18 research outputs found
Safety aspects of HIV-protease inhibitors
The objectives of this thesis were to provide more insight into the risk and risk factors of
adverse drug reactions associated with HIV-protease inhibitor treatment under non-experimental
everyday circumstances. By recognition of risk factors, patients at risk can be
identified beforehand and risk management can be targeted more efficiently, hence
ultimately improving the safety of HIV-protease inhibitor treatment. In the studies presented
in this thesis we applied multiple research strategies. tn which the nationwide ATHENA cohort
played a central role
Effectiveness of MF59â„¢ Adjuvanted Influenza A(H1N1)pdm09 Vaccine in Risk Groups in the Netherlands
Background:The aim of the present study was to estimate the effectiveness of the MF59â„¢-adjuvanted influenza A(H1N1)pdm09 vaccine against medically attended influenza-like illness and RT-PCR confirmed influenza in the at-risk population and persons over 60 in the Netherlands.Methods:We conducted a retrospective cohort study in a Dutch based GP medical record database between 30 November 2009 and 1 March 2010 to estimate the vaccine effectiveness against influenza-like illness. Within the cohort we nested a test negative case-control study to estimate the effectiveness against laboratory confirmed influenza.Results:The crude effectiveness in preventing diagnosed or possible influenza-like illness was 17.3% (95%CI: -8.5%-36.9%). Of the measured covariates, age, the severity of disease and health seeking behaviour through devised proxies confounded the association between vaccination and influenza-like illness. The adjusted vaccine effectiveness was 20.8% (95%CI: -5.4%, 40.5%) and varied significantly by age, being highest in adults up to 50 years (59%, 95%CI: 23%, 78%), and non-detectable in adults over 50 years. The number of cases in the nested case control study was too limited to validly estimate the VE against confirmed influenza.Conclusions:With our study we demonstrated that the approach of combining a cohort study in a primary health care database with field sampling is a feasible and useful option to monitor VE of influenza vaccines in the future
Spironolactone and risk of upper gastrointestinal events: population based case-control study
OBJECTIVE: To confirm and quantify any association between spironolactone
and upper gastrointestinal bleeding and ulcers. DESIGN: Population based
case-control study. SETTING: A primary care information database in the
Netherlands. PARTICIPANTS: All people on the database who were aged 18 or
more between 1 January 1996 and 30 September 2003. Patients with a history
of alcoholism or gastrointestinal cancer were excluded. Ten controls were
matched to each case of gastroduodenal ulcer or upper gastrointestinal
bleeding by age (year of birth), sex, and index date. MAIN OUTCOME
MEASURES: The occurrence of an upper gastrointestinal event (bleeding or
ulcers), adjusted for potential confounders with conditional logistic
regression analysis. RESULTS: Within the source population of 306 645
patients, 523 cases of gastric or duodenal ulcer or upper gastrointestinal
Effectiveness of a MF-59â„¢-adjuvanted pandemic influenza vaccine to prevent 2009 A/H1N1 influenza-related hospitalisation; a matched case-control study
Background: During the 2009 influenza A/H1N1 pandemic, adjuvanted influenza vaccines were used for the first time on a large scale. Results on the effectiveness of the vaccines in preventing 2009 influenza A/H1N1-related hospitalisation are scanty and varying.Methods: We conducted a matched case-control study in individuals with an indication for vaccination due to underlying medical conditions and/or age ≥ 60 years in the Netherlands. Cases were patients hospitalised with laboratory-confirmed 2009 A/H1N1 influenza infection between November 16, 2009 and January 15, 2010. Controls were matched to cases on age, sex and type of underlying medical condition(s) and drawn from an extensive general practitioner network. Conditional logistic regression was used to estimate the vaccine effectiveness (VE = 1 - OR). Different sensitivity analyses were used to assess confounding by severity of underlying medical condition(s) and the effect of different assumptions for missing dates of vaccination.Results: 149 cases and 28,238 matched controls were included. It was estimated that 22% of the cases and 28% of the controls received vaccination more than 7 days before the date of onset of symptoms in cases. A significant number of breakthrough infections were observed. The VE was estimated at 19% (95%CI -28-49). After restricting the analysis to cases with controls suffering from severe underlying medical conditions, the VE was 49% (95%CI 16-69).Conclusions: The number of breakthrough infections, resulting in modest VE estimates, suggests that the MF-59™ adjuvanted vaccine may have had only a limited impact on preventing 2009 influenza A/H1N1-related hospitalisation in this setting. As the main aim of influenza vaccination programmes is to reduce severe influenza-related morbidity and mortality from influenza in persons at high risk of complications, a more effective vaccine, or additional preventive measures, are needed
Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir
BACKGROUND: Prolonged administration of indinavir is associated with the
occurrence of a variety of renal complications in adults. These
well-documented side effects have restricted the use of this potent
protease inhibitor in children. DESIGN: A prospective study to monitor
indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency
virus type 1-infected children treated with indinavir. METHODS: Urinary
pH, albumin, creatinine, the presence of erythrocytes, leukocytes,
bacteria and crystals, and culture were analyzed every 3 months for 96
weeks. Serum creatinine levels were routinely determined at the same time
points. Steady-
Suboptimal gastroprotective coverage of NSAID use and the risk of upper gastrointestinal bleeding and ulcers: An observational study using three European databases
Background: Gastro-protective agents (GPA) are co-prescribed with non-steroidal anti-inflammatory drugs (NSAID) to lower the risk of upper gastrointestinal (UGI) events. It is unknown to what extent the protective effect is influenced by therapy adherence. Aim: To study the association between GPA adherence and UGI events among non-selective (ns) NSAID users. Methods: The General Practice Research Database (UK 1998e2008), the Integrated Primary Care Information database (the Netherlands 1996-2007) and the Health Search/CSD Longitudinal Patient Database (Italy 2000-2007) were used. A nested case-control design was employed within a cohort of nsNSAID users aged ≥50 years, who also used a GPA. UGI event cases (UGI bleeding and/or symptomatic ulcer with/without obstruction/perforation) were matched to event-free members of the cohort for age, sex, database and calendar time. Adherence to GPA was calculated as the proportion of nsNSAID treatment days covered by a GPA prescription. Adjusted OR with 95% CI were calculated. Results: The cohort consisted of 618 684 NSAID users, generating 1 107 266 nsNSAID episodes. Of these, 117 307 (10.6%) were (partly) covered by GPA, 4.9% of which with a GPA coverage 80% (full adherence). 339 patients experienced an event. Among non-adherers, the OR was 2.39 (95% CI 1.66 to 3.44) for all UGI events and 1.89 (95% CI 1.09 to 3.28) for UGI bleeding alone, compared to full adherers. Conclusions: The risk of UGI events was significantly higher in nsNSAID users with GPA non-adherence. This underlines the importance of strategies to improve GPA adherence. Copyright Article author (or their employer) 2011
Not-in-trial simulation I: Bridging cardiovascular risk from clinical trials to real-life conditions
Aims The assessment of heart rate-corrected QT (QTc) interval prolongation relies on the evidence of drug effects in healthy subjects. This study demonstrates the relevance of pharmacokinetic-pharmacodynamic (PKPD) relationships to characterize drug-induced QTc interval prolongation and explore the discrepancies between clinical trials and real-life conditions. Methods d,l-Sotalol data from healthy subjects and from the Rotterdam Study cohort were used to assess treatment response in a phase I setting and in a real-life conditions, respectively. Using modelling and simulation, drug effects at therapeutic doses were predicted in both populations. Results Inclusion criteria were shown to restrict the representativeness of the trial population in comparison to real-life conditions. A significant part of the typical patient population was excluded from trials due to weight and baseline QTc interval criteria. Relative risk was significantly different between sotalol users with and without heart failure, hypertension, diabetes and myocardial infarction (P < 0.01). Although drug effects do cause an increase in the relative risk of QTc interval prolongation, the presence of diabetes represented an increase from 4.0 [95% confidence interval (CI) 2.7-5.8] to 6.5 (95% CI 1.6-27.1), whilst for myocardial infarction it increased from 3.4 (95% CI 2.3-5.13) to 15.5 (95% CI 4.9-49.3). Conclusions Our findings show that drug effects on QTc interval do not explain the observed QTc values in the population. The prevalence of high QTc values in the real-life population can be assigned to co-morbidities and concomitant medications. These findings substantiate the need to account for these factors when evaluating the cardiovascular risk of medicinal products
Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccines: A multinational self-controlled case series in Europe
Background: The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk
Age- and gender-specific incidence of hospitalisation for digoxin intoxication
Background: The safety of digoxin (digitalis) therapy has greatly improved over the past three decades, but recent incidence rates for digoxin intoxication-related hospitalisation are not available. Recent literature suggests that women are at higher risk of digoxin toxicity. Objective: To provide age- and gender-specific incidence rates for digoxin intoxication-related hospitalisation and mortality dur