B.H.Ch. Stricker

The incidence of complex regional pain syndrome: a population-based study.

Abstract The complex regional pain syndrome (CRPS) is a painful disorder that can occur in an extremity after any type of injury, or even spontaneously. Data on the incidence of CRPS are scarce and mostly hospital based. Therefore the size of the problem and its burden on health care and society are unknown. The objective of the present study was to estimate the incidence of CRPS in the general population. A retrospective cohort study was conducted during 1996–2005 in the Integrated Primary Care Information (IPCI) project, a general practice research database with electronic patient record data from 600,000 patients throughout the Netherlands. Potential CRPS cases were identified by a sensitive search algorithm including synonyms and abbreviations for CRPS. Subsequently, cases were validated by electronic record review, supplemented with original specialist letters and information from an enquiry of general practitioners. The estimated overall incidence rate of CRPS was 26.2 per 100,000 person years (95% CI: 23.0–29.7). Females were affected at least three times more often than males (ratio: 3.4). The highest incidence occurred in females in the age category of 61–70 years. The upper extremity was affected more frequently than the lower extremity and a fracture was the most common precipitating event (44%). The observed incidence rate of CRPS is more as four times higher than the incidence rate observed in the only other population‐based study, performed in Olmsted County, USA. Postmenopausal woman appeared to be at the highest risk for the development of CRPS.

Antihypertensive drugs and incidence of dementia: the Rotterdam Study

There is increasing evidence that hypertension may contribute to the development of dementia. We investigated the relation of antihypertensive drug use and the risk of dementia in the cohort of the population based Rotterdam Study. The study cohort included 7046 elderly, free of dementia at baseline. Dementia was diagnosed in a stepwise procedure. Participants were first screened. Screen positives were further tested. Those suspected of dementia underwent a diagnostic work-up. Dementia and its subtypes were diagnosed according to prevailing criteria. A Cox proportional hazards model was used to estimate relative risks. After a mean follow-up of 2.2 years, subjects taking antihypertensive medication at baseline (n = 2015) had a reduced incidence of dementia (adjusted relative risk, 0.76; 95% confidence interval 0.52-1.12). This risk reduction was most pronounced for vascular dementia, (adjusted relative risk, 0.30; 95% confidence interval 0.11-0.99). For Alzheimers disease the relative risk was 0.87, not significant. Dementia may be prevented by antihypertensive treatment. In order to confirm any relation in Alzheimers disease larger observational studies with longer follow-up are needed.

Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme

The use of angiotensin-converting-enzyme (ACE) inhibitors has been associated with increased insulin sensitivity in diabetic patients. Although such an effect could be beneficial in the treatment of hypertension or congestive heart failure in diabetic patients, it might also precipitate severe hypoglycaemia. To test this hypothesis we carried out a nested case-control study, using data in the Dutch PHARMO system (1986-92), among diabetic patients treated with insulin or with oral antidiabetic drugs, who were admitted to hospital with hypoglycaemia. We identified 94 patients who had been admitted with hypoglycaemia and selected 654 controls from the same cohort. With adjustment for a wide range of potential confounding factors, hypoglycaemia was significantly associated with current use of ACE inhibitors (odds ratio 2.8 [95% CI 1.4-5.7]). Both among users of insulin and among users of oral antidiabetic drugs, use of ACE inhibitors was significantly associated with an increased risk of hospital admission for hypoglycaemia (2.8 [1.2-6.4] and 4.1 [1.4-12.2], respectively). Although ACE inhibitors have several advantages over other antihypertensive drugs in diabetes, the risk of hypoglycaemia should be taken into account. Further investigation of the mechanism is needed since as many as 13.8% of all hospital admissions for hypoglycaemia might be attributable to use of ACE inhibitors.

Transmural myocardial infarction with sumatriptan

For sumatriptan, tightness in the chest caused by an unknown mechanism has been reported in 3-5% of users. We describe a 47-year-old woman with an acute myocardial infarction after administration of sumatriptan 6 mg subcutaneously for cluster headache. The patient had no history of underlying ischaemic heart disease or Prinzmetals angina. She recovered without complications.

Analysis of individual drug use as a time-varying determinant of exposure in prospective population-based cohort studies

In pharmaco-epidemiology, the use of drugs is the determinant of interest when studying exposure-outcome associations. The increased availability of computerized information about drug use on an individual basis has greatly facilitated analyses of drug effects on a population-based scale. It seems likely that many negative findings in the early days of pharmaco-epidemiology can be explained by non-differential misclassification because of too simple (yes/no) exposure measures. In this paper, the authors discuss the importance of an adequate definition of drug exposure in pharmaco-epidemiological research and how this time-varying determinant can be analyzed in cohort studies. To reduce the risk of non-differential misclassification, a precise definition of exposure is mandatory and it is important to distinguish the complete follow-up period of a population into mutually exclusive episodes of non-use, past use and current use for each individual. By analyzing exposure to drugs as a time-dependent variable in a Cox regression model, cohort studies with complete coverage of all filled prescriptions can provide us with valid and precise risk estimates of drug-outcome associations. However, such estimates may be biased in the presence of time-dependent confounders which are themselves affected by prior exposure.

Drug-associated anaphylaxis: 20 years of reporting in the Netherlands (1974-1994) and review of the literature

Background Since 1963, the Drug Safety Unit of the Dutch Inspectorate for Health Care (DSU) holds a voluntary reporting system.

Treatment strategies, patterns of drug use and treatment discontinuation in men with LUTS suggestive of benign prostatic hyperplasia: The triumph project

OBJECTIVES We aimed to describe treatment strategies for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), adherence to and persistence with pharmacological treatment and the association between the type of LUTS/BPH complaints and early treatment discontinuation. METHODS Within a large GP database (IPCI) in the Netherlands we identified all males > or =45 years newly diagnosed with LUTS/BPH during 1995-2000. Details on treatment were assessed from the electronic patient records. Logistic regression analysis was used to estimate the association between the type of main urinary complaints and early treatment discontinuation. RESULTS Of the 2214 men with incident LUTS/BPH, 1075 received pharmacological treatment and 238 underwent prostate surgery. The average adherence differed slightly between drugs: 67% for alpha-blockers, 73% for 5alpha-reductase inhibitors and 71% for combination therapy. 26% of the treated patients discontinued treatment early. The probability of early discontinuation was higher if patients mainly expressed one type of complaint: voiding (OR(adj) 3.38; 95%CI: 1.89-6.04), post micturition (OR(adj) 2.37; 95%CI: 1.15-4.87) or storage symptoms (OR(adj) 1.85; 95%CI: 1.16-2.95) as compared to patients expressing a combination of symptoms. The risk of early discontinuation was higher if patients had a normal PSA measurement. Older age and a higher chronic disease score protected against early treatment discontinuation. CONCLUSIONS Almost half of newly diagnosed LUTS/BPH patients are pharmacologically treated, and a quarter discontinues very rapidly. Stopping early is more frequent among younger persons, persons with only one type of main urinary complaint, no other co-morbidity and a normal PSA.

The incidence of sudden cardiac death in the general population

BACKGROUND AND OBJECTIVES To determine the incidence of sudden cardiac death in a general (Dutch) population. METHODS Cohort study in the Integrated Primary Care Information (IPCI) project, a database with all medical data from 150 general practices in The Netherlands. The study population comprised 249,126 subjects with a mean follow-up of 2.54 years. RESULTS In this period 4,892 deaths were identified, 582 of which were classified as (probable) sudden cardiac death. The overall incidence of sudden cardiac death in this population was 0.92 cases per 1,000 person-years (95%CI: 0.85-0.99). The risk was 2.3-fold higher in men than in women, and increased with age. The incidence of sudden cardiac death peaked in October and was lowest in August. CONCLUSIONS The incidence of sudden cardiac death in the general Dutch population was almost 1 per 1,000 person-years per year during the period 1 January, 1995 to 1 April, 2001. Most of the cases occurred at home.

Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974-1994)

In this descriptive study, all 425 reports were included concerning drug‐associated agranulocytosis as registered between 1974 and 1994 in the files of the Drug Safety Unit of the Dutch Inspectorate for Health Care. All reports were analysed as to the probability of agranulocytosis or neutropenia according to previously defined criteria. Subsequently, the causal relationship between exposure and outcome was assessed. It concerned 149 men and 271 women. One hundred and twelve reports were unclassifiable because age, gender, or total number of leukocytes at the time of reaction were unknown. In 100 reports agranulocytosis was probable, in 78 possible, in 8 reports neutropenia was probable, in 20 reports neutropenia was possible, and in 107 reports agranulocytosis or neutropenia were unlikely. In the 13 reports of probable agranulocytosis or neutropenia with a certain causal relationship, causative drugs were cimetidine, dipyrone, sulphasalazine, methyldopa, spironolactone, propylthiouracil (2), thiamazole, sulphamethoxazole with trimethoprim, gentamicin, a combination preparation containing aminophenazone, benzylpenicillin and indomethacin. The individual drugs most often reported to cause agranulocytosis or neutropenia were: dipyrone (19), mianserin (15), sulphasalazine (13), sulphamethoxazole with trimethoprim (11), the group of penicillins (9), cimetidine (8), the thiouracil derivatives (8), phenylbutazone (8), and penicillamine (8). Agranulocytosis is a serious and fairly frequently reported adverse reaction. The reporting system of the Drug Safety Unit can be used very well for signal generation concerning adverse reactions to drugs. Am. J. Hematol. 57:206–211, 1998.

Skin Reactions to Antibacterial Agents in General Practice

OBJECTIVES To quantify the risk of skin reactions to antibacterial drugs under everyday circumstances in a large population with automated data from general practitioners (GP). DESIGN A retrospective cohort study in a dynamic population. SETTING Data came from the Integrated Primary Care Information (IPCI) database. The IPCI database consists of all data on consultations, morbidity, and prescriptions and other interventions, as registered by the GP in a source population of approximately 150,000 persons. METHODS The study period started on April 1, 1994, and ended on September 30, 1995. All patients who were treated with an antibacterial drug were enrolled on the first day of starting treatment until the end of the study period or until the occurrence of one or more of the following diagnoses within the risk period: allergic reaction, rash, erythema, pruritus and urticaria, or a notification of a skin reaction in the free text. Subsequently, patient profiles were assessed by two authors who were blinded to exposure. The risk period was defined as the legend duration of the antibacterial drug plus 14 days to control for carry-over of drug effects and delay in patient presentation. Age, gender, and comedication were examined as potential confounders. RESULTS In the study period 13,679 patients received 19,961 prescriptions of an antibacterial drug. It concerned 5330 men (39.0%) and 8349 (61.0%) women with a mean age of 41 and 42 years, respectively. One hundred thirty-five patients developed a skin reaction in the risk period. Rash, pruritus, urticaria, and miscellaneous skin reactions were encountered in 76 (56.3%), 18 (13.3%), 19 (14.1%), and 22 (16.3%) patients, respectively. The three most frequently reported causes of skin reactions were combinations of trimethoprim with sulfonamides (2.1% of users; incidence density [ID]: 2.1/1000 exposed days), fluoroquinolones (1.6% of users; ID: 1.5/1000 person days), and penicillins (1.1% of users; ID: 1.3/1000 person days). Compared to tetracyclines, the broad-spectrum penicillins showed an incidence density ratio (IDR) of 3.7, the combination of amoxicillin with clavulanic acid of 3.3, the fluoroquinolones of 2.8, and the combination of trimethoprim with sulphonamides of 4.4. The presence of infectious mononucleosis increased the risk of rash in amoxicillin users with a factor of 58. CONCLUSIONS We found that the frequency of skin reactions to antibacterial drugs in general practice is around 1% and highest for the combination of trimethoprim with sulphonamides, penicillins, and fluoroquinolones. The outpatient incidence for skin reactions is probably lower than the incidence in hospitalized patients. Although this may be partly explained by negative misclassification, it is also likely that the actual incidence is lower as some hospitalized patient groups may be more prone to develop a skin reaction.