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.

Middle meatus microbiome in patients with eosinophilic chronic rhinosinusitis in a Japanese population.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease and is subdivided into eosinophilic and noneosinophilic forms. There are few reports investigating the nasal microbiome and its pathological functions in patients with CRS. OBJECTIVE: We sought to analyze factors contributing to variations of the nasal microbiome in CRS, and on the basis of these factors, to elucidate whether the bacterial metabolites were related to the pathogenesis. METHODS: Nasal swabs were collected, and the V3 to V4 variable region of the 16S ribosomal RNA gene was amplified and sequenced. Factors contributing to variations of the nasal microbiome in patients with CRS were compared. The most influential factor was whether CRS was eosinophilic, and we compared α- and ß-diversity, bacterial species, and predictive bacterial functions between the 2 patient groups. In addition, the metabolites of the key bacteria were extracted, and we evaluated the predicted bacterial functions in airway epithelial cells. RESULTS: In total, 110 patients with CRS and 33 control subjects were enrolled. On the basis of the factors of variation, it was found that patients with eosinophilic CRS (n = 65) had different microbiomes with weighted UniFrac ß-diversity and lower α-diversity compared with those with noneosinophilic CRS (n = 45). A higher abundance of Fusobacterium nucleatum and an increased LPS pathway were observed in patients with noneosinophilic CRS compared with those with eosinophilic CRS. In airway epithelial cells, LPS derived from F nucleatum suppressed the expression levels of ALOX15 induced by TH2 cytokines. CONCLUSIONS: The differences in the nasal microbiome may play a key role in the pathophysiology of CRS.

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.

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.

Psychoses after an antiepileptic drug administration: Frequency, timing, and duration.

OBJECTIVES: To clarify the pathophysiology of psychoses after the new administration of antiepileptic drugs (AED), we analyzed the annual incidence, timing of development, and duration of episodes. METHODS: Psychotic outcomes in the first 6-month period after an AED or non-AED administration in patients with focal epilepsy were exhaustively reviewed in eight Japanese neuropsychiatry institutions. In cases with psychotic episodes, the subtype of psychosis, timing of development, previous history of psychosis, and duration of the episode were evaluated. RESULTS: Between 1981 and 2015, 5018 new drugs (4402 AED and 616 non-AED) were administered to 2067 patients with focal epilepsy. In the first 6-month period, 105 psychotic episodes occurred (81 interictal psychosis [IIP] and 24 postictal psychosis). Furthermore, 55 cases were first episodes and 50 were recurrent episodes. The frequency of psychoses is significantly higher after AED administration (n = 102) compared with non-AED administration (n = 3). Psychosis occurred most frequently in the initial 1-month period after new-AED administration and tended to decrease with increasing time. The estimated annual incidence of all psychoses after a new AED administration was 3.5% (2.0% for first-episode psychosis and 1.8% for first-episode IIP). Duration of psychoses (mean, 38.5 weeks) was equivalent to overall IIP. Duration of IIP did not shorten with discontinuation of newly administered AED. SIGNIFICANCE: Patients with epilepsy exhibit psychosis more frequently after new AED administration than after non-AED administration. This study shows the pathophysiology of psychoses after AED administration with annual incidence, the timing of development, and the duration of PAP, which have rarely been reported.

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 infected tooth extraction and improvement of odontogenic maxillary sinusitis.

Objective: Odontogenic maxillary sinusitis (OMS) is a well-recognized disease in otolaryngology and oral and maxillofacial surgery. It is diagnosed comprehensively based on the presence of dental disease and radiographic evaluation. Although the disease involves a combination of dental and otorhinolaryngological features, appropriate criteria have not been well established for prioritizing dental procedures in the initial treatment of OMS. We investigated whether computed tomography (CT) score, including the Lund-Mackay score, can help prioritize tooth extraction as the initial treatment for OMS. Methods: We also investigated the radiographic features of 32 patients with OMS treated by tooth extraction alone. Both pre-and post-extraction CT images of OMS cases were evaluated. Results: Lund-Mackay scores before tooth extraction were significantly lower in postoperatively healed patients than in non-healed patients. Furthermore, CT scores of the anterior and posterior ethmoid sinuses and frontal sinuses, obtained before tooth extraction, were significantly lower in postoperatively healed patients than in non-healed patients. Conclusions: Collectively, low Lund-Mackay and CT scores of the ethmoid and frontal sinuses are significantly associated with healing of OMS treated by tooth extraction alone. The sinus CT score can help identify a treatment strategy for OMS.

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.

Epilepsy in patients with schizophrenia: Pathophysiology and basic treatments.

Schizophrenia is a chronic psychiatric disorder that may lead to epilepsy. However, there are limited findings on the issues. This narrative review aimed to provide a practical perspective on epilepsy in patients with schizophrenia using the current treatment systems for epilepsy. While there has been a debate on the relationship between epilepsy and schizophrenia, i.e., antagonism, affinity, and coincidence, recent large cohort studies have revealed a high frequency of epilepsy in patients with schizophrenia (4-5 times higher than that of general population). The high incidence observed is likely to be due to the bidirectionality between epilepsy and schizophrenia and additional schizophrenia-related conditions, e.g., antipsychotic drugs (APD), substance abuse, and head injury. As for symptomatology of epilepsy, only one small-size study showed that seizures of patients with schizophrenia are equivalent to those of patients without schizophrenia. Patients with schizophrenia exhibit the first seizure in their twenties or later, which are mostly focal seizures. Most of seizures in patients with schizophrenia can be controlled with conventional antiepileptic drugs. Few patients with schizophrenia develop treatment-resistant epilepsy. However, since drug interactions can be more complicated due to multiple conditions, such as pre-existing polypharmacy, heavy smoking, irregular eating, and comorbid metabolic disorders, cautious monitoring for clinical symptoms is required. To improve seizure control and adherence, non-pharmacological approaches are also recommended. Thus far, for seizure treatments in patients with schizophrenia, we have to use many empirical findings or substitute certain findings from population without schizophrenia because evidence is insufficient. The accumulation of clinical findings may contribute to the development of efficient treatment systems.

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.

Quantitative psychopathology of interictal psychosis in epilepsy; interaction between epilepsy-related and psychosis-general effects.

OBJECTIVE: There is a historical debate whether psychopathology of epilepsy psychosis is unique to epilepsy or common to other psychoses. However, a large comprehensive studies on this issue are scarce. To clarify the characteristics of interictal psychosis (IIP), we evaluated psychopathology quantitatively. METHODS: This study included 150 patients with IIP (epilepsy+/psychosis+), 187 patients with schizophrenia (SC: epilepsy-/psychosis+), 182 patients with epilepsy (EP: epilepsy+/psychosis-), and 172 non-clinical individuals (NC: epilepsy-/psychosis-). The IIP group comprised 127 chronic and 23 brief psychoses. Age, sex, and years of education, onset and duration of psychosis, and onset and duration of epilepsy were matched among the groups. The psychopathology was evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS), which comprises three symptom factors namely negative symptoms (NS), positive symptoms (PS), and anxiety-depressive symptoms (ADS). RESULTS: For overall 16-BPRS and NS factor scores, there were significant interactions between epilepsy-related (epilepsy+/-) and psychosis-general (psychosis+/-) effects. The EP exhibited higher scores than did the NC, whereas the IIP exhibited lower scores than did the SC. For PS and ADS factor scores, the IIP and SC exhibited a significant psychosis-general effect. Chronic IIP was associated with more serious psychopathologies than was brief IIP. However, limited with chronic IIP, there was a significant interaction between epilepsy-related and psychosis-general effects on the overall 16-BPRS and NS factor scores. CONCLUSION: These findings demonstrate the first large quantitative evidence on the unique psychopathology of IIP which has been only narratively described. The psychopathology is associated with the interaction between epilepsy-related and psychosis-general effects.

Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis.

Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated. Objective: To determine whether the serum levels of leptin are altered in patients with ECRS. Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient's serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression. Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p < 0.0001 vs. ECRS; p < 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p < 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p < 0.01) and the number of eosinophils in NPs (r = 0.5109, p < 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p < 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p < 0.05). Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.

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.

Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: The pathological features of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) tissues include an eosinophilic infiltration pattern (eosinophilic CRS (ECRS)) or a less eosinophilic pattern (non-ECRS). Recently, it has been suggested that 15-lipoxygenase 1 (15-LOX-1) may have significant roles in allergic disease; however, the significance of 15-LOX-1 in CRS is not well understood. The objective of this study was to demonstrate the expression of 15-LOX-1 in CRS. METHODS: The mRNA expression levels of 15-LOX-1 and periostin in nasal tissues were measured by quantitative real-time polymerase chain reaction. We also performed an immunofluorescence study of nasal tissues. Cells of the Eol-1 eosinophilic leukemic cell line were stimulated with interleukin-33 to test the induction of 15-LOX-1. RESULTS: The expression level of 15-LOX-1 mRNA in nasal polyps (NPs) was significantly higher in ECRS patients than in non-ECRS patients. The immunofluorescence study revealed that both airway epithelial cells and eosinophils in NPs expressed 15-LOX-1. A significant correlation was seen between the number of eosinophils and the mRNA expression levels of 15-LOX-1 and periostin in nasal polyps. Moreover, interleukin-33 enhanced 15-LOX-1 expression in Eol-1 cells. CONCLUSIONS: 15-LOX-1 was shown to be a significant molecule that facilitates eosinophilic inflammation in ECRS.