J.T.H. Nielen

Severity of Diabetes Mellitus and Total Hip or Knee Replacement : A Population-Based Case-Control Study

Abstract It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality. To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity. A population-based case–control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity. Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78–0.94)) and THR (OR = 0.90 (95% CI = 0.82–0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c. This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes.

Safety and efficacy of new oral anticoagulants and low‐molecular‐weight heparins compared with aspirin in patients undergoing total knee and hip replacements

There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery.

Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: the effect of index date selection?

We read with great interest the study by Solomon et al 1 regarding the effect of colchicine on risk of cardiovascular (CV) events and all-cause mortality. In their study, they report a marked reduction in the number of CV events and all-cause mortality with the use of colchicine when compared with a reference group not using this drug. Sensitivity analyses mimicking an intention to treat approach showed similar results. Interestingly, no clear gradient of effect according to duration of use was found. The striking …

Identification of antithrombotic drugs related to total joint replacement using anonymised free-text notes: a search strategy in the Clinical Practice Research Datalink.

Objectives We aimed to design and test a method to extract information on antithrombotic therapy from anonymised free-text notes in the Clinical Practice Research Datalink (CPRD). Setting General practice database representative of the UK. Participants All patients undergoing total hip replacement (THR, n=25 898) or total knee replacement (TKR, n=22 231) between January 2008 and October 2012 were included. Antithrombotic drug use related to THR or TKR was identified using anonymised free text and prescription data. Primary and secondary outcome measures Internal validity of our newly designed method was determined by calculating positive predictive values (PPVs) of hits for predefined keywords in a random sample of anonymised free-text notes. In order to determine potential detection bias, total joint replacement (TJR) patient characteristics were compared as per their status of exposure to antithrombotics. Results PPVs ranging between 97% and 99% for new oral anticoagulants (NOAC) or low-molecular weight heparins (LMWH) exposure related to TJR were obtained with our method. Our search strategy increased detection rates by 57%, yielding a total proportion of 18.5% of all THR and 18.6% of all TKR surgeries. Identified users of NOACs and LMWHs were largely similar with regards to age, sex, lifestyle, disease and drug history compared to patients without identified drug use. Conclusions We have developed a useful method to identify additional exposure to NOACs or LMWHs with TJR surgery.

The Association Between β-Blocker Use and Cardiorespiratory Fitness: The Maastricht Study

Purpose: β-Blockers (BBs) have been associated with a reduced cardiorespiratory fitness (CRF). This is possibly caused by inhibition of β2-receptors in the airways. However, there are limited data available on β-receptor selectivity and CRF. We therefore aimed to assess the association between BB use and CRF and to assess the association between β-receptor selectivity and CRF. Methods: Participants in the Maastricht Study were aged between 40 and 75 years. Exposure to BB use was determined by use of pharmacy records. General linear models were used to obtain adjusted means of 2 proxies for CRF: covered distance during the 6-minute walk test (6MWT) and estimated maximum power output adjusted for body mass (Wmax kg−1) during the submaximal cycle ergometer test. Adjusted means were compared between current, past, and never BB users. Current users were subsequently stratified by β-receptor selectivity and dose. Results: Compared to never use, current use was associated with a lower CRF, based on the 6MWT (current use: 569.7 m; never use: 580.4 m [P = .010]), but not based on the cycling test (current use: 2.14 W kg−1; never use: 2.13 W kg−1 [P = .690]). There was no difference between current selective and current nonselective BB use. Conclusion: β-Blockers use was associated with CRF based on the 6MWT but not the cycling test. There was no difference between current selective and nonselective BB users, possibly due to the small number of nonselective BB users, differential underlying diseases, other pharmacological properties, and limitations related to the proxies of the outcome.

Use of parenteral glucocorticoids and the risk of new onset type 2 diabetes mellitus: A case-control study

BACKGROUND Use of oral glucocorticoids (GCs) has been associated with hyperglycaemia and type 2 diabetes mellitus (T2DM). However, unlike oral GCs, there is minimal or no data on the effect of parenteral GC use on T2DM. OBJECTIVE To assess the association between use of parenteral GCs and the risk of receiving a first prescription of a non-insulin antidiabetic drug (NIAD) as a proxy for new onset of T2DM. METHODS A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 177,154) were defined as patients >18 years of age who had their first ever NIAD prescription between January 1987 and October 2013. Controls were matched by age, gender and general practitioner practice. Conditional logistic regression analyses were used to estimate the risk of NIAD prescription and use of parenteral GCs. Our analyses were statistically adjusted for lifestyle factors, comorbidities and concomitant drug use. RESULTS Although this study confirmed that oral GCs increases the risk of receiving a first prescription of a NIAD (OR 2.63 [95% CI 2.53-2.73]), there was no association between the use of parenterally administered GCs and the risk of receiving a first prescription of a NIAD (OR 0.88 [95% CI 0.76-1.02]). The number of GC prescriptions was not associated with risk of new onset T2DM compared to no parenteral GCs use; neither the type of GC. CONCLUSION Our study does not demonstrate an association between the use of parenteral GCs and the risk of new onset of T2DM.

Association of type 2 diabetes mellitus with self-reported knee pain and clinical knee osteoarthritis: The Maastricht Study

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mercredi 28 fevrier 2018

Disease burden of knee osteoarthritis patients with a joint replacement compared to matched controls: a population-based analysis of a Dutch medical claims database

OBJECTIVE On a population level, the incidence of knee prostheses (KPs) has increased, but excess health care costs per patient, compared to matched controls without a KP, in the years surrounding these procedures and their determinants are largely unknown. We therefore aimed to provide estimates of age- and sex-specific incidence of KPs, revision KPs, and prosthesis complications in patients with knee osteoarthritis (OA) and to determine excess health care costs in the years surrounding surgery compared with matched controls. METHODS All KPs in OA patients in the Achmea Health Database were identified as well as up to four controls. Incidence rates of KPs, revisions, and complications from 2006 to 2013 were determined. Annual health care cost and excess costs (over matched controls) preceding, during, and after surgery were calculated and their determinants were evaluated. RESULTS The increased incidence of KPs, revisions, and complications was strongest in younger age categories and men. The average costs per patient were relatively stable between 2006 and 2012. KP patients annual health care costs increased towards the year of surgery. After surgery, costs decreased, but remained higher as compared to costs prior to surgery. High post-surgery costs were mainly associated with subsequent revisions or additional KPs, but costs were also higher in females, lower age categories, and lower social economic status. CONCLUSION These results underscore the increasing burden and medical need associated with end-stage OA, especially in younger age categories. Improvement of guidelines tailored to individual patient groups aimed at avoiding complications and revisions is required to counteract this increasing burden.

Comments on "Use of metformin and risk of kidney cancer in patients with type 2 diabetes", Chin-Hsiao Tseng, Eur J Cancer, 2016, No. 52, pp. 19-25.

a Department of Internal Medicine, VieCuri Medical Centre, Venlo, The Netherlands b GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands c Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands d Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands e Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands f Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands g NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands h Department of Clinical Epidemiology, VieCuri Medical Centre, Venlo, The Netherlands i CAPHRI School for Public Health and Primary Care, Department of Health Services Research, Maastricht University Medical Centre+, Maastricht, The Netherlands j MRC Life-course Epidemiology Unit, University of Southampton, Southampton, United Kingdom

SAT0333 Use of Glitazones and The Risk of Elective Hip Or Knee Replacement: A Population Based Case-Control Study

Background Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, to date, no disease modifying drug exists for this disease. In vivo studies have shown that glitazones may be used as anti-arthritic drugs. (Kobayashi, 2005; Boileau, 2007). Objectives To determine the risk of total joint replacement (TJR) with the use of glitazones. Methods A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n=94,609) were defined as patients >18 years of age who had undergone TJR surgery between 2000 and 2012. Controls were matched by age, gender and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) associated with use of glitazones. We additionally evaluated risk of TJR in current glitazone users compared to DM patients using other antidiabetic drugs (ADs). In order to determine a dose effect relationship, we also stratified glitazone users by total number of prescriptions prior to surgery. Results There is no difference in risk of TKR (OR=1.11 (95% CI=0.95-1.29)) or THR (OR=0.87 (95% CI=0.74-1.02)) between glitazone users and patients not using glitazones. Furthermore, there is no difference in risk of TKR (OR=1.03 (95% CI=0.88-1.22)) and THR (OR=0.90 (95% CI=0.75-1.08)) when glitazones users are compared to other AD users. Finally, we did not find a dose response effect with increasing number of prescriptions. Conclusions This study did not find any evidence for an anti-arthritic effect of glitazones. References Boileau et al. Arthritis and Rheumatism, 2007; Kobayashi et al. Arthritis & Rheumatism, 2005. Disclosure of Interest J. Nielen: None declared, B. van den Bemt Grant/research support from: Pfizer, Roche, Speakers bureau: Pfizer, Roche, Abbvie and MSD, A. Lalmohamed Grant/research support from: Netherlands Organisation for Scientific Research (NWO), A. de Boer: None declared, A. Boonen Grant/research support from: Amgen Abbvie, Pfizer and Merck, Speakers bureau: Pfizer, UCB and Sandoz, P. Dagnelie: None declared, P. Emans Grant/research support from: Stryker, Active implants, Carbylan Biosurgery, DSM Biomedical, Regentis, Speakers bureau: Biomet and Push braces, F. de Vries: None declared