The effect of selective serotonin re-uptake inhibitors on the risk of myocardial infarction in a cohort of patients with depression.

AIM: To evaluate whether selective serotonin re-uptake inhibitor (SSRI) exposure influences the risk of myocardial infarction (MI) in patients with depression. METHODS: This study included 693 patients with MI (cases) and 2772 controls. Conditional logistic regression was used to calculate the odds ratio (OR). RESULTS: SSRI exposure may be associated with a reduced MI risk (OR = 0.77, 95% CI 0.57, 1.03). However, reduced risk was only observed with longer term use (OR = 0.73, 95% CI 0.53, 1.00) and not with shorter term use (OR = 1.15, 95% CI: 0.65, 2.05). CONCLUSIONS: Only longer term use of SSRIs was associated with reduced MI risk, suggesting that other mechanisms, besides an acute anti-platelet effect, may reduce MI risk.

Is there cross-reactivity between penicillins and cephalosporins?

BACKGROUND: We sought to determine the risk of an allergic reaction to a cephalosporin exposure in those with prior penicillin reactions. METHODS: We conducted a retrospective cohort study using the United Kingdom General Practice Research Database. We selected all patients receiving a prescription for penicillin followed by a prescription for a cephalosporin and identified allergic-like events within 30 days after each prescription. Allergic events were defined by 2 sets of codes: 1 more restrictive, 1 more inclusive. Comparison was made with a population of patients receiving a prescription for a penicillin followed by a prescription for a sulfonamide antibiotic. RESULTS: A total of 3,375,162 patients received a penicillin; 506,679 (15%) received a subsequent cephalosporin. Among patients receiving a penicillin followed by a cephalosporin, the unadjusted risk ratio of an allergic-like event for those who had a prior event, compared with those who had no such prior event, narrowly defined, was 10.1 (confidence interval 7.4-13.8). The absolute risk of anaphylaxis after a cephalosporin was less than 0.001%. The unadjusted risk ratio for sulfonamide antibiotic, rather than cephalosporin after penicillin allergic-like events was 7.2 (confidence interval 3.8-13.5). CONCLUSION: Patients with allergic-like events after penicillin had a markedly increased risk of events after either subsequent cephalosporins or sulfonamide antibiotics. Cross-reactivity is not an adequate explanation for this increased risk, and the risk of anaphylaxis is very low. Thus, our data indicate that cephalosporins can be considered for patients with penicillin allergy.

Represcription of penicillin after allergic-like events.

OBJECTIVE: We sought to determine the frequency of represcription of penicillin to individuals with penicillin allergy and the risk of a second reaction in those who had a previous reaction. METHODS: A retrospective cohort study was conducted within the UK General Practice Research Database. All patients who had received a prescription for penicillin were identified. Within that source population, records of patients who had received at least 2 prescriptions for penicillin at least 60 days apart were selected and examined for allergic-like (hypersensitivity) events on the day of or within 30 days after a prescription. RESULTS: At least one prescription for penicillin was given to 3,375,162 patients. Of 6212 (0.18%) patients who experienced an allergic-like event after the initial prescription, 48.5% were given a second prescription compared with 59.8% of those without an initial allergic-like event (risk ratio, 0.81; 95% CI, 0.79-0.83). Two or more prescriptions for penicillin were given to 2,017,957 patients. Three thousand fourteen (0.15%) patients experienced an allergic-like event after the first prescription, and 57 (1.89%) of those had another event after the second prescription. The unadjusted odds ratio of an allergic-like event after the second prescription for those who experienced an allergic-like event after the first prescription, compared with those who had no initial event was 11.2 (95% CI, 8.6-14.6). Adjusting for confounding had no substantive effect on this result. CONCLUSION: The risk of an allergic-like event after penicillin is markedly increased in those who have had a prior event, although the absolute difference is small (1.72%). Represcription of penicillin to such patients is more frequent than anticipated.

Parenteral ketorolac and risk of myocardial infarction.

PURPOSE: To examine the effects of ketorolac, a non-aspirin non-steroidal anti-inflammatory drug (NANSAID) with antiplatelet properties, on the risk of in-hospital myocardial infarction (MI). METHODS: A retrospective cohort study was performed among hospitalized patients given 10,219 courses of parenteral ketorolac and patients given 10,145 courses of parenteral opioids, without ketorolac, in 35 hospitals. Patients were matched by hospital, admitting service, and date of study drug initiation. Any MI documented in the chart that occurred during the drug course and up to 3 days after the last dose was recorded by trained abstractors. RESULTS: MI occurred in 18 (0.2%) ketorolac and 45 (0.4%) opioid courses (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.23-0.69). This negative association persisted in multivariable analysis adjusting for age, sex, history of diabetes mellitus or cardiovascular disease, and administration of antiplatelet agents (OR 0.42; 95% CI 0.24-0.73). The association also persisted in numerous analyses excluding patients who may have been treated with analgesics for ischemic pain, and when restricting events to those occurring while on the drug (OR 0.34; 95% CI 0.17-0.69). CONCLUSION: These results are consistent with a protective effect of ketorolac against MI. Future research that implements uniform screening for and independent validation of MIs as well as eliminates possible confounding by indication is the next logical step in confirming these findings.

Defining the clinically important difference in pain outcome measures.

The purpose of this study was to determine the levels of change on standard pain scales that represent clinically important differences to patients. Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious. Differences between groups, as summarized by a change in mean values over time, can be difficult to apply to clinical care. Baseline scores vary widely and group mean differences could reflect large changes in a few patients, small changes in many patients, or any combination of these outcomes. Determination of the proportion of patients who have a clinically important improvement in their pain would provide a more interpretable result with direct clinical implications. However, determining a clinically important outcome requires information about the degree of change over time that is clinically important. Data from the titration phase of a multiple cross-over randomized clinical trial of oral transmucosal fentanyl citrate (OTFC) for the treatment of cancer-related breakthrough pain were re-analyzed to examine the differences in pain scores between treatment episodes that did and did not yield adequate pain relief. The scales evaluated were absolute pain intensity difference (PID, 0-10 scale), percentage pain intensity difference (PID%, 0-100% scale), pain relief (PR, 0 (none), 1 (slight), 2 (moderate), 3 (lots), 4 (complete)), sum of the pain intensity difference (SPID over 60 min), percentage of maximum total pain relief (% Max TOTPAR over 60 min), and global medication performance (0 (poor), 1 (fair), 2 (good), 3 (very good), 4 (excellent)). Adequate relief was defined by the patient's decision not to use another dose of opioid medication as a rescue, in addition to the study medication, to treat each painful episode. One hundred thirty OTFC naive patients contributed data on 1268 episodes of breakthrough pain. The scales that were converted to a percentage change yielded the best accuracy in predicting adequate relief, with balanced sensitivity and specificity. The best cut-off point for both the % Max TOTPAR and the PID% was 33%. The best cut-off points for the absolute scales were absolute pain intensity difference of 2, pain relief of 2 (moderate), and SPID of 2. The global medication performance of 2 (good) had excellent values as well. This study presents data-derived cut-off points for the changes in several pain scales, each reflecting the clinically important improvement for patients treating breakthrough cancer pain episodes with OTFC. Confirmation in other patient populations and different pain syndromes will be needed. The use of consistent clinically important cut-off points as the primary outcome in future pain therapy clinical trials will enhance their validity, comparability, and clinical applicability.