Memorandum on the use of information technology to improve medication safety.

BACKGROUND: Information technology in health care has a clear potential to improve the quality and efficiency of health care, especially in the area of medication processes. On the other hand, existing studies show possible adverse effects on patient safety when IT for medication-related processes is developed, introduced or used inappropriately. OBJECTIVES: To summarize definitions and observations on IT usage in pharmacotherapy and to derive recommendations and future research priorities for decision makers and domain experts. METHODS: This memorandum was developed in a consensus-based iterative process that included workshops and e-mail discussions among 21 experts coordinated by the Drug Information Systems Working Group of the German Society for Medical Informatics, Biometry and Epidemiology (GMDS). RESULTS: The recommendations address, among other things, a stepwise and comprehensive strategy for IT usage in medication processes, the integration of contextual information for alert generation, the involvement of patients, the semantic integration of information resources, usability and adaptability of IT solutions, and the need for their continuous evaluation. CONCLUSION: Information technology can help to improve medication safety. However, challenges remain regarding access to information, quality of information, and measurable benefits.

Record linkage in the Cancer Registry of Tyrol, Austria.

OBJECTIVE: Record linkage of patient data originating from various data sources and record linkage for checking uniqueness of patient registration are common tasks for every cancer registry. In Austria, there is no unique person identifier in use in the medical system. Hence, it was necessary and the goal of this work to develop an efficient means of record linkage for use in cancer registries in Austria. METHODS: We adapted the method of probabilistic record linkage to the situation of cancer registries in Austria. In addition to the customary components of this method, we also took into consideration typing errors commonly occurring in names and dates of birth. The method was implemented in a program written in DELPHI(TM) with interfaces optimised for cancer registries. RESULTS: Applying our record linkage method to 130,509 linkages results in 105,272 (80.7%) identical pairs. For these identical pairs, 88.9% of decisions were performed automatically and 11.1% semi-automatically. For results decided automatically, 6.9% did not have simultaneous identity of last name, first name and date of birth. For results decided semi-automatically, 48.4% did not have an identical last name, 25.6% did not have an identical date of birth and 83.1% did not have simultaneous identity of last name and date of birth and first name. CONCLUSIONS: The method implemented in our cancer registry solves all record linkage problems in Austria with sufficient precision.

Using questions and interests to guide data mining for medical quality management.

The healthcare sector is currently facing both the economic necessity and the technical opportunity of a data based approach to quality management. Against this background, a process model for such a data based medical quality management is proposed and intelligent data mining methods are applied to patient data. Intelligent data mining incorporates advantages of both knowledge acquisition from data and from experts. A controlled language for business questions is presented which abstracts from database and data mining terminology to allow high-level interaction. Objective and subjective interestingness of results is measured and used to filter and sort.

Efficacy, safety and tolerability of lovastatin and bezafibrate retard in patients with hypercholesterolemia.

Hyperlipidemia has turned out to be the most important risk factor for coronary heart disease and necessitates frequently lipid lowering long-term treatment. Therefore, efficacy and tolerability of hypolipemic drugs are of great interest. The objective of the present study was to compare the safety, tolerability and effect on plasma lipids of Lovastatin and Bezafibrate retard in patients with hypercholesterolemia. 99 patients with total cholesterol of > or = 250 mg/dl after a 4 week standard lipid-lowering diet were treated another 4 weeks with placebo and then randomized to 400 mg Bezafibrate retard or 20 to 80 mg Lovastatin given once a day for 12 weeks. Mean changes from baseline in total cholesterol, LDL cholesterol and triglycerides were significantly reduced, in HDL cholesterol increased in both treatment-groups (p < or = 0.01). The effects of Lovastatin on total cholesterol and LDL cholesterol were more pronounced than those of Bezafibrate retard (p < or = 0.01), while Bezafibrate had a larger effect on triglycerides (p < or = 0.05). The frequency of clinical adverse experiences was low and similar among treatment groups, the frequency of laboratory adverse experiences was higher in the Lovastatin group. One patient in the Bezafibrate group was withdrawn because of nausea, one patient in the Lovastatin group because of GGT elevation.

[Acute management of myocardial infarct patients in Austria (cross-sectional study of 8 intensive care units)]. / Akutversorgung von Herzinfarktpatienten in Osterreich (Querschnittsuntersuchung an 8 Intensivstationen).

8 Austrian Intensive Care Units provided data from 6,317 cases (including 1,667 cases with acute myocardial infarction) admitted during 1990 and 1991 for a documentation system offered by the Austrian Heart Foundation. Significant differences were observed between the units concerning admission policies and the use of diagnostic methods. 71% of the AMI cases were first infarctions, 10% were Non-Q-infarcts. The median of the prehospital period varied between 2.5 and 6.5 hours. The evaluation of the admission mode showed that on average 42% of the AMI cases had contact to their G.P. before hospital admission, this figure varying, however, between 24 and 90% in different areas. It seems that this contact takes place to a much lower extent in big cities. On average G.P. contact before hospital admission in AMI resulted in doubling of the duration of the prehospital period. Thrombolytic treatment was applied in 24.7% of AMI cases with a variation between 13.9 and 48.4% in the different centers. It is suggested that regular use of this kind of quality control should offer means for optimizing the acute care of infarct patients on a regional and on a national level.

[The nephrotoxic effect of therapy with fumaric acid esters in psoriasis]. / Nephrotoxische Wirkung einer Therapie mit Fumarsäureestern bei Psoriasis.

Two sisters, aged 25 and 29 years, with generalized psoriasis guttata since childhood, developed nausea, upper-abdominal pain, loss of appetite, palpitations and flushes in the course of local and oral administration of fumaric acid esters. Because of these side effects the treatment was discontinued after about two weeks, and the symptoms disappeared. But proteinuria and haematuria were subsequently noted, creatinine concentration rose to 2.2 and 2.5 mg/dl, respectively, while creatinine clearance fell to 44 and 27 ml/min, respectively. Examination of urinary sediments and analysis of urinary proteins gave results compatible with tubular-interstitial renal damage. The abnormal renal functions and urinary findings proved reversible within three weeks.

[Several years observation of a Catergen (cyanidanol-3) induced immunohemolysis]. / Mehrjährige Verlaufsbeobachtung einer durch Catergen (Cyanidanol-3) induzierten Immunhämolyse.

A report is presented on repeated severe episodes of cyanidanol-induced immune hemolysis in a 75-year-old woman suffering from chronic active hepatitis. One year after the first hemolytic episode, high titers of anticyanidanol antibodies were still demonstrated in the patient's serum (as well as sensitization of the patient's lymphocytes by the drug). 4 years later virtually no decrease of the antibody titer was found. Further investigations of the patient's serum revealed antibodies against flavonoids with free hydroxyl groups (cyanidanol and rutin). However, no antibodies against flavonoids with derivatized hydroxyl groups (troxerutin, mixture of hydroxy-ethyl-rutin and silibinin) could be demonstrated. Sensitization with flavonoids other than cyanidanol preceding cyanidanol-induced hemolysis has been proposed by others. In this case storage of approximately 75 flavonoid containing preparations in a chemist's shop in the patient's house may have contributed to the astonishing persistence of dry dependent antibodies.

[Papilledema and macular edema as first symptom of non-Hodgkin's lymphoma]. / Papillen- und Makulaödeme als Erstsymptome bei Non-Hodgkin-Lymphom.

A patient presented in our clinic with impairment of visual acuity due to optic disc and macular oedema. Internal examination revealed chronic lymphatic leukaemia, and the patient was treated with Leukeran and Aprednisolone according to the chemotherapeutic regimen of Knospe. Remission occurred, and the pathological findings of the fundus disappeared.

[Gamma 1 heavy chain disease with immune vasculitis and rheumatoid arthritis]. / Gamma-1-Schwerkettenkrankheit mit Immunvaskulitis und rheumatoider Arthritis.

We are reporting about a case of gamma heavy-chain disease (Franklin's disease) with immunovasculitis and rheumatoid arthritis. The diagnosis was confirmed by the results of immunoelectrophoresis of the patient's serum and also by evidence of stimulated lymphocytes without light chain, but having gamma heavy-chain surface proteins. The immunofixation of the serum showed two protein bands of gamma heavy-chains with different loads. These results are confirmed by a two dimensional electrophoresis and isoelectric focussing of the serum proteins. The pathologic protein consists of at least two different heavy-chain proteins (mol wt 40,000 and 80,000) with isoelectric points between pH 5.5 and 7.3. In the urine of the patient pathological gamma heavy chain-protein was found only in a very low concentration. The predominant clinical symptom of the patient was a necrotizing vasculitis which became a therapeutical problem. In the immunofluorescence examination of the skin biopsy specimens, immunoglobulins and C3-complement could be detected in the stratum papillare. This fact would be compatible with the development of antibodies or immune complexes against deposited heavy-chain proteins. The arthropathy and the positive rheumatoid factor could similarly be explained by an immune complex mechanism.

Cross-over comparison between captopril and nifedipine.

In a cross-over study in 26 patients with mild to moderate essential hypertension The antihypertensive efficacy of captopril 25 mg b.i.d., nifedipine 20 mg b.i.d. and the combination both drugs in non-responders to monotherapy was compared. Of 26 captropril-treated patients 7 were non-responders and needed the addition of nifedipine; of 26 nifedipine-treated patients 3 needed additional captopril. Seven out of 26 patients treated with captopril, 22/26 patients given nifedipine and 9/10 patients receiving the combination reported side effects. In 3 nifedipine patients, 1 captopril patient and 1 patient on both drugs, treatment had to be stopped because of side effects. Captopril and nifedipine in these doses are about equally effective both after acute and chronic administration. The response-rate is somewhat higher with nifedipine, but the side effects are significantly less with captopril. There was no significant additive effect with the combination of the two drugs.

[Recurrent hemolytic-uremic syndrome with positive immunofluorescence]. / Rezidivierendes hämolytisch-urämisches Syndrom mit positiver Immunfluoreszenz.

The hemolytic uremic syndrome is a disease of infancy, its major clinical manifestations include reversible thrombocytopenia, hemolytic anemia, and renal failure. Although a great number of patients with HUS have been published, relapses as well as positive immunofluorescence studies are rare findings. In our patient the disease began at age of 7 years and recovered completely. At 10 1/2 years a relapse occurred and despite therapy the patient died two months later. Renal biopsy showed severe arterial and glomerular changes with remarkable similarity to the histological findings in thrombotic thrombocytopenic purpura, which could be explained as secondary hypertensive damage, and dense granular deposition of fibrinogen, IgG, IgA, C3, and Clq along the capillary loops of the glomerulus and throughout the wall of the renal arteries. The clinical data, histological findings, and the particularities of our patient with this special course of HUS are discussed.

Subtypes of acute postinfectious glomerulonephritis. Synopsis of clinical and pathological features.

42 kidney biopsies from adults and children suffering from acute postinfectious glomerulonephritis were examined by light microscopy, immunofluorescence and electron microscopy. The biopsies were obtained within 9 weeks of the onset of the first clinical symptoms. The results show not only a range of variation in the histological picture (particularly in the accumulation of leukocytes in the capillary lumens, and in the degree of cell proliferation) but also different immunofluorescent patterns which we have called the "starry sky", "garland" and "mesangial" patterns. These patterns correspond to characteristic differences in the electron microscopic picture. The "starry sky" pattern (IgG, IgM and/or IgA, combined with C3) occurs mainly in the first weeks of the disease and is associated with an endocapillary-mesangial glomerulonephritis. This may turn into a "mesangial" pattern (mostly C3 alone) which is associated mainly with mesangial proliferation. Four types of immune deposits can be observed electron microscopically in all three patterns (subendothelial, subepithelial, mesangial and intramembranous), but their different quantitative distribution determines the characteristic picture. Subepithelial deposits (so called "humps") often considered characteristic of poststreptococcal glomerulonephritis play a dominant role in the "garland" pattern. The cases with a "garland" pattern often show strikingly high levels of proteinuria (greater than 5 g/24 hr). It is believed that in patients with postinfectious glomerulonephritis deposition of immune complexes of various composition is responsible for producing the described subtypes depending on their different distribution in the glomeruli. It seems possible that these subtypes have different clinical significance, something which could be confirmed by performing follow-up studies.

[Plasma filtration treatment in thyreotoxic crisis]. / Plasmafiltrationsbehandlung einer thyreotoxischen Krise.

A 65-year-old man was treated three times in 4 consecutive days with plasma filtration for a severe thyroid storm. During the treatment the serum and filtrate levels of thyroxine, triiodothyronine, free T4, free T3, TBG, albumin and reverse-T3 were measured, and the results showed that, apart from reduction of the total hormone amount, the supply of binding sites for the free hormones is an important aspect in the treatment of thyroid storm.

[Atypical, severe pancytopenia in chronic myelomonocytic leukemia (author's transl)]. / Atypische, schwere Panzytopenie bei chronischer myelomonozytärer Leukämie.

Among 17 patients with non acute monocytic (CMoL) and myelomonocytic leukemia (CMML) one patient presented with atypical findings and an unusual clinical course. Prominent massive pancytopenia had occurred ever since the diagnosis was established. To our knowledge this symptom has not been described in cases with CMML and CMoL. Splenectomy afforded temporary improvement of the anemia but induced sustained, marked thrombocytosis. An unusually prolonged survival time of 44 months was achieved, presumably by the continuous, careful replacement of blood, the splenectomy and the relinquishment of cytotoxic therapy. A gradual, continuously developing blastic crisis and finally the transition to an acute leukemia were observed.

[Humoral and cellular immune mechanisms in venous occlusive lung diseases]. / Humorale und zelluläre Immunmechanismen bei veno-okklusiver Erkrankung der Lunge.

In a 73-year-old female patient, pulmonary veno-occlusive disease was diagnosed by the typical histological findings in the lung. Immunofluorescence studies showed granular deposits of IgG and C1q in the lung, suggesting immune complex deposition and complement activation by the classical pathway. Furthermore, the presence of lymphocytes sensitized against collagen was demonstrated using the leukocyte migration inhibition system. These results demonstrate the significance of humoral and cellular immune mechanisms in the pathogenesis of this disease.

Persistent intravascular C3 activation after bilateral nephrectomy in patients with thrombotic microangiopathy.

Four patients with thrombotic microangiopathy had evidence of intravascular C3 activation on presentation which persisted after bilateral nephrectomy. In several serum samples, C3-splitting activity was not associated with the presence of circulating immune complexes, which were detected in all four patients before nephrectomy and in three after nephrectomy.

[Renal function during passive orthostasis (author's transl)]. / Partialfunktionen der Niere während orthostatischer Belastung

Glomerular filtration rate (GRF) as measured by inulin clearance and renal plasma flow (RPF) as measured by PAH clearance were determined in 9 mountaineers before and during suspension. The two step permanent infusion technique was employed for 3 periods of 8 min. GRF decreased from 123.0 +/- 14.9 ml/min to 25.3 +/- 3.9 ml/min and RPF from 791.0 +/- 101.0 ml/min to 129.0 +/- 20.4 ml/min within 24 min. These results are consistent with the occurrence of acute renal failure in mountain climbers after free suspension on the rope even after long periods.

Detection of circulating soluble immune complexes in patients with various renal diseases.

Sera from patients with various types of glomerulonephritis (GN) as well as sera from rabbits with acute serum sickness were studied for the presence of circulating immune complexes (IC). The method used is based on the observation that IC inhibit the uptake of IgG aggregates by guinea-pig peritoneal macrophages. Inhibition significantly greater than with normal human sera was found with sera of patients with membranous GN, membranoproliferative GN, focal glomerular sclerosis, minimal change nephrotic syndrome, acute septicaemic glomerular diseases and systemic lupus erythematous. IC were also detected in rabbits with acute serum sickness during the period of immune elimination.

[Goodpasture's syndrome (author's transl)]. / Klinik und immunologie des goodpasture-syndroms

Goodpasture's syndrome occurred in six patients (four men and two women) aged 18-32 years. Haemoptysis, anaemia and abnormal urinary findings with erythrocyturia were the first signs of the disease in five instances, in one the renal signs predominated. In five patients the disease took a malignant course with uraemia developing within six weeks. One patient is in a spontaneous remission eleven months after the onset of the disease. Three patients died of recurrent haemoptysis (non-nephrectomised), two nephrectomised patients are still alive half a year and three and a half years later, respectively. A typical linear IgG-, beta1A, alpha2D and beta1E deposition along the glomerular capillaries was demonstrated immunohistologically in all subjects. Of three lung biopsies one also had typical IgG and beta1A-positive linear fluorescence along the alveolar basal membrane. Immunoglobulins with basal membrane antibody activity were eluted from renal homogenates in two patients, basal membrane antibody activity in serum was demonstrated only in one of three patients.