Readmissions and adverse drug reactions in internal medicine: the economic impact.

BACKGROUND: Recent studies show that nearly half of the hospitalized patients are readmitted within 6 months from discharge. No data exist about the relationship between adverse drug reactions (ADRs) and readmittance to a department of internal medicine. OBJECTIVES: The primary aims of the study were to determine if ADRs could be used as predictors for recurrent hospitalizations in internal medicine and to evaluate the economic impact of ADRs on hospitalization costs. DESIGN AND SETTING: A cohort-based, prospective, 18-month pharmacoepidemiological survey was conducted in the Department I of Internal Medicine at the University Hospital of Erlangen. All patients were intensively monitored for ADRs by a pharmacoepidemiological team. ADRs were evaluated for their offending drugs, probability, severity, preventability and classified by WHO-ART. During a 6-month period ADR-positive patients were matched to non-ADR patients applying diagnosis-related group categorization in order to measure the impact of ADRs on the duration and frequency of hospitalization. RESULTS: Of 1000 admissions 424 patients had single admissions and 206 patients had recurrent readmissions (min 1, max 9). The prevalence of readmissions was 37% (n = 370). In 145 (23%) of 630 patients, 305 ADRs were observed. The ADR incidence was similar in first admissions and readmissions. ADRs were not found to predict further readmissions and lack of ADRs did not preclude readmissions. ADRs caused hospitalizations in 6.2% of first admissions and in 4.2% of readmissions. According to the Schumock algorithm 135 (44.3%) ADRs were found to be preventable. The occurrence and numbers of ADRs per admission were found to prolong hospitalization period significantly (r = 0.48 and 0.51, P < 0.001, n = 135). Of 9107 treatment days 20% were caused by in-house (1130 days) and community-acquired ADRs (669 days). In admissions and readmissions 11% (>973 days) of all treatment days were judged to be preventable. CONCLUSIONS: Intensified drug monitoring supported by information technology in internal medicine is essential for early detecting and prevention of ADRs and saving hospital resources.

Use of complementary alternative medicine in patients admitted to internal medicine wards.

OBJECTIVE: To evaluate rate and type of complementary alternative medicine (CAM) use in patients admitted to a medical ward. To identify demographic and disease or treatment-related factors associated with CAM use in these patients. To evaluate the awareness of physicians regarding this practice and whether CAM use had contributed to hospital admission. METHODS: This study is based on consecutive interviews and chart reviews of 180 patients admitted to the Department of Internal Medicine, Hadassah Hebrew University Hospital in Jerusalem, Israel. 29 patients were excluded due to impaired cognitive state and 2 patients refused to participate in the study. Patients were asked questions concerning sociodemographic characteristics and CAM use: type, time, duration of use, causes, outcomes and communication about CAM use with their hospital and family physicians. Information about background diseases, acute diagnoses that led to hospitalization, symptoms on admission, drugs taken at home prior to admission was provided by chart reviews. RESULTS: 26% of patients reported a lifetime history of CAM use and 11% during the month prior to admission. Younger age, higher education and Israeli, USA or European origin was associated with more frequent CAM use. Hospital physicians were informed only about 12% of the CAM courses in the month prior to admission, whereas family physicians were aware of about half of them. No direct or indirect harmful effects of CAM were noticed in this study. No essential changes in the regimen of drugs or other conventional treatments due to CAM use were found. If the condition deteriorated, patients did not defer their visit to hospital because of CAM use. CONCLUSIONS: With reservations due to small sample size, it appears that CAM use was not an important factor influencing hospital admissions to a medical ward. Awareness of the hospital physicians regarding CAM use in their patients during the month prior to admission was much lower than that of the family physicians (12% vs. 51.3%).

Paroxetine associated hepatotoxicity: a report of 3 cases and a review of the literature.

We recently encountered 3 patients who had developed reversible paroxetine-associated hepatotoxicity. Two of the patients were over 80 years old and their hepatitis was accompanied by hyponatremia. In the third case, hepatitis was associated with multiple organ failure and the co-administration of trazodone. Here, we will discuss the possible role of preexisting risk factors in the development of paroxetine hepatotoxicity and review the relevant literature.

Compound cardiac toxicity of oral erythromycin and verapamil.

OBJECTIVE: To report a case of complete atrioventricular (AV) block and QTc prolongation following coadministration of high-dose verapamil and erythromycin. CASE SUMMARY: A 79-year-old white woman was admitted to the hospital due to extreme fatigue and dizziness. On admission, heart rate was 40 beats/min and blood pressure was 80/40 mm Hg. An electrocardiogram showed complete atrioventricular (AV) block, escape rhythm of 50 beats/min, and QTc prolongation 583 msec. This event was attributed to concomitant treatment with verapamil 480 mg/d and erythromycin 2,000 mg/d, which was prescribed one week before admission. DISCUSSION: This is the first case published describing complete AV block and prolongation of QTc following coadministration of erythromycin and verapamil. CYP3A4 is the main isoenzyme responsible for metabolism of erythromycin and verapamil. Both drugs are potent inhibitors of CYP3A4 and of P-glycoprotein; this may be the basis for the pharmacokinetic interaction between erythromycin and verapamil. In addition to being a woman, our patient had other risk factors for QT prolongation: slow baseline heart rate (probably induced by verapamil), left-ventricular hypertrophy, and possibly ischemic heart disease. CONCLUSIONS: This life-threatening arrhythmia was probably the result of a pharmacokinetic and/or pharmacodynamic interaction of high-dose verapamil and erythromycin.

Mefloquine-induced acute hepatitis.

Mefloquine is an effective drug for prophylaxis and treatment of malaria caused by Plasmodium falciparum. It is generally well tolerated with few side effects. Minimal elevation of liver function tests has been reported after exposure to mefloquine, especially in susceptible individuals with prior abnormal liver function tests. Our patient, who had had elevated liver function tests attributed to heart failure, experienced an acute elevation of liver transaminases 6 weeks after exposure to mefloquine 250 mg/week. Cessation of the drug caused test results to return to normal. Mefloquine should be prescribed cautiously in patients with liver disease.

Retrospective analysis of the frequency and recognition of adverse drug reactions by means of automatically recorded laboratory signals.

AIMS: To estimate the frequency of adverse drug reactions (ADRs) identified through the use of automatic signals generated from laboratory data (ALS) in hospitalised patients. To determine the frequency of spontaneous recognition of these ADRs by the attending physicians and to assess the potential value of ALS for detection of ADRs. METHODS: Laboratory results of patients hospitalised in a nine bed medical ward were automatically recorded over a period of 17 months. Values exceeding defined boundaries were used as ALS. Charts of every third patient were analysed retrospectively with regard to adverse drug related reactions and causality was evaluated as well as whether the ADR had been recognised during the period of hospitalisation. RESULTS: The charts and ALS of 98 patients were analysed. In 18 cases a drug-related adverse reaction was probable. Awareness to the reaction by the treating physicians was evident in 6 out of these 18 ADRs. Approximately 80% of the ADRs were considered predictable. Three ADRs were regarded as serious. CONCLUSIONS: Adverse drug reactions are common and often preventable. Only one third of ADRs which could have been detected through ALS were recognised by the attending physicians. An increased doctor's awareness of the frequency of drug related abnormal laboratory results by means of ALS is likely to increase the recognition rate of ADRs and might help to prevent them.

Computerized surveillance of adverse drug reactions in hospital: implementation.

OBJECTIVE: To implement and measure the effects of automatic computerized laboratory signals (ALS) as a detection support tool of adverse drug reactions (ADRs) in hospital. METHODS: This was a prospective observational study of a total of 192 patients (199 sequential medical admissions) during a 2-month period in a 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. The study involved the routine (daily) distribution to staff physicians of lists of automatic signals generated from computerized laboratory data as potential indicators of ADRs. Patient charts were reviewed by the clinical pharmacology team for ADRs and to see whether these were recognized by the staff physicians. RESULTS: Seventy-one ADRs were detected in 64 of the 199 (32%) admissions. Twenty-seven per cent of the ADRs were serious, 9% of the admissions were due to ADRs. Two hundred and ninety-five ALS were generated involving 69% of the admissions. Sixty-one per cent of the ADRs were identified by ALS. ALS were present in 58% of the ADR negative admissions. Eighty-five per cent of the ADRs were recognized as such and 19% of the ALS-positive ADRs were not recognized by the staff physicians. CONCLUSIONS: The routine implementation of ALS doubled the number of ADRs recognized by the physicians while patients were hospitalized in the medical ward. The use of the system appeared valid, simple and potentially cost-effective.

Computerized survelliance of adverse drug reactions in hospital: pilot study.

AIMS: To develop and assess the use of computerized laboratory data as a detection support tool of adverse drug reactions (ADRs) in hospital. METHODS: This was a retrospective observational study of 153 sequential medical admissions during a 2-month period to the 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. Measurements made were 1) Retrospective chart review for recognized and unrecognized adverse drug reactions (ADRs) and 2) Analysis of computerizied laboratory data according to defined automatic laboratory signals (ALS) for adverse reactions. RESULTS: Forty ADRs have been detected in 38 out of the 153 hospital admissions (24.8%). Nine reactions were considered severe. Altogether 212 ALS were generated involving 86 admissions. In 25 (65.8%) of the ADR-positive admissions ADRs were detected through automatic signals generated from the laboratory data. ALS were detected in 56 out of the 115 (48.7%) ADR-negative admissions. Twenty-four (60%) of the ADRs were not recognized as such by the attending physicians. Two of these reactions were severe. ALS could have generated an alert for 19 (79.2%) of the unrecognized reactions. CONCLUSIONS: Application of automatic laboratory signals can increase the rate of recognition of the ADRs and thereby improve medical care. The sensitivity and specificity of the method might be increased by refinement and redefinition of the signals.

Tachycardia, orthostatic hypotension and profound weakness due to concomitant use of fluoxetine and nifedipine.

The use of the selective serotonin reuptake inhibitor fluoxetine is associated with only minor cardiovascular effects. However, due to a possible inhibitory effect on the metabolism of calcium channel blockers it may potentiate the activity of nifedipine, causing profound adverse cardiovascular effects. This report describes the appearance of profound weakness, orthostatic hypotension and tachycardia following the initiation of fluoxetine treatment in a nifedipine-treated 80-year-old patient.