Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine.

AIMS: To explore drug exposure, frequency of adverse drug reactions (ADRs), types of ADRs, predisposing risk factors and ADR-related excess hospital stay in medical inpatients. METHODS: Structured data regarding patient characteristics, 'events' (symptoms, laboratory results), diagnoses (ICD10) and drug therapy were collected using a computer-supported data entry system and an interface for data retrieval from electronic patient records. ADR data were collected by 'event monitoring' to minimize possible bias by the drug monitor. The causality of each event was assessed in relation to disease(s) and drug therapy. RESULTS: The analysis included 4331 (100%) hospitalizations. The median observation period was 8 days. The median number of different drugs administered per patient and day was 6 and varied between 4 (Q1 ) and 9 (Q3 ) different drugs in 50% of all hospital days. In 41% of all hospitalizations at least one disease-unrelated event could be possibly attributed to drug therapy. Clinically relevant ADRs occurred in 11% of all hospitalizations. In 3.3% of all hospitalizations ADRs were the cause of hospital admission. The incidence of possibly ADR-related deaths was 1.4. Factors predisposing for clinically relevant ADRs were female gender and polypharmacy. ADR-related excess hospital stay accounted for 8. 6% of hospital days. CONCLUSIONS: These data demonstrate the feasibility of the developed 'event monitoring' system for quantitative analysis of ADRs in medical inpatients. With increasing numbers of recorded patients the pharmacoepidemiological database provides a valuable tool to study specific questions regarding drug efficacy and safety in hospitalized patients.

[Unexpected development during rehabilitation for suspected rheumatic disorder]. / Unerwarteter Verlauf einer Rheumarehabilitation.

The 57 year old woman presented with diffuse muscle spasms and delirium. Prior to presentation, she complained of progressive muscle pain, weakness and a weight loss of 10 kg over several months. Laboratory investigation showed hypopituitarism and a syndrome of inappropriate antidiuretic hormone secretion. Magnetic resonance imaging revealed an empty sella. The primary and secondary syndromes of empty sella are discussed.

Relapsing Whipple's disease presenting with hypopituitarism.

A 44-year-old man with a history of Whipple's disease 8 years ago presented with recurrent grand mal seizures and signs of hypopituitarism on physical examination. Magnetic resonance imaging of the brain revealed a hypothalamic lesion of 1 cm diameter in the region of the rostral infundibulum. Hypopituitarism was confirmed by low levels of serum cortisol, free testosterone and free thyroxine without an elevated TSH. Whipple encephalitis with hypothalamic involvement was suggested and verified by positive polymerase chain reaction (PCR) for Tropheryma whippelii in the cerebrospinal fluid. PCR for T. whippelii has become an important diagnostic tool for establishing the diagnosis of Whipple's disease especially in patients with unusual presentations and if the diagnosis cannot be confirmed histologically. Whipple's disease should be included in the differential diagnosis in hypopituitarism caused by infectious disease.

[Drug addict with ptosis. Myasthenia gravis]. / Drogenpatientin mit Ptose. Myasthenia gravis.

We report a 29 year old female drug addict seen in the emergency room with neck abscesses, dysphagia and a symmetric ptosis. Initially misinterpreted as adverse effect of illegal drug intake these symptoms were due to myasthenia gravis. This case shows an important differential diagnosis of ptosis common in drug addicts.

[Cushing syndrome due to ectopic ACTH secretion: an uncommon case presentation, diagnosis and therapy]. / Cushing-Syndrom infolge ektoper ACTH-Produktion: ungewöhnliches Fallbeispiel, Klinik, Diagnostik und Therapie.

Ectopic ACTH secretion due to malignant tumours is the most frequently underdiagnosed form of Cushing's syndrome. The majority of neoplasms causing ectopic ACTH syndrome are small-cell cancers of the lung or carcinoids. Other well-documented cases include adenocarcinoma of the lung, medullary thyroid carcinoma, pancreatic islet tumours and malignant thymoma. We report a rare case of metastatic colonic adenocarcinoma with ectopic ACTH syndrome. Clinical features such as proximal muscle weakness, peripheral oedema, hypertension or hirsutism in women, or the presence of unexplained hyperglycaemia, hypokalaemia or metabolic alkalosis in patients with known malignancy strongly suggest ectopic ACTH syndrome. Removal of the source of ACTH is the treatment of first choice, but often not feasible. Most often, treatment modalities are only palliative, with drugs directed against hypercortisolism such as aminoglutethimide, metyrapone, ketoconazole or mifepristone.

[Disseminated mycobacteriosis with M. kansasii in a case of AIDS without HIV infection]. / Disseminierte Mykobakteriose mit M. kansasii bei einem Fall von Aids ohne HIV-Infektion.

M. kansasii is an environmental Mycobacterium that causes disease mainly in patients with local or systemic immunodeficiency. We present a case with disseminated M. kansasii infection which led to a severe febrile illness lasting for 9 months. The patient had a combined acquired immunodeficiency syndrome (AIDS) which included CD4+ and CD8+ T-lymphocytopenia, monocytopenia and a deficiency in the IgG subclasses 2 and 4. HIV testing was repeatedly negative. In the published literature only 4 of 10 similar patients (this patient included) survived a disseminated M. kansasii infection. Eleven years after the disseminated infection with M. kansasii a second opportunistic infection, disseminated mollusca contagiosa and hyperparathyroidism, developed, and 14 years later the immunologic abnormalities persist.

[Osteopenia in beta-thalassemia major]. / Osteopenie bei beta-Thalassaemia maior.

Regular blood transfusions in patients with beta-thalassaemia major lead to secondary hemochromatosis in the majority of cases. As a consequence of chronic iron overload, many endocrinopathies may occur. The most frequent endocrine dysfunction is hypogonadotropic hypogonadism, which is mainly responsible for osteopenia in as much as 80% of thalassemic patients. The frequencies of other endocrine disorders (hypothyroidism, diabetes mellitus and hypoparathyroidism) are lower. We investigated 5 female patients aged 22-25 years for endocrine dysfunction and bone density. All presented with hypogonadotropic hypogonadism and amenorrhea (four primary and one secondary). 4 patients showed absent or delayed pubertal development and short stature (below 10th percentile). In all five, hypogonadism is the most relevant cause of osteopenia as demonstrated by osteodensitometry. Endocrine disorders, especially absent pubertal development, should be detected in good time and treated with hormonal replacement. Established osteopenia is treated hormonally and with vitamin D3 and calcium.

Recurrent brain abscesses in an HIV-positive patient with hereditary hemorrhagic telangiectasia and arteriovenous malformations of the lung.

Patients with hereditary hemorrhagic telangiectasia are at risk for the development of brain abscesses. The history of a 47-year-old man infected with the human immunodeficiency virus and with hereditary hemorrhagic telangiectasia is reported. Within eight months, the patient presented twice with life-threatening cerebral abscesses at different sites. On both occasions, Streptococcus anginosus was cultured from the abscess material. Treatment consisted of parenteral antibiotics and neurosurgical drainage. After treatment of the second occurrence, the patient was placed on a prophylactic regimen of clindamycin. He remains relapse-free and is clinically stable 24 months after the second episode.

[Heparin-induced thrombocytopenia. Results from the Comprehensive Hospital Drug Monitoring (CHDM) Bern/St. Gallen]. / Heparininduzierte Thrombozytopenie (HIT). Ergebnisse aus dem Comprehensive Hospital Drug Monitoring (CHDM) Bern/St. Gallen.

Of 23,520 consecutive hospitalizations from 1980-1988 (corresponding to 16,628 individual patients) in three departments of general internal medicine, 8261 were treated with heparin. All observations of patients displaying a probable, possible or questionable relationship of thrombocytopenia to heparin (administered i.v. or subcutaneously) were electronically collected by the CHDM program, revised on the basis of the primary case records and selected by standardized criteria. 13 of the 8261 patients exposed to heparin were considered to have a probable or possible HIT, corresponding to a frequency of 0.157%. In two of them severe thrombocytopenia was observed (corresponding to 0.024%) accompanied in one case by a white clot syndrome. Thrombocytopenia was defined as a platelet value below 100 x 10(9)/l and severe thrombocytopenia as one below 30 x 10(9)/l. In the literature we found slight, asymptomatic thrombocytopenia in < or = 1-8% of heparin treated patients. Our result of 11 out of 8261 (corresponding to 0.133%) is low, partly because the thrombocyte count was not controlled systematically, the heparin used was mainly produced from swine intestinal mucosa, and no antibody tests had been carried out. To prevent severe thrombocytopenia from heparin we propose monitoring the platelet count if the treatment is to be continued for more than 5 days. The newer low molecular weight heparins, all of swine origin, are much safer compared to the traditional preparations in regard to risk of HIT and white clot syndrome.

[Hyperprolactinemia]. / Hyperprolaktinämie.

In clinical endocrinology an elevated prolactin concentration in serum is often encountered. This may be either physiological during pregnancy and lactation or pathological in all other cases. The most frequent causes are drugs (dopamine antagonists, estrogens) and primary hypothyroidism. These hyperprolactinemic states have to be distinguished from prolactinomas and other tumors of the pituitary gland, which can increase the level of prolactin in the serum through different mechanisms. Drug therapy with dopamine agonists will almost always decrease prolactin levels, but will rarely cure the disease. Long-term success rates after surgery are 50% for microadenomas and 10 to 15% for macroadenomas. Therefore, the decision to operate should be made after careful discussion between the surgeon and the endocrinologist. Pregnancy will rarely cause expansion of the tumors, more often with macro- than with microadenomas. Pregnant women with prolactinomas have to be followed clinically, and drug therapy has to be instituted immediately when clinical signs of tumor progression exist.

[Frequency of antibiotics-associated colitis in hospitalized patients in 1974-1991 in "Comprehensive Hospital Drug Monitoring", Bern/St. Gallen]. / Die Häufigkeit der Antibiotika-assoziierten Kolitis bei hospitalisierten Patienten der Jahre 1974-1991 im "Comprehensive Hospital Drug Monitoring" Bern/St. Gallen.

In 3 divisions of internal medicine of teaching hospitals of the Comprehensive Hospital Drug Monitoring (CHDM) Foundation Bern/St Gallen, 42,920 patients consecutively admitted between 1974-1991 were investigated for adverse drug reactions. Of these 16,150 patients (38%) had received at least one systemically administered antibacterial drug during the hospital stay. Antibiotic-associated colitis included the following diagnoses: pseudomembranous colitis, hemorrhagic colitis and milder forms of colitis. We collected the data of these patients by searching for all diagnoses which might represent antibiotic-associated colitis (from the list of WHO adverse drug reaction terminology). 9 individual patients with one episode of probable antibiotic-associated colitis were found. In 5 of these cases, only one drug given during the hospital stay seemed to be implicated. An additional 32 patients were admitted with antibiotic-associated colitis in relation to treatment with the same groups of drugs before hospital admission. Based on the exposure pattern of the 9 patients with antibiotic-associated colitis compared to all patients exposed during hospital stay, we estimated the following frequencies related to the drug groups with at least 1,000 patients exposed: for all antibacterial chemotherapeutics 0.6/1000 (0.25-1.06); all penicillins 0.6/1000 (0.22-1.32), for benzyl-, phenoxy-, ureido-, isoxazolyl penicillins and methicillin 2.0/1000 (0.42-5.92) and aminopenicillin or analogues, with or without clavulanic acid 0.6/1000 (0.18-1.35). For cephalosporins the frequency is 1.4/1000 (0.17-5.12). Under sulfonamides combined with trimethoprim or related substances (5077 exposed patients) and fluoroquinolones (1043 exposed patients) no case was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cerebral toxoplasmosis with central diabetes insipidus and panhypopituitarism in a patient with AIDS]. / Zerebrale Toxoplasmoseinfektion mit Diabetes insipidus centralis und Panhypopituitarismus bei einem Aids-Patienten.

Endocrine disorders in the course of HIV infection are often a result of opportunistic infections of endocrine organs. We describe the case of a 30-year-old HIV positive man in whom diabetes insipidus developed initially with no abnormal findings in cranial magnetic resonance imaging. 2 months later the patient presented with symptoms of panhypopituitarism. At this time, neuroradiologic examination was consistent with cerebral toxoplasmosis. Symptoms and neuroradiologic findings improved after treatment for cerebral toxoplasmosis. Toxoplasmosis is the most frequent opportunistic infection of the brain in patients with AIDS. In HIV positive patients with malfunction of the hypothalamic-hypophyseal system cerebral toxoplasmosis must be considered in differential diagnosis. Treatment of this disorder may alleviate symptoms and signs of endocrine malfunction.

Brucellosis: an occupational hazard for medical laboratory personnel. Report of five cases.

Five cases of laboratory-acquired infection with Brucella melitensis are reported. This pathogen is highly contagious when handled in the laboratory. Clinicians should alert technologists when brucellosis is suspected so that specimens are handled under the most stringent safety measures. Serological surveys and instructions of laboratory workers regarding the clinical diversity of the disease are helpful for early recognition of secondary cases. On the other hand, clinicians should consider brucellosis in medical laboratory workers with unexplained signs and symptoms.

[HIV prevention in HIV-positive drug addicts. A methadone-supported model]. / HIV-Prävention bei HIV-positiven Drogenabhängigen. Ein methadongestütztes Modell.

In Switzerland, an estimated 15-25% of intravenous drug users (IVDUs) are infected with human immunodeficiency virus (HIV). It has been suggested that reduction of HIV-transmission-prone behavior could be achieved in so-called "early intervention programs". Few public prevention programs have so far been targeted to HIV-infected IVDUs. Socially marginalized, jobless, street-based, HIV-infected IVDUs are those hardest to reach for education programs: it was the hypothesis that they can be motivated for HIV-prevention efforts by methadone-based comprehensive social and medical care. The program was established by integrating one additional social worker in an outpatient clinic for infectious diseases in St. Gallen, a city with a population of 70,000 inhabitants in eastern Switzerland. Access to the 29 clients of this study (10 women, 19 men) was facilitated by offering methadone treatment (follow-up 5 to 29 months). Abstinence from additional illegal drugs was not required. Methadone, plus social care and medical treatment was provided by a small team consisting of a social worker, a physician and a nurse. A gradual approach was chosen to establish a working relationship with clients. The first attempt was to satisfy basic medical needs, housing, and financial support as well as to strengthen relevant personal relationships. Once trusting cooperation was established, reduction of transmission-prone behavior was targeted. The results show that social performance can be greatly improved by integrated social, psychological and medical assistance: for the 16 initially homeless housing was found, 14 found a job and for all but 2 basic financial support was eventually guaranteed. Self-reported drug abuse was markedly reduced, as was transmission-prone behavior by prostitution, unsafe sex practices, needle sharing and improper disposal of used syringes. Breaking the isolation of socially marginalized IVDUs seems to be the important move to enhance their social responsibility as carriers of HIV.

[Lead poisoning following administration of "home specialties"]. / Bleivergiftung nach Anwendung von "Hausspezialitäten".

Three cases of lead intoxication after the administration of "house specialties" are illustrated. The lead source could be traced to a lead-containing ointment in all three patients. Two of them suffered lead intoxication as a result of topical application to the lips, while the third had ingested the ointment orally. Clinical signs, diagnosis and therapy of lead poisoning are described in the light of the case reports. The patients were treated with various drugs (N-acetylcysteine and the complex chelators D-penicillamine and 2.3-dimercaptosuccinic acid (2.3-DMSA). The therapeutic effects were determined on specific laboratory features in blood and urine. N-acetylcysteine was not absolutely confirming in our case. D-penicillamine was effective, but only after removal of the source of exposure. Because of its known adverse drug reactions, we preferred the oral lead chelator 2.3-DMSA. Treatment with DMSA resulted in a considerable decrease in the blood lead concentration and in increase in urinary lead output. The urinary excretion of aminolevulinic acid and coproporphyrin normalized under DMSA. The treatment was well tolerated and no appreciable side effects were noticed. The literature on metabolism and the characteristic effects of lead intoxication is reviewed and the production, qualities and administration of emplastrum plumbi are described. All three lead-containing ointments are summarized by the characterizing term "house specialties". One wonders whether it is justified that there is still control and registration of such "house specialties" in Switzerland.

[Pseudopancreatitis in entero-invasive salmonellosis]. / "Pseudopankreatitis" bei enteroinvasiver Salmonellose.

The incidence of pancreatitis in bacterial enterocolitis is disputed. Two cases of young patients with S. enteritidis-induced enterocolitis and markedly elevated amylase and lipase blood levels are described. In both patients there were neither clinical nor ultrasonographic signs of pancreatitis. Furthermore, both had increased intestinal permeability for oral 51Cr-EDTA, a condition discussed as "leaky gut" in other publications. In one patient enzyme levels and 51Cr-EDTA resorption became rapidly normal, while in the other the values remained elevated after a 7-month interval with stool culture negative. Enhanced intestinal absorption of 51Cr-EDTA (mw 391) suggests--but does not definitely prove--an inflammatory response of the mucosa leading to increased intestinal permeability, which in turn may allow resorption of amylase (mw 62,000), lipase (43,000) or other macromolecules. Performance of a 51Cr-EDTA resorption test may be helpful in cases of clinical uncertainty.