Care and Public Health Research Institute CAPHRI

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Care and Public Health Research Institute CAPHRI

Netherlands
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Mercken L.,Care and Public Health Research Institute CAPHRI | Mercken L.,Maastricht University | Steglich C.,University of Groningen | Knibbe R.,Care and Public Health Research Institute CAPHRI | And 3 more authors.
Journal of Studies on Alcohol and Drugs | Year: 2012

Objective: Similarity in alcohol consumption among adolescent friends could be caused by the infl uence of friends or by the selection of friends who consume similar levels of alcohol. This article aims to disentangle infl uence and selection processes while specifi cally examining changes over time in these processes and possible differences between reciprocal and nonreciprocal friendships. Method: The design was longitudinal with four observations (Time 1-Time 4 [T1-T4]). Data consisted of a longitudinal sample of 1,204 Finnish adolescents in 10 junior high schools. The main measurements were adolescents' friendship networks and alcohol consumption. For three successive periods, T1-T2, T2-T3, and T3-T4, actor-based models for the co-evolution of networks and behavior were analyzed (M age: T1 = 13.6 years, T2 = 14.6 years, T3 = 15.6 years, T4 =16.1 years). Results: Selection, as well as infl uence processes, played an important role in adolescent alcohol consumption. Infl uence was found during the fi rst period (T1-T2), whereas support for selection was found during the last two periods (T2-T3 and T3-T4). The strength of infl uence and selection processes did not differ for reciprocal and nonreciprocal friendships. Conclusions: The impact of selection and infl uence processes changed over time such that infl uence was only present during early adolescence, whereas selection was present during mid-adolescence. During early adolescence, youngsters would benefi t from learning to resist social infl uence. Alcohol-consumption prevention programs targeting mid-adolescence should consider peer selection processes. These fi ndings stress the importance of considering changes over time in future practice and research.


Lalmohamed A.,University Utrecht | Vestergaard P.,University of Aalborg | Cooper C.,Southampton General Hospital | Cooper C.,University of Oxford | And 8 more authors.
Stroke | Year: 2012

Background and Purpose: Stroke is a potentially fatal complication of total hip replacements (THR). However, timing of stroke in THR patients compared with matched controls and influence of drug use remain unknown. The objective of this study was to determine timing of stroke in patients with THR compared with matched control subjects. Methods: A nationwide cohort study was conducted within the Danish registers (1998-2007). Included patients were those with a primary THR in the study period (n=66 583) and were matched by age, sex, and region to three referent subjects without THR or total knee replacements. Time-dependent Cox models were used to derive hazard ratios and were adjusted for disease history and drug use. Results: A 4.7-fold increased risk of ischemic stroke (adjusted hazard ratio, 4.69; 95% CI, 3.12-7.06), and a 4.4-fold increased risk of hemorrhagic stroke (adjusted hazard ratio, 4.40; 95% CI, 2.01-9.62) were found within 2 weeks following THR, compared with matched controls. The risk remained elevated during the first 6 postoperative weeks for ischemic stroke, and the first 12 weeks for hemorrhagic stroke. Outpatient antiplatelet drug use lowered the 6-week hazard ratios for ischemic stroke by 70%, although not affecting risk of hemorrhagic stroke. Conclusions: This study shows, that THR patients have a 4.7-fold increased risk of ischemic stroke, and a 4.4-fold increased risk of hemorrhagic stroke during the first 2 weeks postsurgery. Risk assessment of stroke in individual patients undergoing THR (ie, evaluate other risk factors for stroke) should be considered during the first 6 to 12 weeks. © 2012 American Heart Association, Inc.


Mercken L.,Care and Public Health Research Institute CAPHRI | Mercken L.,Maastricht University | Snijders T.A.B.,University of Oxford | Snijders T.A.B.,University of Groningen | And 4 more authors.
Addiction | Year: 2010

Aims: The main goal of this study was to examine differences between adolescent male and female friendship networks regarding smoking-based selection and influence processes using newly developed social network analysis methods that allow the current state of continuously changing friendship networks to act as a dynamic constraint for changes in smoking behaviour, while allowing current smoking behaviour to be simultaneously a dynamic constraint for changes in friendship networks. Design: Longitudinal design with four measurements. Setting: Nine junior high schools in Finland. Participants: A total of 1163 adolescents (mean age = 13.6 years) who participated in the control group of the ESFA (European Smoking prevention Framework Approach) study, including 605 males and 558 females. Measurements: Smoking behaviour of adolescents, parents, siblings and friendship ties. Findings: Smoking-based selection of friends was found in male as well as female networks. However, support for influence among friends was found only in female networks. Furthermore, females and males were both influenced by parental smoking behaviour. Conclusions: In Finnish adolescents, both male and female smokers tend to select other smokers as friends but it appears that only females are influenced to smoke by their peer group. This suggests that prevention campaigns targeting resisting peer pressure may be more effective in adolescent girls than boys. © 2010 Society for the Study of Addiction.


Lalmohamed A.,University Utrecht | MacGregor A.J.,University of East Anglia | de Vries F.,University Utrecht | de Vries F.,Southampton General Hospital | And 6 more authors.
PLoS ONE | Year: 2013

Background: There are concerns that metal-on-metal hip implants may cause cancer. The objective of this study was to evaluate patterns and timing of risk of cancer in patients with metal-on-metal total hip replacements (THR). Methods: In a linkage study between the English National Joint Registry (NJR) and the Clinical Practice Research Datalink (CPRD), we selected all THR surgeries (NJR) between 2003 and 2010 (n = 11,540). THR patients were stratified by type of bearing surface. Patients were followed up for cancer and Poisson regression was used to derive adjusted relative rates (RR). Results: The risk of cancer was similar in patients with hip resurfacing (RR 0.69; 95% Confidence Interval [CI] 0.39-1.22) or other types of bearing surfaces (RR 0.96; 95% CI 0.64-1.43) compared to individuals with stemmed metal-on-metal THR. The pattern of cancer risk over time did not support a detrimental effect of metal hip implants. There was substantial confounding: patients with metal-on-metal THRs used fewer drugs and had less comorbidity. Conclusions: Metal-on-metal THRs were not associated with an increased risk of cancer. There were substantial baseline differences between the different hip implants, indicating possibility of confounding in the comparisons between different types of THR implants. © 2013 Lalmohamed et al.


Wlazlo N.,Catharina Hospital | Wlazlo N.,Maastricht University | Van Greevenbroek M.M.J.,Maastricht University | Ferreira I.,Maastricht University | And 7 more authors.
Diabetes Care | Year: 2013

OBJECTIVE-Adipocyte insulin resistance (IR) is a key feature early in the pathogenesis of type 2 diabetes mellitus (T2DM), and although scarce, data in the literature suggest a direct role for iron and iron metabolism-related factors in adipose tissue function and metabolism. Serum ferritin and transferrin were shown to be associated with muscle insulin resistance (IR) and T2DM, but little is known about the role of iron metabolism on adipose tissue. We therefore investigated whether markers of iron metabolism were associated with adipocyte IR and plasma adiponectin. RESEARCH DESIGN AND METHODS-Serum ferritin, transferrin, total iron, non- transferrin-bound iron (NTBI), transferrin saturation, and plasma adiponectin were determined in 492 individuals. Adipocyte IR was defined by the product of fasting insulin and nonesterified fatty acids (NEFAs). Using linear regression analyses, we investigated the difference in adipocyte IR or adiponectin (in %) according to differences in iron metabolism markers. RESULTS-Serum ferritin (b = 1.00% increase in adipocyte IR per 10 mg/L [95% CI 0.66- 1.34]), transferrin (4.18% per 0.1 g/L [2.88-5.50]), total iron (1.36% per mmol/L [0.61-2.12]), and NTBI (5.14% per mmol/L [1.88-8.52]) were associated with adipocyte IR after adjustment for several covariates, including inflammatory markers. All markers of iron metabolism were also associated with NEFAs (all P < 0.01). In addition, ferritin and transferrin were inversely associated with adiponectin (both P < 0.01). CONCLUSIONS-The observed associations of several markers of iron metabolism with adipocyte IR and adiponectin suggest that factors related to iron and iron metabolism may contribute to adipocyte IR early in the pathogenesis of T2DM.© 2013 by the American Diabetes Association.


Eppenga W.L.,Radboud University Nijmegen | Eppenga W.L.,Hospital Pharmacy ZANOB | Lalmohamed A.,Utrecht Institute for Pharmaceutical science | Lalmohamed A.,University Utrecht | And 10 more authors.
Diabetes Care | Year: 2014

OBJECTIVE: The objective of this study was to determine whether treatment with metformin in patients with renal impairment is associated with a higher risk of lactic acidosis or elevated lactate concentrations compared with users of a noninsulin antidiabetic drug (NIAD) who had never used metformin. RESEARCH DESIGN AND METHODS: A cohort of 223,968 metformin users and 34,571 diabetic patients who had never used metformin were identified from the Clinical Practice Research Datalink (CPRD). The primary outcome was defined as either a CPRD READ code lactic acidosis or a record ofaplasma lactate concentration >5 mmol/L. The associations between renal impairment, dose of metformin, and the risk of lactic acidosis or elevated lactate concentrations were determined with time-dependent Cox models and expressed as hazard ratios (HRs). RESULTS: The crude incidence of lactic acidosis or elevated lactate concentrations in current metformin users was 7.4 per 100,000 person-years (vs. 2.2 per 100,000 person-years in nonusers). Compared with nonusers, risk of lactic acidosis or elevated lactate concentrations in current metformin users was significantly associated with a renal function <60 mL/min/1.73 m2 (adjusted HR 6.37 [95% CI 1.48-27.5]). The increased risk among patients with impaired renal function was further increased in users of ≥730 g of metformin in the preceding year (adjusted HR 11.8 [95% CI 2.27-61.5]) and in users of a recent high daily dose (>2 g) of metformin (adjusted HR 13.0 [95% CI 2.36-72.0]). CONCLUSIONS: Our study is consistent with current recommendations that the renal function of metformin users should be adequately monitored and that the dose of metformin should be adjusted, if necessary, if renal function falls below 60 mL/min/1.73 m2. © 2014 by the American Diabetes Association.


Haeseker M.,Maastricht University | Haeseker M.,Care and Public Health Research Institute CAPHRI | Stolk L.,Maastricht University | Nieman F.,Maastricht University | And 5 more authors.
British Journal of Clinical Pharmacology | Year: 2013

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT •The efficacy target of AUC:MIC > 125 is based on the study of Forrest etal. in 1993. •Recent studies have shown that in ICU patients the ciprofloxacin efficacy target of AUC:MIC > 125 is often not reached. WHAT THIS STUDY ADDS •The efficacy targets of ciprofloxacin in patients in general wards are often not reached. Most patients have low AUC with current i.v. dosing regimens. We suggest increasing the standard dose of ciprofloxacin to 1200mg intravenously24h-1. •Patients in general wards have high interindividual variability of pharmacokinetic parameters and therapeutic drug monitoring could be useful to support dosing. AIM The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC:MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. METHODS In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200mgday-1 i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\PHARM 3.60). A two compartment open model was used. RESULTS Mean (±SD) age was 66 (±17) years, the mean clearance corrected for bodyweight was 0.24lh-1kg-1 and the mean AUC was 49mgl-1h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC:MIC > 125 target with MICs of 0.25 and 0.5mgl-1, respectively. A computer simulated increase in the daily dose from 800mg to 1200mg, decreased these percentages to 1% and 37%, respectively. CONCLUSION A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC:MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC:MIC > 125. © 2012 The British Pharmacological Society.


Bultink I.E.M.,VU University Amsterdam | Harvey N.C.,University of Southampton | Lalmohamed A.,University Utrecht | Cooper C.,University of Southampton | And 8 more authors.
Osteoporosis International | Year: 2014

Summary: The incidence of clinical fractures and the associated factors were assessed in patients with systemic lupus erythematosus (SLE) versus matched controls. We found an increased fracture risk in SLE patients compared to controls. Glucocorticoid use, longer disease duration, neuropsychiatric disease complications and previous osteoporotic fractures were identified as associated factors. Introduction: The aims of this study were to estimate the risk of clinical fractures in patients with SLE versus matched controls and to evaluate the risk factors associated with clinical fractures in SLE. Methods: This is a population-based cohort study using the Clinical Practice Research Datalink (from 1987-2012). Each SLE patient (n=4,343) was matched with up to six controls (n=21,780) by age and sex. Clinical fracture type was stratified according to the WHO definitions into osteoporotic and non-osteoporotic fracture. Cox proportional hazards calculated relative rates (RR) of clinical fracture and time interaction terms to evaluate the timing patterns of fracture. Clinical fracture rates in SLE patients, stratified by age, gender, type of fracture, disease duration and therapy variables, were compared with those rates in controls. Results: Follow-up durations were 6.4 years in SLE patients and 6.6 years in controls. SLE patients had a 1.2-fold increased clinical fracture risk compared to controls (adjusted RR=1.22, 95% CI=1.05-1.42), and the risk further increased with a longer disease duration. Glucocorticoid (GC) use in the previous 6 months raised the risk of clinical fracture (adjusted RR=1.27, 95% CI=1.02-1.58). Cerebrovascular events, seizures and previous osteoporotic fractures were identified as predictors of clinical fractures. Conclusions: We found an increased risk of clinical fracture in SLE patients compared to controls. GC use in the previous 6 months and longer disease duration are associated with the increased fracture risk in SLE. Patients with neuropsychiatric organ damage or previous osteoporotic fractures are also at increased risk of the occurrence of clinical fractures. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.


Beijers H.J.B.H.,Catharina Hospital | Ferreira I.,Maastricht University | Ferreira I.,Cardiovascular Research Institute Maastricht CARIM | Ferreira I.,Care and Public Health Research Institute CAPHRI | And 8 more authors.
Atherosclerosis | Year: 2014

Objective: To investigate whether an adverse body composition is associated with endothelial dysfunction (ED) and the extent to which any such association could be explained by low-grade inflammation (LGI) and/or insulin resistance (HOMA2-IR). Methods: We studied 475 individuals from the Hoorn Study [mean (range) age, 68.9 (60-87) years, 245 women). Body composition was assessed by whole body dual-energy absorptiometry. Endothelial dysfunction was measured functionally, by flow-mediated dilation (FMD) and by circulating biomarkers. Associations were examined with multiple linear regression models and mediation analyses according to the ab product of coefficients method. Results: After adjustment for age, sex, glucose metabolism status, prior cardiovascular disease and lifestyle factors, total and central fat mass were positively associated with the ED score [. β=0.16 (95% CI 0.04-0.29) and β=0.18 (0.05-0.31), respectively] and inversely, although not statistically significantly, with FMD. Peripheral fat mass was not associated with the ED score or FMD. There was a significant favourable association between peripheral lean mass and FMD [. β=0.13 (0.00-0.26)], but not with the ED score. The association between total and central fat mass and the ED score was, to a great extent, mediated by LGI and HOMA2-IR. In contrast, LGI or HOMA2-IR did not mediate the association between peripheral lean mass and FMD. Conclusion: Higher levels of central, but not peripheral fat mass were adversely associated with ED, which was attributable to body composition-related LGI and insulin resistance. In contrast, peripheral lean mass was beneficially associated with ED, but this seemed to be unrelated to LGI or insulin resistance. © 2014 Elsevier Ireland Ltd.

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