James A. Goodbrand

Association between allopurinol use and hip fracture in older patients

BACKGROUND Allopurinol reduces oxidative stress and interacts with purinergic signalling systems important in bone metabolism and muscle function. We assessed whether allopurinol use was associated with a reduced incidence of hip fracture in older people. METHODS Analysis of prospective, routinely-collected health and social care data on patients undergoing health and social work assessment in a single geographical area over a 12year period. Exposure to allopurinol was derived from linked community prescribing data, and hospitalisation for hip fracture and comorbid disease was derived from linked hospitalisation data. Fine and Gray modelling was used to model time to hip fracture accounting for the competing risk of death, incorporating previous use of allopurinol, cumulative exposure to allopurinol as a time dependent variable, and covariate adjustments. RESULTS 17,308 patients were alive at the time of first social work assessment without previous hip fracture; the mean age was 73years. 10,171 (59%) were female, and 1155 (8%) had at least one exposure to allopurinol. 618 (3.6%) sustained a hip fracture, and 4226 (24%) died during a mean follow-up of 7.2years. In fully-adjusted analyses, each year of allopurinol exposure conferred a hazard ratio of 1.01 (95% CI 0.99, 1.02; p=0.37) for hip fracture and 1.00 (0.99, 1.01; p=0.47) for death. Previous use of allopurinol conferred a hazard ratio of 0.76 (0.45, 1.26; p=0.28) for hip fracture and 1.13 (0.99, 1.29; p=0.07) for death. CONCLUSION Greater cumulative use of allopurinol was not associated with a reduced risk of hip fracture or death in this cohort.

Association between bisphosphonate therapy and outcomes from rehabilitation in older people

BACKGROUND Bisphosphonate therapy may have actions beyond bone, including effects on cardiovascular, immune and muscle function. We tested whether bisphosphonate treatment is associated with improved outcomes in older people undergoing inpatient rehabilitation. METHODS Analysis of prospectively collected, linked routine clinical datasets. Participants were divided into never users of bisphosphonates, use prior to rehabilitation only, use after rehabilitation only, and current users (use before and after rehabilitation). We calculated change in 20-point Barthel scores during rehabilitation, adjusting for comorbid disease and laboratory data using multivariable regression analysis. Cox regression analyses were performed to analyse the association between bisphosphonate use and time to death or hospitalisation. RESULTS 2797 patients were included in the analysis. Current bisphosphonate users showed greater improvement in Barthel score during rehabilitation than non-users (5.0 points [95%CI 4.3-5.7] vs 3.8 [95%CI 3.6-3.9]), but no difference compared to those receiving bisphosphonates only after discharge (5.1 [95%CI 4.6-5.5]). Previous bisphosphonate use was significantly associated with time to death (adjusted hazard ratio 1.41 [95%CI 1.15-1.73]) but less strongly with time to combined endpoint of hospitalisation or death (adjusted hazard ratio 1.18 [95%CI 0.98-1.48]). Use after discharge from rehabilitation was associated with reduced risk of death (adjusted hazard ratio 0.64 [95%CI 0.55-0.73]; hazard ratio per year of bisphosphonate prescription 0.98 [95%CI 0.97-0.99]). CONCLUSION Bisphosphonate use is unlikely to be causally associated with improved physical function in older people, but continuing use may be associated with lower risk of death.

Slower Decline in C-Reactive Protein after an Inflammatory Insult Is Associated with Longer Survival in Older Hospitalised Patients.

Background Enhancing biological resilience may offer a novel way to prevent and ameliorate disease in older patients. We investigated whether changes in C-reactive protein (CRP), as a dynamic marker of the acute inflammatory response to diverse stressors, may provide a way to operationalize the concept of resilience in older adults. We tested this hypothesis by examining whether such changes could predict prognosis by identifying which individuals are at greater risk of 6-month mortality. Methods Analysis of prospective, routinely collected datasets containing data on hospitalization, clinical chemistry and rehabilitation outcomes for rehabilitation inpatients between 1999 and 2011. Maximum CRP response during acute illness and CRP recovery indices (time and slope of CRP decay to half maximum, and to <50mg/L if peak values were greater than 50mg/L) was derived from biochemistry data. 6-month survival plots were conducted on quartiles of CRP recovery indices. Cox proportional hazards models were used to test univariate and multivariate predictors of 6-month mortality. Covariates included age, sex, number of medications, serum calcium, haemoglobin level, renal function, and the presence of previous myocardial infarction, stroke, chronic heart failure, COPD and diabetes. Results 3723 patients, mean age 84 years, were included. 1535 (41%) were male and 733 (20%) died during six-month follow-up. The lower an individual’s peak CRP reading, and the longer the time taken for their CRP to fall, the better their 6-month survival. The time for CRP to reach half of its maximum value was the best dynamic CRP index of survival (HR 0.93 per week, 95% CI 0.89 to 0.98; p = 0.004); this remained significant even after adjustment for maximum CRP level and covariates listed above. Conclusion CRP recovery indices are associated with survival in older people; further work is required to explain differences in physiology between patients with a fast and slow CRP recovery.

Association between allopurinol use and hip fracture in older patients discharged from rehabilitation

These abstracts are copied directly from the online submission system and edited for uniformity of format. Authors are invited and given at least a week to notify the sub-editor of amendments. Background Allopurinol reduces oxidative stress and interacts with purinergic signalling systems important in bone metabolism and muscle function. We assessed whether allopurinol use was associated with a reduced incidence of hip fracture in older people who had undergone rehabilitation.