C. Klop

Timing of Acute Myocardial Infarction in Patients Undergoing Total Hip or Knee Replacement A Nationwide Cohort Study

BACKGROUND Limited evidence suggests that the risk of acute myocardial infarction (AMI) may be increased shortly after total hip replacement (THR) and total knee replacement (TKR) surgery. However, risk of AMI in these patients has not been compared against matched controls who have not undergone surgery. The objective of this study was to evaluate the timing of AMI in patients undergoing THR or TKR surgery compared with matched controls. METHODS Retrospective, nationwide cohort study within the Danish national registries. All patients who underwent a primary THR or TKR (n = 95,227) surgery from January 1, 1998, through December 31, 2007, were selected and matched to 3 controls (no THR or TKR) by age, sex, and geographic region. All study participants were followed up for AMI, and disease- and medication history-adjusted hazard ratios (HRs) were calculated. RESULTS During the first 2 postoperative weeks, the risk of AMI was substantially increased in THR patients compared with controls (adjusted HR, 25.5; 95% CI, 17.1-37.9). The risk remained elevated for 2 to 6 weeks after surgery (adjusted HR, 5.05; 95% CI, 3.58-7.13) and then decreased to baseline levels. For TKR patients, AMI risk was also increased during the first 2 weeks (adjusted HR, 30.9; 95% CI, 11.1-85.5) but did not differ from controls after the first 2 weeks. The absolute 6-week risk of AMI was 0.51% in THR patients and 0.21% in TKR patients. CONCLUSIONS Risk of AMI is substantially increased in the first 2 weeks after THR (25-fold) and TKR (31-fold) surgery compared with controls. Risk assessment of AMI should be considered during the first 6 weeks after THR surgery and during the first 2 weeks after TKR surgery.

MORTALITY IN BRITISH HIP FRACTURE PATIENTS, 2000-2010: A POPULATION-BASED RETROSPECTIVE COHORT STUDY

BACKGROUND Data on recent trends in mortality after hip fracture are scarce. Aims were therefore to examine secular trends in all-cause and cause-specific mortality post hip fracture and to compare this to the general population from 2000 to 2010. METHODS Population-based cohort study within the United Kingdom Clinical Practice Research Datalink and linked to cause of death data for 57.7% of patients. Patients with a first hip fracture (n=31,495) were matched to up to four controls by age, sex, index date, and practice. All subjects were followed for death, and lifestyle, disease and medication history adjusted hazard ratios (HRs) were calculated. RESULTS One-year all-cause mortality after hip fracture declined from 2009 and was 14% lower after, compared with before 2009 (22.3% to 20.5%, adj. HR 0.86, 95% CI: 0.81-0.92). The decline was observed for males (≥75years) and females (≥85years). Significant contributors to the decline in mortality post hip fracture were respiratory infections in females as were malignant diseases in males. However, one-year all-cause mortality remained unaltered over the decade when compared to controls with a 3.5-fold and 2.4-fold increased risk in males and females respectively. No significant changes were observed in the relative risks for one-year cause-specific mortality for both genders. CONCLUSIONS One-year mortality after hip fracture has declined over the last decade in the UK. However, the difference in one-year mortality between hip fracture patients and the general population remained unaltered. These observations highlight the need for the continued implementation of evidence-based standards for good hip fracture care.

The Epidemiology of Hip and Major Osteoporotic Fractures in a Dutch Population of Community-Dwelling Elderly: Implications for the Dutch FRAX® Algorithm

Background Incidence rates of non-hip major osteoporotic fractures (MOF) remain poorly characterized in the Netherlands. The Dutch FRAX® algorithm, which predicts 10-year probabilities of hip fracture and MOF (first of hip, humerus, forearm, clinical vertebral), therefore incorporates imputed MOF rates. Swedish incidence rate ratios for hip fracture to MOF (Malmo 1987–1996) were used to perform this imputation. However, equality of these ratios between countries is uncertain and recent evidence is scarce. Aims were to estimate incidence rates of hip fracture and MOF and to compare observed MOF rates to those predicted by the imputation method for the Netherlands. Methods Using hospitalisation and general practitioner records from the Dutch PHARMO Database Network (2002–2011) we calculated age-and-sex-specific and age-standardized incidence rates (IRs) of hip and other MOFs (humerus, forearm, clinical vertebral) and as used in FRAX®. Observed MOF rates were compared to those predicted among community-dwelling individuals ≥50 years by the standardized incidence ratio (SIR; 95% CI). Results Age-standardized IRs (per 10,000 person-years) of MOF among men and women ≥50 years were 25.9 and 77.0, respectively. These numbers were 9.3 and 24.0 for hip fracture. Among women 55–84 years, observed MOF rates were significantly higher than predicted (SIR ranged between 1.12–1.50, depending on age). In men, the imputation method performed reasonable. Conclusion Observed MOF incidence was higher than predicted for community-dwelling women over a wide age-range, while it agreed reasonable for men. As miscalibration may influence treatment decisions, there is a need for confirmation of results in another data source. Until then, the Dutch FRAX® output should be interpreted with caution.

Predicting the 10-year risk of hip and major osteoporotic fracture in rheumatoid arthritis and in the general population: an independent validation and update of UK FRAX without bone mineral density.

Objectives FRAX incorporates rheumatoid arthritis (RA) as a dichotomous predictor for predicting the 10-year risk of hip and major osteoporotic fracture (MOF). However, fracture risk may deviate with disease severity, duration or treatment. Aims were to validate, and if needed to update, UK FRAX for patients with RA and to compare predictive performance with the general population (GP). Methods Cohort study within UK Clinical Practice Research Datalink (CPRD) (RA: n=11 582, GP: n=38 755), also linked to hospital admissions for hip fracture (CPRD-Hospital Episode Statistics, HES) (RA: n=7221, GP: n=24 227). Predictive performance of UK FRAX without bone mineral density was assessed by discrimination and calibration. Updating methods included recalibration and extension. Differences in predictive performance were assessed by the C-statistic and Net Reclassification Improvement (NRI) using the UK National Osteoporosis Guideline Group intervention thresholds. Results UK FRAX significantly overestimated fracture risk in patients with RA, both for MOF (mean predicted vs observed 10-year risk: 13.3% vs 8.4%) and hip fracture (CPRD: 5.5% vs 3.1%, CPRD-HES: 5.5% vs 4.1%). Calibration was good for hip fracture in the GP (CPRD-HES: 2.7% vs 2.4%). Discrimination was good for hip fracture (RA: 0.78, GP: 0.83) and moderate for MOF (RA: 0.69, GP: 0.71). Extension of the recalibrated UK FRAX using CPRD-HES with duration of RA disease, glucocorticoids (>7.5 mg/day) and secondary osteoporosis did not improve the NRI (0.01, 95% CI −0.04 to 0.05) or C-statistic (0.78). Conclusions UK FRAX overestimated fracture risk in RA, but performed well for hip fracture in the GP after linkage to hospitalisations. Extension of the recalibrated UK FRAX did not improve predictive performance.

Individuals With Type 2 Diabetes Mellitus Are at an Increased Risk of Gout But This Is Not Due to Diabetes: A Population-Based Cohort Study.

AbstractThe relationship between type 2 diabetes and gout is complex. The objective of this study was to understand the role of diabetes itself and its comorbidities within the association between type 2 diabetes and gout.We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) GOLD. Persons with type 2 diabetes were identified as persons on a noninsulin antidiabetic drug (NIAD) between 2004 and 2012, and were matched to 1 control based on age, sex, and general practice. We estimated gout risk in NIAD users using Cox regression analysis. All analyses were stratified for sex.In total, 221,117 NIAD users were identified. NIAD users had an increased risk of gout (hazard ratio (HR) 1.48; 95% CI 1.41–1.54). This association was stronger in women (HR 2.23; 95% CI 2.07–2.41) compared with men (HR 1.19; 95% CI 1.13–1.26). After adjustments for BMI, eGFR, hypertension, renal transplantation, diuretics, statins, low-dose aspirin, ciclosporin, and tacrolimus, the risk disappeared in women (HR 1.01; 95% CI 0.92–1.11) and reversed in men (HR 0.61; 95% CI 0.58–0.66) (P for interaction <0.001). When stratifying gout risk according to HbA1c in male and female NIAD users, we found an inverse association between raising HbA1c and incident gout in men only. Further adjustment gave similar results.Individuals with type 2 diabetes are at increased risk of gout. This is not due to diabetes itself, but to the comorbid conditions. Diabetes itself is apparently associated with a decreased risk of gout, especially in men.