Clinical Appraisal of an Article on Prognosis

1. Clinical Appraisal of an Article on Prognosis

2. The Clinical Question What is the risk of mortality among patients with hyperuricemia who received allupurinol? • PUBMED Search/Mesh Terms: • Allopurinol • Hyperuricemia • Mortality • Survival • Advanced Search: • Humans • Males • English

3. Pubmed Search Limit by topics, language and Journal groups Results: • Human, Male, English, Aged 65 +

4. CAT MAKER Death

5. Critical Appraisal Allopurinol and mortality in hyperuricaemic patients Andrew J. Luk1, Gregory P. Levin2, Elya E. Moore3, Xiao-Hua Zhou1, Bryan R. Kestenbaum4 and Hyon K. Choi

6. RELEVANCE Is the objective of the article on prognosis similar to your clinical dilemma? Yes. The study aims to: • Investigate the role of urate-lowering therapy on the risk of premature death associated with gout and hyperuricemia. • Impact of allopurinol, on the risk of mortality in hyperuricaemic patients.

7. Validity Guidelines • Cohort of hyperuricaemic subjects • treated with allopurinol (allopurinol use between 1 January 2000 and 31 December 200 • outpatient serum urate level >416 _mol/l (7.0 mg/dl) within 1 year prior to allopurinol initiation. • Control subjects • being alive at-risk at the time the allopurinol-treated subject initiated allopurinol • Hyperuricaemia during the previous year. Was there a representative sample of patients without the outcome at the start of observation? Yes. VA Consumer Health Information and Performance Sets (CHIPS) database was used: • Consists of veterans ≥40 years of age within the Northwest Veterans Integrated Service Network. • Hyperuricaemic population (outpatient serum urate level >416 μmol/l (7.0 mg/dl) between the years 2000 and 2007) • ExclutionCritreria: estimated glomerular filtration rate (GFR) of <30 ml/min prior dialysis or renal/organ transplantation, or history of malignancy.

8. Validity Guidelines Where the criteria for determining the prognostic factor and outcome explicit and credible? • Yes. The role of Allopurinol on the risk of premature death associated with gout and hyperuricemia was determined. • Cox proportional hazards models, with robust standard errors, were used to estimate the independent association between allopurinol exposure and the risk of death Was follow-up siufficiently long and complete? • Yes, both allopurinol and control subjects began accruing risk time beginning with the time of incident allopurinol use in the allopurinol group and index time in the control group, and were followed until death, study closure, or no further contact with the VA for 18 consecutive months

9. Yes.Multivariate models to adjust: Validity Guidelines Was there adjustment for other prognostic factors? • Charlson index (diagnosis of • MI • (CHF) • peripheral vascular disease • cerebrovascular disease • Dementia • COPD • PUD • Liver disease • DM with complications • Renal disease • Cancer • AIDS/HIV • Demographics (age, race, gender) • BMI • Co-morbidities(HPN,DM,CVD) • Healthcare utilization • CV Medications taken (ACEI, ARB, statins, aspirin, etc) • baseline serum levels of urate • Cholecterol levels • Albumin • Baseline GFR

10. Overall, is the study valid? Since all the validity questions were fulfilled, the study can be considered to be valid.

11. Results How large is the likelihood of outcome to occur in those with the prognostic factor in a specified period of time? Was it statistically significant? • Hazard ratio was used to estimate the relative risk. • After adjusting for baseline urate levels, allopurinol treatment was associated with a lower risk of all-cause mortality [hazard ratio (HR) 0.78; 95% CI 0.67, 0.91)] All these factors are statistical significant at p <0.05

12. Will the Results Help Me in Caring for my patients? Were the study patients similar to my own ? Yes. • 50 year old obese male • diagnosed with gout and azotemia • mostly male (98%) mean age of 62.7 years • hyperuriceamic patients. • Excluded patients with a GFR of <30ml/min, this does not necessarily mean that our patient should be excluded, this very low GFR indicates that they excluded those who already have stage 3 Chronic kidney disease or higher, not patients with azotemia.

13. Will the Results Help in Caring for my Patient? Are results useful for reassuring or counseling patients? • -YES The use of allopurinol will definitely benefit our patient. It is useful not only with lowering the serum uric acid level, but also it shows survival benefit with its use.

14. RESOLUTION OF THE PROBLEM IN THE SCENARIO • Based on the results in the study, I would encourage my patients to undergo allopurinol treatment because it may prolong the life of the patients with gout and hyperuricemia.