syndrome type I. The stones were fragmented successfully by extracorporeal shockwave lithotripsy in all patients; the fragments were extracted endoscopically in 5 patients. Endoscopy plus extracorporeal shockwave lithotripsy was definitive treatment for all patients except one who subsequently underwent cholecystectomy. CONCLUSIONS Gallstones in a cystic duct remnant and in Mirizzi syndrome can be successfully treated by extracorporeal shockwave lithotripsy in conjunction with endoscopic measures. Extracorporeal shockwave lithotripsy is especially useful when surgery is contraindicated.