Publications by authors named "Johanna H M Driessen"

37 Publications

Low-dose oral glucocorticoid therapy and risk of osteoporotic fractures in patients with rheumatoid arthritis: a cohort study using the Clinical Practice Research Datalink.

Rheumatology (Oxford) 2021 Jul 13. Epub 2021 Jul 13.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, the Netherlands.

Objectives: Clinical trials have shown that low-dose glucocorticoid therapy in patients with rheumatoid arthritis (RA) reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA.

Methods: This was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997-2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7-12 months), and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis, and ribs) were estimated by time-dependent Cox proportional-hazards models, adjusted for life-style parameters, comorbidities, and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids.

Results: Among 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98-1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11-2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids.

Conclusion: Clinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased.
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http://dx.doi.org/10.1093/rheumatology/keab548DOI Listing
July 2021

Thiazolidinediones and Glucagon-like Peptide-1 Receptor Agonists and the Risk of Nonalcoholic Fatty Liver Disease: A Cohort Study.

Hepatology 2021 Jun 15. Epub 2021 Jun 15.

CARIM School for Cardiovascular Disease, Maastricht University, Maastricht, the Netherlands.

Thiazolidinediones (TZDs) and glucagon-like peptide-1 (GLP-1) receptor agonists are potential pharmacological treatment options for patients at risk of nonalcoholic fatty liver disease (NAFLD). Therefore, we examined the association between the risk of NAFLD and the use of thiazolidinediones and GLP-1 receptor agonists compared with the use of sulfonylureas (SUs) and insulins. Additionally, we calculated the incidence of hepatocellular carcinoma (HCC) in users of TZDs and GLP-1 receptor agonists. We conducted a population-based cohort study using primary care data from the Clinical Practice Research Datalink (CPRD) database (2007-2018). All patients aged ≥18 with a prescription of an oral glucose-lowering agent or GLP-1 receptor agonist were included. The first prescription defined the start of follow-up. The primary outcome was a new diagnosis of NAFLD. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the primary outcome. Incidence rates of HCC were determined per 1,000 person-years for all exposures. The study identified 207,367 adults with a prescription for a glucose-lowering agent. The risk of NAFLD was lower in patients prescribed a thiazolidinedione than in those prescribed a SU (adjusted HR [aHR], 0.32; 95% CI, 0.20-0.51). No difference in risk of NAFLD was observed comparing GLP-1 receptor agonist use with insulin use (aHR, 1.22; 95% CI, 0.91-1.63). Conclusion: Results of our study endorse the use of TZDs for selected patients at risk of NAFLD but do not support previous findings regarding the beneficial effect of GLP-1 receptor agonists. The low number of events in several subgroups may affect the generalizability of the current findings.
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http://dx.doi.org/10.1002/hep.32012DOI Listing
June 2021

Determinants of treatment modification before and after implementation of the updated 2015 NICE guideline on type 2 diabetes: A retrospective cohort study.

Diabetes Res Clin Pract 2021 Jun 21;176:108828. Epub 2021 Apr 21.

Department of Clinical Pharmacy, Maastricht University Medical Centre+, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre+, Maastricht, the Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, the Netherlands; NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.

Aims: To identify patient-specific factors associated with early metformin treatment modification among type 2 diabetes patients before and after implementation of the updated 2015 NICE (National Institute for Health and Care Excellence) guideline.

Methods: We conducted a population-based cohort study using data from the Clinical Practice Research Datalink GOLD database (2009-2016). Patients ≥ 18 years, newly treated with metformin only, during the period of valid data collection were included. The first prescription defined start of follow-up. Determinants of treatment modification in two cohorts (before and after implementation of the updated guideline) were studied by time-dependent Cox proportional hazards regression.

Results: After implementation of the updated guideline, patients were less likely to receive sulphonylureas (62.3% vs 41.3%) or thiazolidediones (4.7% vs 2.2%) and more likely to receive dipeptidyl peptidase-4 inhibitors (15.8% vs 27.1%) or sodium-glucose cotransporter-2 inhibitors (0.8% vs 9.9%). Some determinants influenced general practitioners' prescribing differently after implementation of the updated guideline compared to before, including a high body mass index and heart failure.

Conclusions: Our results indicate that a first step towards tailored prescribing has been made. However, not all determinants that are important to consider when prescribing second-line glucose-lowering agents were of influence on general practitioners' prescribing.
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http://dx.doi.org/10.1016/j.diabres.2021.108828DOI Listing
June 2021

The risk of community-acquired pneumonia in children using gastric acid suppressants.

Eur Respir J 2021 Mar 18. Epub 2021 Mar 18.

Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical, Pharmacology, University of Utrecht, Utrecht, the Netherlands.

With the increased use of acid suppressants, significant potential complications, such as community-acquired pneumonia are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and community-acquired pneumonia. Our main objective was to evaluate the risk of community-acquired pneumonia in children using acid suppressants (proton pump inhibitors and/or histamine-2-receptor antagonists).We performed a cohort study using data from the Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to 4 unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of community-acquired pneumonia. The cohort consisted of 84 868 exposed and 325 329 unexposed children.Current use of proton pump inhibitors and histamine-2-receptor antagonists was associated with an increased risk of community acquired pneumonia, adjusted hazard ratio 2.05 (95% CI 1.90 to 2.22) and 1.80 (95% CI 1.67 to 1.94), respectively. The risk was even greater in patients with respiratory disease. Long term use >211 days of proton pump inhibitors and histamine-2-receptor antagonists led to a significantly greater risk of community-acquired pneumonia compared to short term use <31 days. After cessation of therapy, the risk remained increased for the following 7 months.The use of acid suppressants in children was associated with a doubled risk of community-acquired pneumonia. This risk increased with chronic use, respiratory disease and remained increased after discontinuation of therapy.
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http://dx.doi.org/10.1183/13993003.03229-2020DOI Listing
March 2021

Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporotic fractures among patients with rheumatoid arthritis: a population-based cohort study.

Ann Rheum Dis 2020 Dec 11. Epub 2020 Dec 11.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, The Netherlands

Background: Patients with rheumatoid arthritis (RA) commonly use oral glucocorticoids (GCs) and proton pump inhibitors (PPIs), both associated with osteoporotic fractures. We investigated the association between concomitant use of oral GCs and PPIs and the risk of osteoporotic fractures among patients with RA.

Methods: This was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral GCs and PPIs was stratified by the most recent prescription as current use (<6 months), recent use (7-12 months) and past use (>1 year); average daily and cumulative dose; and duration of use. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, statistically adjusted for lifestyle parameters, comorbidities and comedications.

Results: Among 12 351 patients with RA (mean age of 68 years, 69% women), 1411 osteoporotic fractures occurred. Concomitant current use of oral GCs and PPIs was associated with a 1.6-fold increased risk of osteoporotic fractures compared with non-use (adjusted HR: 1.60, 95% CI: 1.35 to 1.89). This was statistically different from a 1.2-fold increased osteoporotic fracture risk associated with oral GC or PPI use alone. Most individual fracture sites were significantly associated with concomitant use of oral GCs and PPIs. Among concomitant users, fracture risk did not increase with higher daily dose or duration of PPI use.

Conclusions: There was an interaction in the risk of osteoporotic fractures with concomitant use of oral GCs and PPIs. Fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs.
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http://dx.doi.org/10.1136/annrheumdis-2020-218758DOI Listing
December 2020

Use of Sodium-Glucose Co-Transporter-2-Inhibitors (SGLT2-Is) and Risk of Lower Limb Amputation.

Curr Drug Saf 2021 ;16(1):62-72

Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands.

Background: Treatment with sodium-glucose co-transporter-2-inhibitors (SGLT2-Is), such as canagliflozin, has been associated with an increased risk of lower limb amputations (LLAs) in type 2 diabetes mellitus (T2DM). However, conflicting results have been reported for different SGLT2-Is and the underlying mechanism is unclear.

Objective: To investigate the risk of LLA and diabetic foot ulcer with SGLT2-I use compared to other anti-diabetic drugs and to explore hypovolemia as a potential underlying mechanism.

Methods: A cohort study was conducted using data from the Clinical Practice Research Datalink GOLD (2013-2019). The study population (N=51,847) consisted of T2DM patients over 18 years of age with at least one prescription of a non-insulin anti-diabetic drug. Concomitant diuretic use and the presence of signs of hypovolemia were determined to assess the potential underlying mechanism. Cox proportional hazard models were used to estimate the hazard ratio (HR) for LLA in current SGLT2-I use versus current sulphonylurea (SU) use. Analyses were adjusted for lifestyle variables, comorbidities, and concomitant drug use.

Results: Current SGLT2-I use was not associated with an increased risk of LLA compared to current SU use (fully adjusted HR 0.70; 95% confidence interval 0.38-1.29). Concomitant use of diuretics and the presence of signs of hypovolemia were not associated with an increased risk of LLA.

Conclusion: Use of SGLT2-Is, with or without signs of hypovolemia, was not associated with an increased risk of LLA or DFU versus current SU use. Future studies powered to detect potential differences between individual SGLT2-Is are required to rule out a canagliflozin-specific effect.
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http://dx.doi.org/10.2174/1574886315666200805103053DOI Listing
January 2021

Factors Associated with Antihypertensive Medication Non-Adherence: A Cross-Sectional Study Among Lebanese Hypertensive Adults.

Patient Prefer Adherence 2020 1;14:663-673. Epub 2020 Apr 1.

Department of Chemistry and Biochemistry, Faculty of Sciences, Lebanese University, Beirut, Lebanon.

Background: Poor adherence to antihypertensives is associated with negative outcome of the disease as well as loss of health-care resources. Addressing the epidemic of poor adherence requires identifying factors associated with this behaviour. The aim of this study is to describe adherence to antihypertensive medication among Lebanese hypertensive patients and to evaluate the association between socio-economic, patient- and conditions-related factors and non-adherence.

Methods: A cross-sectional study was carried out on adherence to antihypertensive medications covering all governorates of Lebanon. This study was conducted between February 2018 and January 2019 on a random sample of 1497 hypertensive patients. A face-to-face questionnaire was used to assess adherence to antihypertensive medication and its determinants according to the five World Health Organization (WHO) main categories. Logistic regression analysis was performed to test the adjusted association between the multiple exposure factors, and drug adherence data were collected by trained interviewers.

Results: Adherence to antihypertensive medications was reported by 1253 (83.7%) of the patients. After multivariate analysis, patients who tried to control their stress level (OR = 0.77, 95% CI [0.38-0.95]), those who had normal BP readings (OR =0.49, 95% CI [0.18-0.97]), and those who believed in the effectiveness of their treatment (OR = 0.31, 95% CI [0.14-0.76]) had a significantly lower chance to exhibit non-adherence to their treatment. However, older patients (OR= 1.87, 95% CI [1.23-2.21]), divorced/separated patients (OR= 2.14, 95% CI [1.31-5.48]), married (OR=1.96, 95% CI [1.27-3.90]), widowed (OR=2.11, 95% CI [1.62-6.50]), obese patients (OR = 1.76, 95% CI [1.21-1.94]), and patients who smoked hookah and cigarettes (OR = 2.62, 95% CI [1.17-6.76]) were more likely to exhibit non-adherence.

Conclusion: Our study highlights the influence of factors such as old age, marital status, BMI and high level of emotional stress on non-adherence to medication in hypertensive patients. These determinants should be incorporated into adherence improving strategies.
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http://dx.doi.org/10.2147/PPA.S238751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132025PMC
April 2020

No decrease in fracture risk despite 15 years of treatment evolution for multiple myeloma patients: A Danish nationwide case-control study.

Bone 2020 05 22;134:115299. Epub 2020 Feb 22.

Department of Clinical Pharmacy and Pharmacology, Medical Center Leeuwarden, Leeuwarden, the Netherlands; Unit of Pharmacotherapy, Epidemiology and Economics, Department of Pharmacy, University of Groningen, Groningen, the Netherlands.

Rationale: While treatment strategies for multiple myeloma have evolved radically over the last decades, little is known about the risk of fractures for symptomatic multiple myeloma patients over time.

Objective: To determine the effect of different treatment periods (1996-2000, 2001-2006 and 2007-2011) on the risk of fractures in patients with multiple myeloma.

Methods: This retrospective case-control study included patients with multiple myeloma in Denmark, using the Danish National Health Service. Cases were defined as patients who had sustained a fracture between 1996 and 2011, and controls were those without a fracture. Exposure was defined as an ICD code for multiple myeloma. Vertebral fractures, gender, and age were considered in secondary analyses. Conditional logistic regression was used to estimate odd ratios (ORs) of fracture risk, and the analyses were adjusted for comorbidities and recent drug use.

Results: The study population consisted of 925,341 cases, and the same number of matched controls, of whom 1334 patients with multiple myeloma. Among cases, the risk of any fracture was higher in multiple myeloma patients compared to patients without multiple myeloma (any fracture: OR[95% CI] 1996-2000: 1.7[1.3-2.3]; 2001-2006: 1.3[1.1-1.6]; 2007-2011: 1.7[1.4-2.2]). Although fractures were mainly non-vertebral, the risk of vertebral fractures in particular was higher in multiple myeloma patients (vertebral fracture: OR[95% CI] 1996-2000: 3.5[1.4-8.6]; 2001-2006: 4.0[1.9-8.2]; 2007-2011: 3.0[1.6-5.7]).

Conclusions: Despite new treatment strategies and improved supportive care, this study showed no decreased fracture risk for multiple myeloma patients over time. New treatment strategies, even if they have a positive impact on overall survival, offer no guarantee for a corresponding reduction in bone lesions.
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http://dx.doi.org/10.1016/j.bone.2020.115299DOI Listing
May 2020

Drug utilization in the Maastricht Study: A comparison with nationwide data.

Medicine (Baltimore) 2020 Jan;99(1):e18524

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center.

Within the southern region of the Netherlands, the Maastricht Study is an on-going observational prospective population-based cohort study that focuses on the etiology of Type 2 diabetes mellitus (T2DM). Representativeness of the participating population is a crucial but often an unknown factor in population-based cohort studies such as the Maastricht Study. We therefore aimed to assess the representativeness of the study population by comparing drug utilization of the participants of the Maastricht Study with the general population of the Netherlands.Since T2DM patients were oversampled in this study, a sampling method was applied in order to ensure a similar distribution of T2DM over the study population. Drug use in the study population was compared with drug use in the population of the Netherlands, using a Z-test to compare 2 independent proportions.In general, drug use in the study was similar compared with national data. However, in the age group 65 to 74 years total drug use was lower in the study population (833/1000 persons) versus nationwide data (882/1000 persons). The use of pulmonary medications was lower (104/1000 persons vs 141/1000 persons) and the use of hypnotics/anxiolytics was higher (90/1000 persons vs 36/1000 persons) in the Maastricht Study as compared with national data.Drug use in the Maastricht Study population is largely comparable to that in the total Dutch population aged 45 to 74. Therefore, data on drug use by participants in the Maastricht Study can be used to perform studies assessing outcomes associated with drug use.
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http://dx.doi.org/10.1097/MD.0000000000018524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946313PMC
January 2020

C-reactive protein as a biomarker of response to inhaled corticosteroids among patients with COPD.

Pulm Pharmacol Ther 2020 02 27;60:101870. Epub 2019 Nov 27.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, the Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, the Netherlands. Electronic address:

Aims: C-reactive protein (CRP) is an important biomarker in systemic inflammation in COPD; reports have suggested inhaled corticosteroids (ICS) attenuate CRP levels. We evaluated the risk of moderate-to-severe exacerbations, severe exacerbations and all-cause mortality among patients with COPD currently exposed to Inhaled corticosteroids (ICS) stratified by CRP levels compared to never ICS users with low CRP levels.

Methods: We included subjects age 40 or more who had a diagnosis of COPD from January 1, 2005 to January 31, 2014 from the UK Clinical Practice Research Datalink (CPRD). ICS exposure was determined time-dependently, as current, recent, past or never users. We evaluated the risk of moderate-to-severe exacerbations, severe exacerbations and all-cause mortality among ICS users stratified by CRP levels.

Results: 17,722 subjects diagnosed with COPD met the inclusion criteria. Among current or never ICS with elevated CRP levels we found, no significantly reduced risk of moderate-to-severe or severe exacerbations. For patients currently exposed ICS with CRP levels ≥8 mg/L there was no reduced risk of moderate-to-severe exacerbations (adjusted hazard ratio [adj. HR] 0.99; 95% confidence interval [CI] 0.76-1.31) or severe exacerbations (adj.HR 1.52; 95% CI 0.71-3.27). However, we found an increased risk of all-cause mortality among COPD patients with CRP levels ≥8 mg/L irrespective of ICS exposure.

Conclusion: We did not find a reduced risk of moderate and/or severe COPD exacerbations among COPD patients with varying CRP levels currently exposed to ICS. However, low-grade systemic inflammation was associated with all-cause mortality among COPD patients.
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http://dx.doi.org/10.1016/j.pupt.2019.101870DOI Listing
February 2020

Chlamydia trachomatis and the Risk of Pelvic Inflammatory Disease, Ectopic Pregnancy, and Female Infertility: A Retrospective Cohort Study Among Primary Care Patients.

Clin Infect Dis 2019 10;69(9):1517-1525

Department of Sexual Health, Infectious Diseases and Environmental Health, Public Health Service South Limburg, Heerlen.

Background: We evaluated the risk of pelvic inflammatory disease (PID), ectopic pregnancy, and infertility in women with a previous Chlamydia trachomatis (CT) diagnosis compared with women who tested negative for CT and CT untested women, considering both targeted and incidental (ie, prescribed for another indication) use of CT-effective antibiotics.

Methods: This was a retrospective study of women aged 12-25 years at start of follow-up within the Clinical Practice Research Datalink GOLD database linked to index of multiple deprivation quintiles, 2000-2013. CT test status and antibiotic use were determined in a time-dependent manner. Risk of PID, ectopic pregnancy, or female infertility were evaluated using of Cox proportional hazard models.

Results: We studied 857 324 women, contributing 6 457 060 person-years. Compared with women who tested CT-negative, women who tested CT-positive had an increased risk of PID (adjusted hazard ratio [aHR], 2.36; 95% confidence interval [CI], 2.01-2.79), ectopic pregnancy (aHR, 1.87; 95% CI, 1.38-2.54), and infertility (aHR, 1.85; 95% CI, 1.27-2.68). The PID risk was higher for women with 2 or more positive CT tests than those with 1 positive test. PID risk increased with the number of previous antibiotic prescriptions, regardless of CT test status.

Conclusions: We showed an association between CT-positive tests and 3 adverse reproductive health outcomes. Moreover, this risk increased with repeat CT infections. CT-effective antibiotic use showed no decreased risks of subsequent PID regardless of CT history. Our results confirm the reproductive health burden of CT, which requires adequate public health interventions.
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http://dx.doi.org/10.1093/cid/ciz429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792126PMC
October 2019

Secular trends in major osteoporotic fractures among 50+ adults in Denmark between 1995 and 2010.

Osteoporos Int 2019 Nov 15;30(11):2217-2223. Epub 2019 Aug 15.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.

We investigated the incidence trend in all major osteoporotic fractures for the whole country of Denmark between 1995 and 2010. Hip and other osteoporotic fractures declined for the general population and especially among women. But, we observed some increasing trend among men which needs more attention.

Purpose: The trend in osteoporotic fractures is varied across the globe, and there is no updated information in the case of Denmark for all major osteoporotic fractures (MOF). Thus, we investigated the incidence rates (IRs) of MOF among 50+ adults in Denmark over the period 1995-2010.

Methods: A series of cross-sectional analyses was done using the Danish National Health Service Register. Participants were 50+ adults in the full country Denmark with a MOF between 1995 and 2010. Gender- specific IRs of MOF per 10,000 person years (PYs) were estimated, in addition to IRs of individual fracture sites (hip, vertebrae, humerus, and radius/ulna), and women-to-men IR ratios for MOF.

Results: A general decline was observed in IRs of MOF for the whole population (from 169.8 per 10,000 PYs in 1995, to 148.0 in 2010), which was more pronounced among women. Thirty-one and nineteen percent of decline was observed in hip fracture rates among women and men, respectively. The trend in clinical vertebral fracture was slightly decreasing for women and increasing for men. The women-to-men rate ratio of MOF decreased noticeably from 2.93 to 2.72 during study period.

Conclusions: We observed declining trends in MOF and hip fracture for both sexes. However, a lower rate of decrease of hip fracture and an increasing trend in vertebral fracture was noticed among men. Considering our observations and the major economic burden that accompanies this devastating disease, more attention should be paid to MOF, especially in men.
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http://dx.doi.org/10.1007/s00198-019-05109-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811370PMC
November 2019

Retraction Note to: Secular trends in major osteoporotic fractures among 50+ adults in Denmark between 1995 and 2010.

Arch Osteoporos 2019 Jul 8;14(1):77. Epub 2019 Jul 8.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.

The publisher has retracted this article [1] from Archives of Osteoporosis in order to publish in Osteoporosis International as originally intended by the authors and the Editors of Osteoporosis International. Springer Nature apologizes to readers and the authors.
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http://dx.doi.org/10.1007/s11657-019-0614-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828341PMC
July 2019

Blood Eosinophil Counts, Withdrawal of Inhaled Corticosteroids and Risk of COPD Exacerbations and Mortality in the Clinical Practice Research Datalink (CPRD).

COPD 2019 04 23;16(2):152-159. Epub 2019 May 23.

a Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre , Maastricht , the Netherlands.

Although recently introduced in the pharmacological treatment algorithm of chronic obstructive pulmonary disease (COPD), there is a need for more data supporting the use of blood eosinophil counts as a biomarker to guide inhaled corticosteroids (ICS) therapy. The aim of this study was to evaluate the risk of moderate and/or severe exacerbations and all-cause mortality in a large primary care population after withdrawal of ICS compared to continued users stratified by elevated blood eosinophil counts. In this population based cohort study, we used data from the Clinical Practice Research Datalink (CPRD) in the United Kingdom. We included subjects' aged 40 years or more who had a diagnosis of COPD. We excluded subjects with a history of asthma, pulmonary fibrosis, cardiac arrhythmia and bronchiectasis, COPD exacerbations occurring within 6 weeks prior to index date, or with a myocardial infarction within 3 months prior to index date. Continuous users were subjects who received their most recent ICS prescription within 3 months before the start of an interval. ICS withdrawals were those who discontinued ICS for more than 3 months. We evaluated the risk of moderate and/or severe exacerbations and all-cause mortality among subjects with various blood eosinophil thresholds who withdrew from ICS compared to continuous ICS users with elevated blood eosinophil levels using Cox regression analysis adjusted for potential confounders. We identified 48,157 subjects diagnosed with COPD between 1 January 2005 to 31 January 2014. Withdrawal of ICS was not associated with an increased risk of moderate-to-severe exacerbations among subjects with absolute blood eosinophil counts ≥0.34 × 10 cells/L [adjusted hazard ratio (adj. HR) 0.72; 95% confidence interval (CI) 0.63-0.81] or relative counts ≥ 4.0% (adj. HR 0.72; 95% CI: 0.66-0.78). Similarly, withdrawal of ICS was not associated with an increased risk of severe exacerbations among subjects with absolute blood eosinophil ≥0.34 × 10 cells/L (adj. HR 0.82; 95% CI: 0.61-1.10) or relative blood eosinophil counts ≥4.0% (adj. HR 0.80; 95% CI: 0.61-1.04). No increased risk of all-cause mortality was observed among subjects who withdrew from ICS irrespective of elevated absolute or relative blood eosinophil counts. In a real-world primary care population, we did not observe an increased risk of moderate and/or severe COPD exacerbations or all-cause mortality among subjects with eosinophilia who withdrew their use of ICS.
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http://dx.doi.org/10.1080/15412555.2019.1608172DOI Listing
April 2019

Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness: the Maastricht Study.

J Hypertens 2019 02;37(2):365-371

Department of Internal Medicine, Maastricht University Medical Centre.

Introduction: Type 2 diabetes (T2D) is associated with cardiovascular disease complications such as myocardial infarction and stroke. These complications are at least partially the consequence of diabetes-associated increased arterial stiffness. Metformin, a first choice oral glucose-lowering drug, has been associated with potential cardio-protective effects. However, there are no data on the association between real-life metformin use and arterial stiffness. The objective of the current study is to investigate in a population-based sample of individuals with T2D the association between metformin use and aortic stiffness (i.e. carotid-femoral pulse wave velocity, cfPWV) and carotid stiffness [i.e. carotid distensibility coefficient and Young's elastic modulus (YEM)].

Methods: We used data from The Maastricht Study, an ongoing observational prospective population-based cohort study (current N = 3451). All participants with T2D, based on pharmacy records (N = 672, 31.3% women, mean age 62.6 ± 7.7), were included in the current study. Linear regression analyses were used to study the association between current metformin use and cfPWV, distensibility coefficient and YEM, as compared with no metformin use. Furthermore, metformin use was stratified by cumulative dose (in grams), continuous duration of use (in days), average daily dose (in grams) and time since first prescription (in years). Regression coefficients of distensibility coefficient were multiplied by -1, consequently, for all arterial stiffness indices, a positive regression coefficient signifies increasing arterial stiffness.

Results: Linear regression showed that neither current metformin use was associated with cfPWV [adjusted B: -0.04 (-0.11 to 0.02)] nor metformin use was as stratified by cumulative dose, by continuous duration of use, by average daily dose or by time since first prescription. Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0.12 (0.01 to 0.23)], but not with YEM [0.10 (-0.03 to 0.22)]. However, there was no consistent pattern with the different stratifications of metformin use when further investigating the association with distensibility coefficient.

Conclusion: We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.
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http://dx.doi.org/10.1097/HJH.0000000000001892DOI Listing
February 2019

Trends in moderate and severe exacerbations among COPD patients in the UK from 2005 to 2013.

Respir Med 2018 11 17;144:1-6. Epub 2018 Sep 17.

CIRO+, Centre for Specialised Treatments Chronic Respiratory Diseases, Horn, the Netherlands; Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands.

Introduction: Exacerbations of chronic obstructive pulmonary disease are characterised by increased symptoms such as dyspnoea, cough and sputum production and/or purulence, leading to greater risk of hospitalisation and mortality. Very few studies have measured long term trends in the incidence of exacerbations of chronic obstructive pulmonary disease. We therefore investigated the incidence of moderate and severe exacerbations in the UK general population.

Methods: A population based-study including Clinical Practice Research Datalink (CPRD) patients ≥ 40 years of age with a current diagnosis of COPD within the United Kingdom from 2004 to 2013 was conducted. Individuals with a history of asthma were excluded from main analyses. We calculated the incidence rates for any, moderate, and severe exacerbations. Patients contributed time at risk from January 1st up to the date of the first outcome within each year. The incidence rate for any, moderate and severe exacerbations for COPD in each calendar year was calculated as follows: the sum of any or moderate or severe exacerbations for COPD in that year divided by the total duration of follow-up in the same calendar year from 2005 through to 2013. We then analysed these rates by gender and age categories (40-59 years, 60-79 years and ≥80 years).

Results: Among 213,561 with incident COPD diagnosis, 86,300 patients were included in the study. From 2005 to 2013, the incidence rate of any exacerbations increased from 89 to 98 per 1000 person years (PYs) (p = 0.005). Women had significantly higher incidence rates of any exacerbation for each calendar year when compared to men (p < 0.0001). The incidence rate of any and moderate exacerbations increased with age from 2005 to 2007. For severe exacerbations incidence decreased from 2005 to 2007 before increasing from 2008 until the end of follow-up (43 per 1000 PYs (95% confidence interval, 42-45/1000PYs) in 2013). Incidence rates of severe exacerbations were similar by gender and patients aged 80 + years had a higher incidence rate of severe exacerbation from 2005 to 2008 after which their incident rate dropped in subsequent years.

Conclusion: This is the first study that reports the long-term changes in the incidence rates of moderate and severe exacerbations within the UK general practice. Women showed a substantially higher risk of any COPD exacerbations, and their risk is increasing. The incidence rates of any exacerbations increased during the study period, while severe exacerbations were variable. Furthermore, incidence rates varied substantially by age group.
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http://dx.doi.org/10.1016/j.rmed.2018.09.010DOI Listing
November 2018

Secular trends in major osteoporotic fractures among 50+ adults in Denmark between 1995 and 2010.

Arch Osteoporos 2018 08 27;13(1):91. Epub 2018 Aug 27.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.

We investigated the incidence trend in all major osteoporotic fractures for the whole country of Denmark between 1995 and 2010. Hip and other osteoporotic fractures declined for the general population and especially among women. But, we observed some increasing trend among men which needs more attention.

Purpose: The trend in osteoporotic fractures is varied across the globe, and there is no updated information in the case of Denmark for all major osteoporotic fractures (MOF). Thus, we investigated the incidence rates (IRs) of MOF among 50+ adults in Denmark over the period 1995-2010.

Methods: A series of cross-sectional analyses was done using the Danish National Health Service Register. Participants were 50+ adults in the full country Denmark with a MOF between 1995 and 2010. Gender- specific IRs of MOF per 10,000 person years (PYs) were estimated, in addition to IRs of individual fracture sites (hip, vertebrae, humerus, and radius/ulna), and women-to-men IR ratios for MOF.

Results: A general decline was observed in IRs of MOF for the whole population (from 169.8 per 10,000 PYs in 1995, to 148.0 in 2010), which was more pronounced among women. Thirty-one and nineteen percent of decline was observed in hip fracture rates among women and men, respectively. The trend in clinical vertebral fracture was slightly decreasing for women and increasing for men. The women-to-men rate ratio of MOF decreased noticeably from 2.93 to 2.72 during study period.

Conclusions: We observed declining trends in MOF and hip fracture for both sexes. However, a lower rate of decrease of hip fracture and an increasing trend in vertebral fracture was noticed among men. Considering our observations and the major economic burden which accompanies this devastating disease, more attention should be paid to MOF, especially in men.
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http://dx.doi.org/10.1007/s11657-018-0503-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132403PMC
August 2018

Increased risk of all-cause mortality associated with domperidone use in Parkinson's patients: a population-based cohort study in the UK.

Br J Clin Pharmacol 2018 11 9;84(11):2551-2561. Epub 2018 Aug 9.

Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

Aims: Domperidone is used to treat gastrointestinal symptoms in patients with Parkinson's disease (PD) and is linked to an increased risk of mortality. We sought to examine the risk of all-cause mortality associated with domperidone exposure in PD.

Methods: We conducted a cohort study using data from the Clinical Practice Research Datalink database (1987-2011). The first recorded PD diagnosis defined index date. Time-dependent Cox proportional hazards models estimated hazard ratios (HRs) of all-cause mortality associated with domperidone use. PD patients were stratified by domperidone use (current/recent/past), with never used as the referent. Current domperidone users were stratified by daily dose, domperidone duration and other anti-Parkinson's medications. A secondary analysis compared PD patients to matched (1:1) non-PD patients.

Results: A total of 5114 PD patients were identified. Current use of domperidone among PD patients was associated with a two-fold increase in all-cause mortality (HR  = 2.00, 95% confidence interval [CI]: 1.64-2.45), as compared to patients never exposed to domperidone. All-cause mortality risk was highest in those starting domperidone in the previous month [HR  = 2.97, 95% CI: 2.06-4.27]. When compared to matched non-PD patients, PD was associated with a 43% increased risk of all-cause mortality, yet this increased to a 2.4-fold increased risk among PD patients currently using domperidone.

Conclusion: Current use of domperidone was associated with a two-fold increased mortality risk in PD patients, as compared to PD patients that never used domperidone. The risk is highest in the first month of use and does not appear to be attributable to PD alone.
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http://dx.doi.org/10.1111/bcp.13708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177707PMC
November 2018

The Impact of Dose and Simultaneous Use of Acid-Reducing Agents on the Effectiveness of Vemurafenib in Metastatic BRAF V600 Mutated Melanoma: a Retrospective Cohort Study.

Target Oncol 2018 06;13(3):363-370

Department of Pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands.

Background: The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown.

Objectives: To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs.

Patient And Methods: A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012-March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital. Cox regression analysis was used to estimate the risk of progression with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n = 77). Analyses were adjusted for age and sex.

Results: In total, disease progression occurred in 55% of treated patients on vemurafenib, with a median progression-free survival of 6.0 (95% confidence interval [CI] 5.0-6.9) months. Compared to patients on vemurafenib alone, there was no increased risk of progression among patients requiring vemurafenib at a reduced dose or among patients receiving simultaneous therapy with vemurafenib and ARAs. In addition, there was no increased risk of progression among patients who used reduced-dose vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole therapy. However, a tendency for progression was observed among patients who used full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted hazard ratio [HRa] 2.37; 95% CI 0.97-5.76), which became statistically significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51-13.75).

Conclusions: There was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating  full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation.
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http://dx.doi.org/10.1007/s11523-018-0564-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004282PMC
June 2018

Impact of cumulative exposure to high-dose oral glucocorticoids on fracture risk in Denmark: a population-based case-control study.

Arch Osteoporos 2018 Mar 18;13(1):30. Epub 2018 Mar 18.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.

We examined the effect of cumulative exposure to high doses of oral glucocorticoids on fracture risk. Compared to short-course users (daily dose ≥ 15 mg + cumulative < 1 g), heavy users (daily dose ≥ 15 mg + cumulative dose ≥ 1 g) had the highest risk of fracture. These patients should be monitored for fracture management strategies.

Purpose: The effect of cumulative exposure to high daily doses of oral glucocorticoids on fracture risk remains debated. We therefore aimed to examine the hip fracture risk associated with short courses and heavy use of high-dosed oral glucocorticoids.

Methods: We conducted a population-based case-control study using the Danish National Health Service data, 1996-2011. Cases were those aged ≥ 18 years who sustained a hip (primary outcome) fracture (n = 81,342). Vertebral and forearm fractures were considered in secondary analyses. Controls (matched 1:1) were those without a fracture. Average daily dose (DD) and total cumulative dose (CD) were calculated among current oral glucocorticoid users. Among patients with a high daily dose (DD ≥ 15 mg), we identified short-course users as those with a CD < 1 g and heavy users as those with a CD ≥ 1 g. We estimated adjusted odds ratio (adj.OR) of fracture with current glucocorticoid use compared to never-use, using conditional logistic regression.

Results: A high DD (≥ 15 mg) and high CD (≥ 1 g) were independently associated with an increased hip fracture risk (adj.OR 2.5; 95% CI 2.2-2.9; adj.OR 1.6; 95% CI 1.5-1.8, respectively). However, the risk was substantially increased among heavy users (DD ≥ 15 mg and CD ≥ 1 g: adj.OR 2.9; 95% CI 2.5-3.4) as compared to short-course users (DD ≥ 15 mg and CD < 1 g: adj.OR 1.4; 95% CI 1.1-1.9). Associations were stronger for vertebral fractures, yet little association was identified for forearm fractures.

Conclusion: Among patients receiving a high DD (≥ 15 mg), heavy users (≥ 1 g CD) showed the most substantial increase in hip fracture risk. Among those receiving high DD, a threshold of 1 g CD may identify heavy users that are candidates for focused fracture management services.
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http://dx.doi.org/10.1007/s11657-018-0424-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857556PMC
March 2018

Use of high-dose intermittent systemic glucocorticoids and the risk of fracture in patients with chronic obstructive pulmonary disease.

Bone 2018 05 17;110:238-243. Epub 2018 Feb 17.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands; MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom. Electronic address:

Introduction: Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow obstruction and respiratory symptoms. While short course systemic GCs are prescribed in patients with acute COPD exacerbations, little is known of the risk of fractures with intermittent exposure to high-dose GC and the effect of proxies of disease severity.

Methods: A case-control study was conducted using the Danish National Hospital Discharge Registry (NHDR) between January 1996 to December 2011. Conditional logistics regression models were used to derive adjusted odds ratios (OR) risk of fractures in subjects with COPD stratified by intermittent high-dose, and proxies of disease severity.

Result: A total of 635,536 cases and the same number of controls were identified (mean age 67.5±13.8, 65% female). COPD patients with intermittent use of high average daily dose oral glucocorticoids did not have an increased risk of any, osteoporotic, hip or clinically symptomatic vertebral fracture compared to non-COPD patients (adj. OR 0.65; 95% CI: 0.50-0.86, 0.70; 95% CI: 0.70-0.99, 1.17; 95% CI: 0.59-2.32, 1.98; 95% CI: 0.59-6.65 respectively). We identified an elevated risk of osteoporotic fracture among patients who visited the emergency unit (adj. OR 1.47; 95% CI 1.20-1.79) or were hospitalised in the past year for COPD (adj. OR 1.76; 95% CI 1.66-1.85). Current GC use among COPD patients was associated with an increased risk of osteoporotic, hip and clinically symptomatic vertebral fractures compared to patients without COPD.

Conclusion: Intermittent high-dose GCs was not associated with an increased risk of any, osteoporotic, hip or clinically symptomatic vertebral fractures in patients with COPD. Current GC use was however associated with an increased risk of hip and clinically symptomatic vertebral fractures. Therefore, emphasis on prophylactic treatment of fractures may not be essential in patients with COPD receiving intermittent dose of GCs, whereas this should be considered for high-dose long-term users with advanced COPD disease stage, postmenopausal women and men over 40years.
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http://dx.doi.org/10.1016/j.bone.2018.02.007DOI Listing
May 2018

Risk of a first-ever acute myocardial infarction and all-cause mortality with sulphonylurea treatment: A population-based cohort study.

Diabetes Obes Metab 2018 04 27;20(4):1056-1060. Epub 2017 Dec 27.

Department of Clinical Pharmacy, Maastricht University Medical Centre+, Maastricht, The Netherlands.

We investigated the association between the current use of individual sulphonylureas and the risk of a first-ever acute myocardial infarction (AMI) and all-cause mortality, in a population-based cohort study, using primary care data from the Clinical Practice Research Datalink database (2004-2012). New users (N = 121 869), aged ≥18 years, with at least one prescription for a non-insulin antidiabetic agent were included. The first prescription defined start of follow-up. Time-dependent Cox proportional hazard models were used to estimate the risk of a first-ever AMI and all-cause mortality associated with the use of individual sulphonylureas, and other non-insulin glucose-lowering drugs. No differences in risk of a first-ever AMI (adjusted hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.70-1.50) or all-cause mortality (adjusted HR 0.97, 95% CI 0.80-1.17) were observed when comparing gliclazide use with non-gliclazide sulphonylurea use. Similar results were found for each individual sulphonylurea. As evidence is accumulating that gliclazide is no safer than other sulphonylureas, current guidelines suggesting superiority should be carefully evaluated.
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http://dx.doi.org/10.1111/dom.13168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873381PMC
April 2018

Prescribing Errors With Low-Molecular-Weight Heparins.

J Patient Saf 2017 Aug 28. Epub 2017 Aug 28.

From the *Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center+; †School CAPHRI, Maastricht University, Maastricht; ‡Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht, the Netherlands; §Department of Internal Medicine, ∥Thrombosis Expertise Center, Maastricht University Medical Center+, Maastricht; and ¶Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands.

Background: Low-molecular-weight heparins (LMWHs) are used in the prevention and treatment of venous thromboembolism (VTE). Bleeding is the primary major complication of LMWH therapy, which is associated with dose. The administration of appropriate dosages of LMWHs depends on the patient's risk of VTE, risk of bleeding, bodyweight, and renal function. Therefore, LMWH prescribing is prone to errors. However, no earlier study has explored the frequency of prescribing errors with LMWH.

Purpose: The aim of the study was to determine the frequency and determinants of in-hospital LMWH-prescribing errors.

Methods: A cross-sectional study was conducted to examine the frequency and determinants of LMWH prescribing errors between April and August 2014. We randomly selected 500 patients 18 years and older with at least one LMWH prescription during inpatient hospitalization. A prescribing error was a deviation from the internal hospital guidelines. Logistic regression estimated determinants of prescribing error.

Results: A prescribing error was present with 34% of all LMWH users. The most frequently recorded error was a dose that was not adjusted to body weight and/or renal function (85%). Prophylactic LMWH prescribing in medical wards was associated with a higher risk of prescribing error as compared with surgical wards.

Conclusions: The frequency of prescribing errors was 34% in a tertiary care hospital. Being a patient with prophylactic LMWH use on a medical ward is a determinant for LMWH prescribing error. Interventions that will lead to better electronic recording of body weight and more awareness among medical doctors may reduce the total number of prescribing errors.
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http://dx.doi.org/10.1097/PTS.0000000000000417DOI Listing
August 2017

Long-term use of dipeptidyl peptidase-4 inhibitors and risk of fracture: A retrospective population-based cohort study.

Diabetes Obes Metab 2017 03 19;19(3):421-428. Epub 2017 Jan 19.

Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands.

Aims: To investigate the association between long-term dipeptidyl peptidase-4 (DPP-4) inhibitor use and risk of fracture among people with type 2 diabetes mellitus (T2DM).

Methods: A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink database (2007-2015), was conducted. All those (N = 328 254) with at least one prescription for a non-insulin antidiabetic drug (NIAD), aged ≥18 years at the time of data collection, were included. Cox proportional hazards models were used to estimate the hazard ratios of any fracture, osteoporotic fracture and hip fracture in DPP-4 inhibitor users compared with those using other NIADs. Analyses were stratified by continuous duration of DPP-4 inhibitor use. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and concomitant drug use.

Results: Current use of DPP-4 inhibitors was not associated with risk of any fracture (adjusted hazard ratio [HR] 0.99 [95% confidence interval {CI} 0.93-1.06]) as compared with current other NIAD use. Current use of DPP-4 inhibitors was also not associated with risk of osteoporotic or hip fracture. After stratification by continuous duration of DPP-4 inhibitor use the highest category was not associated with any (>4.0-8.5 years of use, adjusted HR 0.99 [95% CI 0.70-1.41]), osteoporotic (>3.0-8.5 years of use, adjusted HR 0.75 [95% CI 0.52-1.09]) or hip (>2.0-8.5 years of use; adjusted HR 1.24 [95% CI 0.85-1.79]) fracture.

Conclusion: Continuous long-term DPP-4 inhibitor use (defined as >4.0-8.5 years of DPP-4 inhibitor use for any fracture, >3.0-8.5 years for osteoporotic fracture and >2.0-8.5 years for hip fracture was not associated with risk of any, osteoporotic or hip fracture. These findings may be of value for clinical decisions regarding treatment of patients with T2DM, especially those at high risk of fracture.
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http://dx.doi.org/10.1111/dom.12843DOI Listing
March 2017

Use of incretin agents and risk of acute and chronic pancreatitis: A population-based cohort study.

Diabetes Obes Metab 2017 03 7;19(3):401-411. Epub 2017 Feb 7.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Aim: To determine the association between the use of incretin agents (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) for the treatment of type 2 diabetes mellitus (T2DM) and the risk of any, acute and chronic pancreatitis.

Research Design And Methods: A population-based cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD 2007-2012). A total of 182 428 adult patients with ≥1 non-insulin antidiabetic drug (NIAD) prescription were matched to control subjects without diabetes. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatitis in incretin-users (N = 28 370) compared with controls and with other NIAD users. Adjustments were made for lifestyle, disease and drug history. In a sensitivity analysis, a new-user design was used.

Results: Current incretin users had a 1.5-fold increased risk of any pancreatitis compared with NIAD users (adjusted HR 1.47, 95% CI 1.06-2.04). In incident current incretin users the risk of any and acute pancreatitis was increased 2.1- and 2.0-fold compared with NIAD users (adjusted HR 2.12, 95% CI 1.31-3.43 and adjusted HR 1.96, 95% CI 1.13-3.41), whereas there was no increased risk found for chronic pancreatitis.

Conclusions: Incretin use was associated with an increased risk of any pancreatitis. Moreover, risk of any and acute pancreatitis was higher when applying a new-user design. We were not able to detect an association with chronic pancreatitis, but the number in this subgroup was small.
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http://dx.doi.org/10.1111/dom.12833DOI Listing
March 2017

The use of incretins and fractures - a meta-analysis on population-based real life data.

Br J Clin Pharmacol 2017 04 7;83(4):923-926. Epub 2016 Dec 7.

Department of Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands.

The aim of the present study was to estimate the effect of incretins on fracture risk in the real-world situation by meta-analysis of the available population-based cohort data. Pubmed and Embase were searched for original articles investigating use of incretin agents, and fracture risk up to December 2015. Adjusted results were extracted and pooled by use of generic inverse variance methods, assuming a random-effects model. Neither current dipeptidyl peptidase 4-inhibitor use nor current glucagon-like peptide 1 receptor agonist use was associated with a decreased risk of fracture: pooled relative risk (pooled RR [95% confidence interval]: 1.02 [0.91-1.13] and 1.03 [0.87-1.22]), respectively. This meta-analysis demonstrated that current use of incretin agents, was not associated with decreased fracture risk. Our findings show the value of representative real-world populations, and the risks associated with suggesting benefits for medications on the basis of safety reporting in randomized controlled trials.
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http://dx.doi.org/10.1111/bcp.13167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346876PMC
April 2017
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