Successful switch to cisplatin-based chemotherapy in a patient with lung cancer who developed a carboplatin-induced hypersensitivity reaction.

INTRODUCTION: Platinum-based chemotherapy is the mainstay of first-line therapy for advanced-stage non-small cell lung cancer (NSCLC). Although carboplatin-induced hypersensitivity reactions (HSRs) commonly occur following multiple cycles of therapy, they are rarely observed during the first cycle of the treatment. CASE REPORT: Here, we report the case of a 70-year-old man with advanced-stage NSCLC who developed HSR possibly caused by carboplatin during the first cycle of induction with platinum-doublet chemotherapy plus pembrolizumab. The patient presented with bronchial obstruction due to a centrally located tumor. No driver mutations were detected, and the programmed death-ligand 1 expression ranged from 1% to 24%. Consequently, the patient was treated with pembrolizumab combined with carboplatin and paclitaxel. However, immediately after the start of carboplatin, the blood pressure and oxygen levels of the patient dropped and he began exhibiting an altered level of consciousness. These findings indicated carboplatin-induced anaphylaxis. Hypotension and oxygen desaturation improved following carboplatin discontinuation and normal saline administration. MANAGEMENT AND OUTCOME: The basophil activation test for both carboplatin and cisplatin was negative. Thus, the risk of anaphylaxis owing to both drugs was ruled out, and carboplatin was believed to have induced grade 3 HSR. Subsequently, carboplatin-based chemotherapy was switched to cisplatin-based chemotherapy. HSR was not observed during the four treatment cycles with pembrolizumab, cisplatin, and pemetrexed, and best response was partial response. DISCUSSION: Cisplatin-based chemotherapy could be used as an alternate treatment in patients with NSCLC who develop severe carboplatin-induced HSR.

Fecundity is optimized by levels of nutrient signal-dependent expression of Dve and EcR in Drosophila male accessory gland.

Steroid hormones play various physiological roles including metabolism and reproduction. Steroid hormones in insects are ecdysteroids, and the major form in Drosophila melanogaster is ecdysone. In Drosophila males, the accessory gland is responsive to nutrient-dependent regulation of fertility/fecundity. The accessory gland is composed of two types of binucleated epithelial cells: a main cell and a secondary cell (SC). The transcription factors Defective proventriculus (Dve), Abdominal-B, and Ecdysone receptors (EcRs) are strongly expressed in adult SCs. We show that this EcR expression is regulated by parallel pathways of nutrient signaling and the Dve activity. Induction of Dve expression is also dependent on nutrient signaling, and it becomes nutrient signal-independent during a restricted period of development. Forced dve expression during the restricted period significantly increased the number of SCs. Here, we provide evidence that the level of nutrient signal-dependent Dve expression during the restricted period determines the number of SCs, and that ecdysone signaling is also crucial to optimize male fecundity through nutrient signal-dependent survival and maturation of SCs.

Real-world predictors of divorce among outpatients with bipolar disorder: sex differences and clinical implications.

BACKGROUND: Bipolar disorder is a mental illness characterized by recurring episodes of mania and depression and is known to cause social impairment. Additionally, it has been revealed that bipolar disorder increases the risk of divorce and loss of family member support, which can worsen the prognosis. However, there is limited evidence regarding the predictive factors of divorce among patients with bipolar disorder in real-world settings. METHODS: This study utilized an observational approach and involved psychiatrists from 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. They were requested to conduct a retrospective review of medical records and complete a questionnaire focused on patients diagnosed with bipolar disorder. The data collection period for baseline patient characteristics spanned from September to October 2017. Next, we investigated the incidence of divorce over a 2-year period, ranging from baseline to September to October 2019. RESULTS: A total of 1071 outpatients with bipolar disorder were included in the analysis, and 2.8% (30/1071) experienced divorce during the first 2 years of observation. The incidence of divorce in this population was considerably higher than that in the general Japanese population. Binomial logistic regression analysis confirmed that a younger baseline age and lower BMI values were statistically significant predictors of divorce occurrence for all study participants. The predictors of divorce were then examined separately by sex. The results revealed that for men, a younger age at baseline and having bipolar I disorder compared to bipolar II disorder were statistically significant predictors of divorce. In contrast, for women, having a lower BMI and using anxiolytics emerged as statistically significant predictors of divorce. CONCLUSIONS: In this study, a younger baseline age and lower BMI values were statistically significant predictors of divorce in patients with bipolar disorder. Notably, the predictors of divorce varied significantly between men and women. These findings provide important insights from a family perspective regarding social support for individuals with bipolar disorder in real-world clinical settings.

Prognostic Impact of Central Nervous System Recurrence After Surgery in Patients With Epidermal Growth Factor Receptor Mutation-positive Non-small-cell Lung Cancer.

BACKGROUND/AIM: Adjuvant therapy using third-generation tyrosine kinase inhibitors (TKI) demonstrated improved central nervous system (CNS) disease-free survival after surgery in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, the prognostic impact of CNS recurrence in surgical patients remains unknown. We evaluated the effect of CNS recurrence on post-recurrence survival (PRS) in patients with postoperatively recurrent NSCLC. PATIENTS AND METHODS: We assessed the prognostic impact of CNS recurrence using a cohort from a prospective observational study (Kyushu University Lung Surgery Group Study 2: KLSS-2). Based on data from 340 patients in whom EGFR mutations were assessed among 498 total patients in the KLSS-2 cohort, factors related to CNS recurrence and prognosis after postoperative recurrence were analyzed. RESULTS: We noted no marked differences in the presence of EGFR mutations (p=0.14) between patients with CNS recurrence and those without CNS recurrence. Among the patients tested for EGFR mutations with stage IV recurrences (n=219), survival analysis of patients with EGFR mutations showed that the CNS group had a significantly poorer PRS than the no-CNS group (MST: 36.8 vs. 43.9 months, p=0.035). In multivariate survival analysis of stage IV EGFR mutation-positive cases, recurrence in multiple organs and recurrence of brain metastases were independent poor prognostic factors (hazard ratio=2.2, p=0.029; hazard ratio=3.2, p=0.0006, respectively). CONCLUSION: Postoperative CNS recurrence was associated with a poor prognosis among patients with EGFR mutation-positive lung cancer in the period when third-generation EGFR-TKIs were not available. In EGFR mutation-positive lung cancer, prevention of CNS recurrence after surgery may improve post-recurrence prognosis.

Costs of psychotropics for outpatients with bipolar disorder in Japan; the MUSUBI 2016 survey.

BACKGROUND: Although the costs of bipolar disorder (BD) treatments are associated with local and universal factors, data from non-Western countries remain limited. The associations between clinical features and costs of outpatient pharmacotherapy have not been well characterize. To estimate the costs of outpatient BD treatments and their associations with clinical features in a Japanese population, we investigated with special reference to the costs of medicines constituted the bulk of the total healthcare expense and were steadily increasing. METHODS: The Multicenter Treatment Survey for Bipolar Disorder (MUSUBI) retrospectively evaluated 3130 patients with BD who visited 176 Japanese psychiatric outpatient clinics in 2016. Clinical features and drug prescriptions were recorded, and the total daily costs of psychotropic drug treatment were calculated. The annual medical costs related to outpatient BD treatments in Japan were estimated based on the corresponding demographics. The associations between daily medical costs and patients' clinical features were analyzed using multiple regression analysis. RESULTS: The daily costs of psychotropic drugs ranged from zero to JPY3245 (mean, JPY349 equivalent to USD32.5) and were exponentially distributed. The annual costs for outpatients BD treatments were approximately 51.9 billion Japanese yens (519 million US dollars). Subsequent multiple regression analysis revealed that social adjustment, depressive symptoms, age, rapid cycling, psychotic symptoms, and comorbid mental disorders correlated strongly with the daily cost of psychotropic drugs. CONCLUSION: The estimated annual costs for outpatient BD treatment in Japan were equivalent to those in OECD countries (except for the US) and higher than those in some Asian countries. The cost of psychotropic treatments was associated with individual characteristics and psychopathological conditions.Key MessagesPsychotropic treatment for an outpatient with bipolar disorder has a daily cost approximately JPY350.The annual outpatient treatment cost for bipolar disorder in Japan was estimated to 51.9 billion Japanese yen in 2016.Individual characteristics and psychopathological conditions affected the cost of drug treatment.

Clinical characteristics and prescriptions associated with a 2-year course of rapid cycling and euthymia in bipolar disorder: a multicenter treatment survey for bipolar disorder in psychiatric clinics.

Objective: In patients with bipolar disorder (BD), rapid cycling (RC) presents a risk for a more severe illness, while euthymia (EUT) has a better prognosis. This study focused on the progression of RC and EUT, which are contrasting phenomenology, and aimed to clarify the influence of patient backgrounds and prescription patterns on these different progressions, using a large sample from the first and second iterations of a multicenter treatment survey for BD in psychiatric clinics (MUSUBI). Methods: In the cross-sectional study (MUSUBI), a questionnaire based on a retrospective medical record survey of consecutive BD cases (N = 2,650) was distributed. The first survey was conducted in 2016, and the second one in 2017. The questionnaire collected information on patient backgrounds, current episodes, and clinical and prescribing characteristics. Results: In the first survey, 10.6% of the participants had RC and 3.6% had RC for two consecutive years, which correlated with BP I (Bipolar disorder type I), suicidal ideation, duration of illness, and the use of lithium carbonate and antipsychotic medications. Possible risk factors for switching to RC were comorbid developmental disorders and the prescription of anxiolytics and sleep medication. Moreover, 16.4% of the participants presented EUT in the first survey, and 11.0% presented EUT for two consecutive years. Possible factors for achieving EUT included older age; employment; fewer psychotic symptoms and comorbid personality disorders; fewer antidepressants, antipsychotics, and anxiolytics, and more lithium prescriptions. Conclusion: RC and EUT generally exhibit conflicting characteristics, and the conflicting social backgrounds and factors contributing to their outcomes were distinctive. Understanding these clinical characteristics may be helpful in clinical practice for management of patients with BD.

Impact of the pretreatment prognostic nutritional index on the survival after first-line immunotherapy in non-small-cell lung cancer patients.

BACKGROUND: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. MATERIALS AND METHODS: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. RESULTS: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51-0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32-0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). CONCLUSION: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy.

Predictors of psychiatric hospitalization among outpatients with bipolar disorder in the real-world clinical setting.

Background: Bipolar disorder is a psychiatric disorder that causes recurrent manic and depressive episodes, leading to decreased levels of social functioning and suicide. Patients who require hospitalization due to exacerbation of bipolar disorder have been reported to subsequently have poor psychosocial functioning, and so there is a need to prevent hospitalization. On the other hand, there is a lack of evidence regarding predictors of hospitalization in real-world clinical practice. Methods: The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was an observational study conducted to provide evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked, as part of a retrospective medical record survey, to fill out a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. Our study extracted baseline patient characteristics from records dated between September and October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. The incidence and predictors of hospitalization among patients with bipolar disorder over a 1-year period extending from that baseline to September-October 2017 were examined. Results: In total, 2,389 participants were included in our study, 3.06% of whom experienced psychiatric hospitalization over the course of 1 year from baseline. Binomial logistic regression analysis revealed that the presence of psychiatric hospitalization was correlated with bipolar I disorder, lower baseline GAF scores, unemployment, substance abuse and manic state. Conclusions: Our study revealed that 3.06% of outpatients with bipolar disorder were subjected to psychiatric hospitalization during a 1-year period that extended to September-October 2017. Our study suggested that bipolar I disorder, lower baseline GAF scores, unemployment, substance abuse and baseline mood state could be predictors of psychiatric hospitalization. These results may be useful for clinicians seeking to prevent psychiatric hospitalization for bipolar disorder.

Domain analysis of Drosophila Blimp-1 reveals the importance of its repression function and instability in determining pupation timing.

The PRDM family transcription repressor Blimp-1 is present in almost all multicellular organisms and plays important roles in various developmental processes. This factor has several conserved motifs among different species, but the function of each motif is unclear. Drosophila Blimp-1 plays an important role in determining pupation timing by acting as an unstable transcriptional repressor of the ßftz-f1 gene. Thus, Drosophila provides a good system for analyzing the molecular and biological functions of each region in Blimp-1. Various Blimp-1 mutants carrying deletions at the conserved motifs were induced under the control of the heat shock promoter in prepupae, and the expression patterns of ßFTZ-F1 and Blimp-1 and pupation timing were observed. The results showed that the regions with strong and weak repressor functions exist within the proline-rich middle section of the factor and near the N-terminal conserved motif, respectively. Rapid degradation was supported by multiple regions that were mainly located in a large proline-rich region. Results revealed that pupation timing was affected by the repression ability and stability of Blimp-1. This suggests that both the repression function and instability of Blimp-1 are indispensable for the precise determination of pupation timing.

Successful treatment of relapsing polychondritis with circumferential bronchial wall thickening including the tracheomembranous area with tumor necrosis factor-α inhibitor.

This is a case of a 55-year-old man who presented with cough and anterior chest pain. Tracheal biopsy confirmed the diagnosis of relapsing polychondritis (RP). Although the patient had circumferential bronchial wall thickening extending to the tracheomembranous area and was positive foRPR3-ANCA, he did not meet the diagnostic criteria for granulomatosis with polyangiitis. The patient was refractory to prednisolone + methotrexate + azathioprine and responded to adalimumab, a biologic tumor necrosis factor-α inhibitor effective in RP refractory cases. Herein, we report a rare case of RP with circumferential bronchial wall thickening extending to the tracheomembranous area.

Effect of age and sex on prescriptions for outpatients with bipolar disorder in the MUSUBI study: a cross­sectional study.

BACKGROUND: Childbearing-aged female patients and elderly patients with bipolar disorder need special attention for pharmacological treatments, but current guidelines provide little information on their pharmacological treatment. In particular, the risk/benefit balance of pharmacological treatment for childbearing-aged females with bipolar disorder is a growing concern. Therefore, we aimed to address the effect of age and sex on psychotropic drug prescription for outpatients with bipolar disorder. METHODS: The MUlticenter treatment SUrvey for BIpolar disorder in Japanese psychiatric clinics (MUSUBI) study was conducted, and data on age, sex, and details of pharmacological treatment were collected. RESULTS: A total of 3106 outpatients were included in this study. Among young females (age ≤ 39), 25% were prescribed valproate. There was no significant difference in the frequency and daily dose of valproate prescription for young females among all groups. Valproate prescriptions were significantly less frequent among young males and more frequent among middle-aged males. Lithium prescriptions were significantly less frequent among young females and more frequent among older males (age ≥ 65) and older females. Lamotrigine prescriptions were significantly more frequent among young males and young females and less frequent among older males and older females. Carbamazepine prescriptions were significantly less frequent among young males and more frequent among older males. CONCLUSIONS: Biased information about the risk and safety of valproate and lithium for young females was suggested, and further study to correct this bias is needed. Older patients were prescribed lithium more commonly than lamotrigine. Further studies are needed to determine the actual pharmacotherapy for elderly individuals.

Determinants of three-year clinical outcomes in real-world outpatients with bipolar disorder: The multicenter treatment survey for bipolar disorder in psychiatric outpatient clinics (MUSUBI).

BACKGROUND: There is limited evidence regarding predictors of long-term clinical outcomes in patients with bipolar disorder (BD). The objective of this study was to describe 3-year clinical outcomes and identify their predictors from participants in the multicenter treatment survey for BD in psychiatric outpatient clinics (MUSUBI). METHODS: The MUSUBI was a naturalistic study investigating patients with BD in real-world clinical practice. Our study extracted data regarding 1647 outpatients with BD from 2016, 2017, and 2019 as baseline, 1-year, and 3-year assessments. As clinical outcomes, we assessed the presence of time ill (depressive and manic) during the 1 year prior to the 3-year assessment and durable remission (53 weeks or more) prior to the 3-year assessment. RESULTS: Participants with durable remission prior to the 3-year assessment had significant associations with diagnosis of a personality disorder and duration of continuous remission at baseline. Regarding the presence of depressive symptoms during the 1 year prior to the 3-year assessment, work status, Global Assessment of Functioning (GAF) scores, suicidal ideation, and duration of continuous remission at baseline had significant associations with this outcome. CONCLUSIONS: At the 3-year assessment, 19.3% of participants (318/1647) achieved durable remission, while 47.5% of them (782/1647) were not remitted. Our findings can help clinicians predict the illness course of BD by understanding demographic and clinical characteristics.

Relationship Between Employment Status and Unstable Periods in Outpatients with Bipolar Disorder: A Multicenter Treatment Survey for Bipolar Disorder in Psychiatric Outpatient Clinics (MUSUBI) Study.

Purpose: To clarify the relationship between the length of unstable periods and employment status of patients with bipolar disorder. Patients and Methods: Medical records of outpatients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics were investigated during September-October 2016, and details of their medical care and employment were surveyed using a questionnaire. The odds ratios (ORs) of length of unstable period and unemployment were analyzed with a logistic regression model. Results: The study included 816 patients, of whom 707 were employed full-time (continuous employment) and 70 were unemployed (loss of employment). Univariate analysis showed that ORs were statistically significant for patients who were unstable for "almost all" of the year (OR = 10.4 [4.48-24.28] p < 0.001), but not for "few" unstable periods (OR = 1.06 [0.56-1.98] p = 0.849) and for "significant" unstable periods (OR = 1.65 [0.73-3.74] p = 0.231) were not significantly different. Multivariate analysis showed that ORs were statistically "significant" for patients who were unstable for "almost all" (OR = 12.1 [4.37-33.3] p < 0.001), but not for "few" unstable periods (OR = 1.07 [0.55-2.07] p = 0.846) and for "significant" unstable periods (OR = 1.62 [0.66-3.98] p = 0.290) did not differ significantly. Conclusion: Patients with bipolar disorder with a long unstable period were associated with a higher risk of unemployment.

Analysis of nationwide hemophilia care: A cohort study using two Japanese healthcare claims databases.

BACKGROUND AND AIMS: In many developed countries, hemophilia care is provided by specialized centers which can offer standardized high-quality care for patients and collect data for patient registries. However, in countries with less centralized provision of hemophilia care, registry data lacks accuracy and medical care is inconsistent among providers. Claims databases can be an alternative for obtaining nationwide data on hemophilia care, and we applied this approach to evaluate inequalities in hemophilia care in Japan. METHODS: Medical records of hemophilia A patients were collected by a combination of ICD-10 code (D66) and prescribed coagulation factors from two major Japanese claims databases (JMDC and Medical Data Vision [MDV]). Patient records with an anti-inhibitor coagulant complex were excluded.Based on the annual number of hemophilia A patients, medical facilities were categorized into specialized facilities (SP, ≥5 patients) and nonspecialized facilities (N-SP, <5 patients). Patient age, comorbidities, diagnostic testing, prescribed drugs and their dosages were compared between facility types. RESULTS: The JMDC and MDV databases included 274 and 1266 hemophilia A patients, respectively. In the MDV database, SP facilities prescribed extended half-life factor VIII (FVIII) products for more patients (31.8% vs 24.3%) than N-SP. The mean annual FVIII consumption per patient was higher in SP facilities (240 333 IU [international units] vs 210 334 IU), and the mean FVIII dosage was higher in SP facilities for all types of FVIII products. The proportion of patients who received diagnostic blood tests was higher in SP (75.7% vs 56.2%). CONCLUSION: The MDV database revealed disparities in hemophilia A care between SP and N-SP facilities in types of FVIII products prescribed, FVIII consumption, and frequency of the relevant management such as blood tests. Claims databases can be an alternative for the assessment of nationwide hemophilia care patterns in countries without a well-established registry.

Differences in prescription patterns between real-world outpatients with bipolar I and II disorders in the MUSUBI survey.

OBJECTIVE: There is limited information available on the prescription of psychotropic agents to patients with bipolar I (BD-I) and bipolar II disorder (BD-II). The purpose of this study was to investigate the characteristics of drug therapy in BD-I and BD-II outpatients, particularly with regard to antidepressants. METHODS: In 2017, the MUlticenter treatment SUrvey for BIpolar disorder in Japanese psychiatric clinics (MUSUBI) study collected data on current mental status, medications, and other factors from 2774 outpatients with BD-I or BD-II. RESULTS: There were significant differences in the rates of prescriptions for mood stabilizers, antipsychotics and antidepressants. Mood stabilizers and antipsychotics were prescribed at higher rates to patients with BD-I (mood stabilizers; BD-I 86.0%, BD-II 80.8%, p < 0.001; antipsychotics; BD-I 61.5%, BD-II 47.8%, p < 0.001), and antidepressants were prescribed at higher rates to patients with BD-II (BD-I 32.1%, BD-II 46.4%, p < 0.001). The most commonly prescribed antidepressants were escitalopram for patients with BD-I and duloxetine for patients with BD-II. Selective serotonin reuptake inhibitors (SSRIs) were the most common class of antidepressants prescribed to patients with BD. With regard to combination therapy, combinations containing antidepressants were often prescribed to patients with BD-II. CONCLUSION: There was a difference in the prescription of psychotropic agents between patients with BD-I and BD-II. The outpatient prescriptions for BD in Japan were mood stabilizers and antipsychotics, which generally followed the guidelines. There is insufficient evidence regarding the effects of the prescribed antidepressants and the risk of manic episodes, and further evidence needs to be collected.

Real-world clinical predictors of manic/hypomanic episodes among outpatients with bipolar disorder.

BACKGROUND: Bipolar disorder is a mental illness in which manic and depressive states are repeated, causing psychosocial dysfunction. Manic/hypomanic episodes cause problems with interpersonal, social and financial activities, but there is limited evidence regarding the predictors of manic/hypomanic episodes in real-world clinical practice. METHODS: The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was administered in an observational study that was conducted to accumulate evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics by conducting a retrospective medical record survey. Our study extracted baseline patient characteristics from September to October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. We investigated the presence or absence of manic/hypomanic episodes over the course of one year from baseline to September-October 2017. RESULTS: In total, 2231 participants were included in our study, 29.1% of whom had manic/hypomanic episodes over the course of one year from baseline. Binomial logistic regression analysis revealed that the presence of manic/hypomanic episodes was correlated with lower baseline GAF scores, rapid cycling, personality disorder, bipolar I disorder, and a mood state with manic or mixed features. Substance abuse was also a risk factor for manic episodes. There was no significant association between a baseline antidepressant prescription and manic/hypomanic episodes. CONCLUSIONS: In Japan, 29.1% of outpatients with bipolar disorder had manic/hypomanic episodes over the course of one year. Our study suggested that a low GAF score, rapid cycling, personality disorder, bipolar I disorder, substance abuse, and baseline mood state could be predictors of manic/hypomanic episodes. Based on our findings, an antidepressant prescription is not a predictor of manic/hypomanic episodes.

Relationship Between Mood Episode and Employment Status of Outpatients with Bipolar Disorder: Retrospective Cohort Study from the Multicenter Treatment Survey for Bipolar Disorder in Psychiatric Clinics (MUSUBI) Project.

OBJECTIVE: The objective of this study was to clarify the relationship between mood episode and employment in patients with bipolar disorder to help improve their employment status. METHODS: All medical records of patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics in September-October 2016 were investigated in September-October 2017. Details of the medical care received were investigated using a survey sheet, which included employment status. Odds ratios of mood episodes for employment status were analyzed using a logistic regression model. RESULTS: Among patients aged 60 years or less, 2292 described their occupation. On univariate analysis, odds ratios were statistically significant for depressive episode (OR = 2.68 [1.50-4.78] p = 0.001) and manic episode (OR = 2.64 [1.07-6.47] p = 0.034), whereas no significant difference was noted for mixed episode (OR = 1.72 [0.69-4.33] p = 0.246). On multivariate analysis, odds ratios were statistically significant for depressive episode (OR = 2.16 [1.13-4.13], p = 0.020) and manic episode (OR = 3.55 [1.36-9.25], p = 0.010), whereas no significant difference was noted for mixed episode (OR = 1.83 [0.65-5.14] p = 0.254). CONCLUSION: Employment status among these patients with bipolar disorder receiving outpatient treatment was 43.5%. Compared to remission episodes, manic and depressive episodes were associated with a higher risk of unemployment.

Estimated model of psychotropic polypharmacy for bipolar disorder: Analysis using patients' and practitioners' parameters in the MUSUBI study.

OBJECTIVE: This study aims to clarify the relevant factors influencing practitioners' methods of prescribing medications for bipolar disorder, in a nation-wide survey in Japan. METHODS: The clinical records of 3130 outpatients with bipolar disorder were consecutively reviewed from 176 psychiatric outpatient clinics. Fifteen parameters, that is, five patients' including five general characteristics (sex, age, education, occupation, and social adjustment), five patients' aspects of mental functioning (onset age, comorbid mental illness, rapid-cycling, psychopathologic severity, and followed-up years), and five practitioners' characteristics (sex, age, specialist experience, clinic standing years, and location), were evaluated. The number of psychotropic drugs (mood stabilizers, antidepressants, antipsychotic drugs, anxiolytics, and hypnotics) was used as an index of pharmacotherapy. Converted data from each practitioner-unit were analyzed. RESULTS: Seven factors (patient's social adjustment, patient's psychopathology, patient's comorbid mental disorders, patient's followed-up years, doctor's age, clinic running years, and patient's education years) were correlated to the number of psychotropic drugs. Multiple regression analysis showed that the severity of illness (poor social adjustment, and comorbid mental illness) and an intractable disease course (long followed-up years), were significantly associated with the number of psychotropic drugs. CONCLUSION: Our findings indicated that patient-related conditions affected psychotropic polypharmacy more strongly than did practitioner-related conditions.

Convenience Comparison Study of Reconstitution Devices for the Blood Coagulation Factor VIII Products Rurioctocog Alfa Pegol and Antihemophilic Factor (Recombinant).

INTRODUCTION: The Baxject® II Hi-Flow device has previously been used to reconstitute the factor VIII products antihemophilic factor (recombinant) (ADVATE®) and rurioctocog alfa pegol (ADYNOVATE®). METHODS: In this crossover study in healthy men, the convenience of an advanced device, Baxject III® with and without a nonslip sleeve, was compared with that of Baxject II Hi-Flow. The primary endpoint was the operational time for reconstitution; secondary endpoints included participants' assessment of the usability of the devices for reconstitution and their preference for using each of the devices. RESULTS: Twelve healthy adult men (mean ± standard deviation [SD] age: 36.7 ± 7.0 years) and 12 healthy elderly men (mean ± SD age: 70.3 ± 4.8 years) participated in the study. In the adult group, the mean operational time for reconstitution was shorter using Baxject III (mean ± SD: 19.7 ± 2.7 and 19.9 ± 5.2 seconds with and without a nonslip sleeve, respectively) than when using Baxject II Hi-Flow (49.6 ± 7.2 seconds, P < 0.0001 for both comparisons). Adult participants rated preference (P < 0.0001) and ease of reconstitution (P < 0.0001) as higher for Baxject III with a nonslip sleeve than for Baxject II Hi-Flow. Results were consistent regardless of age group or the use of the nonslip sleeve. CONCLUSION: Owing to the convenience of Baxject III, this device will improve the reconstitution process for patients with hemophilia treated with rurioctocog alfa pegol or antihemophilic factor (recombinant) at home.

Real-world clinical features of and antidepressant prescribing patterns for outpatients with bipolar disorder.

BACKGROUND: Several evidence-based practice guidelines have been developed to better treat bipolar disorder. However, the articles cited in these guidelines were not sufficiently based on real-world clinical practice. METHODS: The MUlticenter treatment SUrvey on BIpolar disorder in Japanese psychiatric clinics (MUSUBI) is a study conducted to accumulate evidence on the real-world practical treatment of bipolar disorder. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder by performing a retrospective medical record survey. The questionnaire included patient characteristics (age, gender, height, weight, academic background, and occupational status), comorbidities, mental status, treatment period, Global Assessment of Functioning (GAF) score, and details of pharmacological treatment. RESULTS: Data on 2705 patients were included in this study. The proportion of patients receiving antidepressant prescriptions was 40.9%. The most commonly used antidepressant was duloxetine, and the most frequently used antidepressant class was selective serotonin reuptake inhibitors (SSRIs). Binomial logistic regression analysis and bivariate analysis revealed that the usage of antidepressants was correlated with low prescription rates for mood stabilizers, high prescription rates for anxiolytics and hypnotics, and low GAF scores. In addition, patients in a depressive state had a significantly higher rate of antidepressant prescriptions than patients with other mental states. CONCLUSIONS: Approximately 40% of patients in Japan with a diagnosis of bipolar disorder have received antidepressants. Antidepressants were most often prescribed in combination with mood stabilizers, antipsychotics or both. Patients who were prescribed antidepressants received fewer mood stabilizers, more anxiolytics, and more hypnotics than those who did not receive antidepressant prescriptions.