Development of a computerised alert system, ADEAS, to identify patients at risk for an adverse drug event.

INTRODUCTION: Adverse drug events (ADEs) are frequent and pose an important risk for patients treated with drugs. Fortunately, a substantial part of ADEs is preventable, and computerised physician order entry with a sophisticated clinical decision support system may be used to reach this goal. OBJECTIVE: To develop a new automated system that could improve the quality of medication surveillance. The system should focus on detecting patients at risk for an ADE by combining data from the hospital information system and computerised physician order entry (drug prescription data, drug-drug interaction alerts, clinical chemical laboratory parameters, demographic features), using clinical rules. METHODS: The clinical rules were formulated in a multidisciplinary team, based on seven risk categories. The new system was composed in a guideline-based decision support framework consisting of both a guideline development module and a decision support module. A total of 121 clinical rules were built into the system. Validation of the system and a proof of principle test were performed. RESULTS: The adverse drug event alerting system (ADEAS) was developed and validated successfully. The proof of principle test showed that ADEAS has potential clinical usefulness. ADEAS generated alerts and detected additional potential risk situations, which were not generated by the conventional medication surveillance. CONCLUSION: We developed a pharmacy decision support system ADEAS that focuses on the detection of situations prone to lead to an ADE and might help clinicians to take timely corrective interventions and thereby can prevent patient harm.

[Tetany due to excessive use of alcohol: a possible magnesium deficiency]. / Tetanie bij overmatig alcoholgebruik: mogelijk een magnesiumtekort.

Two alcoholic patients, a woman aged 64 and a man aged 69 years, were admitted with tetany. Both had severe electrolyte disorders, with low plasma levels of calcium, magnesium and potassium. Following mineral supplementation both patients recovered. Hypomagnesaemia plays a central role in the pathophysiology of this syndrome. Chronic alcohol abuse results in hypomagnesaemia in 30% of patients by decreasing renal tubular reabsorption. Hypomagnesaemia leads to suppression of parathyroid-hormone secretion, parathyroid-hormone resistance and vitamin-D suppression, resulting in hypocalcaemia. Hypomagnesaemia also causes kaliuresis leading to hypokalaemia. Supplementation with magnesium is crucial in the treatment of this combined electrolyte disorder.

[Methemoglobinemia due to ingestion of isobutyl nitrite ('poppers')]. / Methemoglobinemie door drinken van isobutylnitriet ('poppers').

Two male students, aged 20 and 21 years, developed central cyanosis shortly after drinking 5 ml of 'poppers' (isobutyl nitrite). They presented with methaemoglobinaemia and were hospitalised. After treatment with oxygen and intravenous fluids they could be discharged in good health the following day. Poppers are alkyl nitrites with vasdilative and oxidizing properties. They are used as party drugs (i.e. inhaled) because of their short-lived euphoric effect. Overdose can result in methaemoglobinaemia: the presence of oxidized haemoglobin which is unable to transport oxygen. Depending on the serum level of methaemoglobin this may result in central cyanosis, unconsciousness, coma and even death. Patients with high methaemoglobin levels should be treated with i.v. methylene blue.

Food choice in hyperthyroidism: potential influence of the autonomic nervous system and brain serotonin precursor availability.

We explored energy and macronutrient intake in patients with Graves' hyperthyroidism. We specifically hypothesized that hyperthyroidism is associated with increased appetite for carbohydrates, because of enhanced sympathetic tone and diminished serotonin mediated neurotransmission in the brain. To test this hypothesis, we measured food intake by dietary history and food selected for lunch in the laboratory in 14 patients with Graves' hyperthyroidism. Twenty-four-hour catecholamine excretion was used as a measure of activity of the sympathetic nervous system (SNS) and the plasma [Trp]/[NAA] ratio was measured to estimate (rate limiting) precursor availability for brain 5-hydroxytryptamine synthesis. All measurements were repeated after the subjects had been treated to establish euthyroidism. In addition, the effects of nonselective beta-adrenoceptor blockade upon these parameters were studied to evaluate the influence of beta-adrenergic hyperactivity on food intake. Hyperthyroidism was marked by increased SNS activity and reduced plasma [Trp]/[NAA] ratio. Accordingly, energy intake was considerably and significantly increased in hyper vs. euthyroidism, which was fully attributable to enhanced carbohydrate consumption, as protein and fat intake were not affected. These results suggest that hyperthyroidism alters the neurophysiology of food intake regulation. Increased SNS activity and reduced Trp precursor availability for 5-hydroxytryptamine synthesis in the brain may drive the marked hyperphagia and craving for carbohydrates that appears to characterize hyperthyroid patients. Because propranolol did not affect food intake in hyperthyroidism, the potential effect of catecholamines on food intake might be mediated by alpha-adrenoceptors.

Lactic acidosis: pathophysiology, diagnosis and treatment.

Lactic acidosis is common in severely ill patients. We describe four patients with a lactic acidosis combined with other acid-base disturbances. In daily practice it is important to consider these combined disturbances since there is no specific treatment in lactic acidosis. Treating the underlying causes of the acid-base disturbances is the only warranted intervention. However, lactic acidosis is still associated with high mortality.

Hyponatremia due to hypothyroidism: a pure renal mechanism.

Hyponatremia is a common disorder. When hyponatremia is the result of hypothyroidism it can be successfully treated with thyroid hormone substitution. We followed cumulative sodium- and fluid balances of a patient with hyponatremia, resulting from hypothyroidism. We concluded that hyponatremia in hypothyroidism is due to a pure renal mechanism, and cannot be ascribed to inappropriate secretion of antidiuretic hormone.

Sixty-eight-year-old patient with hypokalemia.

A 68-year-old patient with severe hypokalemia and metabolic alkalosis is described. Six years before admission he had been treated for a small cell bronchial carcinoma. We discuss the diagnostic approach of hypokalemia and the way in which we reached the diagnosis. The patient suffered from metastatic small cell carcinoma with a very high plasma adrenocorticotropic hormone concentration, possibly due to production of corticotropin-releasing hormone by the malignancy.

[Patient with eosinophilic polymyositis]. / Een patiënt met eosinofiele polymyositis.

In a 36-year-old patient with a severe polymyositis peripheral eosinophilia and abundant infiltration of muscle tissue by eosinophilic granulocytes were observed. Eosinophilic polymyositis was diagnosed. Treatment consisted of high dose prednisone, immunoglobulin and azathioprine, resulting in complete remission of the disease. Idiopathic eosinophilic polymyositis is an uncommon disorder, first described in 1976. The eosinophilic granulocyte is essential in the pathogenesis (by releasing toxic mediators and the production of cytokines), but the cause of the activation is still unknown. Treatment is aimed at immune suppression and consists first of all in administration of prednisone.

[Role of the morning report in the training of internists]. / De rol van het ochtendrapport in de opleiding tot internist.

The morning report constitutes an important part of the daily routine in the Department of Internal Medicine. According to the literature, this procedure makes an effective contribution to the training of internists, provided that a number of conditions are fulfilled (a critical but not hostile atmosphere, broad participation, a large number of patients). We compared the diseases discussed in the morning report retrospectively with the final attainment levels for the training of internists as described in the recently published 'Outline of Internal Medicine'. Of the diseases described in this outline, almost two-thirds (62.4%) had been discussed on the morning report within a period of 6 months. The morning report would seem to be an important addition to the other forms of knowledge transfer within the training of internists.

[Very-low-calorie diet in treatment of morbidly obese patient with diabetes mellitus type 2]. / Het zeer laagcalorisch dieet als behandeling voor de zeer adipeuze patiënt met diabetes mellitus type 2.

A 40-year-old woman with type 2 diabetes mellitus, hypertension, central obesity (body mass index: 40 kg/m2) and mixed hyperlipidaemia was treated with oral hypoglycaemic, antihypertensive and hypolipidaemic drugs as well as with intramuscular insulin. She kept gaining weight and developed hiatus hernia with regurgitation. Treatment was changed to a very low caloric diet during 9 months. She lost 18 kg of body weight and all drugs could be discontinued, as she became normoglycaemic, normotensive and normolipidaemic. Obesity is a risk factor for insulin resistance and type 2 diabetes mellitus. To reach euglycaemia in overweight type 2 diabetics is a difficult task. Oral hypoglycaemic agents and insulin are often used in combination with dietary intervention without adequate results. Losing body weight should be first-line treatment. However, compliance with weight-reducing methods is often low. The pathophysiologic importance of significant weight loss in the treatment of (morbid) obesity in type 2 diabetic patients is great.

[Clinical thinking and decision making in practice. An elderly patient with vertigo and high sedimentation rate]. / Klinisch denken en beslissen in de praktijk. Een oudere patiënte met duizeligheidsklachten en hoge bezinking.

A 77-year-old woman was admitted because of progressive vertigo, nausea and a dysarthric speech disorder. The patient's history of diabetes mellitus, hypertension and hypercholesterolaemia, and the finding of murmurs over peripheral arteries at physical examination led to a presumptive diagnosis of cerebellar ischaemia in the context of generalized atherosclerosis. However, the diagnosis was revised when bilateral cerebellar infarction was demonstrated radiologically, and a biopsy of a temporal artery revealed giant cell arteritis. Despite treatment with prednisone (60 mg daily) the patient's neurological condition deteriorated, and she succumbed several months later to pneumonia. The case illustrates the pitfalls in the diagnostic approach of elderly patients with multiple pathology and it also emphasizes that in an elderly person with high erythrocyte sedimentation rate (> 100 mm in the first hour) temporal arteritis should be ruled out as soon as possible to prevent further neurological damage.

[Metabolic acidosis caused by hyperalimentation; a dangerous complication of parenteral nutrition]. / Metabole acidose ten gevolge van hyperalimentatie; een gevaarlijke complicatie bij parenterale voeding.

A man aged 46 developed oesophageal obstruction due to carcinoma. He was admitted with dehydration following strongly reduced fluid intake leading to prerenal kidney failure. He had had a renal transplantation, after which a moderate renal insufficiency persisted. During 12 days he received parenteral nutrition upon which he developed severe hyperchloraemic metabolic acidosis. The treatment of this condition consists of discontinuation of the parenteral nutrition and administration of bicarbonate. If the parenteral nutrition needs to be continued, the amount of chloride must be diminished and acetate be added. It is important to monitor the acid-base balance and plasma electrolytes in patients with parenteral nutrition, especially in the presence of renal failure. The patient recovered from the metabolic acidosis but later died of metastatic oesophageal carcinoma.

[Addisonian crisis provoked by levothyroxine substitution therapy]. / Addison-crisis uitgelokt door substitutietherapie met levothyroxine.

A women aged 36 with a positive family anamnesis for autoimmune endocrine diseases and a history of thyroid diseases, developed major complaints of general malaise, orthostatic hypotension and loss of appetite after the start of a treatment with levothyroxin because of (sub)clinical hypothyroidism. She was found to suffer from primary adrenocortical insufficiency masked by excessive use of liquorice and a lowered metabolism, but which via the suppletion with thyroid hormone had led to an addisonian crisis.

[The hyperglycemic dehydration syndrome]. / Het hyperglykemisch dehydratiesyndroom.

Two patients, men aged 47 and 64 years, were found in a comatose condition in their homes, after a period of fatigue, polyuria and polydipsia. They had not been known to suffer from diabetes mellitus, but now displayed a hyperglycaemic hyperosmolar non-ketoacidotic disorder as the first manifestation of diabetes mellitus type 2. In that condition, just sufficient insulin is present to counteract ketone production, but not enough to prevent hyperglycaemia. Neurological and thromboembolic manifestations, possibly fatal, may result from severe dehydration brought about by a vicious circle in which osmotic diuresis reduces the effective circulating volume, causing renal function to decrease and hyperglycaemia to increase even more. Both patients recovered fully after adequate treatment with solutions of NaCl and glucose.

[Clinical thinking and decision making in the practice. A patient with fever of unknown origin]. / Klinisch denken en beslissen in de praktijk. Een patiënte met febris e causa ignota.

A 75-year-old woman was admitted because of fever of unknown origin (FUO). In the year before the current admission she developed myalgias and was treated for polymyalgia rheumatica with low-dose prednisone. Her complaints persisted and prednisone was discontinued. Five months before the present admission she developed fever (37.7-38.9 degrees C), malaise, fatigue and occipital headache. Laboratory tests showed an elevated erythrocyte sedimentation rate (98 mm in the first hour) and a severe hypochromic, slightly microcytic, anaemia. Although a recent temporal artery biopsy was negative, a second biopsy was taken which showed giant cell arteritis. The patient was treated with high-dose prednisone (60 mg daily) and made a full recovery. It is emphasized that temporal arteritis is a common cause of FUO in the elderly.

[Clinical decision making in family practice. A patient with abdominal pain and chills]. / Klinisch denken en beslissen in de praktijk. Een patiënt met buikpijn en een koude rilling.

An 82-year-old man was admitted because of abdominal pain and a shaking chill. His medical history revealed ileocecal resection because of ileitis associated with a Yersinia infection 3 years before admission. One year later he was readmitted because of bowel obstruction due to recurrent ileitis. He was treated with trimethoprim-sulfamethoxazole for two weeks because of positive serological tests for Yersinia and made a full recovery except for chronic diarrhoea. On the current admission, stool cultures yielded Campylobacter upsaliensis. Further analysis showed severe non-specific ulcerative ileitis without colitis. A diagnosis of Crohn's disease was made. The patient was treated with prednisone and mesalazine and made a full recovery. The chronic diarrhoea disappeared. The course was complicated by a cerebro-vascular thrombosis and severe thrombocytosis due to polycythaemia vera. Treatment with hydroxyurea was effective in lowering the thrombocyte count.

[Clinical reasoning and decision making in the practice. A woman with abdominal complaints]. / Klinisch denken en beslissen in de praktijk. Een patiënte met buikklachten.

A female patient aged 28 years suffered from recurrent episodes of diarrhoea. Giardia lamblia was isolated once. By rigorous application of basic clinical skills, such as thorough history taking and physical examination, together with laboratory tests the correct diagnosis was established (in this patient systemic lupus erythematosus). Two important aspects of clinical reasoning, viz. returning to the patient when new information becomes available (cyclic way of working) and pattern recognition ensured a fruitful diagnostic process.

[Clinical thinking and decision making in practice. A patient with icterus]. / Klinisch denken en beslissen in de praktijk. Een patiënt met icterus.

A 55-year-old man was admitted because of cholestatic jaundice. Extrahepatic obstruction and viral causes were excluded. A diagnosis of liver damage due to the combination preparation amoxicillin and clavulanic acid (Augmentin) was made. The patient had an uneventful recovery. It is pointed out that in case of cholestatic jaundice drug-induced cholestasis should be suspected early in the course. History taking is an important tool. If a suspected drug is found other causes of the disease can be excluded with simple tests.

[Clinical thinking and decision making in practice. A patient with pain in the upper abdomen]. / Klinisch denken en beslissen in de praktijk. Een patiënt met pijn boven in de buik.

A 74-year-old woman was admitted because of abdominal pain. A few weeks before this admission she had had a cerebral infarction in the right hemisphere, reflected by a left sided paralysis, dysarthria, depression and a slight cognitive disorder. The night before admission she woke up from a sharp, continuous pain in the right upper abdomen. Physical examination disclosed pain in the right upper abdomen on palpation. Laboratory tests showed a slight elevation of all 'liver' enzymes. A differential diagnosis of cholecystitis or pyelonephritis was made. Additional tests did not confirm either of these diagnoses. Because of immobilisation pulmonary embolism was then suspected. This diagnosis was confirmed by scintigraphy. The patient was treated and made a full recovery. Diagnostic errors can be made by faulty triggering and omitting verification. The diagnostic strategy for pulmonary embolism is a ventilation perfusion scan, which is followed in case of a non high-probability result by pulmonary angiography. It is emphasized that the presentation of pulmonary embolism can be aspecific.