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Biomedical subjects

Hubert G M Leufkens

Publications and source records attributed to Hubert G M Leufkens.

At least 19 recordsLinked to original sources
PubMed2007

Fracture risk with intermittent high-dose oral glucocorticoid therapy.

OBJECTIVE: To evaluate the risk of fracture in patients receiving intermittent therapy with high-dose oral glucocorticoids (GCs). METHODS: The study group comprised 191,752 patients from the UK General Practice Database who were 40 years of age and older and received therapy with GCs. The followup time period was divided into the categories of "current" and "no exposure." The daily dose and cumulative dose for each time period were determined. Relative risks were estimated using Cox proportional hazards models, adjusted for age, sex, body mass index, smoking, disease history, and drug history. Fractures of the radius/ulna, humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation. RESULTS: Patients who intermittently received high-dose GCs (daily dose > or =15 mg) and had no or little previous exposure to GCs (cumulative exposure < or =1 gm) had a small increased risk of osteoporotic (but not hip/femur) fracture; this risk increased substantially with increasing cumulative exposure. Among patients who received a daily dose > or =30 mg and whose cumulative exposure was >5 gm, the relative risk (RR) of osteoporotic fracture was 3.63 (95% confidence interval [95% CI] 2.54-5.20), the RR of fracture of the hip/femur was 3.13 (95% CI 1.49-6.59), and the RR of vertebral fracture was 14.42 (95% CI 8.29-25.08). CONCLUSION: Intermittent use of high-dose oral GCs (daily dose > or =15 mg and cumulative exposure < or =1 gm) may result in a small increased risk of osteoporotic fracture. Conversely, patients who receive several courses of high-dose GCs (daily dose > or =15 mg and cumulative exposure >1 gm) have a substantially increased risk of fracture.

Adult↗
PubMed2007

Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study.

INTRODUCTION: Administration of beta-2 agonists decreased bone mineral density in rats. But the association between bronchodilators and fracture risk has not been studied in humans. OBJECTIVES: To examine the association between use of beta-2 agonists and risk of hip/femur fracture. METHODS: We conducted a population-based case-control study (6763 cases) in the Dutch PHARMO database. Current beta-2 agonist use was compared to never use. We adjusted for severity of the underlying respiratory disease and disease and drug history. RESULTS: A hospitalisation for asthma/COPD in the year before index date increased risk of hip/femur fracture: crude OR 2.17 (95% CI, 1.41-3.34). Patients using higher doses of beta-2 agonists had increased risk of hip/femur fracture: crude OR 1.94 (95% CI, 1.41-2.66) for daily dosages of >or=1600 microg albuterol equivalent. The excess fracture risk reduced after adjustment for disease severity (1.46; 95% CI, 1.02-2.08) and after exclusion of oral glucocorticoid users (1.31; 95% CI, 0.80-2.15). Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. CONCLUSION: We found increases in the risk of hip/femur fracture in patients using higher doses of beta-2 agonists. However, the excess risk of hip/femur fracture substantially reduced after exclusion of oral glucocorticoid users and after adjustment for the underlying disease. Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. The severity of the underlying disease, rather than the use of beta-2 agonists, may play an important role in the aetiology of hip/femur fractures in patients using beta-2 agonists.

Adrenergic beta-2 Receptor Agonists↗
PubMed2007

Hospitalisations and emergency department visits due to drug-drug interactions: a literature review.

PURPOSE: Our objective was to evaluate the incidence of adverse patient outcomes due to drug-drug interactions (D-DIs), the type of drugs involved and the underlying reason. As a proxy for adverse patient outcomes, emergency department (ED) visits, hospital admissions and re-hospitalisations were assessed. METHODS: A literature search in the Medline and Embase database (1990-2006) was performed and references were tracked. An overall cumulative incidence was estimated by dividing the sum of the cases by the sum of the study populations. RESULTS: Twenty-three studies were found assessing the relationship between D-DIs and ED-visits, hospitalisations or re-hospitalisations. The studies with a large study size showed low incidences and vice versa. D-DIs were held responsible for 0.054% of the ED-visits, 0.57% of the hospital admissions and 0.12% of the re-hospitalisations. In the elderly population, D-DIs were held responsible for 4.8% of the admissions. Drugs most often involved were NSAIDs and cardiovascular drugs. The reasons for admissions or ED-visits, which were most often found were GI-tract bleeding, hyper- or hypotension and cardiac rhythm disturbances. CONCLUSION: This review provides information on the overall incidence of D-DIs as a cause of adverse patient outcomes, although there is still uncertainty about the impact of D-DIs on adverse patient outcomes. Our results suggest that a limited number of drugs are involved in the majority of cases and that the number of reasons for admission as a consequence of D-DIs seems to be modest.

Drug Interactions↗
PubMed2007

Angiotensin-converting enzyme inhibitor use and protection against pneumonia in patients with diabetes.

OBJECTIVES: Because of the high risk of pneumonia in patients with diabetes, we aimed to assess the effect of angiotensin-converting enzyme (ACE) inhibitor use on the occurrence of pneumonia in a general population of patients with diabetes. METHODS: The study population comprised all patients in the UK General Practice Research Database who had a diagnosis of diabetes (both type 1 and type 2) between 1987 and 2001. Cases were defined as patients with a first diagnosis of pneumonia. For each case, up to four controls were matched by age, gender, practice, and index date. Patients were classified as current ACE inhibitor user when the index date was between the start and end date of ACE inhibitor therapy. Conditional logistic regression analysis was used to estimate the strength of the association between ACE inhibitor use and pneumonia risk. RESULTS: ACE inhibitors were used in 12.7% of 4719 cases and in 13.7% of 15,322 matched controls [crude odds ratio (OR)=0.92, 95% confidence interval (CI)=0.82-1.01]. After adjusting for confounding, ACE inhibitor therapy was associated with a significant reduction in pneumonia risk (adjusted OR=0.72, 95% CI=0.64-0.80). The protective association was consistent across different relevant subgroups with the strongest association in patients with a history of stroke. There was a significant dose-effect relationship (P for trend < 0.001). CONCLUSIONS: The use of ACE inhibitors is associated with a significant reduction in pneumonia risk and, apart from blood pressure-lowering properties, may be useful in the prevention of pneumonia in patients with diabetes.

Aged↗
PubMed2006

Availability of comparative trials for the assessment of new medicines in the European Union at the moment of market authorization.

AIMS: To investigate the availability of information about premarketing randomized active-control trials (RaCTs) involving medicines with a new active substance at the moment of market authorization in the European Union. METHODS: Information was obtained from the EMEA European Public Assessment Reports and the MEDLINE and EMBASE databases. RESULTS: Between 1999 and 2005, 48% of recently approved medicines (n = 122) had been studied in comparison with existing medicines at the moment of market authorization. About one-third of these trials were published and publicly available at that moment. CONCLUSIONS: For most new medicines evidence-based assessment of the (added) therapeutic value is not really possible at the moment of market authorization.

Clinical Trials as Topic↗
PubMed2006

Which pharmacists contribute to high-level pharmacotherapy audit meetings with general practitioners?

BACKGROUND: In the Netherlands, community pharmacists and general practitioners (GPs) collaborate in pharmacotherapy audit meetings (PTAMs) to optimize pharmacotherapy. OBJECTIVE: To identify associations between the quality level of PTAMs and characteristics of pharmacists. METHODS: We used a cross-sectional questionnaire design in a Dutch general practice and community pharmacy setting to estimate the contribution of pharmacists to the quality level of PTAMs. The questionnaire was sent to 123 community pharmacies working closely with 104 GP practices. The outcome variable was the quality level of PTAMs. The questionnaire provided information on 4 topics that were used as independent variables: characteristics of the PTAMs, provision of pharmacotherapy activities, characteristics of the pharmacists, and characteristics of the pharmacies. RESULTS: In total, 109 (88.6%) pharmacists completed the questionnaire, with 103 participating in 62 different PTAMs. Seventeen pharmacists participated in level 1 PTAMs (lowest level), 57 in level 2, 21 in level 3, and 8 in PTAMs at the highest level. The multinomial logistic regression identified only one significant association: pharmacists who participated in the highest quality level reported that they undertake initiatives in PTAMs (OR 2.98; 95% CI 1.07 to 8.26) more frequently compared with pharmacists participating on the lowest level. CONCLUSIONS: In light of existing evidence, the role of pharmacists in PTAMs seems to be important. Pharmacists should create a distinct profile of their expertise, allowing them to professionalize PTAMs by undertaking more initiatives. PTAMs offer pharmacists a great opportunity to become integral members of the prescribing process.

Community Pharmacy Services↗
PubMed2006

In-hospital cardiac arrest is associated with use of non-antiarrhythmic QTc-prolonging drugs.

AIMS: QTc interval-prolonging drugs have been linked to cardiac arrhythmias, cardiac arrest and sudden death. In this study we aimed to quantify the risk of cardiac arrest associated with the use of non-antiarrhythmic QTc-prolonging drugs in an academic hospital setting. METHODS: We performed a case-control study in which patients, for whom intervention of the advanced life support resuscitation team was requested for cardiac arrest between 1995 and 2003 in the Academic Medical Centre, Amsterdam, were compared with controls regarding current use of non-antiarrhythmic QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusting for potential confounding factors. RESULTS: A statistically significant increased risk of cardiac arrest (OR 2.1, 95% CI 1.2, 3.5) was observed in patients who received QTc-prolonging drugs (42/140). The risk was more pronounced in patients receiving doses > 1 defined daily dose (OR 2.5, 95% CI 1.1, 5.9), patients taking > 1 QTc-prolonging drug simultaneously (OR 4.8, 95% CI 1.6, 14) and patients taking pharmacokinetic interacting drugs concomitantly (OR 4.0, 95% CI 1.2, 13). CONCLUSIONS: Use of non-antiarrhythmic QTc-prolonging drugs in hospitalized patients with several underlying disease is associated with an increased risk of cardiac arrest. The effect is dose related and pharmacokinetic drug-drug interactions increase the risk substantially. Physicians caring for inpatients should be made aware of the fact that these non-antiarrhythmic drugs may be hazardous, so that potential risks can be weighed against treatment benefits and additional cardiac surveillance can be requested, if necessary.

Aged↗
PubMed2006

Linking community pharmacy dispensing data to prescribing data of general practitioners.

BACKGROUND: Databases are frequently used for pharmacoepidemiological research. However, most of these databases consist either of prescribing, dispensing or administrative data and therefore lack insight in the interaction between the several health professionals around the patient. METHODS: To determine the success rate of linking records from the dispensing database of the Foundation for Pharmaceutical Statistics to the prescribing database of the second Dutch national survey of general practice, conducted by NIVEL (Netherlands Institute for Health Services Research), a deterministic record linkage approach was used with patient and prescription characteristics as matching variables between the two databases. RESULTS: The catchment area included 123 community pharmacies, 90 GP practices and approximately 170,000 unique patients. Overall 110,102 (64.8%) unique patients were linked using the matching variables patient's gender, year of birth, the 4-digit part of the postal code, date of dispensing/prescribing and ATC-code. The final database contains of the 110,102 both prescribing data from 83 GP practices and dispensing data of 112 community pharmacies. CONCLUSION: This study shows that linkage of dispensing to prescribing data is feasible with a combination of patient characteristics, such as gender, year of birth and postal code, and prescription characteristics like prescription date and ATC-code. We obtained a linkage proportion of 64.8% resulting in complete prescribing and dispensing history of 110,102 patients. This offers an opportunity to gain insight in the mechanisms and factors influencing drug utilisation in general practice.

Adult↗
PubMed2006

Prior outpatient antibacterial therapy as prognostic factor for mortality in hospitalized pneumonia patients.

STUDY OBJECTIVES: To assess whether prior outpatient treatment is associated with outcome in patients hospitalized for community-acquired pneumonia (CAP). PATIENTS AND METHODS: All patients with a first hospital admission for CAP between 1995 and 2000 were selected. Patients were divided into two groups, one of patients with use of antibacterial agents prior to hospitalization and one of patients treated as inpatient directly. The main outcome measures were duration of hospital stay and in-hospital mortality. RESULTS: The two patient groups comprised 296 and 794 patients, respectively. The median duration of hospital stay was 10 days and was similar for both groups. In patients with respiratory diseases or heart failure, the median duration of hospital stay was 12 and 14 days, respectively. The overall in-hospital mortality was 7.2% and did not largely differ between both groups. In patients with congestive heart failure, the mortality was 9.8% for controls and 23.3% for patients hospitalized after initial outpatient treatment (adjusted OR 2.78, 95% CI 1.01-7.81). CONCLUSIONS: Prior outpatient antibacterial therapy is not associated with outcome in hospitalized pneumonia patients. In patients with underlying chronic heart failure, prior outpatient antibiotic is associated with a significant increased mortality.

Adult↗
PubMed2006

Pharmacogenetics of drug-induced arrhythmias: a feasibility study using spontaneous adverse drug reactions reporting data.

PURPOSE: The bottleneck in pharmacogenetic research on rare adverse drug reactions (ADR) is retrieval of patients. Spontaneous reports of ADRs may form a useful source of patients. We investigated the feasibility of a pharmacogenetic study, in which cases were selected from the database of a spontaneous reporting system for ADRs, using drug-induced arrhythmias as an example. METHODS: Reports of drug-induced arrhythmias to proarrhythmic drugs were selected from the database of the Netherlands Pharmacovigilance Centre (1996-2003). Information on the patient's general practitioner (GP) was obtained from the original report, or from another health care provider who reported the event. GPs were contacted and asked to recruit the patient as well as two age, gender and drug matched controls. Patients were asked to fill a questionnaire and provide a buccal swab DNA sample through the mail. DNA samples were screened for 10 missense mutations in 5 genes associated with the congenital long-QT (LQT) syndrome (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2). RESULTS: We identified 45 eligible cases, 29 GPs could be contacted of which seven were willing to participate. Four cases and five matched controls could be included in the study, giving an overall participation rate of 9% (4/45). The main reason for GPs not being willing to participate was lack of time. Variants were identified in KCNH2, SCN5A and KCNE1. CONCLUSIONS: Spontaneous reporting systems for ADRs may be used for pharmacogenetic research. The methods described, however, need to be improved to increase participation and international collaboration may be required.

Adult↗
PubMed2006

Risk of aplastic anemia in patients using antiepileptic drugs.

PURPOSE: To assess the association between exposure to antiepileptic drugs (AEDs) and the occurrence of aplastic anemia. METHODS: A retrospective case-control study was conducted using data from the U.K. General Practitioners Research Database (GPRD). Cases were defined as patients diagnosed with aplastic anemia. For each case, up to three control patients were matched on age, sex, and medical practice. Cases and controls were compared with respect to AED use. The effects of duration of AED use were assessed. Characteristics of individual cases with AED use were reviewed. RESULTS: The study population comprised 173 cases and 497 controls. AED use was more prevalent among cases (9.2%) than among controls (0.8%). After adjustment for confounders, the use of AEDs was significantly associated with aplastic anemia (adjusted odds ratio (OR), 9.5; 95% confidence interval (CI), 3.0-39.7). The most frequently used AEDs were carbamazepine (CBZ), valproic acid (VPA), and phenytoin. The 16 exposed cases were heterogeneous with respect to patient and exposure characteristics: the age of these patients varied from 1 to 92 years, and the duration of AED use varied from 17 days to 6.8 years. CONCLUSIONS: This study indicates that use of AEDs, in particular CBZ and VPA, is associated with a ninefold increased risk of aplastic anemia. Physicians should be alert to the possibility of AED-associated aplastic anemia.

Adult↗
PubMed2006

Rare essentials: drugs for rare diseases as essential medicines.

Since 1977, the WHO Model List of Essential Medicines (EML), published by WHO, has provided advice for Member States that struggle to decide which pharmaceutical technologies should be provided to patients within their public health systems. Originating from outside WHO, an incentive system has been put in place by various governments for the development of medicines for rare diseases ("orphan drugs"). With progress in pharmaceutical research (e.g. drugs targeted for narrower indications), these medicines will feature more often on future public health agendas. However, when current definitions for selecting essential medicines are applied strictly, orphan drugs cannot be part of the WHO Essential Medicines Programme, creating the risk that WHO may lose touch with this field. In our opinion WHO should explicitly include orphan drugs in its policy sphere by composing a complementary Orphan Medicines Model List as an addition to the EML. This complementary list of "rare essentials" could aid policy-makers and patients in, for example, emerging countries to improve access to these drugs and stimulate relevant policies. Furthermore, inconsistencies in the current EML with regard to medicines for rare diseases can be resolved. In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme.

Cost-Benefit Analysis↗
PubMed2005

Patient characteristics associated with prescribing of a newly introduced drug: the case of rofecoxib.

OBJECTIVE: To identify socio-demographic characteristics of the first patients receiving a new drug--rofecoxib. OUTCOME MEASUREMENT: Patients starting on rofecoxib or another non-steroidal anti-inflammatory drug (NSAID) and who had not received any NSAIDs the 90 days prior to starting. RESULTS: Starting on rofecoxib was associated with an increasing age (OR in age 80 years and older 8.7; 95% CI 6.7-11.2), a poor self-perceived health (OR=2.4; 95% CI 1.8-3.3), female gender (OR=1.4; 95% CI 1.2-1.6), private insurance (OR=1.3; 1.1-1.5) and previous acetaminophen use (OR=1.3; 1.1-1.7). CONCLUSION: This study noted that specific patient characteristics were associated with getting rofecoxib prescribed shortly after marketing. General practitioners should be aware of selectively prescribing new drugs to specific patients because it may place patients at unintentional and avoidable risk.

Adult↗
PubMed2005

The trade-off between cardiovascular and gastrointestinal effects of rofecoxib.

BACKGROUND: The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients. OBJECTIVE: To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID. SETTING: Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001. DESIGN: New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice. RESULTS: A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (OR(adj) = 2.09; 95%CI = 1.65-2.66). These patients were also more likely to have cardiovascular co-morbidity (OR = 1.90; 95%CI = 1.60-2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis. CONCLUSIONS: In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants.

BACKGROUND: Serotonin plays a role in platelet aggregation. Because antidepressants influence blood serotonin levels, their use may be associated with an increased risk of abnormal bleeding. However, previous studies were inconclusive regarding this association. The aim of this study was to estimate the risk of abnormal bleeding associated with the use of antidepressants and to establish the relationship between serotonin reuptake inhibition and the risk of bleeding. METHODS: We used data collected from 1992 through 2000 to conduct a nested case-control study of a cohort of more than 64 000 new antidepressant users. Cases were identified as all patients hospitalized for a primary diagnosis of abnormal bleeding, and they were matched with controls for age and sex. We classified exposure according to the degree (high, intermediate, or low) of serotonin reuptake inhibition and performed logistic regression analysis to calculate odds ratios. RESULTS: There were 196 cases of abnormal bleeding. The risk of hospitalization increased with the use of inhibitors providing intermediate (odds ratio, 1.9; 95% confidence interval, 1.1-3.5) and high degrees of serotonin reuptake inhibition (odds ratio, 2.6; 95% confidence interval, 1.4-4.8). CONCLUSIONS: In a large population of new antidepressant users we found a significant association between degree of serotonin reuptake inhibition by antidepressants and risk of hospital admission for abnormal bleeding as the primary diagnosis. An increased risk of abnormal bleeding was strongly associated with the degree of serotonin reuptake inhibition.

Antidepressive Agents↗
PubMed2004

Are inhaled corticosteroids associated with an increased risk of fracture in children?

Inhaled corticosteroids are widely used in the long-term management of asthma in children. Data on the relationship between inhaled corticosteroid therapy and osteoporotic fracture are inconsistent. We address this issue in a large population-based cohort of children aged 4-17 years in the UK (the General Practice Research Database). The incidence rates of fracture among children aged 4-17 years taking inhaled corticosteroids (n=97,387), taking bronchodilators only (n=70 984) and a reference group (n=345,758) were estimated. Each child with a non-vertebral fracture (n=23,984) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. Fracture incidence was increased in children using inhaled corticosteroids, as well as in those receiving bronchodilators alone. With an average daily beclomethasone dose of 200 microg or less, the crude fracture risk relative to nonusers was 1.10 [95% confidence interval (CI), 0.96-1.26]; with dosage of 201-400 microg, it was 1.23 (95% CI, 1.08-1.39); and with dosages over 400 microg, it was 1.36 (95% CI, 1.11-1.67). This excess risk disappeared after adjustment for indicators of asthma severity. The increased risk of fracture associated with use of inhaled corticosteroids is likely to be the result of the underlying illness, rather than being directly attributable to inhaled corticosteroid therapy.

Administration, Inhalation↗