On the Nature of AX J2049.6+2939 and AX J2050.0+2914

AX J2049.6+2939 is a compact X-ray source in the vicinity of the southern blow-up region of the Cygnus Loop supernova remnant (Miyata et al. 1998a). This source was the brightest X-ray source inside the Cygnus Loop observed during the ASCA survey project. The X-ray spectrum was well fitted by a power-law function with a photon index of $-2.1 \pm 0.1$. Short-term timing analysis was performed and no coherent pulsation was found. Follow-up observations with ASCA have revealed a large variation in X-ray intensity by a factor of $\simeq$ 50, whereas the spectral shape did not change within the statistical uncertainties. In the second ASCA observation, we found another X-ray source, AX J2050.0+2941, at the north east of AX J2049.6+2939. During the three ASCA observations, the X-ray intensity of AX J2050.0+2941 varied by a factor of $\simeq$4. No coherent pulsations could be found for AX J2050.0+2941. We have performed optical photometric and spectroscopic observations in the vicinity of AX J2049.6+2939 at the Kitt Peak National Observatory (KPNO). As a result, all objects brighter than $B$-band magnitude of 22 in the error box can be identified with normal stars. Combined with the X-ray results and the fact that there are no radio counterparts, AX J2049.6+2939 is not likely to be either an ordinary rotation-powered pulsar or an AGN. The nature of AX J2049.6+2939 is still unclear and further observations over a wide energy band are strongly required. As to AX J2050.0+2941, the long-term X-ray variability and the radio counterpart suggests that it is an AGN.Comment: 23 pages, 4 figures, Accepted for publication by Astrophysical Journa

ASCA Observation of the New Transient X-ray Pulsar XTE J0111.2-7317 in the Small Magellanic Cloud

The new transient X-ray pulsar XTE J0111.2-7317 was observed with Advanced Satellite for Cosmology and Astrophysics (ASCA) on 1998 November 18, a few days after its discovery with the Proportional Counter Array onboard the Rossi X-ray Timing Explorer. The source was detected at a flux level of 3.6x10^-10 erg cm^-2 s^-1 in the 0.7--10.0 keV band, which corresponds to the X-ray luminosity of 1.8x10^38 erg s^-1, if a distance of 65 kpc for this pulsar in the Small Magellanic Cloud is assumed. Nearly sinusoidal pulsations with a period of 30.9497 +/- 0.0004 s were unambiguously detected during the ASCA observation. The pulsed fraction is low and slightly energy dependent with average value of \~27%. The energy spectrum shows a large soft excess below ~2 keV when fitted to a simple power-law type model. The soft excess is eliminated if the spectrum is fitted to an ``inversely broken power-law'' model, in which photon indices below and above a break energy of 1.5 keV are 2.3 and 0.8, respectively. The soft excess can also be described by a blackbody or a thermal bremsstrahlung when the spectrum above ~2 keV is modeled by a power-law. In these models, however, the thermal soft component requires a very large emission zone, and hence it is difficult to explain the observed pulsations at energies below 2 keV. A bright state of the source enables us to identify a weak iron line feature at 6.4 keV with an equivalent width of 50 +/- 14 eV. Pulse phase resolved spectroscopy revealed a slight hardening of the spectrum and marginal indication of an increase in the iron line strength during the pulse maximum.Comment: 8 pages, 5 Figures, to be published in ApJ. Also available at http://www-cr.scphys.kyoto-u.ac.jp/member/jun/job

Heart Disease, Other Circulatory Diseases, and Onset of Major Depression among Community Residents in Japan: Results of the World Mental Health Survey Japan 2002-2004

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95%Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.</p

Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study

Background: To implement clinical practice guidelines (CPGs), it is necessary for psychiatrists to deepen their understanding of the CPGs. The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide dissemination and implementation study of two sets of CPGs for schizophrenia and major depressive disorder (MDD). Methods: A total of 413 psychiatrists (n = 212 in 2016; n = 201 in 2017) learned the two CPGs in the education program of the EGUIDE project, and clinical knowledge of these CPGs was evaluated at baseline and after the programs. To improve the correct answer rate for clinical knowledge after the programs, we revised the lecture materials associated with items that had a low correct answer rate in 2016 and used the revised lecture materials with the CPGs in 2017. The rates of correct answers after the programs between the 2016 and 2017 groups were compared. Results: The correct answer rate of one item on the schizophrenia CPG and one item on the MDD CPG tended to be improved (S-D5 and D-C6) and that of one on the MDD CPG was significantly improved (D-D3, P = 0.0008) in the 2017 group compared to those in the 2016 group. Conclusions: We reported improvements in clinical knowledge of CPGs after the EGUIDE program in the 2017 group following revision of the lecture materials based on results from the 2016 group. These attempts to improve the degree of understanding of CPGs may facilitate the successful dissemination and implementation of psychiatric guidelines in everyday practice

Clozapine and Antipsychotic Monotherapy

Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10−6). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer

EGUIDE project and treatment guidelines

Background Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. Aims The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. Method A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. Results All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. Conclusions All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists

Which is more generalizable, powerful and interpretable in meta-analyses, mean difference or standardized mean difference?

Background: To examine empirically whether the mean difference (MD) or the standardised mean difference (SMD) is more generalizable and statistically powerful in meta-analyses of continuous outcomes when the same unit is used. Methods: From all the Cochrane Database (March 2013), we identified systematic reviews that combined 3 or more randomised controlled trials (RCT) using the same continuous outcome. Generalizability was assessed using the I-squared (I2) and the percentage agreement. The percentage agreement was calculated by comparing the MD or SMD of each RCT with the corresponding MD or SMD from the meta-analysis of all the other RCTs. The statistical power was estimated using Z-scores. Meta-analyses were conducted using both random-effects and fixed-effect models. Results: 1068 meta-analyses were included. The I2 index was significantly smaller for the SMD than for the MD (P < 0.0001, sign test). For continuous outcomes, the current Cochrane reviews pooled some extremely heterogeneous results. When all these or less heterogeneous subsets of the reviews were examined, the SMD always showed a greater percentage agreement than the MD. When the I2 index was less than 30%, the percentage agreement was 55.3% for MD and 59.8% for SMD in the random-effects model and 53.0% and 59.8%, respectively, in the fixed effect model (both P < 0.0001, sign test). Although the Z-scores were larger for MD than for SMD, there were no differences in the percentage of statistical significance between MD and SMD in either model. Inclusions: The SMD was more generalizable than the MD. The MD had a greater statistical power than the SMD but did not result in material differences