Association between mental health social worker staffing in psychiatric emergency wards and readmission outcomes: A nationwide survey in Japan.

Aim: The mental healthcare system in Japan is transitioning from institution-based to community-based treatment. To prevent prolonged hospitalization and community integration of psychiatric patients, mental health social workers (MHSWs) are pivotal in coordinating post-discharge arrangements for psychiatric inpatients. This study aimed to propose a care model to improve clinical outcomes in psychiatric emergency wards in Japan. Methods: We conducted a mail-in questionnaire survey targeting medical facilities with psychiatric emergency wards. We collected data of the psychiatric care system, including facility profiles, staffing conditions and caseloads, and the provided psychiatric services and treatment options. Using multiple regression analyses, we explored associations between these data and clinical outcomes, focusing on the average number of days for hospitalization and the integration of patients into a community. Results: Data were collected from 82 facilities (response rate, 45.8%). The average number of days for hospitalization and community integration were 64.7 and 327.9 days, respectively. The caseloads for MHSWs were significantly associated with longer hospitalization (ß = 0.31, p = 0.009) and shorter duration of community living (ß = -0.28, p = 0.027). Conclusion: The clinical performance in psychiatric emergency wards surpassed the Japanese government's targets regarding these outcomes. We found that heavy caseloads on MHSWs were associated with worse clinical outcomes for patients in psychiatric emergency wards. These findings suggest that reducing MHSW caseloads (≤20 cases) may be a potential interventional strategy to prevent prolonged hospitalization and promote successful community integration of patients.

The effectiveness of the mental health social worker-led multiprofessional program in preventing long-term hospitalization and readmission in acute psychiatric inpatients in Japan: A retrospective analysis.

Aim: The large number of new long-stay (NLS) patients and high readmission rates in psychiatric hospitals are longstanding concerns in Japan despite reforms to encourage multidisciplinary support of such patients. Staffing shortages of specialists, especially mental health social workers (MHSWs), may be one of the reasons for these problems to remain unsolved. Methods: The authors examined the effectiveness of the MHSW-centered multidisciplinary care model in preventing NLSs and rehospitalization in terms of both patient dynamics and cost by retrospective comparison of before and after program implementation. Results: After our program was introduced, NLS was almost completely prevented. In addition, a significant decrease in readmissions of involuntarily admitted patients was also observed. On the other hand, the resulting decrease in treatment costs and hospital revenues was mismatched by an increase in personnel costs. Conclusion: While MHSW-centered multidisciplinary care is effective for the community integration of patients, there are cost challenges. State policy changes are needed to resolve staffing problems, along with the introduction of appropriate indicators of community integration.

Randomised controlled trial on the effect of video-conference cognitive behavioural therapy for patients with schizophrenia: a study protocol.

INTRODUCTION: Cognitive behavioural therapy for psychosis (CBTp) has demonstrated effectiveness in reducing positive symptoms, improving depression, enhancing coping skills and increasing awareness of illness. However, compared with cognitive behavioural therapy for depression and anxiety, the spread of CBTp in clinical practice is minimal. The present study designed a randomised controlled trial (RCT) research protocol to evaluate whether real-time remote video-conference CBTp (vCBTp) could facilitate access to psychosocial interventions and effectively improve symptoms compared with usual care (UC) for patients with schizophrenia. METHODS AND ANALYSIS: This exploratory RCT will consist of two parallel groups (vCBTp+UC and UC alone) of 12 participants (n=24) diagnosed with schizophrenia, schizoaffective disorder or paranoid disorder, who remain symptomatic following pharmacotherapy. Seven 50-min weekly vCBTp interventions will be administered to test efficacy. The primary outcome will be the positive and negative syndrome scale score at week 8. The secondary outcome will be the Beck Cognitive Insight Scale to assess insight, the Patient Health Questionnaire-9 to assess depression, the Generalised Anxiety Disorder-7 to assess anxiety, the 5-level EuroQol 5-dimensional questionnaire to assess quality of life and the Impact of Event Scale-Revised to assess subjective distress about a specific stressful life event. We will take all measurements at 0 weeks (baseline) and at 8 weeks (post-intervention), and apply intention-to-treat analysis. ETHICS AND DISSEMINATION: We will conduct this study in the outpatient department of Cognitive Behavioral Therapy Center at Chiba University Hospital. Further, all participants will be informed of the study and will be asked to sign consent forms. We will report according to the Consolidated Standards of Reporting Trials. TRIAL REGISTRATION NUMBER: UMIN000043396.

Oxytocin system dysfunction in patients with treatment-resistant schizophrenia: Alterations of blood oxytocin levels and effect of a genetic variant of OXTR.

Treatment-resistant schizophrenia (TRS) has a quite complex pathophysiology that includes not only severe positive symptoms but also other symptom domains. Much attention has been devoted to the overlapping psychological and biological profiles of schizophrenia and autistic spectrum disorder (ASD). We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on general cognitive and social cognitive impairment and oxytocin system dysfunction. Our analyses revealed that there was no difference in oxytocin concentration among the three groups. The TRS patients' oxytocin blood concentrations were positively correlated with their processing speed and theory-of-mind scores, whereas the RemSZ and ASD groups had no significant relation with any measures. Rs53576, a single nucleotide polymorphism on the oxytocin receptor gene, affected social cognition abilities in the schizophrenia group. Although the overall findings are preliminary, they indicate that oxytocin system dysfunction could be involved in the serious cognitive deficits in TRS patients. Further, these results suggest that patients with TRS might have early neurodevelopmental abnormalities based on their shared biological features with ASD patients.

Autistic traits and cognitive profiles of treatment-resistant schizophrenia.

The complex pathophysiology of treatment-resistant schizophrenia (TRS) includes severe positive symptoms but also other symptom domains. The overlapping psychological profiles of schizophrenia and autistic spectrum disorder (ASD) are not established. We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on both neurodevelopmental aspects and general and social cognitive impairments. The TRS group performed the worst on general neurocognition (measured by the MATRICS Consensus Cognitive Battery) and social cognition (measured by the theory of mind and emotional expression). The RemSZ group performed the best among the three groups. Regarding autistic traits, all measurements by the Autism-Spectrum Quotient/Autism Screening Questionnaire/Pervasive Developmental Disorder Assessment Rating Scale showed that (1) the ASD patients had the highest autistic traits (2) the TRS patients' scores were less severe than the ASD group's, but (3) the overall trends placed the TRS group between the ASD and the RemSZ group. These findings indicate that TRS patients and remitted patients could have distinctive neurodevelopmental and cognitive profiles. Further, the degrees of social cognitive dysfunction and autistic traits in TRS patients could be close to those of ASD patients, suggesting similarities between TRS and ASD.

Successful rechallenge with paliperidone after clozapine treatment for a patient with dopamine supersensitivity psychosis.

We describe the case of a 49-year-old Japanese male patient successfully treated with a paliperidone rechallenge following 2-year treatment with clozapine for treatment-resistant schizophrenia. He had responded well to conventional antipsychotic treatment for the initial psychotic episode but gradually developed dopamine supersensitivity; even treatment with paliperidone and another antipsychotic medication (a total up to 1700 mg in chlorpromazine-equivalent dose) had not improved his psychotic symptoms. Clozapine treatment produced temporary symptomatic relief, but the clozapine dose could not be increased to > 150 mg due to the patient's intolerance. Following low-dose clozapine treatment for 2 years, a rechallenge with paliperidone monotherapy ameliorated his psychotic symptoms. This suggests that clozapine may have the potential to release the dopamine supersensitivity state. Our patient's case indicates that for patients with dopamine supersensitivity psychosis, a rechallenge with a previously ineffective antipsychotic after clozapine treatment may be successful.

Increased Serum Levels of Oxytocin in 'Treatment Resistant Depression in Adolescents (TRDIA)' Group.

OBJECTIVE: 'Treatment-resistant depression' is depression that does not respond to an adequate regimen of evidence-based treatment. Treatment-resistant depression frequently becomes chronic. Children with treatment-resistant depression might also develop bipolar disorder (BD). The objective of this study was to determine whether serum levels of oxytocin (OXT) in treatment-resistant depression in adolescents (TRDIA) differ from non-treatment-resistant depression in adolescents (non-TRDIA) or controls. We also investigated the relationships between serum OXT levels and the clinical symptoms, severity, and familial histories of adolescent depressive patients. METHODS: We measured serum OXT levels: TRDIA (n = 10), non-TRDIA (n = 27), and age- and sex- matched, neurotypical controls (n = 25). Patients were evaluated using the Children's Depression Rating Scale-Revised (CDRS-R) and the Depression Self-Rating Scale for Children-Japanese Version (DSRS-C-J). The patients were also assessed retrospectively using the following variables: familial history of major depressive disorder and BD (1st degree or 2nd degree), history of disruptive mood dysregulation disorder, recurrent depressive disorder (RDD), history of antidepressant activation. RESULTS: Serum levels of OXT among the TRDIA and non-TRDIA patients and controls differed significantly. Interestingly, the rates of a family history of BD (1st or 2nd degree), RDD and a history of antidepressant activation in our TRDIA group were significantly higher than those of the non-TRDIA group. CONCLUSIONS: Serum levels of OXT may play a role in the pathophysiology of TRDIA.

Risperidone long-acting injectable in the treatment of treatment-resistant schizophrenia with dopamine supersensitivity psychosis: Results of a 2-year prospective study, including an additional 1-year follow-up.

UNLABELLED: Dopamine supersensitivity psychosis (DSP) resulting from antipsychotic treatment is related to treatment-resistant schizophrenia (TRS), and its treatment has not been established to date. Maintaining thoroughly stable occupancy of the dopamine D2 receptor by risperidone long-acting injectable (RLAI) is one strategy for treatment. In this study, RLAI was given as an adjunctive medication to oral antipsychotic(s), which were switched partially and gradually to RLAI in 108 treatment-resistant patients for an additional 1-year follow-up in a 2-year study, and to compare the effects in 72 patients with a DSP history (DSP group) and 36 patients without this history (NonDSP group). Although both groups showed significant improvements in the total Brief Psychotic Rating Scale (BPRS) score during the follow-up period, greater improvement was observed for the DSP group than the NonDSP group. High doses (> 850 mg chlorpromazine-dose combined of oral antipsychotics and RLAI) did not significantly change in both groups throughout the study period; however, extrapyramidal symptoms, including tardive dyskinesia, were significantly improved only in the patients with DSP. This study strongly suggested that the RLAI treatment, even with only partial switching, provides relief from refractory symptoms, particularly for patients with a history of DSP. CLINICAL TRIAL REGISTRATION: http://www.umin.ac.jp/:UMIN000008487.

Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study.

BACKGROUND: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood. METHODS: We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs), moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines. RESULTS: Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10). Baseline serum levels of interleukin-6 (Z=-2.155; P=0.031) and interleukin-8 (Z=-2.616; P=0.009) were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs). Serum levels of macrophage inflammatory protein-1ß showed a significant continuous decrease from the baseline level (Friedman's test: χ (2)=23.9, df=4, P<0.001) only in non-responders. CONCLUSION: These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1ß as potential blood biomarkers could be utilized to identify the responsiveness of patients to serotonin and norepinephrine reuptake inhibitor like milnacipran, or to identify those patients who may experience AEs strong enough to warrant discontinuation of treatment.

Decreased levels of serum oxytocin in pediatric patients with Attention Deficit/Hyperactivity Disorder.

Attention Deficit/Hyperactivity Disorder (ADHD) and autism spectrum disorder (ASD) are highly comorbid, and both disorders share executive function deficits. Accumulating evidence suggests that ASD patients have significantly lower peripheral oxytocin (OXT) levels compared with their normal counterparts, and that the repetitive behavior seen in ASD is related to abnormalities in the OXT system. In this study, we investigated whether serum levels of OXT are altered in pediatric patients with ADHD. We measured serum OXT levels: drug naive ADHD (n=23), medicated ADHD (n=13), and age- and sex- matched, neurotypical controls (n=22). Patients were evaluated using the ADHD-RS. Serum levels of OXT in total subjects with ADHD were significantly decreased compared with those of neurotypical controls, and serum levels of OXT in drug naive ADHD patients were significantly lower than those in medicated ADHD patients. Interestingly, there was a significant negative correlation between serum OXT levels and ADHD-RS total scores, as well as ADHD-RS inattentive scores in all ADHD patients. In conclusion, this study suggests that decreased levels of OXT may play a role in the pathophysiology of patients with ADHD and its inherent inattentiveness.

A prospective comparative study of risperidone long-acting injectable for treatment-resistant schizophrenia with dopamine supersensitivity psychosis.

OBJECTIVE: Dopamine supersensitivity psychosis (DSP) is considered to be one cause of treatment-resistant schizophrenia (TRS). The authors investigated the efficacy of risperidone long-acting injections (RLAI) in patients with TRS and DSP. METHOD: This is a multicenter, prospective, 12-month follow-up, observational study that included unstable and severe TRS patients with and without DSP. 115 patients with TRS were recruited and divided into two groups according to the presence or absence of DSP which was judged on the basis of the clinical courses and neurological examinations. RLAI was administered adjunctively once every 2weeks along with oral antipsychotics. We observed changes in scores for the Brief Psychiatric Rating Scales (BPRS), Clinical Global Impression-Severity of Illness (CGI-S), Global Assessment of Functioning Scale (GAF), and Extrapyramidal Symptom Rating Scale (ESRS) during the study. Of the assessed 94 patients, 61 and 33 were categorized into the DSP and NonDSP groups, respectively. RESULTS: While baseline BPRS total scores, CGI-S scores and GAF scores did not differ, the ESRS score was significantly higher in the DSP group compared with the NonDSP group. Treatment significantly reduced BPRS total scores and CGI-S scores, and increased GAF scores in both groups, but the magnitudes of change were significantly greater in the DSP group relative to the NonDSP group. ESRS scores were also reduced in the DSP group. Responder rates (≥20% reduction in BPRS total score) were 62.3% in the DSP group and 21.2% in the NonDSP group. CONCLUSIONS: It is suggested that DSP contributes to the etiology of TRS. Atypical antipsychotic drugs in long-acting forms, such as RLAI, can provide beneficial effects for patients with DSP. CLINICAL TRIALS REGISTRATION: UMIN (UMIN000008487).

Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study.

BACKGROUND: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK)-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD) symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD. SUBJECTS AND METHODS: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0) received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS), Japanese version, and the Das-Naglieri Cognitive Assessment System (DN-CAS), Japanese version. RESULTS: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores) improved significantly (P<0.001). Furthermore, a comparison of baseline DN-CAS total scores and 4-week end-point scores showed a mild trend of improvement (P=0.093). Tipepidine was well tolerated, with no patients discontinuing medication because of side effects. CONCLUSION: Our pilot study suggests that tipepidine therapy may prove to be an effective alternative treatment for pediatric patients with ADHD. Nonetheless, more detailed randomized, double-blind trials are needed to confirm tipepidine's efficacy.

Effectiveness of Information Technology Aided Relapse Prevention Programme in Schizophrenia excluding the effect of user adherence: a randomized controlled trial.

BACKGROUND: A relapse prevention program called the Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) has been developed and is reported to be highly effective. However the effectiveness was influenced by user adherence to the protocol of the program, the exact effectiveness and the role of the ITAREPS have been partially uncertain. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of the ITAREPS excluding the effect of user adherence to the protocol of the program. METHOD: We attempted to perform a randomized controlled trial by the devised method with visiting nurse service. Outpatients with schizophrenia were randomized to the ITAREPS (n=22) or control group (n=23) and were observed for 12 months. RESULTS: The risk of rehospitalization was reduced in the ITAREPS group (2 [9.1%]) compared with the control group (8 [34.8%]) (hazard ratio=0.21, 95% CI 0.04-0.99, p=0.049; number needed to treat (NNT)=4, 95% CI 2.1-35.5). The mean number of inpatient days was significantly lower in the ITAREPS group (18.5 days) compared with the control group (88.8 days) (p=0.036). The ratio of the number of rehospitalizations to that of relapses was significantly lower (p=0.035) and the mean change in total BPRS scores at relapse from baseline was significantly less in the ITAREPS group (p=0.019). CONCLUSIONS: The relapse prevention effectiveness of the ITAREPS was high, and we confirmed that the ITAREPS, i.e., detecting signs of relapse and increasing medication during the warning state, is an effective intervention during the early stages of relapse.

[Efficacy and safety of maintenance intravesical instillation therapy with bacillus Calmette-Guerin and epirubicin for non-muscle invasive bladder cancer].

The objectives of this study were to evaluate the efficacy and toxicity of maintenance intravesical instillation therapy with bacillus Calmette-Guerin (BCG) and epirubicin for non-muscle invasive bladder cancer. From April 1999 to March 2010, 27 eligible patients were enrolled in this study. After receiving one cycle of epirubicin (100 mg/100 ml) by intravesical instillation, all patients received 6 weekly alternate intravesical instillation of BCG (80 mg/50 ml) and epirubicin (50 mg/50 ml), followed by 10 monthly instillations. Among the 27 patients, 19 were men and 8 were women, with a median age of 62.4 years (range, 37-78 years). Tumor pathologic stage was pTa in 25 patients, pT1 in 2 and there were no concomitant carcinoma in situ cases. Median follow-up was 37.1 months (range, 11-82 months). The 3- year recurrence-free and progression-free survival rates were 75.3% and 96.1%, respectively. Furthermore, a high completion rate of 81.5% was achieved in this study. Adverse events of grade 3 or higher occurred in 3 patients (11.1%), 1 patient had anaphylaxis. There were no treatment-related deaths. Maintenance intravesical instillation therapy with BCG and epirubicin is a favorable therapeutic option for non-muscle invasive bladder cancer. Given the safety and benefit profile found in this study, appropriate patient selection is warranted in the future.

[Initial division of the left renal vein before dissection of left renal vein occluded by intracaval tumor thrombus].

Between November 2008 and March 2010, we performed initial division of the left renal vein occluded by the tumor thrombus in six cases of left renal cancer at Toranomon Hospital. The left renal vein was completely occluded by the tumor thrombus in all cases. In order to ligate the left renal artery first behind the dilated left renal vein, we must dissect the left kidney with arterial blood flow. Massive bleeding from the numerous engorged collateral veins around the left kidney is inevitable. Furthermore, access to the left renal artery is difficult because of the large tumor. We therefore initially divided the left renal vein without arterial blood flow followed by division of the left renal artery. After nephrectomy by dissecting the tumor without blood flow we extirpated the intracaval tumor thrombus. The median time of the operation was 7 hours 35 minutes and the median amount of blood loss was 2,869 ml. The tumor stage was pT3b in four cases and pT3c in two cases. No complications were observed during and after surgery except for one case of lymphocele and another case of chylous ascites. The initial division of the left renal vein is considered to be a useful surgical approach in left renal cancer with occluded left renal vein, especially when the tumor is large.