Study design and patient population
This historical cohort study was conducted as part of a multicenter cohort study known as the Japan Adverse Drug Events (JADE) Study [17, 18]. As part of the JADE study series, we collected information using the standard JADE protocol. [3, 17, 18] Data were collected from the psychiatric inpatient units at one psychiatric hospital and one tertiary care teaching hospital. There were a total of 438 psychiatric inpatient beds between these two hospitals, including beds in acute care units, nursing care units, and medical care units. The acute care unit comprises the main section of a psychiatric department in which patients with an acute mental disorder receive targeted mental care. Psychiatric patients who have recovered from the acute stage of their condition but who still require nursing care are admitted to nursing care units. Medical care units are specialized sections within a psychiatric department that provide treatment to psychiatric patients with physical medical conditions. Both hospitals included in this study used electronic medical records.
At the tertiary care teaching hospital, patients were treated both by attending psychiatrists and by resident psychiatrists, who have <3 years of training after obtaining their medical license. Resident psychiatrists practiced under the supervision of attending psychiatrists and primarily ordered medications. In contrast, most of the psychiatrists at the psychiatric hospital were attending psychiatrists. Both hospitals admitted patients to the acute care or medical care units within the psychiatry department if psychiatric disorders were the main presenting problem and the patients’ physical problems were considered to be mild; internists provided medical consultations as needed. Conversely, if patients’ physical complications were considered to be more severe than their psychiatric problems, or if patients required intensive care (for example, as a result of myocardial infarction or femoral fracture, or if they required intubation), they were discharged from the psychiatric department and transferred to non-psychiatric wards for subsequent care.
Data were collected from all psychiatric inpatients who were admitted to and discharged from the acute, nursing and medical care units from April 1, 2010 through March 31, 2011. The main measures that were evaluated were patient-days and the number of admissions. The study was approved by the institutional review boards of the Kyoto Prefectural University of Medicine and by the institutional review boards of the two participating hospitals. The need for informed consent was waived because all data were collected as part of the hospitals’ daily practices.
The primary outcome measured in this study was the number of ADEs, defined as drug-related injuries resulting from medical intervention [1, 2]. The term ADE has a wide spectrum of definitions, including harm caused by drugs at a usual dosage (adverse drug reactions: ADRs) or at an unusual dosage, and also including harm from dose reduction and discontinuation of drug therapy . For example, an extrapyramidal symptom, such as akathisia, occurring after a patient receives antipsychotics, and with no other apparent cause, is considered to be an ADE. Rebound insomnia that occurs following discontinuation of sedatives is another example of an ADE. An ADE was then categorized by severity as fatal, life-threatening, serious or significant. Fatal ADEs were those that resulted in death. Life-threatening ADEs were those that caused such issues as respiratory depression or suicidal behavior. Serious ADEs included gastrointestinal bleeding, falls, or a decrease in blood pressure. Significant ADEs included cases with milder symptoms, such as diarrhea, constipation, extrapyramidal symptoms or drowsiness.
A secondary outcome that was measured in this study was medication errors. Medication errors could occur at any step of the medication use process (ordering, transcribing, dispensing, administering or monitoring), and medication errors may or may not cause ADEs. If a medication error was found, the type of error and the stage in the process where it occurred were classified. The medication use process included the following stages: ordering by psychiatrists or other physicians; transcription by nurses; dispensing by pharmacists (or by psychiatrists and nurses, as was the case during the night shift and on weekends in the psychiatric hospital); administration by nurses or by patients; and monitoring by psychiatrists, other health professionals or by patients themselves.
ADEs were categorized as either preventable or non-preventable. An ADE was considered to be preventable if it resulted from a medication error or was otherwise ameliorable by available means (e.g., switching to a different drug or cautious monitoring after administration). An ADE that occurred in the absence of a medication error was defined as a non-preventable ADE. For example, a rash that occurred due to lamotrigine use in a patient without a history of lamotrigine-induced rash would not be considered a preventable ADE, but it would be considered as a preventable ADE if the patient had a history of such a rash.
We also classified ADEs according to their potential for causing injury. A potential ADE was an error that had the potential for injury but did not actually result in injury, either because of specific circumstances, chance, or because the error was intercepted. For example, if hypnotics were administered several hours earlier than prescribed, this would constitute a medication error and potential ADE, even if no negative effects were observed because hypnotics may cause immediate somnolence. On the other hand, early administration of anti-dementia drugs would be classified as a medication error but not a potential ADE because the drug rarely causes acute side effects.
Data collection and classification
The definitions and methods used in this study were consistent with those from prior studies on this topic [3, 17, 18]. In this study, four psychiatrists and two physicians, all with experience in the classification of ADEs as a result of previous research on this topic, reviewed all patient charts from each participating hospital, along with laboratory results, incident reports and prescription queries. Research assistants used patient charts to compile demographic characteristics and administrative data for all enrolled patients in the cohort.
Once all data were collected from participating hospitals, the reviewers independently classified relevant incidents as an ADE, potential ADE or medication error, while also recording the details of those incidents. This included information about the name, dose, route and class of the drugs, the details of symptoms resulting from ADEs, and the details related to medication errors such as type, stage and persons who were in charge at the time the error occurred. The reviewers also independently classified all incidents according to their severity and preventability. After all suspected incidents were collected, the reviewers met to confirm the final classification for each incident. When the reviewers disagreed on the classification of an incident, they reached a consensus through discussion.
The incidences per 1000 patient-days, crude rates per 100 admissions, and 95 % confidence intervals (CIs) were calculated as a whole and by unit types (acute care unit, nursing care unit, and medical care unit). Continuous variables are presented as means with standard deviations (SDs) or medians with interquartile ranges (IQRs), and categorical variables are shown as numbers and percentages. We used the χ2 test to assess the relationship between drug classes and preventable ADEs. We calculated inter-rater reliabilities using k statistics. Kappa scores between reviewers regarding the presence of an ADE were 0.96 (ADE v. potential ADE or exclude). The kappa for preventability was 0.95 (preventable v. non-preventable), while the kappa for severity was 0.43 (significant v. serious or life-threatening). These values were similar to those published in previous reports by Rothschild et al. (2007) and Morimoto et al. (2011). We performed all analyses using JMP V.11.2 (SAS Institute, Cary, North Carolina, USA) software.