This was a retrospective cohort study reviewing the medical charts of patients admitted to Shinshu University Hospital, Japan.
Setting and study population
The inclusion criteria of this investigation were as follows: 1) admitted to any internal medicine department at Shinshu University Hospital, Japan, between April 2009 and December 2018, 2) admitted to a multi-patient room in a general ward, 3) older than 75 years, and 4) unscheduled or unexpected admission, to identify patients at a higher risk of delirium. The exclusion criteria were as follows: 1) transfer from another hospital, 2) regularly taking anti-delirium medicine before admission, and 3) already delirious on admission. Patients who were transferred from another hospital were excluded due to a lack of data. Anti-delirium medicine was defined as any of haloperidol, quetiapine, perospirone, olanzapine, risperidone, tiapride, mianserin, trazodone, or yokukansan. Delirious at admission was defined as already exhibiting delirium with event, which was the main outcome of this study (described below), within 3 hours after admission.
The data of eligible patients were collected from hospital medical records and included basic clinical information, sequential organ failure assessment (SOFA) score, performance status (PS), Charlson comorbidity index (CCI), daily medicine use before admission, co-incidence of dementia, and main disease for admission. To calculate SOFA score, we referred to blood test data obtained within 24 hours after admission and predicted the partial pressure of oxygen in arterial blood from peripheral oxygen saturation using the Hill Eq. 21. We obtained PS scores as assessed by nurses on patient admission. CCI, the co-incidence of dementia, and the main disease for admission were ascertained using the records of the registered disease name on admission. The main disease for admission was classified as a central nervous system disorder, cardiovascular disease, infection, malignancy, or other.
Exposure of interest
At Shinshu University Hospital, multi-patient rooms in general wards can accommodate up to 4 or 6 patients. In rooms for 4 patients, the 2 beds closest to the window were defined as window-side beds and the 2 remaining beds were considered non-window-side beds (Fig. 1). In rooms for 6 patients, the 2 beds closest to the window were judged as window-side beds and the remaining 4 beds were defined as non-window-side beds. The eligible patients were divided into the group admitted to a window-side bed (window group) or the group admitted to a non-window-side bed (non-window group).
We measured the bedside luminosity in the east ward of the seventh floor using an EM-9300SD device (SATOSHOJI, Japan). Luminosity was considerably higher at window-side beds than at non-window-side beds in the daytime, regardless of whether the room faced south or north. Luminosity was undetectable at 9:00 P.M., after lights-out (see Supplementary Fig. S1).
The primary outcome was delirium with event within 14 days after admission. The definition and abstraction method of this outcome are as follows. First, 2 physicians reviewed the medical charts of eligible hospitalized patients and identified delirium development using a reported chart abstraction method22. In this method, the physicians searched for key terms indicating acute mental change (e.g., delirium, mental state change, inattention, disorientation, hallucinations, agitation, inappropriate behavior, etc.). If the acute mental change could not be explained by reasons other than delirium (e.g., central nerve system disorder or dementia), the patient was defined as having delirium. Next, the physicians assessed whether the abstracted delirium was accompanied by any of the following events: 1) use of drugs as sedatives for delirium, including anti-delirium medicine, benzodiazepines, and first-generation antihistamines, 2) physical restraint, 3) transfer to another bed, 4) transient stay in the staff room for monitoring, and 5) self-removal of drip line or catheter23,24. If the delirium was accompanied by any such event, we classified the case as delirium with event. To enhance the reproducibility and specificity of the main outcome, we selected delirium with event over delirium. The observation period for the primary outcome was limited to 14 days after admission to exclude the influence of a long hospital stay on delirium. Fourteen days was also chosen since Japanese medical staff are basically recommended to discharge patients within 14 days considering that some medical fees are covered by national healthcare for only 14 days of admission.
Both physicians reviewed the medical charts independently and were blinded to whether the patient was in the window or non-window group. If their judgment differed on a primary outcome, mutual consensus was reached by discussion.
We also assessed the secondary outcomes of delirium with event within 30 days after admission, delirium within 14 or 30 days after admission, hospital stay longer than 14 days, transfer to the ICU, and death during hospitalization.
Sample size decision
Previous literature suggested the primary outcome to occur at a frequency of approximately 10%12. To detect an absolute difference of 5% in the ratio of the primary outcome between the 2 groups (i.e., 7.5% in the window group and 12.5% in the non-window group) with 80% power at a 5% significance level, a total of 1280 patients (divided in a 2:3 ratio) were required. Based on this calculation, we set the final recruitment target at 1500 patients.
Descriptive statistics were employed to summarize the demographic factors of the patients stratified by 2 groups. Continuous variables were presented as the median and interquartile range (IQR) and compared using the Wilcoxon–Mann–Whitney test. Categorical variables were presented as the number and percentage and assessed by means of the two-tailed t-test.
At the assessment of delirium with event or delirium, observation was censored when the following events were recorded for reasons other than delirium: 1) use of anti-delirium medicine, 2) physical restraint, 3) transfer to another bed (apart from window-side bed to window-side bed or non-window-side bed to non-window-side bed), 4) transient stay in the staff room for monitoring, and 5) self-removal of drip line or catheter. Kaplan–Meier curves of cumulative outcome incidence were calculated and compared between the groups using the log-rank test. The hazard ratio of the window group for the main outcome was estimated using multivariable Cox proportional hazard models to adjust for such potential confounders as age, sex, low body weight (i.e., body mass index less than 18.5), SOFA score, regular use of risk drugs for delirium before admission (e.g., benzodiazepines, non-benzodiazepines, anti-histamines, and narcotic analgesics), PS, CCI, admission for central nervous system disorders, and co-incidence of dementia25–27. Concerning the assessments of hospital stay for longer than 14 days, transfer to the ICU, and death during hospitalization, the observation period was limited not to 14 days, but to the entire time of hospitalization, and censoring was not taken into account. The adjusted odds ratios of the window group for those outcomes were estimated using logistic regression models.
Multiple imputation was performed to account for missing data values for PS and SOFA scores in 269 patients. We replaced each missing value with a set of substituted plausible values by creating 20 filled-in complete data sets by multiple imputation using a chained equation method28. To test the robustness of the results with the multiple imputation method, complete case analysis and median imputation analysis were also performed as sensitivity analyses.
Additional subgroup analyses were conducted using various factors related to the environment of the inpatient and bed, including the type of room, direction of ward, direction of room and window, and season of admission. We assessed the adjusted hazard ratio of the window group for the primary outcome in each subgroup.
All statistical analyses were performed using IBM SPSS statistics version 27.0 (IBM, Armonk, NY). Values of p < 0.05 were considered statistically significant.
Ethics approval and consent to participate
This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. It was performed in accordance with the tenets set forth in the Declaration of Helsinki and approved by the ethics committee of Shinshu University Hospital (authorization number: 4329). Informed written consent was waived in this study by the ethics committee of Shinshu University Hospital due to its retrospective nature using medical records that did not subject the patients to new interventions. The collected data were anonymously stored and used for analysis. As an alternative to written informed consent, an opt-out document was created and posted on the hospital website that contained information on the design of the research and publication of the results to provide subjects the opportunity to halt the provision of their medical data.