Application of lag-time into exposure definitions to control for protopathic bias

PURPOSE: To control for protopathic bias, some studies have incorporated the concept of lag-time into their exposure definition (time period before the index date that was not considered in assessing exposure). The objective of this study was to introduce a procedure to identify the best lag-time to be applied in studies where control for protopathic bias is required. METHODS: We used data from a case-control study carried out to assess the association between exposure to proton pump inhibitors (PPIs) and risk of gastric cancer, using RAMQ databases. Exposure was defined as the number of defined daily doses of PPIs dispensed during the 5-year period prior to the index date (divided into four quartiles). Thirty-one different lag-times were applied (0-30 months) based on 1-month intervals. Logistic regression was used to estimate the matched odds ratio (OR) for each lag-time. The change point in the ln(ORs) was identified by applying a two-compartmental model and a segmented regression model. RESULTS: A trend of decreasing ORs was found with the application of an increasing lag-time. As an illustration, the ORs for the 1st quartile of defined daily doses, when applying the 31 different lag-times, ranged between 3.52 when applying a 0 lag-time and 0.97 when applying a 30 months lag-time. Applying the two methods for the different lag-times showed that the ORs stabilized at around 6 months. CONCLUSION: For the purpose of controlling for protopathic bias in pharmacoepidemiological studies, we have provided a method to assess the most appropriate lag-time that should be applied for the assessment of drug exposure.     

Comparison of myocardial performance index obtained either by conventional echocardiography or tissue Doppler echocardiography in healthy subjects and patients with heart failure

This study was planned to investigate the normal reference values of myocardial performance index (MPI) obtained by tissue Doppler echocardiography (TDE) and the agreement between MPI measured by TDE and conventional MPI measured by pulsed-wave Doppler (PWD) in healthy subjects and patients with heart failure (HF). Two hundred and three patients with HF and 190 healthy subjects were enrolled in this study. Isovolumic contraction and relaxation time (ICT and IRT) and ejection time (ET) were measured from mitral inflow and left ventricular (LV) outflow. Tissue Doppler echocardiography recordings were obtained at the septal, lateral, inferior, and anterior of the mitral annulus and same time intervals were measured. Myocardial performance index was calculated. The functional capacity of the patients with HF was determined according to New York Heart Association classification. TDE-MPI values were higher than conventional PWD-MPI values in both groups (53% ± 8% vs 48% ± 11%, P < 0.0001 in the healthy subjects; 84% ± 21% vs 72% ± 19%, P <0.0001 in the patients with HF). Moderate agreement was found between PWD-MPI and LV mean TDE-MPI in both groups. In identifying patients with moderately or severely decreased LV ejection fraction, TDE-MPI had higher cutoff values than conventional PWD-MPI, and TDE-MPI had higher specificity, sensitivity, negative predictive value, and diagnostic accuracy. In patients with HF, TDE-MPI had a stronger correlation with LV ejection fraction and functional capacity than did PWD-MPI. TDE-MPI is an alternative to conventional PWD-MPI in assessment of cardiac function. However, the higher MPI cutoff points should be considered when this method is used for the evaluation of cardiac function.     

Continuous alfentanil infusion in pediatric patients undergoing general anesthesia for complete oral restoration

STUDY OBJECTIVE: To study the safety and efficacy of continuous alfentanil infusions in children. DESIGN: Randomized open study. SETTING: Outpatient pediatric anesthesia at a university medical center. PATIENTS: Forty pediatric patients aged 2 to 12 years about to undergo anesthesia for complete oral restoration. INTERVENTIONS: Twenty patients were anesthetized with halothane and nitrous oxide (N2O), and 20 patients were anesthetized with N2O and a 100 micrograms/kg bolus of alfentanil followed by a continuous alfentanil infusion. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements, emergence times, and postoperative side effects were measured. Hemodynamic stability was maintained in both groups. Although children emerged faster and were extubated earlier when anesthetized with alfentanil, they required longer times until they could be discharged from the outpatient anesthesia area. Children anesthetized with alfentanil had a higher occurrence of postoperative emesis compared with children anesthetized with halothane. These differences, however, were not statistically significant. CONCLUSIONS: Alfentanil appears to be a safe anesthetic. The reason for prolonged discharge time in the alfentanil-anesthetized patient is unclear, but it may be related to postoperative vomiting.