1. 1 Journal Club Alcohol, Other Drugs, and Health: Current Evidence July–August 2011

2. 2 Featured Article Association between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths Bohnert AS, et al. JAMA. 2011;305(13):1315-21.

3. 3 Study Objective To examine the association between prescribed daily opioid dose and dosing schedule and risk of opioid overdose death among patients with cancer, chronic pain, acute pain, or substance use disorders.

4. 4 Study Design Case cohort study comparing Department of Veterans Affairs (VA) prescription and diagnosis data in a random sample of patients who received opioids for pain in 2004 or 2005 (N=155,434). Seven hundred fifty patients in the sample had died from unintentional prescription opioid overdose by 2008.

5. 5 Assessing Validity of an Article About Harm Are the results valid? What are the results? How can I apply the results to patient care?

6. 6 Are the Results Valid? Did the investigators demonstrate similarity in all known determinants of outcomes? Did they adjust for differences in the analysis? Were exposed patients equally likely to be identified in the two groups? Were the outcomes measured in the same way in the groups being compared? Was follow-up sufficiently complete?

7. 7 Did the investigators demonstrate similarity in all known determinants of outcomes? Did they adjust for differences in the analysis? Cox proportional hazards models were used to examine the relationship of opioid dose (expressed as milligrams of morphine equivalents per day) and risk of opioid overdose death adjusting for age group, sex, race, ethnicity, and comorbid conditions. Multivariable modeling was restricted to periods when individuals were prescribed at least 1 opioid.

8. 8 Were exposed patients equally likely to be identified in the groups?  Yes.  For each patient, observation time began on the date of the first opioid fill that occurred after the first medical visit.  Prescription medication data came from the VA Pharmacy Benefits Management Services.

9. 9 Were the outcomes measured in the same way in the groups being compared?  Opioid overdose death was determined using National Death Index files and defined using underlying-cause-of-death codes from the International Statistical Classification of Diseases (10 th Rev.) −Included all opioid-related deaths that were ruled unintentional or indeterminant. −Deaths coded as intentional ovedoses were not included.

10. 10 Was follow-up sufficiently complete? Yes. –Death certificates and cause-of-death codes were obtained for >99% of known deaths in the sample.

11. 11 What are the Results? How strong is the association between exposure and outcomes? How precise is the estimate of the risk?

12. How strong is the association between exposure and outcome? How precise is the estimate of the risk? Adjusted hazard ratios (HRs) associated with a prescribed dose of ≥100 mg/d, compared with the dose category 1–<20 mg/d, were as follows: –4.54 among patients with substance use disorders (95% confidence interval [CI], 2.46–8.37; absolute risk difference approximation [ARDA]=0.14%). –7.18 among those with chronic pain (95% CI, 4.85– 10.65; ARDA=0.25%) –6.64 among those with acute pain (95% CI, 3.31– 13.31; ARDA=0.23%). –11.99 among those with cancer (95%CI, 4.42–32.56; ARDA=0.45%).

13. 13 How Can I Apply the Results to Patient Care? Were the study patients similar to the patients in my practice? Was the duration of follow-up adequate? What was the magnitude of the risk? Should I attempt to stop the exposure?

14. 14 Were the study patients similar to the patients in my practice? The sample was comprised of VA patients from across the US. More than 93% were men; the majority were white and over age 40.

15. 15 Was the duration of follow-up adequate? Observation time began in 2004 and ended on the day of death or the end of 2008 (whichever came first).

16. 16 What was the magnitude of the risk? The frequency of unintentional fatal overdose over the study period among individuals treated with opioids was 0.04%.

17. 17 Should I attempt to stop the exposure? This study adds to others that demonstrate increasing morbidity and mortality with increasing doses of opioids after adjusting for confounders. Prescribers should appreciate that doses of opioids >100 mg morphine equivalents per day appear to be associated with increased mortality.