1. www.aodhealth.org1 Journal Club Alcohol, Other Drugs, and Health: Current Evidence March–April 2010

2. www.aodhealth.org2 Featured Article Opioid Prescriptions for Chronic Pain and Overdose Dunn KM, et al. Ann Intern Med. 2010;152(2):85–92.

3. www.aodhealth.org3 Study Objective To estimate rates of overdose and their association with an average prescribed daily opioid dose among patients receiving long- term opioid therapy.

4. www.aodhealth.org4 Study Design Prospective cohort study estimating overdose risk as a function of average daily opioid dose received at the time of overdose. Participants included 9940 HMO patients who received 3 or more opioid prescriptions within a 90-day period for chronic noncancer pain between 1997 and 2005.

5. www.aodhealth.org5 Study Design (cont’d) Average daily opioid dose estimates (expressed as morphine equivalents) over the 90-day period were extracted from pharmacy data. Primary outcomes were nonfatal and fatal overdoses, identified through diagnostic codes from inpatient and outpatient care and death certificates, and confirmed by medical record review.

6. www.aodhealth.org6 Assessing Validity of an Article About Harm Are the results valid? What are the results? How can I apply the results to patient care?

7. www.aodhealth.org7 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?

8. www.aodhealth.org8 Did the investigators demonstrate similarity in all known determinants of outcomes? Did they adjust for differences in the analysis? Yes. Analyses were adjusted using multivariable Cox proportional hazards models. –Opioid dose was included as a time-varying covariable; i.e., the dose for a person who overdosed (evaluated at the time of the event), was compared with the dose for all other persons at risk for overdose at the same number of days since entering the study. –Analyses were further adjusted for age, sex, smoking, depression diagnosis, substance-abuse diagnosis, index-pain diagnosis, and chronic-disease comorbidity.

9. www.aodhealth.org9 Were exposed patients equally likely to be identified in the groups?  Yes. –Using 90-day exposure windows, participants were classified as either exposed to opioids (at any of 4 dosage levels) or unexposed on any given day on the basis of their average daily opioid dose during the previous 90 days.

10. www.aodhealth.org10 Were the outcomes measured in the same way in the groups being compared?  Yes. –Surveillance for overdose was conducted uniformly among cases and controls using electronic medical record review and a statewide mortality registry.

11. www.aodhealth.org11 Was follow-up sufficiently complete? No. –Of the total cohort, 61% had complete follow-up (from entry into the cohort until the end of the study period or until an overdose event occurred). –Thirty-two percent left the HMO during the study. –Seven percent died.

12. www.aodhealth.org12 What are the Results? How strong is the association between exposure and outcomes? How precise is the estimate of the risk?

13. www.aodhealth.org13 How strong is the association between exposure and outcome? How precise is the estimate of the risk? Compared with patients receiving 1–20 mg/day of opioids (0.2% annual overdose rate), patients receiving 50–99 mg/day had a 3.7-fold increase in overdose risk (95% CI, 1.5–9.5) and a 0.7% annual overdose rate. Patients receiving ≥100 mg/day had an 8.9-fold increase in overdose risk (95% CI, 4.0–19.7) and a 1.8% annual overdose rate.

14. www.aodhealth.org14 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?

15. www.aodhealth.org15 Were the study patients similar to the patients in my practice? Participants were participants in a statewide HMO based in Seattle, WA. The mean age of the cohort was 54 years, and 60% were women. Two-thirds of the cohort had a diagnosis of back or extremity pain. Patients with cancer or extreme dietary intake (>2 interquartile ranges above the 75th or below the 25th percentile of Box-Cox log-transformed energy intake) were excluded.

16. www.aodhealth.org16 Was the duration of follow-up adequate? Yes. –Participants were followed for a mean of 42 months (range, <1–119 months) from their initial 90-day exposure window.

17. www.aodhealth.org17 What was the magnitude of the risk? The magnitude of the risk increased from 3.7 to 8.9 for those receiving 50 – 99 mg per day and ≥100 mg per day, respectively, compared with patients receiving 1 – 20 mg per day of opioids.

18. www.aodhealth.org18 Should I attempt to stop the exposure? The decision to stop the exposure depends upon an individualized risk-benefit decision between the provider and the patient. Providers should be aware of the risk and discuss this with patients.