Medical record review
This retrospective cohort study was conducted at Yokohama Rosai Hospital, a tertiary medical center in Japan. We reviewed the medical records of patients (a) who were suspected to have any psychiatric disorder by physicians in departments other than the Department of Psychosomatic Medicine, (b) who were referred to the Department of Psychosomatic Medicine from March 2019 to October 2019, (c) who had been diagnosed with delirium by psychosomatic physicians, and (d) who were not under continuous sedation.
We defined the first 24 hours from 9:00 p.m. on the referral date as day 1, and every subsequent period of the following 24 hours as day N. We reviewed the medical charts to determine whether patients had presented with delirium on day 3, which was denoted as the outcome. Day 3 was selected because a previous study suggested that an outcome evaluation on this day could be used to estimate the treatment effectiveness , and this outcome has been widely adopted [14, 15]. Patients were evaluated based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (American Psychiatric Association, 2013). Two authors (K.K. and M.D.) evaluated the outcomes independently, and any disagreements were resolved by discussion. The reproducibility of the evaluation was analyzed using the kappa statistic.
The number of drugs prescribed on the referral date was counted, excluding general infusion fluids, nutritional or electrolytic products, and psychotropic agents.
We used the t-test to compare the means of continuous variables, and Fisher’s exact test or the chi-squared test to compare the proportions of categorical variables in patients with and without delirium symptoms on day 3.
We performed the following analyses to determine the cutoff for polypharmacy [16, 17]. First, we developed a classification and regression tree (CART) model in which the maximum tree depth was fixed at one and the Gini index was used as the splitting metric. We considered the splitting value of the root node to be the cutoff value. We also generated a receiver operating characteristic (ROC) curve and calculated the Youden index for each cutoff point. The cutoff that maximized the Youden index was considered the optimal cutoff value.
We calculated the odds ratio (OR) of polypharmacy for the persistence of delirium on day 3 using a logistic regression model with the propensity score as a covariate. Propensity scores were calculated using a logistic regression model based on the following variables: age, sex, the presence of 17 diseases in the updated Charlson comorbidity index (an index to predict mortality based on the presence of comorbid conditions) , the Karnofsky Performance Status (an index of physical performance ability)  score on admission, and psychotropics (five categories: antipsychotics, benzodiazepine or Z-drugs, ramelteon or suvorexant, antidepressants, and others). The Karnofsky Performance Status was used as an index of the severity of patients. Psychotropics were included because of their potential effects on delirium [1, 20]. To confirm the sufficiency of the sample size, we performed a power analysis of the univariate logistic regression model.
All analyses were conducted using R version 4.0.0 (R Foundation for Statistical Computing, Vienna, Austria, 2019) with the packages ‘powerMeditation’ (version 0.3.2), ‘ROCR’ (version 1.0–11), ‘rpart’ (version 4.1–15), and ‘vcd’ (version 1.4-7). A P-value < 0.05 was considered statistically significant.