Key result
Excluding misclassified cases receiving end-of-life care reduced the odds ratio for sudden cardiac death associated with domperidone exposure from 2.09 to 1.71 compared with non-use.
Why the study?
Does exposure to domperidone increase the risk of out-of-hospital sudden cardiac death in a general practice cohort?
Case-Control (n=681,104)
Does exposure to domperidone increase the risk of out-of-hospital sudden cardiac death in a general practice cohort?
Answers are grounded in this paper and cite their sources.
Properly identifying and excluding end-of-life care patients in electronic health records reduces protopathic bias and attenuates the apparent association between domperidone and sudden cardiac death.
BACKGROUND: The ascertainment of sudden cardiac death (SCD) in electronic health databases is challenging. OBJECTIVES: Our objective was to evaluate the applicability of the validated computer definition of SCD developed by Chung et al. in a retrospective study of SCD and domperidone exposure in the Clinical Practice Research Datalink (CPRD). METHODS: We assessed out-of-hospital SCD by applying the validated computer definition and linking data with Hospital Episode Statistics and death certificates. We developed a separate algorithm to identify end-of-life care in noninstitutionalized patients and excluded associated deaths from the analysis to address their misclassification as SCD. RESULTS: Of the 681,104 patients in the study cohort, 3444 were initially classified as out-of-hospital SCD. Next, 163 deaths were identified as expected deaths by our algorithm for end-of-life home care. After review of patient profiles, 162 were classified as expected deaths because of evidence that the patient received palliative or end-of-life care, but one was a false negative. The exclusion of such cases appreciably changed the odds ratio for current exposure to domperidone compared with non-use of study medications from 2.09 (95 % confidence interval [CI] 1.16-3.74) to 1.71 (95 % CI 0.92-3.18). A similar effect on the odds ratio was observed for current exposure to metoclopramide but not to proton pump inhibitors. CONCLUSIONS: Our algorithm to identify end-of-life care at home in the CPRD performed well, with only one false negative. The exclusion of misclassified cases of SCD reduced the magnitude of the odds ratios for SCD associated with domperidone and metoclopramide exposure by controlling protopathic bias.
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Varas‐Lorenzo et al. (2016) conducted a case-control in Out-of-hospital sudden cardiac death (n=681,104). Domperidone vs. Non-use of study medications was evaluated on Out-of-hospital sudden cardiac death (after excluding end-of-life care cases) (OR 1.71, 95% CI 0.92-3.18). Excluding misclassified cases receiving end-of-life care reduced the odds ratio for sudden cardiac death associated with domperidone exposure from 2.09 to 1.71 compared with non-use.
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