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Purpose Hydrocodone, codeine, oxycodone, and tramadol are frequently prescribed to adolescents for moderate pain related to minor trauma or dental, surgical, or medical procedures. Pharmacokinetic and pharmacodynamic differences between these opioids could affect their relative safety. We aimed to compare occurrence of opioid-related adverse events in adolescents without cancer or other severe conditions taking hydrocodone, codeine, oxycodone, and tramadol. Methods Retrospective cohort study of 201 940 Tennessee Medicaid enrollees 12 to 17 years of age without cancer, other severe conditions, or evidence of substance abuse with 529 731 filled prescriptions for study opioids. Adverse events were defined as an emergency department visit, hospital admission, or death related to opioid use, confirmed by medical record review. Serious events had opioid-related escalation of care, hospitalization, or death. Propensity-score adjusted hazard ratios (HRs) were calculated with hydrocodone as the reference category. Results The incidence of opioid-related adverse events per 10 000 person-years of opioid exposure was 97.5 for hydrocodone (127 events/13 026 person-years), 91.2 for codeine (58/6,359), 229.7 for oxycodone (43/1,872), and 317.7 for tramadol (47/1479). The HRs for tramadol in comparison with hydrocodone for all and serious events were 2.98 (2.03-4.39) and 2.94 (1.81-4.75), respectively. Increased risk for tramadol was consistently present when the adverse events were restricted to those with neurologic-respiratory depression/other symptoms of possible overdose. Conclusion In adolescents without cancer or other severe conditions prescribed short-acting opioids, the incidence of both all opioid-related adverse events and more serious events with opioid-related escalation of care, hospitalization, or death was consistently greater for tramadol than for hydrocodone.

There is frequent and growing use of medications that prevent abnormal blood clotting, including anticoagulants, antifibrinolytics, and platelet inhibitors. However, their therapeutic benefits must be balanced against the risk of bleeding complications, which for some of these drugs are relatively frequent. Warfarin, the most commonly used oral anticoagulant, substantially increases the risk of major bleeding complications, including hemorrhagic stroke and gastrointestinal hemorrhage,1 to as high as 3%-8% per year.2 Similarly, serious bleeding is a frequent complication of platelet P2Y12 adenosine diphosphate receptor antagonists 3-5 such as clopidogrel. Indeed, the elevated incidence of serious bleeding for prasugrel may deter use of this newer drug in high-risk patients.5 Thus, optimal clinical use of anti-clotting agents requires accurate information on the risk of serious bleeding complications. The clinical trials that establish efficacy provide valuable information. However, trial patients often have lower risk of adverse effects than do those in actual practice. Trials often exclude the highest risk patients, include procedures that are not part of routine clinical practice to reduce the occurrence of adverse effects, and may have insufficient power to examine drug-drug or drug-disease interactions.6 Epidemiologic studies of patients in actual clinical practice thus are essential to quantify the risk of bleeding complications for commonly prescribed anti-clotting agents. Automated databases of medical care encounters for defined populations are a potentially valuable resource for epidemiologic studies of bleeding complications. These databases include records of prescriptions written by clinicians, filled by patients or administered in institutions, records that provide a reliable measure of drug exposure that would be difficult or very expensive to obtain in other ways.7 These prescription records permit classification of anti-clotting drug exposure on a day-to-day basis, which is important because increased bleeding generally is an acute effect of these drugs. Similarly, the use of other medications that may alter the risk of bleeding8 can be closely tracked. A prerequisite for the study of bleeding complications with automated databases is a reliable definition for bleeding endpoints. One could identify potential endpoints from the computerized files and review medical records to determine ultimate endpoint status.9 However, this is not always possible and, even when possible, may be expensive and time-consuming. We thus developed a case definition for serious bleeding designed for use in automated databases. We report here its validation relative to a definition based upon review of medical records, utilizing a sample from an in-progress cohort study of warfarin-related bleeding in a Tennessee Medicaid population.

Purpose Computerized definitions are used to identify serious infections and congestive heart failure leading to hospitalizations in studies of medication safety. However, information on their accuracy is limited. We evaluated the ability of computerized definitions to identify these conditions as the reason for admission among patients diagnosed with rheumatoid arthritis (RA). Methods Medical charts were randomly selected from a systematic sample of hospitalizations for selected conditions in a cohort of Medicaid patients with RA. We calculated positive predictive values (PPVs) for computerized definitions for community-acquired pneumonia, invasive pneumococcal disease, sepsis, opportunistic mycoses, and congestive heart failure using charts reviews as gold standard and computed inter-reviewer agreement statistics. Results From 2667 hospitalizations, 336 (13%) records were selected for review. A total of 277 charts (82%) were available. Based on any discharge diagnosis, PPVs for hospitalizations due to community-acquired pneumonia, invasive pneumococcal disease, sepsis, and opportunistic mycoses were 84, 100, 80, and 62%, respectively. Restricting definitions to principal diagnoses yielded higher PPVs, 95% for pneumonia and 100% for other diagnoses. The PPV of a principal diagnosis for congestive heart failure was 100%. Inter-reviewer agreement was at least 77% for all outcomes. Conclusion These findings suggest that computerized definitions can identify congestive heart failure and selected infections leading to hospitalization in Medicaid patients with RA. Copyright © 2008 John Wiley & Sons, Ltd.

Bleeding complications are a serious adverse effect of medications that prevent abnormal blood clotting. To facilitate epidemiologic investigations of bleeding complications, we developed and validated an automated database case definition for bleeding-related hospitalizations.The case definition utilized information from an in-progress retrospective cohort study of warfarin-related bleeding in Tennessee Medicaid enrollees 30 years of age or older. It identified inpatient stays during the study period of January 1990 to December 2005 with diagnoses and/or procedures that indicated a current episode of bleeding. The definition was validated by medical record review for a sample of 236 hospitalizations.We reviewed 186 hospitalizations that had medical records with sufficient information for adjudication. Of these, 165 (89%, 95%CI: 83-92%) were clinically confirmed bleeding-related hospitalizations. An additional 19 hospitalizations (10%, 7-15%) were adjudicated as possibly bleeding-related. Of the 165 clinically confirmed bleeding-related hospitalizations, the automated database and clinical definitions had concordant anatomical sites (gastrointestinal, cerebral, genitourinary, other) for 163 (99%, 96-100%). For those hospitalizations with sufficient information to distinguish between upper/lower gastrointestinal bleeding, the concordance was 89% (76-96%) for upper gastrointestinal sites and 91% (77-97%) for lower gastrointestinal sites.A case definition for bleeding-related hospitalizations suitable for automated databases had a positive predictive value of between 89% and 99% and could distinguish specific bleeding sites.

Purpose To facilitate studies of medications and sudden cardiac death, we developed and validated a computer case definition for these deaths. The study of community dwelling Tennessee Medicaid enrollees 30–74 years of age utilized a linked database with Medicaid inpatient/outpatient files, state death certificate files, and a state ‘all-payers’ hospital discharge file. Methods The computerized case definition was developed from a retrospective cohort study of sudden cardiac deaths occurring between 1990 and 1993. Medical records for 926 potential cases had been adjudicated for this study to determine if they met the clinical definition for sudden cardiac death occurring in the community and were likely to be due to ventricular tachyarrhythmias. The computerized case definition included deaths with (1) no evidence of a terminal hospital admission/nursing home stay in any of the data sources; (2) an underlying cause of death code consistent with sudden cardiac death; and (3) no terminal procedures inconsistent with unresuscitated cardiac arrest. This definition was validated in an independent sample of 174 adjudicated deaths occurring between 1994 and 2005. Results The positive predictive value of the computer case definition was 86.0% in the development sample and 86.8% in the validation sample. The positive predictive value did not vary materially for deaths coded according to the ICO-9 (1994–1998, positive predictive value = 85.1%) or ICD-10 (1999–2005, 87.4%) systems. Conclusion A computerized Medicaid database, linked with death certificate files and a state hospital discharge database, can be used for a computer case definition of sudden cardiac death. Copyright © 2009 John Wiley & Sons, Ltd.