Publications by authors named "Frank de Vries"

170 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

Risperidone versus aripiprazole fracture risk in children and adolescents with autism spectrum disorders.

Autism Res 2021 Jun 3. Epub 2021 Jun 3.

Department of Clinical Pharmacy and Toxicology, Maastricht UMC+, Maastricht, The Netherlands.

Risperidone and aripiprazole, commonly used antipsychotics in children with autism spectrum disorder (ASD), have previously been associated with elevated fracture risk in other populations. The aim of this study was to evaluate and compare the risk of fracture among children with ASD using risperidone or aripiprazole. This was a retrospective, propensity-score matched cohort study, set between January 2013 and December 2018. We used the MarketScan Medicaid insurance data, which covers multiple states of the United States. We included ASD children aged 2-18 years, who were new users of aripiprazole or risperidone and with no prior history of antipsychotic use or fractures. The main exposure was the continued use of aripiprazole or risperidone. The incidence rates of any fracture during follow-up were evaluated, and the risk between aripiprazole and risperidone was compared via Cox-proportional hazard models. Results were stratified by age, sex, duration of exposure and fracture site. In total, 3312 patients (78% male; mean [SD] age 11.0 [3.7] years) were identified for each cohort. Over the full duration of follow-up, fracture incidence rates per 1000 patient-years were 23.2 for risperidone and 38.4 for aripiprazole (hazard ratio and 95% confidence interval: 0.60 [0.44-0.83]). Risks were similar between cohorts throughout the first 180 days on treatment, but significantly higher in the aripiprazole group thereafter. Extremity fractures drove most of the increased risk, with the biggest differences in lower leg and ankle fractures. Differences widened for children aged 10 years or younger (HR [95% CI]: 0.47 [0.30-0.74]). In conclusion, compared to aripiprazole, risperidone was associated with 40% lower risk of fracture. Further analysis on the mechanism and long-term bone health of antipsychotic-treated children with ASD is warranted. LAY SUMMARY: We compared the risk of bone fractures among 6624 children with autism spectrum disorder (ASD), half of whom used risperidone and half of whom used aripiprazole. Taking other factors into account, risks were similar between the two groups throughout the first 180 days on treatment, but significantly higher in the aripiprazole group thereafter. The biggest differences were in lower leg and ankle fractures. Overall, compared with aripiprazole, risperidone was associated with 40% lower risk of fracture.
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http://dx.doi.org/10.1002/aur.2541DOI 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

Liquid Chromatography-Tandem Mass Spectrometry to Monitor Unbound and Total Ceftriaxone in Serum of Critically Ill Patients.

Curr Clin Pharmacol 2020 Dec 27. Epub 2020 Dec 27.

Department of Hospital Pharmacy, VieCuri Medical Centre . Netherlands.

Background: Ceftriaxone is recommended for empiric antimicrobial therapy in patients with sepsis. Therapeutic drug monitoring (TDM) guided dose optimisation could elucidate pharmacokinetic variabilities, improving treatment efficacy. However, detailed data on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for unbound ceftriaxone quantification in serum are scarce.

Objective: The authors aimed to develop a reliable UPLC-MS/MS method for serum ceftriaxone quantification and exhibit its application potential in routine hospital settings.

Methods: In this observational, single centre study, UPLC-MS/MS method validation included specificity, carry-over, linearity, repeatability, intermediate precision, accuracy, limit of quantification, and plasma protein binding. Unbound and total ceftriaxone were quantified in the serum of 5 critically ill patients. Pharmacokinetic/pharmacodynamic (PK/PD) target attainment calculations were performed for both unbound and total ceftriaxone. The PK/PD target for unbound ceftriaxone in serum was set at 4 times the non-species related minimum inhibitory concentration breakpoint of 1 mg/L for at least 60% of the dosing interval.

Results: The UPLC-MS/MS method revealed acceptable limits for clinical samples, with coefficients of variation < 15.0% for concentrations between 0.2 - 400.0 mg/L. Ceftriaxone eluted at 1.94 min and ceftazidime, as internal standard, eluted at 1.42 min. Patients demonstrated a median unbound ceftriaxone fraction of 29.1% (IQR: 15.2 - 52.2). Day 1 of ceftriaxone treatment presented a median PK/PD target attainment of 100.0% (IQR: 81.1 - 100.0) for unbound ceftriaxone in serum, while for calculations based on total concentrations, this figure was 23.9 % (IQR: 10.5 - 80.6).

Conclusion: The described UPLC-MS/MS method enables reliable and rapid ceftriaxone quantification in the serum of critically ill patients. Method feasibility was exhibited for TDM purposes in routine clinical practice.
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http://dx.doi.org/10.2174/1574884715666201228115150DOI Listing
December 2020

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

Increased Risk of Falls, Fall-related Injuries and Fractures in People with Type 1 and Type 2 Diabetes - A Nationwide Cohort Study.

Curr Drug Saf 2021 ;16(1):52-61

Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark.

Introduction: People with diabetes could have an increased risk of falls as they show more complications, morbidity and use of medication compared to the general population. This study aimed to estimate the risk of falls and to identify risk factors associated with falls in people with diabetes. The second aim was to estimate fall-related injuries, such as lesions and fractures, including their anatomic localization in people with diabetes compared with the general population.

Methods: From the Danish National Patient Register, we identified people with Type 1 Diabetes (T1D) (n=12,975) Type 2 Diabetes (T2D) (n=407,009). The cohort was divided into two groups, with respective control groups matched on age and sex (1:1). All episodes of people hospitalized with a first fall from 1996 to 2017 were analyzed using a Cox proportional-hazards model. Risk factors such as age, sex, diabetic complications, a history of alcohol abuse and the use of medication were included in an adjusted analysis. The incidence rate, incidence rate difference and incidence rate ratio (IRR) of falls and the anatomic localization of fall-related injuries as lesions and fractures were identified.

Results And Discussion: The cumulative incidence, of falls requiring hospital treatment, was 13.3% in T1D, 11.9% in T2D. In the adjusted analysis, T1D and T2D were associated with a higher risk of falls [T1D, Hazard Ratio (HR): 1.33 (95% CI: 1.25 - 1.43), T2D, HR: 1.19 (95% CI:1.16 - 1.22), respectively]. Women [group 1, HR 1.21 (CI:95%:1.13 - 1.29), group 2, HR 1.61 (CI:95%:1.58-1.64)], aged >65 years [groups 1, HR 1.52 (CI:95%:1.39 - 1.61), group 2, HR 1.32 (CI:95%:1.58-1.64)], use of selective serotonin receptor inhibitors (SSRI) [group 1, HR 1.35 (CI:95%:1.1.30 - 1.40), group 2, HR 1.32 (CI:95%:1.27-1.38)], opioids [group 1, HR 1.15 (CI:95%:1.12 - 1.19), group 2, HR 1.09 (CI:95%:1.05-1.12)] and a history of alcohol abuse [group 1, HR 1.77 (CI:95%:1.17 - 2.15), group 2, HR 1.88 (CI:95%:1.65-2.15)] were significantly associated with an increased risk of falls in both groups. The IRR of fall-related injuries as hip, radius, humerus and skull/facial fractures were higher in people with T2D than controls [IRR 1.02 (CI:95%:1.01-1.04), IRR 1.39 (CI:95%: 1.18-1.61), IRR 1.24 (CI:95%: 1.12-1.37) and IRR 1.15 (CI:95%:1.07-1.24)]. People with T1D had a higher IRR of hip fractures than controls [IRR: 1.11 (CI:95%:1.02 - 1.23)].

Conclusion: People with diabetes have an increased risk of first fall and a higher incidence of fall- related injuries, including fractures. Advanced aging and sex are non-modifiable risk factors, whereas diabetes, the use of SSRIs and opioids and alcohol abuse could be potentially modifiable risk factors for falls. Gaining information on risk factors for falls could guide the management of diabetes treatment, i.e., choice of drugs, which enables us to improve treatment, particularly in people with a high risk of falls and fractures associated with high mortality.
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http://dx.doi.org/10.2174/1574886315666200908110058DOI Listing
January 2021

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

Pregnancies and Time to Pregnancy in Women With and Without a Previous Chlamydia trachomatis Infection.

Sex Transm Dis 2020 11;47(11):739-747

From the Epidemiology and Surveillance Unit, Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven.

Background: A Chlamydia trachomatis infection (chlamydia) can result in tubal factor infertility in women. To assess if this association results in fewer pregnant women, we aimed to assess pregnancy incidences and time to pregnancy among women with a previous chlamydia infection compared with women without one and who were participating in the Netherlands Chlamydia Cohort Study (NECCST).

Methods: The NECCST is a cohort of women of reproductive age tested for chlamydia in a chlamydia screening trial between 2008 and 2011 and reinvited for NECCST in 2015 to 2016. Chlamydia status (positive/negative) was defined using chlamydia screening trial-nucleic acid amplification test results, chlamydia immunoglobulin G presence in serum, or self-reported chlamydia infections. Data on pregnancies were collected via questionnaires in 2015-2016 and 2017-2018. Overall pregnancies (i.e., planned and unplanned) and time to pregnancy (among women with a pregnancy intention) were compared between chlamydia-positive and chlamydia-negative women using Cox regressions.

Results: Of 5704 women enrolled, 1717 (30.1%; 95% confidence interval [CI], 28.9-31.3) women was chlamydia positive. Overall pregnancy proportions were similar in chlamydia-positive and chlamydia-negative women (49.0% [95% CI, 46.5-51.4] versus 50.5% [95% CI, 48.9-52.0]). Pregnancies per 1000 person-years were 53.2 (95% CI, 51.5-55.0) for chlamydia negatives and 83.0 (95% CI, 78.5-87.9) for chlamydia positives. Among women with a pregnancy intention, 12% of chlamydia-positive women had a time to pregnancy of >12 months compared with 8% of chlamydia negatives (P < 0.01).

Conclusions: Overall pregnancy rates were not lower in chlamydia-positive women compared with chlamydia-negative women, but among women with a pregnancy intention, time to pregnancy was longer and pregnancy rates were lower in chlamydia-positive women.

Trial Registration Number: Dutch Trial Register NTR-5597.
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http://dx.doi.org/10.1097/OLQ.0000000000001247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553199PMC
November 2020

Mortality, causes of death and influence of medication use in patients with systemic lupus erythematosus vs matched controls.

Rheumatology (Oxford) 2021 01;60(1):207-216

Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht.

Objectives: We wanted to estimate the magnitude of the risk from all-cause, cause-specific and sex-specific mortality in patients with SLE and relative risks compared with matched controls and to evaluate the influence of exposure to medication on risk of mortality in SLE.

Methods: We conducted a population-based cohort study using the Clinical Practice Research Datalink, Hospital Episode Statistics and national death certificates (from 1987 to 2012). Each SLE patient (n = 4343) was matched with up to six controls (n = 21 780) by age and sex. Cox proportional hazards models were used to estimate overall and cause-specific mortality rate ratios.

Results: Patients with SLE had a 1.8-fold increased mortality rate for all-cause mortality compared with age- and sex-matched subjects [adjusted hazard ratio (HR) = 1.80, 95% CI: 1.57, 2.08]. The HR was highest in patients aged 18-39 years (adjusted HR = 4.87, 95% CI: 1.93, 12.3). Mortality rates were not significantly different between male and female patients. Cumulative glucocorticoid use raised the mortality rate, whereas the HR was reduced by 45% with cumulative low-dose HCQ use. Patients with SLE had increased cause-specific mortality rates for cardiovascular disease, infections, non-infectious respiratory disease and for death attributable to accidents or suicide, whereas the mortality rate for cancer was reduced in comparison to controls.

Conclusion: British patients with SLE had a 1.8-fold increased mortality rate compared with the general population. Glucocorticoid use and being diagnosed at a younger age were associated with an increased risk of mortality. HCQ use significantly reduced the mortality rate, but this association was found only in the lowest cumulative dosage exposure group.
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http://dx.doi.org/10.1093/rheumatology/keaa267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312724PMC
January 2021

Obstructive sleep apnea and the risk of gout: a population-based case-control study.

Arthritis Res Ther 2020 04 25;22(1):92. Epub 2020 Apr 25.

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

Background: Patients with obstructive sleep apnea (OSA) might be at risk of gout because of pathophysiological mechanisms that can lead to hyperuricemia and eventually gout or because of shared risk factors between both diseases. The objective of the present study was to investigate the risk of gout in patients with OSA.

Methods: A population-based case-control study using the UK Clinical Practice Research Datalink GOLD including all patients aged 40 years and older with a first diagnosis of gout between 1987 and 2014. Gout cases were matched by year of birth, sex, and practice to non-gout controls. Conditional logistic regression estimated the risk of gout with an earlier diagnosis of OSA. Analyses were adjusted for lifestyle factors, comorbidities, and recent drug use.

Results: One hundred eleven thousand five hundred nine cases were matched with 210,241 controls. Patients with OSA were at increased risk of gout (OR 1.86; 95%CI (1.71-2.02). However, this association disappeared (OR 1.05; 95% CI 0.96-1.16) after adjustment for smoking status, body mass index (BMI), alcohol use, a history of heart failure, diabetes mellitus, renal function, and recent use of diuretics and other medications. Among females with OSA and patients with OSA associated with heart failure, renal impairment, or higher BMI, the risk of gout was however still increased when compared to the total control population.

Conclusion: This study showed that the observed association between OSA and gout disappeared after adjustment.
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http://dx.doi.org/10.1186/s13075-020-02176-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183677PMC
April 2020

Letter to the Editor. Cognitive performance of patients with low-grade glioma.

Authors:
Frank de Vries

J Neurosurg 2020 Apr 24:1-2. Epub 2020 Apr 24.

1Maastricht University Medical Centre, Maastricht, The Netherlands.

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http://dx.doi.org/10.3171/2020.1.JNS2097DOI Listing
April 2020

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

The stability of the ADO score among UK COPD patients from The Health Improvement Network.

ERJ Open Res 2020 Jan 10;6(1). Epub 2020 Feb 10.

Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

The ADO (age, dyspnoea, airflow obstruction) score predicts 3-year overall mortality among chronic obstructive pulmonary disease (COPD) patients. Information on the changes in COPD prognostic scores is sparse and it is unclear if the ADO score should be measured serially. We followed 4804 UK COPD patients with three or more ADO measurements from The Health Improvement Network (2005-2014) in a retrospective open cohort design. Patient's ADO scores were calculated once per year unless an obstruction or dyspnoea measurement was missing. Cox regression models assessed the independent role of serial ADO scores on mortality. The associations between baseline patient characteristics and long-term change in ADO scores were assessed using linear mixed effect models. Fewer than 7% of patients had worsened ( increased) by ≥1 point per year after a median follow-up of 4.4 years. There was strong evidence that patients with more rapid worsening in ADO scores had increased mortality (hazard ratio 2.00 (95% CI 1.59-2.52) per 1 point increase in ADO per year). More rapid ADO score worsening was seen among current smokers (rate difference 0.059 (95% CI 0.031-0.087); p=0.001) and ex-smokers (0.028 (95% CI 0.003-0.054); p=0.032) and patients with depression (0.038 (95% CI 0.005-0.071); p=0.022), while overweight (-0.0347 (95% CI -0.0544- -0.0150); p=0.001) and obese (-0.0412 (95% CI -0.0625- -0.0198); p<0.001) patients had a less rapid ADO score worsening. Serial assessment of the ADO score can identify patients with worsening disease and update their prognosis, especially for patients who smoke, are depressed or have lower body mass index.
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http://dx.doi.org/10.1183/23120541.00196-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008137PMC
January 2020

Letter regarding "Cognitive outcomes in meningioma patients undergoing surgery: individual changes over time and predictors of late cognitive functioning".

Authors:
Frank de Vries

Neuro Oncol 2020 04;22(4):580-581

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

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http://dx.doi.org/10.1093/neuonc/noz247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158652PMC
April 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

The Association of Oral Bisphosphonate Use With Mortality Risk Following a Major Osteoporotic Fracture in the United Kingdom: Population-Based Cohort Study.

J Am Med Dir Assoc 2020 06 12;21(6):811-816. Epub 2019 Dec 12.

Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center+, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; MRC Epidemiology Lifecourse Unit, Southampton General Hospital, Southampton, United Kingdom. Electronic address:

Objectives: Bisphosphonates (BPs) might have extra benefits in reducing mortality because of their anti-atherosclerotic effects, but studies reported conflicting results. We investigated the association between oral BP use and mortality risk following a major osteoporotic fracture (MOF) in the United Kingdom.

Design: This was a population-based cohort study.

Setting And Participants: In total, 163,273 adults aged 50 years and older with an MOF between 2000 and 2018 from the Clinical Practice Research Datalink in the United Kingdom.

Methods: Cox proportional hazards models were used to estimate the risk of all-cause mortality in current (0‒6 months), recent (7‒12 months), and past (>1 year) exposures to oral BPs after nonhip MOF and hip fracture. In addition, stratification by sex, BP type, and duration of follow-up was performed.

Results: Compared with never users of oral BPs, current BP use was associated with a 7% higher all-cause mortality risk after nonhip MOF, whereas a 28% lower all-cause mortality risk was observed after hip fracture. Past BP exposure was associated with a 14% and 42% lower risk after nonhip MOF and hip fracture, respectively. When considering only the first 5 years of follow-up, mortality risk associated with current BP use was significantly lower for both fracture groups, and the greatest reduction in mortality risk was observed within the first year. Women had slightly lower risk compared with men.

Conclusions And Implications: We found a slight increased risk of all-cause mortality with current BP exposure after a nonhip MOF; however, a protective effect was observed following a hip fracture. Both the timing and the effect size of an association based on the anti-atherosclerotic hypothesis of BPs are not supported by our results. The decreasing trend of the mortality risk with shorter durations of follow-up suggests that the observed association is likely due to unknown distortion or unknown pleiotropic properties of BPs.
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http://dx.doi.org/10.1016/j.jamda.2019.11.003DOI Listing
June 2020

Validation of an analytical method using HPLC-MS/MS to quantify osimertinib in human plasma and supplementary stability results.

Biomed Chromatogr 2020 Apr 3;34(4):e4771. Epub 2020 Feb 3.

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

A new method for quantification of osimertinib (OSIM) in human plasma using a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated. Methanol was used for protein precipitation and pazopanib as internal standard. Separation was performed on a HyPURITY®C analytical column (50 × 2.1 mm; 3 μm) using a gradient elution of ammonium acetate in water and ammonium acetate in methanol, both acidified with formic acid 0.1%. Detection and quantification of OSIM and pazopanib was performed using a triple quadruple mass spectrometer after electrospray ionization. This method led to robust results, as the selectivity, carryover, precision and accuracy all met pre-specified requirements. OSIM was stable in human serum when stored at -80°C. Reduced stability was found when stored at 2-4°C or room temperature. Degradation of OSIM slowed down in EDTA-plasma and acidified human serum. The limited stability of OSIM at room temperature should be considered for transport and sample preparation. Plasma samples should be frozen as soon as possible and sample preparation should be performed on dry-ice. In the future, EDTA-plasma and sample acidification may be used to improve OSIM stability at room temperature. However, more research and validation of such an approach are required.
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http://dx.doi.org/10.1002/bmc.4771DOI Listing
April 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

Psychostimulants/Atomoxetine and Serious Cardiovascular Events in Children with ADHD or Autism Spectrum Disorder.

CNS Drugs 2020 01;34(1):93-101

Personalized Health Care Data Science, Real World Data, F. Hoffmann-La Roche Ltd., Grenzacherstrasse. 124, 4070, Basel, Switzerland.

Background: Psychostimulants and atomoxetine have been shown to increase blood pressure, heart rate, and QT interval in children and adolescents; however, based on current literature, it is unclear if these "attention-deficit/hyperactivity disorder (ADHD) medications" are also associated with serious cardiovascular (SCV) events. We addressed this question in commonly exposed groups of children and adolescents with either ADHD or autism spectrum disorder (ASD).

Methods: Using commercial (years 2000-2016) and Medicaid (years 2012-2016) administrative claims data from the United States (US), we conducted two case-control studies, nested within respective cohorts of ADHD and ASD children aged 3-18 years. We defined cases by a composite outcome of stroke, myocardial infarction, or serious cardiac arrhythmia. For each case, we matched ten controls on age, sex, and insurance type. We conducted conditional logistic regression models to test associations between SCV outcomes and a primary exposure definition of current ADHD medication use. Additionally, we controlled for resource use, cardiovascular and psychiatric comorbidities, and use of medications in a variety of sensitivity analyses.

Results: We identified 2,240,774 children for the ADHD cohort and 326,221 children for the ASD cohort. For ADHD, 33.9% of cases (63 of 186) versus 32.2% of controls (598 of 1860) were exposed, which yielded an odds ratio (OR) and 95% confidence interval (CI) of 1.08 (0.78-1.49). For ASD, 12.5% of cases (6 of 48) versus 22.1% of controls (106 of 480) were exposed [OR 0.49 (0.20-1.20)]. Covariate-adjusted results and results for individual outcomes and other exposure definitions were consistent with no increased risk of SCV events.

Conclusion: Using large US claims data, we found no evidence of increased SCV risk in children and adolescents with ADHD or ASD exposed to ADHD medications.
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http://dx.doi.org/10.1007/s40263-019-00686-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982643PMC
January 2020

External Validation Of The Updated ADO Score In COPD Patients From The Birmingham COPD Cohort.

Int J Chron Obstruct Pulmon Dis 2019 24;14:2395-2407. Epub 2019 Oct 24.

Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Background: Reviews suggest that the ADO score is the most discriminatory prognostic score for predicting mortality among chronic obstructive pulmonary disease (COPD) patients, but a full evaluation and external validation within primary care settings is critical before implementation.

Objectives: To validate the ADO score in prevalent and screen-detected primary care COPD cases at 3 years and at shorter time periods.

Patients And Methods: One thousand eight hundred and ninety-two COPD cases were recruited between 2012 and 2014 from 71 United Kingdom general practices as part of the Birmingham COPD Cohort study. Cases were either on the practice COPD register or screen-detected. We validated the ADO score for predicting 3-year mortality with 1-year and 2-year mortality as secondary endpoints using discrimination (area-under-the-curve (AUC)) and calibration plots.

Results: One hundred and fifty-four deaths occurred within 3 years. The ADO score was discriminatory for predicting 3-year mortality (AUC= 0.74; 95% CI: 0.69-0.79). Similar performance was found for 1- (AUC= 0.73; 0.66-0.80) and 2-year mortality (0.72; 0.67-0.76). The ADO score showed reasonable calibration for predicting 3-year mortality (calibration slope 0.95; 0.70-1.19) but over-predicted in cases with higher predicted risks of mortality at 1 (0.79; 0.45-1.13) and 2-year (0.79; 0.57-1.01) mortality.

Discussion: The ADO score showed promising discrimination in predicting 3-year mortality in a primary care population including screen-detected cases. It may need to be recalibrated if it is used to provide risk predictions for 1- or 2-year mortality since, in these time-periods, over-prediction was evident, especially in cases with higher predicted mortality risks.
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http://dx.doi.org/10.2147/COPD.S212381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818100PMC
April 2020

Economic impact of Patient's Own Medication use during hospitalisation: a multicentre pre-post implementation study.

Int J Clin Pharm 2019 Dec 8;41(6):1658-1665. Epub 2019 Nov 8.

Department of Clinical Pharmacy, Amphia Hospital, Breda, The Netherlands.

Background Medication is frequently thrown away after a patient's discharge from hospital, with undesirable economic and environmental consequences. Because of the rising costs of healthcare, interventions to reduce medication wastage (and associated costs) are warranted. Using Patient's Own Medication during hospitalisation might decrease medication wastage and associated costs. Objective To study the economic impact of patient's own medication use on medication waste and hospital staff's time spent during hospitalisation. Setting In seven Dutch hospitals, of which university, teaching, general, and specialised hospitals, eight different hospital wards, surgical and medical, were selected. Method In this prospective pre-post intervention study data on the economic value of medication waste and time spent by healthcare professionals were collected for a 2 months period each. The economic value of medication waste was defined as the value (€) of wasted medication per 100 patient days. For each ward, time spent on medication process activities was measured 10 times per staff member. The average time spent (in hours) on medication process steps (multiple activities) per staff member per 100 patients and associated salary costs were calculated for both periods. Main outcome measure The primary outcome of the study was the total economic value (€) of wasted medication per 100 patient days. Results Implementation of Patient's Own Medication decreased the economic value of wasted medication by 39.5% from €3983 to €2411 per 100 patient days. The mean time spent on the total medication process was reduced with 5.2 h per 100 patients (from 112.7 to 104.4 h per 100 patients). We observed a shift in professional activities, as physicians and nurses spent less time on the medication process, whereas pharmacy technicians had a greater role in it. When time spent was expressed as salary; €1219 could be saved per 100 patients. Conclusions This study showed that 'Patient's Own Medication' implementation may have a positive economic impact, as the value of medication waste decreases, hospital staff devoted less time on the medication process, and staff deployment is more efficient.
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http://dx.doi.org/10.1007/s11096-019-00932-1DOI Listing
December 2019

Mortality risk in atrial fibrillation: the role of aspirin, vitamin K and non-vitamin K antagonists.

Int J Clin Pharm 2019 Dec 8;41(6):1536-1544. Epub 2019 Oct 8.

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

Background As an alternative to vitamin K antagonist and low-dose aspirin (< 325 mg), non-vitamin K oral anticoagulants are available for the prevention of stroke in patients with atrial fibrillation. However, the mortality risk associated with these drugs in daily practice remains unclear. Objective To evaluate the risk of all-cause mortality associated with non-Vitamin K antagonist oral anticoagulants, vitamin K antagonists or aspirin in patients with atrial fibrillation. Setting A cohort study conducted among atrial fibrillation patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). Method New users of vitamin K antagonists, non vitamin K oral anticoagulants, low-dose aspirin, or combination therapy were followed from the date of first prescription to the date of death, as recorded in the UK datalink. Cox proportional hazard models estimated the hazard ratio (HR) of all-cause mortality for users of NOACs, aspirin, or combination use, as compared to vitamin K antagonist. Analyses were adjusted for confounders. Main outcome measure All-cause mortality. Results We identified 31,497 patients. Non vitamin K antocoagulant use (adjusted HR [aHR] = 1.42; 95% Confidence Interval [CI] 1.18-1.71) and aspirin use (aHR = 1.64; 95% CI 1.57-1.77) were both significantly associated with a higher mortality risk than use of vitamin K antagonists. The higher mortality risk for the non vitamin K anticoagulant use was observed in men (aHR = 1.72; 95% CI 1.25-2.36), but not in women (aHR = 1.28; 95% CI 0.92-1.79. Compared to  vitamin K antagonists, mortality risk associated with the non vitamin K anticoagulants and aspirin use was significantly increased in patients with higher stroke risk (CHADS-VASc > 2). Conclusion Non vitamin K oral anticoagulants are  associated with a higher risk on all-cause mortality, particularly in men and in patients with higher stroke risk.
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http://dx.doi.org/10.1007/s11096-019-00916-1DOI Listing
December 2019

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

Association between vildagliptin and risk of angioedema, foot ulcers, skin lesions, hepatic toxicity, and serious infections in patients with type 2 diabetes mellitus: A European multidatabase, noninterventional, postauthorization safety study.

Endocrinol Diabetes Metab 2019 Jul 21;2(3):e00084. Epub 2019 Jun 21.

Novartis Pharma AG Basel Switzerland.

Objectives: This noninterventional, multidatabase, analytical cohort study explored whether vildagliptin is associated with an increased risk of specific safety events of interest, namely angioedema, foot ulcers, or skin lesions, adverse hepatic events, or serious infections compared with other noninsulin antidiabetic drugs (NIADs) using real-world data from five European electronic healthcare databases.

Design: Patients with type 2 diabetes mellitus aged ≥18 years on NIAD treatment were included between January 2005 and June 2014. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the outcomes of interest were estimated using negative binomial regression.

Patients: Approximately 2.8% of the included patients (n = 738 054) used vildagliptin at any time during the study, with an average follow-up time of 1.4 years.

Results: The adjusted IRRs (vildagliptin vs. other NIADs) were in the range of 0.87-3.71 (angioedema), 0.73-1.19 (foot ulcers), 0.37-1.18 (skin lesions), 0.24-1.14 (composite of foot ulcer or skin lesions), 0.29-0.55 (serious hepatic events), and 0.59-1.04 (serious infections), with no lower bound of the 95% CIs > 1.

Conclusions: Overall, there was no increased risk of the events of interest in association with vildagliptin use compared with other NIADs.
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http://dx.doi.org/10.1002/edm2.84DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613220PMC
July 2019
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