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.

A revision of JPOS/JASCC clinical guidelines for delirium in adult cancer patients: a summary of recommendation statements.

OBJECTIVE: The Japanese Psycho-Oncology Society and the Japanese Association of Supportive Care in Cancer have recently revised the clinical practice guidelines for delirium in adult cancer patients. This article reports the process of developing the revised guidelines and summarizes the recommendations made. METHODS: The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multi-disciplinary members, created three new clinical questions: non-pharmacological intervention and antipsychotics for the prevention of delirium and trazodone for the management of delirium. In addition, systematic reviews of nine existing clinical questions have been updated. Two independent reviewers reviewed the proposed articles. The certainty of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development, and Evaluation system. The modified Delphi method was used to validate the recommended statements. RESULTS: This article provides a compendium of the recommendations along with their rationales, as well as a short summary. CONCLUSIONS: These revised guidelines will be useful for the prevention, assessment and management of delirium in adult cancer patients in Japan.

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.

[Management of Delirium in Patients with Cancer].

Delirium is a condition in which the main symptom is a mild disturbance of consciousness caused by a physical abnormality or medication, and various symptoms such as cognitive dysfunction, hallucinations, delusions, and mood swings appear with any disease. Delirium is frequently observed in patients with cancer, especially in the terminal stage, and is observed in about 90% of patients just before death. Hypercalcemia due to bone metastases, brain metastases, and the use of opioids and steroids for symptom relief are direct factors in the development of delirium. Furthermore, there are many opportunities to encounter delirium at the end of life caused by conditions that are difficult to recover from, such as brain metastasis, liver failure, and hypoxic encephalopathy. In the management of delirium, "search for the cause(s)and its treatment"and"environmental adjustment"are the most important. Then, pharmacotherapy is considered to reduce the severity of delirium. Antipsychotics are the basic medication of choice. The route of administration, half-life, dosage form, adverse events of medication, as well as patient factors such as the presence or absence of diabetes and the subtype of delirium should be comprehensively considered when selecting a medication. The timing of medication discontinuation should also be kept in mind once medication therapy is initiated. On the other hand, when delirium is caused by factors that are difficult to recover from, the goal of treatment is to alleviate the painful symptoms caused by delirium, and it is important to take a holistic approach for patients and family members.

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.

JPOS/JASCC clinical guidelines for delirium in adult cancer patients: a summary of recommendation statements.

BACKGROUND: The Japanese Psycho-Oncology Society and Japanese Association of Supportive Care in Cancer recently launched the clinical practice guidelines for delirium in adult cancer patients. The aim of the guidelines was to provide evidence-based recommendations for the clinical assessment and management of delirium in cancer patients. This article reports the process of developing the guideline and summarizes the recommendations made. METHODS: The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multidisciplinary members, formulated nine clinical questions. A systematic literature search was conducted to identify relevant articles published prior to through 31 May 2016. Each article was reviewed by two independent reviewers. The level of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development and Evaluation system. The modified Delphi method was used to validate the recommendation statements. RESULTS: This article provides a summary of the recommendations with rationales for each, as well as a short summary. CONCLUSIONS: These guidelines will support the clinical assessment and management of delirium in cancer patients. However, additional clinical studies are warranted to further improve the management of delirium.

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.

Pilot Study for the Development of a Self-Care System for Type 2 Diabetes Patients Using a Personal Digital Assistant (PDA).

PURPOSE: The primary objective of the present pilot study was to investigate the feasibility and acceptability of the newly developed self-care system using personal digital assistance in patients with type 2 diabetes. The secondary objective was to investigate changes in daily calorie intake, body weight, and hemoglobin A1c after using the system for 6 months. METHOD: The participants were nine outpatients with type 2 diabetes, aged 34-72 and living in Tokyo or surrounding prefectures. They were instructed to use the electronic food diary and to review the graphs of the total energy intake to control food intake under their own target value for 6 months. After they completed the study, the feasibility indicated by adherence rate for food recording and acceptability of the system rated with 6-point Likert scale from 1 (worst) to 6 (best) by the participants were investigated. RESULTS: Seven participants out of nine completed the study protocol. The median adherence rate for food recording was 80.6 %. Regarding the acceptability, six patients rated 6 for desire to use the system while one rated 5. In addition, regarding improvement in self-care for diabetes, the median score was 5. Daily calorie intake, body weight, and HbA1c, however, did not change significantly over the 6-month period. CONCLUSION: The newly developed self-care system might be feasible and acceptable in diabetes patients, which could be applied as an ecological momentary intervention tool, although there was some room to refine it to raise adherence.

Economic costs for outpatient treatment of eating disorders in Japan.

BACKGROUND: Few studies have examined the economic costs of outpatient care for eating disorders in Japan. This study aimed to clarify the reimbursement for outpatient treatment of eating disorders and compare the costs between the departments of Psychosomatic Medicine and Psychiatry in Japan. METHOD: A multicenter, prospective, observational study of patients with an eating disorder was conducted in the Psychosomatic Medicine departments of three centers and the Psychiatry departments of another three centers in Japan. We analyzed medical reimbursement for an outpatient revisit, time of clinical interviews, and the treatment outcome measured by the Eating Disorder Examination Questionnaire (EDE-Q) global scores and body mass index (BMI) at 3 months. Multivariate linear regression models were performed to adjust for covariates. RESULTS: This study included 188 patients in the Psychosomatic Medicine departments and 68 in the Psychiatry departments. The average reimbursement cost for an outpatient revisit was 4670 yen. Even after controlling for covariates, the Psychosomatic Medicine departments had lower reimbursement points per minute of interviews than the Psychiatry departments (coefficient = - 23.86; 95% confidence interval = - 32.09 to - 15.63; P < 0.001). In contrast, EDE-Q global scores and BMI at 3 months were not significantly different between these departments. CONCLUSIONS: This study clarifies the economic costs of treating outpatients with eating disorders in Japan. The medical reimbursement points per interview minute were lower in Psychosomatic Medicine departments than in Psychiatry departments, while there were no apparent differences in the treatment outcomes. Addressing this issue is necessary to provide an adequate healthcare system for patients with eating disorders in Japan.

This study examined the cost of outpatient care for eating disorders in Japan, comparing treatment costs between the Psychosomatic Medicine and Psychiatry departments. The actual cost of outpatient care for eating disorders in Japan was clarified. The results indicate that Psychosomatic Medicine departments have lower reimbursement points per interview time compared to the Psychiatry departments, but there were no noticeable differences in treatment outcomes between the two. This highlights the need to address this cost difference to improve the healthcare system for patients with eating disorders in Japan.

Development of computer adaptive testing for measuring depression in patients with cancer.

The usefulness of depression scales for patients with cancer based on item response theory (IRT) and computer adaptive testing (CAT) has not yet been fully explored. This study thus aimed to develop an IRT-based tool for measuring depression in patients with cancer. We analyzed data from 393 patients with cancer from four tertiary centers in Japan who had not received psychiatric treatment. They answered 62 questions across five categories regarding their psychiatric status over the previous week. We selected 28 items that satisfied the assumptions of IRT, fitted a graded response model to these items, and performed CAT simulations. The CAT simulation used an average of 6.96 items and showed a Pearson's correlation coefficient of 0.916 (95% confidence interval, 0.899-0.931) between the degree of depression estimated by simulation and that estimated using all 28 items. The measurement precision of CAT with only four items was superior to that of the estimation using the calibrated Patient Health Questionnaire-9. These results imply that this scale is useful and accurate for measuring depression in patients with cancer.

Trajectories of objectively measured physical activity and mood states in older Japanese adults: longitudinal data from the Nakanojo Study.

BACKGROUND: Japan, like many developed countries, now faces fiscal problems from the escalating health-care expenditures associated with an aging population. Mental health problems such as depression contribute as much to these growing demands as physical disease, and measures to prevent depression are important to controlling costs. There are few longitudinal studies examining the relation between objectively measured physical activity and depressive symptoms. Therefore, the aims of our study were to explore the patterns of change of physical activity in older Japanese adults for 5 years through the use of trajectory analysis and to examine the relation between physical activity trajectories and depressive mood states. MAIN BODY: Ninety-two male and 99 female volunteers aged 65-85 years were asked to equip themselves with an electronic accelerometer with a 60-day storage capacity for at least 5 years. The parameters calculated each July for the 5 years were the average daily step count and the average daily duration of activity > 3 METs (moderate to vigorous physical activity: MVPA). Hospital Anxiety and Depression Scale (HADS) assessed corresponding mood states (HADS-A and HADS-D). Trajectories of the accelerometer data were analyzed and fifth-year HADS-D and HADS-A scores were compared among trajectory groups using an analysis of covariance (ANCOVA) that controlled for baseline scores and for baseline scores and age. Six and five distinct trajectories were identified for daily step count and for daily duration of MVPA, respectively. Using ANCOVA controlling for baseline scores, HADS-D scores differed significantly among trajectory groups classed by daily duration of MVPA (p = 0.04), and Tukey's multiple comparison tests showed significant differences between group 2, whose pattern was stable with the middle duration of MVPA, and group 1, whose pattern was stable with the lowest duration of MVPA (p = 0.02), while the results were not significant controlling for both baseline scores and age. CONCLUSIONS: Older people with less MVPA continued to do less MVPA over the 5 years of study, which may be related to a future more depressive mood. Further clinical studies will be necessary to clarify these findings.

Thrombopoietin and thrombocytopenia in anorexia nervosa with severe liver dysfunction.

OBJECTIVE/METHOD: Patients with anorexia nervosa (AN) display various physical complications. One such problem is thrombocytopenia. However, no studies have investigated links between AN and thrombopoietin (TPO), which is the primary regulator of megakaryocyte and platelet production produced mainly in the liver, although TPO has been recently reported to play a role in thrombocytopenia in liver diseases. We therefore clarified temporal relationships between platelet counts and TPO level in a woman with AN and severe liver dysfunction in whom platelet count decreased to 53 x 109/L. RESULTS: While international normalized ratio (INR) was low, serum TPO level was relatively low despite low platelet counts. After INR and liver enzymes improved in conjunction with improved nutritional status, a rapid increase in TPO was observed and platelet count began to rise. DISCUSSION: These findings thus suggest that decreased TPO production accompanying liver dysfunction may be related to thrombocytopenia besides myelosuppression in AN with malnutrition.

Preceding psychological factors and calorie intake in patients with type 2 diabetes: investigation by ecological momentary assessment.

BACKGROUND: Psychological factors have been reported to have influence on the eating habits of patients with diabetes. However, previous studies have used questionnaires to investigate the association, and thus include recall bias. To overcome this disadvantage, ecological momentary assessment (EMA) can be used to record subjective symptoms and behavior in subjects' daily lives. Therefore, the aim of the present study was to investigate the influence of preceding psychological factors on calorie intake using computerized EMA for 6 months. METHODS: The participants were nine outpatients with type 2 diabetes, aged 34-72. They were instructed to use a personal digital assistant as an electronic diary for 6 months to record subjective symptoms, such as psychological stress, anxiety, and depressive mood, and the food and drink that they consumed. The association between a preceding psychological factor and calorie intake within 5 hours was investigated using multilevel modeling. RESULTS: Preceding psychological stress was positively associated with calorie intake from snacks. Preceding psychological stress, anxiety, and depressive mood were negatively associated with calorie intake from regular meals. CONCLUSIONS: Preceding psychological factors influence the calorie intake of patients with type 2 diabetes. Understanding the role of these factors will be useful for developing psychological interventions to prevent overeating. TRIAL REGISTRATION: The trial registration number: UMIN000002992. Date of registration: 2010/01/07.

A series of patients with purging type anorexia nervosa who do "tube vomiting".

BACKGROUND: It is important for clinicians to assess their patients' purging behavior. Various methods of purging, such as self-induced vomiting are well-known. Because patients do not always report their purging behavior, knowing the clinical signs that indicate the behavior is useful. However, we have experienced patients who did not have the reported physical signs of self-induced vomiting because they used hoses instead of their fingers to purge their stomach contents, which they call "tube vomiting". No other previous studies have reported the use of hoses as a purging tool. CASE PRESENTATION: We present as our main case a 20-year-old Japanese woman with anorexia nervosa who engaged in "tube vomiting." Although she recovered well under medical treatment in our hospital, she began to lose weight and blood potassium soon after discharge. We found that she used a garden hose instead of her fingers to perform self-induced vomiting,. She inserted the hose into her stomach and evacuated the stomach contents through it, without pain. She learned this technique through a blog about eating disorders. We also present two other similar cases. In fact, many patients discuss "tube vomiting" on the internet. CONCLUSION: Our experience suggests that a sudden decrease in the weight and blood potassium level could indicate "tube vomiting". In addition, because many information resources are available on the internet, medical practitioners should be aware of these sites.

Development of an ecological momentary assessment scale for appetite.

BACKGROUND: An understanding of eating behaviors is an important element of health education and treatment in clinical populations. To understand the biopsychosocial profile of eating behaviors in an ecologically valid way, ecological momentary assessment (EMA) is appropriate because its use is able to overcome the recall bias in patient-reported outcomes (PROs). As appetite is a key PRO associated with eating behaviors, this study was done to develop an EMA scale to evaluate the within-individual variation of momentary appetite and uses this scale to discuss the relationships between appetite and various psychological factors. METHODS: Twenty healthy participants (age 23.6 ± 4.2 years old) wore a watch-type computer for a week. Several times a day, including just before and after meals, they recorded their momentary psychological stress, mood states, and ten items related to appetite. In addition, they recorded everything they ate and drank into a personal digital assistant (PDA)-based food diary. Multilevel factor analysis was used to investigate the factor structure of the scale, and the reliability and validity of the scale were also explored. RESULTS: Multilevel factor analyses found two factors at the within-individual level (hunger/fullness and cravings) and one factor at the between-individual level. Medians for the individually calculated Cronbach's alphas were 0.89 for hunger/fullness, 0.71 for cravings, and 0.86 for total appetite (the sum of all items). Hunger/fullness, cravings, and total appetite all decreased significantly after meals compared with those before meals, and hunger/fullness, cravings, and total appetite before meals were positively associated with energy intake. There were significant negative associations between both hunger/fullness and total appetite and anxiety and depression as well as between cravings, and depression, anxiety and stress. CONCLUSIONS: The within-individual reliability of the EMA scale to assess momentary appetite was confirmed in most subjects and it was also validated as a useful tool to understand eating behaviors in daily settings. Further refinement of the scale is necessary and further investigations need to be conducted, particularly on clinical populations.

Assessment of Cancer-Related Fatigue, Pain, and Quality of Life in Cancer Patients at Palliative Care Team Referral: A Multicenter Observational Study (JORTC PAL-09).

INTRODUCTION: Cancer-related fatigue greatly influences quality of life in cancer patients; however, no specific treatments have been established for cancer-related fatigue, and at present, no medication has been approved in Japan. Systematic research using patient-reported outcome to examine symptoms, particularly fatigue, has not been conducted in palliative care settings in Japan. The objective was to evaluate fatigue, pain, and quality of life in cancer patients at the point of intervention by palliative care teams. MATERIALS AND METHODS: Patients who were referred to palliative care teams at three institutions and met the inclusion criteria were invited to complete the Brief Fatigue Inventory, Brief Pain Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative. RESULTS: Of 183 patients recruited, the majority (85.8%) were diagnosed with recurrence or metastasis. The largest group (42.6%) comprised lung cancer patients, of whom 67.2% had an Eastern Cooperative Oncology Group Performance Status of 0-1. The mean value for global health status/quality of life was 41.4, and the highest mean European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative symptom item score was for pain (51.0). The mean global fatigue score was 4.1, and 9.8%, 30.6%, 38.7%, and 20.8% of patients' fatigue severity was classified as none (score 0), mild (1-3), moderate (4-6), and severe (7-10), respectively. DISCUSSION: Cancer-related fatigue, considered to occur more frequently in cancer patients, was successfully assessed using patient-reported outcomes with the Brief Fatigue Inventory for the first time in Japan. Results suggested that fatigue is potentially as problematic as pain, which is the main reason for palliative care.

Development of a hand-held personal digital assistant-based food diary with food photographs for Japanese subjects.

Hand-held personal digital assistant (PDA)-based food diaries have been developed for self-monitoring of dietary intake, but the accuracy of these diaries is unclear for patients with diabetes. The aim of the study was to assess the accuracy and feasibility of use of a new PDA-based food diary, including food photographs. The study included 44 Japanese participants without diabetes (mean age 23 years) and 16 Japanese patients with type 2 diabetes (mean age 53 years). The PDA-based food diary was used for 7 consecutive days. Information about all dietary intake on the 7th day of PDA self-monitoring was collected by a 24-hour recall interview on the 8th day. The PDA-based data for dietary intake on the 7th day were then compared to the 24-hour recall data for the same period. Feasibility was assessed based on the frequency and timeliness of self-monitoring. There was no significant difference in daily totals for energy, protein, carbohydrate, and fat between the two methods in each group. Pearson's correlation and intraclass correlation coefficients showed strong significant relationships for all variables between the two methods in both groups. Bland-Altman plots did not indicate any bias in estimated daily caloric intake. Participants recorded 98% of their meals in the PDA, with 75% of entries recorded within 6 hours after the meal starting time. The findings suggest that the PDA-based food diary is a potential clinical method to estimate dietary intake and may be a beneficial tool for self-monitoring of dietary intake.

Comparison of temporal changes in psychological distress after hematopoietic stem cell transplantation among the underlying diseases of Japanese adult patients.

BACKGROUND: Although hematopoietic stem cell transplantation (HSCT) can potentially cure some hematological malignancies, patients who undergo HSCT experience psychological distress. However, there have been few studies on the short-term influence of HSCT on psychological distress. METHODS: The subjects were 71 patients with hematological malignancies who underwent HSCT: 33 with acute leukemia, 19 with chronic leukemia, nine with myelodysplastic syndrome, and 10 with malignant lymphoma. Psychological distress was assessed prior to HSCT and on the seventh day after HSCT using the Profile of Mood States (POMS). RESULTS: With regard to Anger-Hostility, the interaction of time (pre- and post-HSCT) and group (the four groups) was significant in male patients (p = 0.04), but not in female patients. With regard to the other subscales of POMS, there was no significant main effect or interaction in male or female patients. CONCLUSION: It may be important to provide psychological support to patients throughout the period of HSCT in consideration of differences in mood changes associated with the underlying disease and patient sex in order to provide efficient psychiatric intervention for both better psychiatric and survival outcomes.