Effectiveness of antipsychotics for managing agitated delirium in patients with advanced cancer: a secondary analysis of a multicenter prospective observational study in Japan (Phase-R).

PURPOSE: Delirium is a common and serious comorbidity in patients with advanced cancer, necessitating effective management. Nonetheless, effective drugs for managing agitated delirium in patients with advanced cancer remain unclear in real-world settings. Thus, the present study aimed to explore an effective pharmacotherapy for this condition. METHODS: We conducted a secondary analysis of a multicenter prospective observational study in Japan. The analysis included patients with advanced cancer who presented with agitated delirium and received pharmacotherapy. Agitation was defined as a score of the Richmond Agitation-Sedation Scale for palliative care (RASS-PAL) of ≥ 1. The outcome was defined as -2 ≤ RASS-PAL ≤ 0 at 72 h after the initiation of pharmacotherapy. Multiple propensity scores were quantified using a multinomial logistic regression model, and adjusted odds ratios (ORs) were calculated for haloperidol, chlorpromazine, olanzapine, quetiapine, and risperidone. RESULTS: The analysis included 271 patients with agitated delirium, and 87 (32%) showed -2 ≤ RASS-PAL ≤ 0 on day 3. The propensity score-adjusted OR of olanzapine was statistically significant (OR, 2.91; 95% confidence interval, 1.12 to 7.80; P = 0.030). CONCLUSIONS: The findings suggest that olanzapine may effectively improve delirium agitation in patients with advanced cancer.

Just-in-Time Adaptive Intervention for Stabilizing Sleep Hours of Japanese Workers: Microrandomized Trial.

BACKGROUND: Sleep disturbance is a major contributor to future health and occupational issues. Mobile health can provide interventions that address adverse health behaviors for individuals in a vulnerable health state in real-world settings (just-in-time adaptive intervention). OBJECTIVE: This study aims to identify a subpopulation with vulnerable sleep state in daily life (study 1) and, immediately afterward, to test whether providing mobile health intervention improved habitual sleep behaviors and psychological wellness in real-world settings by conducting a microrandomized trial (study 2). METHODS: Japanese workers (n=182) were instructed to collect data on their habitual sleep behaviors and momentary symptoms (including depressive mood, anxiety, and subjective sleep quality) using digital devices in a real-world setting. In study 1, we calculated intraindividual mean and variability of sleep hours, midpoint of sleep, and sleep efficiency to characterize their habitual sleep behaviors. In study 2, we designed and conducted a sleep just-in-time adaptive intervention, which delivered objective push-type sleep feedback messages to improve their sleep hours for a subset of participants in study 1 (n=81). The feedback messages were generated based on their sleep data measured on previous nights and were randomly sent to participants with a 50% chance for each day (microrandomization). RESULTS: In study 1, we applied hierarchical clustering to dichotomize the population into 2 clusters (group A and group B) and found that group B was characterized by unstable habitual sleep behaviors (large intraindividual variabilities). In addition, linear mixed-effect models showed that the interindividual variability of sleep hours was significantly associated with depressive mood (ß=3.83; P=.004), anxiety (ß=5.70; P=.03), and subjective sleep quality (ß=-3.37; P=.03). In study 2, we found that providing sleep feedback prolonged subsequent sleep hours (increasing up to 40 min; P=.01), and this effect lasted for up to 7 days. Overall, the stability of sleep hours in study 2 was significantly improved among participants in group B compared with the participants in study 1 (P=.001). CONCLUSIONS: This is the first study to demonstrate that providing sleep feedback can benefit the modification of habitual sleep behaviors in a microrandomized trial. The findings of this study encourage the use of digitalized health intervention that uses real-time health monitoring and personalized feedback.

The optimal cut-off score of the Eating Attitude Test-26 for screening eating disorders in Japan.

PURPOSE: The Eating Attitude Test-26 (EAT-26) is a screening tool for eating disorders (EDs) in clinical and non-clinical samples. The cut-off score was suggested to be varied according to target population. However, no studies have examined the appropriateness of the originally proposed score of 20 for screening DSM-5 eating disorders in Japan. This study aimed to identify an appropriate cut-off score to better differentiate clinical and non-clinical samples in Japan for EDs. METHODS: The participants consisted of 54 patients with anorexia nervosa restricting type, 58 patients with anorexia nervosa binge-eating/purging type, 37 patients with bulimia nervosa diagnosed according to DSM-5 criteria, and 190 healthy controls (HCs). Welch's t test was used to assess differences in age, body mass index (BMI), and total EAT-26 scores between HCs and patients with EDs. Receiver operating characteristic (ROC) analysis was conducted to identify the optimal cut-off score. RESULTS: The HCs had significantly higher BMI and lower total EAT-26 mean scores than patients with EDs. The area under the ROC curve was 0.925, indicating that EAT-26 had excellent performance in discriminating patients with EDs from HCs. An optimal cut-off score of 17 was identified, with sensitivity and specificity values of 0.866 and 0.868, respectively. CONCLUSIONS: The result supports the suggestions that optimal cut-off score should be different according to target populations. The newly identified cut-off score of 17 would enable the identification of patients with EDs who have been previously classified as non-clinical samples in the EAT-26 test. LEVEL OF EVIDENCE: III: evidence obtained from case-control analytic study.

Influence of dosing pattern of antipsychotics on treatment outcome of delirium in patients with advanced cancer.

BACKGROUND: Clinical guidelines recommend antipsychotics for the treatment of delirium; however, there has been no confirmed recommendation regarding their administrating patterns. This study aims to investigate whether different dosing patterns of antipsychotics (single or multiple administrations) influence the outcomes of delirium treatment. METHODS: This is a secondary analysis of a prospective observational study involving patients with advanced cancer and delirium receiving antipsychotics. The Delirium Rating Scale Revised-98 was administered at baseline and after 72 h of starting pharmacotherapy. Patients were classified into single administration group (received a single dosage within 24 h before the assessment) and multiple administration group (received more than one dosage). RESULTS: A total of 555 patients (single administration 492 (88.6%); multiple administration 63 (11.4%)) were subjected to analyses. The patients in the multiple administration group were more likely to be male, in psycho-oncology consulting settings, with lower performance status, with hyperactive delirium and with severer delirium symptoms. In the multivariate analysis, single administration was significantly associated with better improvement of delirium (p < 0.01, 95% confidence interval: 1.83-5.87) even after controlling covariates. There were no significant differences in the mean dosages of antipsychotics per day in chlorpromazine equivalent (single administration 116.8 mg/day, multiple administration 123.5 mg/day) and the incidence of adverse events between the two groups. CONCLUSIONS: In this observational study sample, Delirium Rating Scale severity score improvement in single administration was higher than that seen in multiple administration. There was no difference in adverse events between the two groups.

Early specialized palliative care for patients with metastatic lung cancer receiving chemotherapy: a feasibility study of a nurse-led screening-triggered programme.

BACKGROUND: Strategies to implement early specialized palliative care have not yet been established. The present study investigated the feasibility of a nurse-led, screening-triggered early specialized palliative care intervention programme and obtained data to design a randomized controlled trial. METHODS: Patients with metastatic lung cancer undergoing first-line platinum-based chemotherapy were eligible. The intervention consisted of (1) a questionnaire-based screening programme and (2) advanced-level nurse counselling and care coordination with interdisciplinary team approach. The primary endpoint was the completion rate of the assessment questionnaire after the second course of first-line chemotherapy (T2). Secondary endpoints included changes in Functional Assessment of Cancer Therapy-Lung scores, depression and anxiety rates based on the Patient Health Questionnaire 9 and the Hospital Anxiety and Depression Scale, and the contents of specialized palliative care. RESULTS: A total of 50 patients were enrolled between August 2012 and March 2014. Median age was 66 years (range, 40-78 year) and 84% were male. A total of 38 patients had stage IV non-small cell lung carcinoma and 12 had extensive disease small-cell lung carcinoma. The completion rate was 70% (95% confidence interval 56.0-81.0). The median duration between baseline and T2 was 53 days. Improvement from baseline were observed at T2 in Functional Assessment of Cancer Therapy-Lung scores (86.0 ± 18.1 vs 94.9 ± 18.2, P = 0.057), depression (16.0 vs 5.7%; P = 0.26) and anxiety (32.0 vs 22.9%; P = 0.65); however, these results were not statistically significant. CONCLUSIONS: This early specialized palliative care intervention is feasible and could be useful in improving patients' quality of life. The present results justify the initiation of a randomized control trial.

Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings.

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference -4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference -3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event.

A decision tree prediction model for a short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions: A secondary analysis of a multicenter and prospective observational study (Phase-R).

OBJECTIVE: There is no widely used prognostic model for delirium in patients with advanced cancer. The present study aimed to develop a decision tree prediction model for a short-term outcome. METHOD: This is a secondary analysis of a multicenter and prospective observational study conducted at 9 psycho-oncology consultation services and 14 inpatient palliative care units in Japan. We used records of patients with advanced cancer receiving pharmacological interventions with a baseline Delirium Rating Scale Revised-98 (DRS-R98) severity score of ≥10. A DRS-R98 severity score of <10 on day 3 was defined as the study outcome. The dataset was randomly split into the training and test dataset. A decision tree model was developed using the training dataset and potential predictors. The area under the curve (AUC) of the receiver operating characteristic curve was measured both in 5-fold cross-validation and in the independent test dataset. Finally, the model was visualized using the whole dataset. RESULTS: Altogether, 668 records were included, of which 141 had a DRS-R98 severity score of <10 on day 3. The model achieved an average AUC of 0.698 in 5-fold cross-validation and 0.718 (95% confidence interval, 0.627-0.810) in the test dataset. The baseline DRS-R98 severity score (cutoff of 15), hypoxia, and dehydration were the important predictors, in this order. SIGNIFICANCE OF RESULTS: We developed an easy-to-use prediction model for the short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions. The baseline severity of delirium and precipitating factors of delirium were important for prediction.

Increased prevalence of eating disorders in Japan since the start of the COVID-19 pandemic.

PURPOSE: The study aimed to investigate the effect of the COVID-19 pandemic on the prevalence of eating disorders in Japan. METHODS: We retrospectively reviewed the medical records of new patients with eating disorders who visited an outpatient eating disorders clinic of a single university hospital in Tokyo, Japan, from April 2020 to March 2021 (FY2020) and April 2019 to March 2020 (FY2019). We determined whether the onset or course in each patient in FY2020 was associated with the COVID-19 pandemic and classified COVID-19-associated medical histories into the following categories: (1) fatness phobia, (2) acceleration of dieting, (3) family relationships, (4) social factors, and (5) mood change. We performed the Kolmogorov-Smirnov test to compare the cumulative distribution of disease onset by month in FY2020 and FY2019. RESULTS: We reviewed the records of 112 and 77 patients with eating disorders in FY2020 and FY2019, respectively. The onset or course of 35 patients (31.3%) in FY2020 was associated with the COVID-19 pandemic. We classified 14 patients to fatness phobia category, 11 to acceleration of dieting, 4 to family relationships, 2 to social factors, and 4 to mood change. No COVID-19-associated cases were associated with fear of contracting the disease. The cumulative distribution of disease onset differed significantly in FY2020 and FY2019 (D = 0.248; P = 0.007). CONCLUSION: This chart review suggests that the COVID-19 pandemic may increase the prevalence of eating disorders. LEVEL OF EVIDENCE: III, cohort study.

Evaluation of quality indicators near death in older adult cancer decedents in Japan: A nationwide retrospective cohort study.

OBJECTIVES: End-of-life cancer care is important; however, data on hospitalization and costs for older patients have been lacking. We aimed to examine quality indicators and costs for older patients in Japan. METHODS: Using the Diagnosis Procedure Combination database, a national database of acute-care hospitals in Japan, we retrospectively collected data on cancer decedents aged ≥65 years. We evaluated the quality indicators (hospitalizations, length of stay in the hospital, emergency hospitalizations, emergency hospitalizations using an ambulance, intensive care unit [ICU] admissions, length of stay in the ICU, interval between last chemotherapy use and death, and chemotherapy within 14 days before death) and hospitalization costs at 30, 90 and 180 days before death. We compared the outcomes across age groups (65-74, 75-84 and ≥ 85 years). RESULTS: Between January 2011 and March 2015, we identified 369 616 cancer decedents. From 180 to 30 days before death, there were increases in emergency hospitalizations, emergency hospitalizations using an ambulance, and the mean costs per hospital day. Overall, 16.7% of patients receiving chemotherapy last received this treatment on the day before death or the day of death. Costs decreased with increasing age. The group aged ≥85 years had the shortest hospital and ICU stays and the lowest multiple hospitalizations, ICU admissions, chemotherapy within 14 days before death, and costs. CONCLUSIONS: Many older adult patients had emergency hospitalizations and received chemotherapy just prior to death, and there is room for improvement in appropriate end-of-life care. Oldest old patients consumed relatively few medical resources.

Death by suicide, other externally caused injuries and cardiovascular diseases within 6 months of cancer diagnosis (J-SUPPORT 1902).

OBJECTIVE: To conduct the first national population-based study in Japan to characterize risks of death by suicide, other externally caused injuries and cardiovascular diseases within 6 months of cancer diagnosis. METHODS: Cancer patients diagnosed between 1 January and 30 June 2016 and registered in the National Cancer Registry in Japan were followed up until death or 6 months after diagnosis. We calculated standardized mortality ratios and excess absolute risks per 10 000 person-years for death by suicide, other externally caused injuries and cardiovascular diseases compared with the Japanese general population. RESULTS: Of 546 148 patients with cancer (249 116 person-years at risk), we observed 145 suicides, 298 deaths due to other externally caused injuries and 2366 cardiovascular deaths during the follow-up period. Standardized mortality ratios within 6 months were 2.68 for suicide (95% confidence interval, 2.26-3.16; excess absolute risk, 3.65), 1.49 for other externally caused injuries (95% confidence interval, 1.32-1.67; excess absolute risk, 3.92) and 1.38 for cardiovascular diseases (95% confidence interval, 1.33-1.44; excess absolute risk, 26.85). Risks were highest during the first month after cancer diagnosis (standardized mortality ratios: suicide, 4.06 [95% confidence interval, 2.90-5.53]; other externally caused injuries, 2.66 [95% confidence interval, 2.17-3.12] and cardiovascular diseases, 2.34 [95% confidence interval, 2.18-2.51]). CONCLUSIONS: The first 6 months, and especially the first month, after cancer diagnosis were found to be a critical period for risks of death by suicide, other externally caused injuries and cardiovascular diseases. Our findings suggest that oncologists need to evaluate suicidal and cardiovascular risks of patients immediately after cancer diagnosis and provide preventive interventions.

Diets with high carbohydrate contents were associated with refeeding hypophosphatemia: A retrospective study in Japanese inpatients with anorexia nervosa.

OBJECTIVE: Refeeding hypophosphatemia (RH) is a potentially fatal complication in patients with anorexia nervosa (AN), and its dietary preventive strategy is not well established. We aimed to examine the association between carbohydrate content in the diet and the occurrence of RH in inpatients with AN via retrospective medical chart review. METHOD: We performed a chart review to collect data of patients with AN hospitalized at the Department of Psychosomatic Medicine of the University of Tokyo Hospital between April 1, 2012, and February 29, 2020. Receiver operating characteristic (ROC) analysis was performed to determine the cutoff point of the percentage of carbohydrate content in the diet for the occurrence of RH. Multivariate logistic regression analysis was performed with occurrence of RH as the dependent variable and the carbohydrate content of more than the identified cutoff point as the independent variable adjusting for the risk factors for RH. RESULTS: The percentage of carbohydrate content that is higher than the cutoff point obtained from the ROC analysis (58.4%) was significantly associated with the occurrence of RH, even after adjusting for variables associated with RH in univariate logistic regression analysis (age and body mass index) as well as the average daily calorie intake (odds ratio, 5.37; 95% confidence interval, 1.60-18.1; p = .0066). DISCUSSION: We identified that diets with higher carbohydrate contents were associated with RH in inpatients with AN, even after adjusting for known risk factors. Our findings may promote the development of dietary preventive strategies against RH in inpatients with AN.

Psychometric properties of the Eating Disorder Examination-Questionnaire and psychopathology in Japanese patients with eating disorders.

OBJECTIVE: The Eating Disorder Examination-Questionnaire (EDE-Q) is one of the most widely used tools to assess the core psychopathology of eating disorders (ED). However, recent empirical findings did not support the original four-factor structure. The aims of the present study were to investigate the factor structure of the EDE-Q in Japanese ED patients, to test the reliability and convergent validity of the EDE-Q, to examine group differences between various ED groups and healthy participants, and to explore the main behavioral features of Japanese ED patients using the newly developed Japanese version of EDE-Q. METHOD: A total of 148 ED patients and 469 healthy participants completed the EDE-Q, Eating Attitudes Test-26 (EAT-26), and Eating Disorder Inventory-2 (EDI-2). The factor structure, reliability, and validity of the EDE-Q were assessed in ED patients. Group differences were assessed using the new Japanese version of the EDE-Q (EDE-Q-J). RESULTS: The EDE-Q-J had three factors. Cronbach's alphas ranged from 0.83 to 0.93. Total score and subscale scores of "Dieting" and "Bulimia and Food Preoccupation" of EAT-26 and of "Drive for Thinness," "Body Dissatisfaction," and "Bulimia" of EDI-2 correlated with the global score and three subscale scores of the EDE-Q-J. DISCUSSION: For Japanese female ED patients, the EDE-Q-J had three subscales that were not consistent with the original subscales, but were interpretable. It demonstrated sufficient reliability and validity. Japanese female patients with restricting-type anorexia nervosa (AN-R) displayed less dissatisfaction with shape and weight than healthy participants. AN-R patients in Japan might present with a non-fat-phobic symptom profile.

Association between ambulance use and hospitalization costs among heart failure patients.

Heart failure is the main cause of hospitalization, which burdens the healthcare system. Although many hospitalizations for heart failure follow ambulance use, it is unknown whether ambulance use increases hospitalization costs. Using the Diagnosis Procedure Combination database in Japan, we examined all hospitalizations of patients with heart failure from April 2014 to March 2015. Patients were divided into those with and those without ambulance use. We performed a multiple regression analysis to examine the association between ambulance use and total hospitalization costs, adjusting for age, sex, length of day, and activities of daily living. We identified 126,067 hospitalizations for heart failure. The percentages of ambulance use were 29%, 27%, 30%, and 50% among patients with NYHA Functional Classification I, II, III, and IV, respectively. For patients categorized as NYHA I (n = 9,700), multiple linear regression analysis revealed that ambulance use was significantly associated with higher hospitalization cost (coefficient 723 USD; 95% confidence interval 109-1337; p = 0.021). Even for heart failure patients with NYHA I, ambulances were frequently used. Ambulance use was independently associated with increased hospital costs. Future research is needed on transitional care to limit unnecessary ambulance use.

Psychometric properties of the fear of food measure in Japanese women.

PURPOSE: The aim of the present study was to investigate the psychometric properties of the fear of food measure (FOFM) in Japanese women. METHODS: This study was a cross-sectional, observational, and multicenter study conducted at the University of Tokyo and Kyushu University. Participants were comprised of 169 healthy women and 149 patients with eating disorders. First, the present study explored the factor structure of FOFM in Japanese women using exploratory factor analyses. Then, the Cronbach's alpha and McDonald's omega were calculated to assess reliability. Concurrent validity was examined by calculating correlation coefficients with the Eating Attitudes Test, negative affect of Positive and Negative Affect Schedule, and Hospital Anxiety and Depression Scale. Additionally, the Wilcoxon rank-sum test was used to compare scores between the healthy control and patient group. RESULTS: The final model had four subscales. The subscales, thus, had high reliability and showed significant positive correlations with the questionnaires. The scores of subscales in the patient group were significantly higher than those in the healthy control group. CONCLUSIONS: The FOFM had a four-factor structure in Japanese women. Its reliability and validity were verified and it could be used as a tool to assess fear of food. LEVEL OF EVIDENCE: III, case-control analytic study.

Are common delirium assessment tools appropriate for evaluating delirium at the end of life in cancer patients?

OBJECTIVES: The objectives of this study are to investigate how many advanced cancer patients became unconscious or non-communicative after pharmacological treatment for delirium, and to explore whether existing delirium assessment tools can successfully evaluate its severity at the end of life. METHODS: This was a secondary analysis of a registry study that examined the efficacy and safety of antipsychotics for advanced cancer patients with delirium. A total of 818 patients were recruited from 39 specialized palliative care services in Japan. The severity of delirium was measured using the Richmond Agitation-Sedation Scale-Palliative care version, the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Nursing Delirium Screening Scale (Nu-DESC) on Day 3. Data from 302 patients with motor anxiety with an Agitation Distress Scale score ≥2 on Day 0 were analyzed for this study. The patients were categorized into four treatment response groups: complete response (CR: no agitation and fully communicative), partial response (PR: no/mild agitation and partially communicative), unconscious/non-communicative (UC), and no change (NC). RESULTS: On Day 3, 29 (10%; 95% confidence intervals [CI], 7-13) and 2 (1%; 95% CI, 0-2) patients became unconscious and non-communicative, respectively. Forty-four patients were categorized as CR, 97 as PR, 31 as UC, and 96 as NC. The scores of the DRS-R-98 and Nu-DESC in the UC group were rated higher than patients in the NC group were. CONCLUSIONS: A considerable number of cancer patients with delirium became unconscious or non-communicative. Existing delirium assessment tools may be inappropriate for measuring the severity of delirium in end-of-life.

Peak C-reactive protein levels do not predict 30-day mortality for bacteremia: A retrospective cohort study.

INTRODUCTION: Although peak C-reactive protein (CRP) levels are correlated with the prognosis of some diseases, there have been no reports regarding the association between peak CRP levels and mortality in patients with bacteremia. The present study aimed to determine the association between peak CRP levels and prognosis in patients with bacteremia. METHODS: This retrospective cohort study was conducted in a single tertiary hospital and included patients with bacteremia admitted to the emergency department from November 2012 to March 2017. Cox regression analysis was performed to examine the association between peak CRP levels and 30-day mortality. We also performed propensity score adjustment using potential confounding factors. RESULTS: One hundred fifty-nine patients were included in the study. Peak CRP levels were significantly higher in the ß-hemolytic streptococci (P = 0.001) and Streptococcus pneumoniae (P = 0.003) groups. The C-statistic of the multivariate logistic regression model for the propensity score was 0.88. For 30-day mortality, peak CRP levels >20 mg/dL did not show significance in the Cox regression analysis (hazard ratio, 0.866; 95% confidence interval, 0.489-1.537; P = 0.62). Even after propensity score adjustment, no significance was noted (hazard ratio, 0.865; 95% confidence interval, 0.399-1.876; P = 0.71). CONCLUSIONS: Peak CRP levels were not an independent predictor of mortality in patients with bacteremia in the emergency department. Clinicians should consider that patients with extremely high peak CRP levels do not necessarily have high mortality and vice versa.

Current Pharmacotherapy Does Not Improve Severity of Hypoactive Delirium in Patients with Advanced Cancer: Pharmacological Audit Study of Safety and Efficacy in Real World (Phase-R).

BACKGROUND: Pharmacotherapy is generally recommended to treat patients with delirium. We sought to describe the current practice, effectiveness, and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer, and to explore predictors of the deterioration of delirium symptoms after starting pharmacotherapy. SUBJECTS, MATERIALS, AND METHODS: We included data of patients with advanced cancer who were diagnosed with hypoactive delirium and received pharmacotherapy for treatment of delirium. This was a pharmacovigilance study characterized by prospective registries and systematic data-recording using internet technology, conducted among 38 palliative care teams and/or units. The severity of delirium and other outcomes were assessed using established measures at days 0 (T0), 3 (T1), and 7 (T2). RESULTS: Available data were obtained from 218 patients. The most frequently used agent was haloperidol (37%). A total of 67 and 42 patients (31% and 19%) had died or discontinued pharmacotherapy by T1 and T2, respectively. Delirium symptoms deteriorated between T0 and T1, but this trend did not reach statistical significance. The most prevalent adverse event was sedation (9%). Delirium severity worsened after starting pharmacotherapy in 121 patients (56%) at T1. In patients whose death was expected within a few days and those with delirium caused by organ failure, symptoms of delirium were significantly more likely to deteriorate after starting pharmacotherapy. CONCLUSION: Current pharmacotherapy for hypoactive delirium in patients with advanced cancer is not recommended, especially in those whose death is expected within a few days and in those with delirium caused by organ failure. IMPLICATIONS FOR PRACTICE: Delirium is common among patients with advanced cancer, and hypoactive delirium is the dominant motor subtype in the palliative care setting. Pharmacotherapy is recommended and regularly used to treat delirium. This article describes the effectiveness and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer. The findings of this study do not support the use of pharmacotherapy for treatment of hypoactive delirium in the palliative care setting. Pharmacotherapy should especially be avoided in patients whose death is expected within a few days and in those with delirium caused by organ failure.

Body mass index cut-off point associated with refeeding hypophosphatemia in adults with eating disorders.

OBJECTIVE: Refeeding hypophosphatemia (RH) is a life-threatening complication in underweight patients with eating disorders (EDs). Although a lower body mass index (BMI) has been reported as a risk factor for RH, the exact BMI cut-off point is not known. Herein, we aimed to identify the optimal BMI cut-off point for RH in adults with EDs. METHOD: The medical charts of Japanese inpatients with EDs at our hospital between April 1, 2012 and March 31, 2017 were retrospectively reviewed. The optimal BMI cut-off point for RH was determined via receiver operating characteristic analysis. Logistic regression analysis was subsequently performed to assess the association between RH and the BMI cut-off point after adjusting for the propensity score, which was based on known risk factors for RH. RESULTS: The optimal BMI cut-off point was identified as 12.6 kg/m2 . A BMI lower than the cut-off point significantly correlated with the occurrence of RH after adjusting for the propensity score. DISCUSSION: The optimal BMI cut-off point for the occurrence of RH was 12.6 kg/m2 in adults with EDs. The findings of the present study may facilitate clinical decision making and early identification of patients who require prophylactic treatment for RH.

Changes in and Interactions between Physical and Mental Health in Older Japanese: The Nakanojo Study.

BACKGROUND: An age-related decrease in functional capacity is consistently reported, but it is not consistently related to a worsening of health-related quality of life (HRQOL) or psychological adjustment. A poor functional capacity and HRQOL have been associated with anxiety or depression, but the possible causal nature and direction of the relationship remain to be explored using long-term longitudinal data. OBJECTIVE: The purpose of this study was to examine age-related changes in functional capacity, HRQOL, and scores on the Hospital Anxiety and Depression Scale (HADS), and possible causal interrelationships between these variables. METHODS: Study participants were 5,124 Japanese aged ≥65 years. After the baseline study (2003), annual follow-up observations continued for 10 years. Generalized linear mixed models examined age-related changes in Barthel index (BI), Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), HRQOL, and HADS. Cross-lagged effects models tested possible causal interrelationships. RESULTS: With age, functional capacity and HRQOL scores showed similar declines in both sexes. Changes in mental health, anxiety, and depression developed more slowly than decreases in physical health (BI, TMIG-IC, and physical functioning scores). Cross-lagged effects models demonstrated that functional capacity had positive effects on psychological adjustment, and that psychological adjustment had positive effects on functional capacity 5 years later. Interactions between functional capacity and psychological adjustment showed no sex differences. A decline in functional capacity negatively affected psychological adjustment, but reduced psychological adjustment had no significant impact on functional capacity 5 and 10 years later. Moreover, functional capacity and poor psychological adjustment showed no interactions in either sex. CONCLUSION: Functional capacity and mood state are interrelated. Greater function could sustain vitality and mental health, possibly reducing anxiety and depression.

Long-term influence of adjuvant breast radiotherapy on cognitive function in breast cancer patients treated with conservation therapy.

BACKGROUND: The mechanisms underlying cognitive decline after radiotherapy not directed at brain areas remains unclear. We previously suggested that adjuvant breast radiotherapy in breast conservation therapy could lower memory function soon after therapy, and that the process might be partially mediated by plasma interleukin (IL)-6 levels. The present study investigated how that relationship changes longitudinally. METHODS: We performed the Wechsler Memory Scale-Revised (WMS-R) test and measured plasma IL-6 levels for 47 breast cancer surgical patients within 1 year after the initial therapy (study 1) and more than 2 years after study 1 (study 2). We also performed 2 × 2 mixed [the radiotherapy group (n = 25) or the no-radiotherapy group (n = 22) × study 1 or study 2] analysis of covariance on the WMS-R indices and plasma IL-6 levels. The association between changes in plasma IL-6 levels and changes in the WMS-R indices between the two studies was evaluated using Pearson's correlation coefficient. RESULTS: The Immediate Verbal Memory Index was significantly higher in study 2. The Delayed Recall Index was significantly higher in study 2 and significantly lower in the radiotherapy group only in study 1. There was a significant correlation between changes in plasma IL-6 levels and changes only in the Delayed Recall Index of the WMS-R. CONCLUSIONS: Memory decline in breast cancer patients soon after adjuvant breast radiotherapy was restored approximately 3 years after treatment, and decreased plasma IL-6 levels might be involved in the recovery process.