Journal Club Alcohol and Health: Current Evidence March-April 2007

Featured Article Alcohol consumption as a trigger of recurrent gout attacks. Zhang Y, et al. Am J Med. 2006;119(9):800.e13–800.e18.

Study Objective To examine whether… –alcohol use may trigger recurrent gout attacks

Study Design Web-based case-crossover study –A case-crossover study is a method to assess transient effects of exposures on the risk of acute events. It addresses whether an event was triggered by something that happened just before the event. –To estimate relative risk, the exposure frequency just before the event occurred is compared with exposure frequencies during one or more control times (each case serves as its own control). –This design, therefore, controls for confounding by permanent subject characteristics and also between the trigger's acute and chronic effects. Maclure M, et al. Annu Rev Pub Health. 2000;21:193–221.

Study Design (cont.) All subjects had a gout attack in the past year and were recruited online. Medical records were reviewed to confirm the diagnosis. Online surveys assessed subjects’ alcohol use and other risk factors for gout attacks during … a hazard period (2 days before an attack) and 4 attack-free control periods (study entry and then 3, 6, and 9 months later)

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

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?

Did the investigators demonstrate similarity in all known determinants of outcomes? Did they adjust for differences in the analysis? The case-crossover design is similar to a case-control study. –But, the case-crossover design does not have 2 groups of people because cases serve as their own controls. –Therefore, demonstrating similarity in static determinants of outcomes is unnecessary given that cases and controls are the same. Researchers did not report the similarity of characteristics (diuretic use and total purine intake) in the hazard and control periods (the relevant timeframes) but did adjust for them in analyses.

Were exposed patients equally likely to be identified in the two groups?  The case-crossover design eliminates this concern, which applies to a classic case-control study.  All subjects had an attack; some attacks occurred with prior alcohol exposure, others did not.  All subjects contributed data from both hazard and control time periods. Therefore, exposed and unexposed periods are equally identified.

Were the outcomes measured in the same way in the groups being compared? Cases and controls are the same so the outcomes could not be measured differently. Hazard and control time periods are compared. Risk factors were measured in the same way during both of these periods.

Was follow-up sufficiently complete? The report does not state how many people completed all assessments. However, 197 subjects provided data on hazard and control periods; some provided more than others.

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

What are the Results? 197 subjects enrolled and completed both hazard and control period questionnaires. –91% met American College of Rheumatology criteria for gout. –95% of 172 medical records reviewed confirmed the diagnosis. Over 1 year of follow-up, 321 gout attacks occurred. 53 subjects consumed no alcohol.

How strong is the association between exposure and outcome? *Adjusted for diuretic use and purine intake Time Before Attack Sample Odds Ratios* Comparing Drinking Vs. Not Drinking P for trend 24 hours before1.4 (95% CI, 0.6–2.4) for 1–2 drinks 3.1 (95% CI, 1.0–11.0) for >7 drinks < hours before1.1 (95% CI, 0.7–2.0) for 1–2 drinks 2.5 (95% CI, 1.1–5.9) for >7 drinks <0.005

How strong is the association between exposure and outcome? (cont.) Risk did not increase with drinking in the hours before an attack… –although the odds ratio was 7.3 [95% CI, 1.8–29.2] for >7 drinks. In analyses also adjusted for total alcohol consumption, the risk of an attack was not associated with any specific alcoholic beverage.

How precise is the estimate of the risk? Confidence intervals for the odds ratio risk estimates for all drinking levels within the 48 hours of an attack included 1… –except for >7 drinks within the last 25–48 hours: OR 7.3, 95% CI, 1.8–29.2. At this and other drinking levels, the intervals are wide. So, estimates for each level are not precise. However, the trend was statistically significant.

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?

Were the study patients similar to the patients in my practice? The subjects were recruited online with paid advertisements linking to a search term “gout.” –How this might affect selection is not known. 91% fulfilled criteria of gout. Most were middle-aged white males with more than a high school education. Drinking patterns over time (e.g., heavy occasional, heavy constant, always moderate) were not reported.

Was the duration of follow-up adequate? Follow-up duration was one year. –However, follow-up is not very relevant to the question at hand. There were many hazard and control time periods for comparison. The time periods of clinical interest were short but adequate to answer the question about recent alcohol exposure as a risk factor.

What was the magnitude of the risk? The magnitude of the absolute risk cannot be calculated. But the odds ratio provides an estimate: 2–3 fold odds of an attack after drinking >5 drinks. –The trend towards increased risk with recent drinking (within 24 hours of the attack), however, began with any drinking. The attributable and absolute risks would depend on the number of attacks an individual had and the prevalence of drinking in people with gout (73% 1- year prevalence of any drinking in this sample).

Should I attempt to stop the exposure? You should probably attempt to stop the exposure if the goal is to reduce the likelihood of a gout attack. Physician advice can lead to decreased drinking. –And decreased drinking would likely be associated with fewer gout attacks, according to this study and prior assumptions.