Frank Mehnert

Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study

Objective To assess the association between atrial fibrillation and flutter and use of bisphosphonates for osteoporosis among women. Design Population based case-control study, using medical databases from Denmark. Setting Northern Denmark. Participants 13 586 patients with atrial fibrillation and flutter and 68 054 population controls, all with complete hospital and prescription history. Main outcome measure Adjusted relative risk of atrial fibrillation and flutter. Results 435 cases (3.2%) and 1958 population controls (2.9%) were current users of bisphosphonates for osteoporosis. Etidronate and alendronate were used with almost the same frequency among cases and controls. The adjusted relative risk of current use of bisphosphonates compared with non-use was 0.95 (95% confidence interval 0.84 to 1.07). New users had a relative risk of 0.75 (95% confidence interval 0.49 to 1.16), broadly similar to the estimate for continuing users (relative risk 0.96, 95% confidence interval 0.85 to 1.09). The relative risk estimates were independent of number of prescriptions and the position of the atrial fibrillation and flutter diagnosis in the discharge record, and were similar for inpatients and outpatients. Conclusion No evidence was found that use of bisphosphonates increases the risk of atrial fibrillation and flutter.

Knee arthroplasty in Denmark, Norway and Sweden. A pilot study from the Nordic Arthroplasty Register Association.

Background and purpose The number of national arthroplasty registries is increasing. However, the methods of registration, classification, and analysis often differ. Methods We combined data from 3 Nordic knee arthroplasty registers, comparing demographics, methods, and overall results. Primary arthroplasties during the period 1997–2007 were included. Each register produced a dataset of predefined variables, after which the data were combined and descriptive and survival statistics produced. Results The incidence of knee arthroplasty increased in all 3 countries, but most in Denmark. Norway had the lowest number of procedures per hospital—less than half that of Sweden and Denmark. The preference for implant brands varied and only 3 total brands and 1 unicompartmental brand were common in all 3 countries. Use of patellar button for total knee arthroplasty was popular in Denmark (76%) but not in Norway (11%) or Sweden (14%). Uncemented or hybrid fixation of components was also more frequent in Denmark (22%) than in Norway (14%) and Sweden (2%). After total knee arthroplasty for osteoarthritis, the cumulative revision rate (CRR) was lowest in Sweden, with Denmark and Norway having a relative risk (RR) of 1.4 (95% CI: 1.3–1.6) and 1.6 (CI: 1.4–1.7) times higher. The result was similar when only including brands used in more than 200 cases in all 3 countries (AGC, Duracon, and NexGen). After unicompartmental arthroplasty for osteoarthritis, the CRR for all models was also lowest in Sweden, with Denmark and Norway having RRs of 1.7 (CI: 1.4–2.0) and 1.5 (CI: 1.3–1.8), respectively. When only the Oxford implant was analyzed, however, the CRRs were similar and the RRs were 1.2 (CI: 0.9–1.7) and 1.3 (CI: 1.0–1.7). Interpretation We found considerable differences between the 3 countries, with Sweden having a lower revision rate than Denmark and Norway. Further classification and standardization work is needed to permit more elaborate studies.

Risk factors for venous thromboembolism in patients undergoing total hip replacement and receiving routine thromboprophylaxis.

BACKGROUND Data on the risk factors for venous thromboembolism among patients undergoing total hip replacement and receiving pharmacological thromboprophylaxis are limited. The purpose of this study was to examine potential patient-related risk factors for venous thromboembolism following total hip replacement in a nationwide follow-up study. METHODS Using medical databases, we identified all patients who underwent primary total hip replacement and received pharmacological thromboprophylaxis in Denmark from 1995 to 2006. The outcome measure was hospitalization with venous thromboembolism within ninety days of surgery. We considered age, sex, indication for primary total hip replacement, calendar year of surgery, and comorbidity history as potential risk factors. RESULTS The overall rate of hospitalization for venous thromboembolism within ninety days following a primary total hip replacement was 1.02% (686 hospitalizations after 67,469 procedures) at a median of twenty-two days. The incidence of symptomatic deep venous thrombosis and of nonfatal pulmonary embolism was 0.7% (499 of 67,469) and 0.3% (205 of 67,469), respectively. The incidence of death due to venous thromboembolism or from all causes was 0.05% (thirty-eight patients) and 1.0% (678 patients), respectively. Patients with rheumatoid arthritis had a reduced relative risk for venous thromboembolism compared with patients with primary osteoarthritis (adjusted relative risk = 0.47; 95% confidence interval, 0.25 to 0.90). Patients with a high score on the Charlson comorbidity index had an increased relative risk for venous thromboembolism compared with patients with a low score (adjusted relative risk = 1.45; 95% confidence interval, 1.02 to 2.05). Patients with a history of cardiovascular disease (relative risk = 1.40; 95% confidence interval, 1.15 to 1.70) or prior venous thromboembolism (relative risk = 8.09; 95% confidence interval, 6.07 to 10.77) had an increased risk for venous thromboembolism compared with patients without that history. CONCLUSIONS The cumulative incidence of a venous thromboembolism within ninety days of surgery among patients with total hip replacement receiving pharmacological thromboprophylaxis was 1%. This information on the associated risk factors could be used to better anticipate the risk of venous thromboembolism for an individual patient.

Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study

Objectives To examine the risk of atrial fibrillation or flutter associated with use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclo-oxygenase (COX) 2 inhibitors. Design Population based case-control study using data from medical databases. Setting Northern Denmark (population 1.7 million). Participants 32 602 patients with a first inpatient or outpatient hospital diagnosis of atrial fibrillation or flutter between 1999 and 2008; 325 918 age matched and sex matched controls based on risk-set sampling. Main outcome measures Exposure to NSAID use at the time of admission (current use) or before (recent use). Current use was further classified as new use (first ever prescription redemption within 60 days before diagnosis date) or long term use. We used conditional logistic regression to compute odds ratios as unbiased estimates of the incidence rate ratios. Results 2925 cases (9%) and 21 871 controls (7%) were current users of either non-selective NSAIDs or COX 2 inhibitors. Compared with no use, the incidence rate ratio associating current drug use with atrial fibrillation or flutter was 1.33 (95% confidence interval 1.26 to 1.41) for non-selective NSAIDs and 1.50 (1.42 to 1.59) for COX 2 inhibitors. Adjustments for age, sex, and risk factors for atrial fibrillation or flutter reduced the incidence rate ratio to 1.17 (1.10 to 1.24) for non-selective NSAIDs and 1.27 (1.20 to 1.34) for COX 2 inhibitors. Among new users, the adjusted incidence rate ratio was 1.46 (1.33 to 1.62) for non-selective NSAIDs and 1.71 (1.56 to 1.88) for COX 2 inhibitors. Results for individual NSAIDs were similar. Conclusions Use of non-aspirin NSAIDs was associated with an increased risk of atrial fibrillation or flutter. Compared with non-users, the association was strongest for new users, with a 40-70% increase in relative risk (lowest for non-selective NSAIDs and highest for COX 2 inhibitors). Our study thus adds evidence that atrial fibrillation or flutter needs to be added to the cardiovascular risks to be considered when prescribing NSAIDs.

Allogeneic blood transfusion and prognosis following total hip replacement: a population-based follow up study

BackgroundAllogeneic red blood cell transfusion is frequently used in total hip replacement surgery (THR). However, data on the prognosis of transfused patients are sparse. In this study we compared the risk of complications following THR in transfused and non-transfused patients.MethodsA population-based follow-up study was performed using data from medical databases in Denmark. We identified 28,087 primary THR procedures performed from 1999 to 2007, from which we computed a propensity score for red blood cell transfusion based on detailed data on patient-, procedure-, and hospital-related characteristics. We were able to match 2,254 transfused with 2,254 non-transfused THR patients using the propensity score.ResultsOf the 28,087 THR patients, 9,063 (32.3%) received at least one red blood cell transfusion within 8 days of surgery. Transfused patients had higher 90-day mortality compared with matched non-transfused patients: the adjusted OR was 2.2 (95% confidence interval (CI): 1.2-3.8). Blood transfusion was also associated with increased odds of pneumonia (OR 2.1; CI: 1.2-3.8), whereas the associations with cardiovascular or cerebrovascular events (OR 1.4; CI: 0.9-2.2) and venous thromboembolism (OR 1.2; CI: 0.7-2.1) did not reach statistical significance. The adjusted OR of reoperation due to infection was 0.6 (CI: 0.1-2.9).ConclusionsRed blood cell transfusion was associated with an adverse prognosis following primary THR, in particular with increased odds of death and pneumonia. Although the odds estimates may partly reflect unmeasured bias due to blood loss, they indicate the need for careful assessment of the risk versus benefit of transfusion even in relation to routine THR procedures.

Statistical analysis of arthroplasty data II. Guidelines

It is envisaged that guidelines for statistical analysis and presentation of results will improve the quality and value of research. The Nordic Arthroplasty Register Association (NARA) has therefore developed guidelines for the statistical analysis of arthroplasty register data. The guidelines are divided into two parts, one with an introduction and a discussion of the background to the guidelines (, see pages x-y in this issue), and this one with a more technical statistical discussion on how specific problems can be handled. This second part contains (1) recommendations for the interpretation of methods used to calculate survival, (2) recommendations on howto deal with bilateral observations, and (3) a discussion of problems and pitfalls associated with analysis of factors that influence survival or comparisons between outcomes extracted from different hospitals.

Nonsteroidal anti‐inflammatory drugs and the risk of skin cancer

Nonsteroidal anti‐inflammatory drugs (NSAIDs) may prevent the development of cancer by inhibiting cyclooxygenase (COX) enzymes, which are involved in carcinogenesis. Therefore, the authors of this report examined the association between NSAID use and the risk of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM).

Glucocorticoid use and risk of atrial fibrillation or flutter: a population-based, case-control study.

BACKGROUND Glucocorticoid use is associated with increased risk of myocardial infarction, stroke, and heart failure, but data are limited on the risk of atrial fibrillation or flutter. We examined whether glucocorticoid use is associated with the risk of atrial fibrillation or flutter. METHODS For this population-based, case-control study, we identified all patients with a first hospital diagnosis of atrial fibrillation or flutter from January 1, 1999, through December 31, 2005, in Northern Denmark (population, 1.7 million). For each case we selected 10 population controls matched by age and sex. We obtained data on glucocorticoid prescriptions within 60 days (current users) or longer before the index date (former users), comorbidity, and medications from medical databases. We used conditional logistic regression to compute odds ratios (ORs), controlling for potential confounders. RESULTS Among 20,221 patients with atrial fibrillation or flutter, 1288 (6.4%) were current glucocorticoid users and 2375 (11.7%) were former users. Among 202,130 population controls, 5245 (2.6%) were current glucocorticoid users and 19 940 (9.9%) were former users. Current glucocorticoid use was associated with an increased risk of atrial fibrillation or flutter compared with never use (adjusted OR, 1.92; 95% confidence interval [CI], 1.79-2.06). Among new glucocorticoid users, the adjusted OR was 3.62 (95% CI, 3.11-4.22) and among long-term users it was 1.66 (95% CI, 1.53-1.80). The increased risk remained robust in patients with and without pulmonary and cardiovascular diseases. Former glucocorticoid use was not associated with increased risk (adjusted OR, 1.00; 95% CI, 0.96-1.06). CONCLUSION Current glucocorticoid use was associated with an almost 2-fold increased risk of atrial fibrillation or flutter.

Risk of revision of a total hip replacement in patients with diabetes mellitus: A POPULATION-BASED FOLLOW UP STUDY

We have evaluated the extent to which diabetes affects the revision rate following total hip replacement (THR). Through the Danish Hip Arthroplasty Registry we identified all patients undergoing a primary THR (n = 57 575) between 1 January 1996 and 31 December 2005, of whom 3278 had diabetes. The presence of diabetes among these patients was identified through the Danish National Registry of Patients and the Danish National Drug Prescription Database. We estimated the relative risk for revision and the 95% confidence intervals for patients with diabetes compared to those without, adjusting for the confounding factors. Diabetes is associated with an increased risk of revision due to deep infection (relative risk = 1.45 (95% confidence interval 1.00 to 2.09), particularly in those with type 2 diabetes (relative risk = 1.49 (95% confidence interval 1.02 to 2.18)), those with diabetes for less than five years prior to THR (relative risk = 1.69 (95% confidence interval 1.24 to 2.32)), those with complications due to diabetes (relative risk = 2.11 (95% confidence interval 1.41 to 3.17)), and those with cardiovascular comorbidities prior to surgery (relative risk = 2.35 (95% confidence interval 1.39 to 3.98)). Patients and surgeons should be aware of the relatively elevated risk of revision due to deep infection following THR in diabetes particularly in those with insufficient control of their glucose level.

Registration of acute stroke: validity in the Danish Stroke Registry and the Danish National Registry of Patients.

Background The validity of the registration of patients in stroke-specific registries has seldom been investigated, nor compared with administrative hospital discharge registries. The objective of this study was to examine the validity of the registration of patients in a stroke-specific registry (The Danish Stroke Registry [DSR]) and a hospital discharge registry (The Danish National Patient Registry [DNRP]). Methods Assuming that all patients with stroke were registered in either the DSR, DNRP or both, we first identified a sample of 75 patients registered with stroke in 2009; 25 patients in the DSR, 25 patients in the DNRP, and 25 patients registered in both data sources. Using the medical record as a gold standard, we then estimated the sensitivity and positive predictive value of a stroke diagnosis in the DSR and the DNRP. Secondly, we reviewed 160 medical records for all potential stroke patients discharged from four major neurologic wards within a 7-day period in 2010, and estimated the sensitivity, specificity, positive predictive value, and negative predictive value of the DSR and the DNRP. Results Using the first approach, we found a sensitivity of 97% (worst/best case scenario 92%–99%) in the DSR and 79% (worst/best case scenario 73%–84%) in the DNRP. The positive predictive value was 90% (worst/best case scenario 72%–98%) in the DSR and 79% (worst/best case scenario 62%–88%) in the DNRP. Using the second approach, we found a sensitivity of 91% (95% confidence interval [CI] 81%–96%) and 58% (95% CI 46%–69%) in the DSR and DNRP, respectively. The negative predictive value was 91% (95% CI 83%–96%) in the DSR and 72% (95% CI 62%–80%) in the DNRP. The specificity and positive predictive value did not differ among the registries. Conclusion Our data suggest a higher sensitivity in the DSR than the DNRP for acute stroke diagnoses, whereas the positive predictive value was comparable in the two data sources.