Diagnostic and prognostic significance of tartrate-resistant acid phosphatase type 5b in newly diagnosed prostate cancer with bone metastasis: A real-world multi-institutional study.

OBJECTIVES: Approximately, 90% of men with advanced prostate cancer will develop bone metastasis. However, there have been few reports about noninvasive biomarker to detect and predict clinical outcome of bone metastasis (BM) in prostate cancer patients. METHODS: We examined 1127 patients who underwent prostate biopsy from August 2012 to June 2017. We also investigated bone turnover markers such as bone-specific alkaline phosphatase, type I collagen cross-linked N-terminal telopeptide, C-terminal pyridinoline cross-linked telopeptide of type I collagen, and tartrate-resistant acid phosphatase type 5b (TRACP 5b). RESULTS: A total of 282 patients were diagnosed as prostate cancer with complete clinical data, and 34 patients with bone metastasis. Multivariate analysis revealed C-terminal pyridinoline cross-linked telopeptide of type I collagen, tartrate-resistant acid phosphatase type 5b, and prostate-specific antigen (PSA) were independent biomarkers in detection of BM (p < 0.05, respectively). Furthermore, we developed predictive model formula based on tartrate-resistant acid phosphatase type 5b and PSA, for which the area under the curve was 0.95. In patients with bone metastasis, multivariate cox proportional hazards analysis revealed that this model was significantly associated with poor clinical outcome of cancer-specific survival (p < 0.05). In validation cohort with 137 patients, we also confirmed the utility of this model for diagnosis of BM (the area under the curve = 0.95). CONCLUSIONS: Our developed formula of tartrate-resistant acid phosphatase type 5b in accordance with PSA may serve as the useful tool in diagnosis and prediction of clinical outcome for prostate cancer with bone metastasis.

Cost-effectiveness analyses of augmented cognitive behavioral therapy for pharmacotherapy-resistant depression at secondary mental health care settings.

AIM: Pharmacotherapy is the primary treatment strategy in major depression. However, two-thirds of patients remain depressed after the initial antidepressant treatment. Augmented cognitive behavioral therapy (CBT) for pharmacotherapy-resistant depression in primary mental health care settings proved effective and cost-effective. Although we reported the clinical effectiveness of augmented CBT in secondary mental health care, its cost-effectiveness has not been evaluated. Therefore, we aimed to compare the cost-effectiveness of augmented CBT adjunctive to treatment as usual (TAU) and TAU alone for pharmacotherapy-resistant depression at secondary mental health care settings. METHODS: We performed a cost-effectiveness analysis at 64 weeks, alongside a randomized controlled trial involving 80 patients who sought depression treatment at a university hospital and psychiatric hospital (one each). The cost-effectiveness was assessed by the incremental cost-effectiveness ratio (ICER) that compared the difference in costs and quality-adjusted life years, and other clinical scales, between the groups. RESULTS: The ICERs were JPY -15 278 322 and 2 026 865 for pharmacotherapy-resistant depression for all samples and those with moderate/severe symptoms at baseline, respectively. The acceptability curve demonstrates a 0.221 and 0.701 probability of the augmented CBT being cost-effective for all samples and moderate/severe depression, respectively, at the threshold of JPY 4.57 million (GBP 30 000). The sensitivity analysis supported the robustness of our results restricting for moderate/severe depression. CONCLUSION: Augmented CBT for pharmacotherapy-resistant depression is not cost-effective for all samples including mild depression. In contrast, it appeared to be cost-effective for the patients currently manifesting moderate/severe symptoms under secondary mental health care.

[A Case of Brain, Lung, and Adrenal Metastasis from Colorectal Cancer Controlled by Loco-Regional Surgery].

A 64-year-old man presented with the chief complaint of weakness in the left half of his body. He fell down on the road while riding a bicycle and was transported to the emergency room. A contrast-enhanced brain MRI revealed a 28mm ringshaped mass in the right frontal lobe. A craniotomy was performed 14 days later. The histopathological diagnosis showed the tumor as a well-differentiated tubular adenocarcinoma. Postoperative examination revealed a rectal cancer and a left lung mass. A low-anterior resection was performed 1 month after the craniotomy, and a partial lung resection was performed 2 months after the rectal excision. Metachronous solitary metastasis of the left adrenal gland was noticed 10 months after the removal of the lung metastasis and we subsequently performed a left adrenalectomy. The patient is not undergoing any active treatment 13 months after the adrenalectomy, but has no signs of recurrence. The loco-regional surgery was enabled for local control of multi-relapsed lesions from rectal cancer.

Distributional patterns of item responses and total scores on the PHQ-9 in the general population: data from the National Health and Nutrition Examination Survey.

BACKGROUND: Recently, item responses and total scores on depression screening scales have been reported to have characteristic distributions in the general population. The distributional pattern of responses to the Patient Health Questionnaire-9 (PHQ-9) in the general population has not been well studied. Thus, we carried out a pattern analysis of the PHQ-9 item responses and total scores in US adults. METHODS: Data (5372 individuals) were drawn from the 2013-2014 National Health and Nutrition Examination Survey in the United States. The item responses and total score distributions of the PHQ-9 data were investigated with graphical analysis and exponential regression model. RESULTS: Lines of item responses showed the same pattern among the nine items, characterized by crossing at a single point between "not at all" and "several days" and a parallel pattern from "several days" to "nearly every day" on a log-normal scale. The total score distribution of the PHQ-9 exhibited an exponential pattern, except for at the lower end of the distribution. CONCLUSIONS: The present results support that the item responses and total scores on the PHQ-9 in the general population show the same characteristic patterns, consistent with the previous studies using the Center for Epidemiologic Studies Depression Scale (CES-D) and Kessler Screening Scale for Psychological Distress (K6).

Civilians in World War II and DSM-IV mental disorders: results from the World Mental Health Survey Initiative.

PURPOSE: Understanding the effects of war on mental disorders is important for developing effective post-conflict recovery policies and programs. The current study uses cross-sectional, retrospectively reported data collected as part of the World Mental Health (WMH) Survey Initiative to examine the associations of being a civilian in a war zone/region of terror in World War II with a range of DSM-IV mental disorders. METHODS: Adults (n = 3370) who lived in countries directly involved in World War II in Europe and Japan were administered structured diagnostic interviews of lifetime DSM-IV mental disorders. The associations of war-related traumas with subsequent disorder onset-persistence were assessed with discrete-time survival analysis (lifetime prevalence) and conditional logistic regression (12-month prevalence). RESULTS: Respondents who were civilians in a war zone/region of terror had higher lifetime risks than other respondents of major depressive disorder (MDD; OR 1.5, 95% CI 1.1, 1.9) and anxiety disorder (OR 1.5, 95% CI 1.1, 2.0). The association of war exposure with MDD was strongest in the early years after the war, whereas the association with anxiety disorders increased over time. Among lifetime cases, war exposure was associated with lower past year risk of anxiety disorders (OR 0.4, 95% CI 0.2, 0.7). CONCLUSIONS: Exposure to war in World War II was associated with higher lifetime risk of some mental disorders. Whether comparable patterns will be found among civilians living through more recent wars remains to be seen, but should be recognized as a possibility by those projecting future needs for treatment of mental disorders.

Web-Based Cognitive Behavioral Therapy Blended With Face-to-Face Sessions for Major Depression: Randomized Controlled Trial.

BACKGROUND: Meta-analyses of several randomized controlled trials have shown that cognitive behavioral therapy (CBT) has comparable efficacy to antidepressant medication, but therapist availability and cost-effectiveness is a problem. OBJECTIVE: This study aimed to evaluate the effectiveness of Web-based CBT blended with face-to-face sessions that reduce therapist time in patients with major depression who were unresponsive to antidepressant medications. METHODS: A 12-week, assessor-masked, parallel-group, waiting- list controlled, randomized trial was conducted at 3 medical institutions in Tokyo. Outpatients aged 20-65 years with a primary diagnosis of major depression who were taking ≥1 antidepressant medications at an adequate dose for ≥6 weeks and had a 17-item GRID-Hamilton Depression Rating Scale (HAMD) score of ≥14 were randomly assigned (1:1) to blended CBT or waiting-list groups using a computer allocation system, stratified by the study site with the minimization method, to balance age and baseline GRID-HAMD score. The CBT intervention was given in a combined format, comprising a Web-based program and 12 45-minute face-to-face sessions. Thus, across 12 weeks, a participant could receive up to 540 minutes of contact with a therapist, which is approximately two-thirds of the therapist contact time provided in the conventional CBT protocol, which typically provides 16 50-minute sessions. The primary outcome was the alleviation of depressive symptoms, as measured by a change in the total GRID-HAMD score from baseline (at randomization) to posttreatment (at 12 weeks). Moreover, in an exploratory analysis, we investigated whether the expected positive effects of the intervention were sustained during follow-up, 3 months after the posttreatment assessment. Analyses were performed on an intention-to-treat basis, and the primary outcome was analyzed using a mixed-effects model for repeated measures. RESULTS: We randomized 40 participants to either blended CBT (n=20) or waiting-list (n=20) groups. All patients completed the 12-week treatment protocol and were included in the intention-to-treat analyses. Participants in the blended CBT group had significantly alleviated depressive symptoms at week 12, as shown by greater least squares mean changes in the GRID-HAMD score, than those in the waiting list group (-8.9 points vs -3.0 points; mean between-group difference=-5.95; 95% CI -9.53 to -2.37; P<.001). The follow-up effects within the blended CBT group, as measured by the GRID-HAMD score, were sustained at the 3-month follow-up (week 24) and posttreatment (week 12): posttreatment, 9.4 (SD 5.2), versus follow-up, 7.2 (SD 5.7); P=.009. CONCLUSIONS: Although our findings warrant confirmation in larger and longer term studies with active controls, these suggest that a combined form of CBT is effective in reducing depressive symptoms in patients with major depression who are unresponsive to antidepressant medications. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000009242; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010852 (Archived by WebCite at http://www.webcitation. org/729VkpyYL).

[A Case of Polyarteritis Nodosa Diagnosed from Pathological Findings of Refractory Epididymitis].

A 54-year-old man was admitted to internal medicine due to unidentified fever persisting for 3 months, and was examined. Then, he was referred to our department for suspected pyelonephritis. Although he was initially being treated for pyelonephritis, right epididymitis occurred during the course of treatment. Antibiotics were ineffective, and symptoms such as weakness and subctaneous nodules also appeared. We performed epididymectomy to differentiate this intractable epididymitis from other systemic diseases. Pathological findings were fibrinoid necrotic vasculitis of middle and small arteries. Of the diagnostic criteria for polyarteritis nodosa, 4 major symptoms and histological findings were satisfied. After we started oral administration of predonin, the fever went down and the creative protein level decreased immediatately.

Characteristic distribution of the total and individual item scores on the Kessler Screening Scale for Psychological Distress (K6) in US adults.

BACKGROUND: The distributional pattern of total scores on depression screening scales in the general population has not been well studied. Recent studies suggest that the total scores on depression screening scales follow an exponential pattern, with the exception of the lower end of the distribution. To further investigate the findings, we determined the distributions of the total and individual item scores on the Kessler Screening Scale for Psychological Distress (K6). METHODS: Data were obtained from the National Survey of Midlife Development in the United States. Participants comprised 6,223 individuals between the ages of 25 and 74. The distributions of the total and individual item scores in various combinations were investigated with histograms and regression analysis. RESULTS: Irrespective of the combination of items, the total and individual item scores followed an exponential pattern except at the lower scores. The estimated rate parameters of regression analysis were similar among distributions with the same number of chosen items. At the lower scores, the distributional patterns of total scores varied according to the ratio of "a little" to "none" for each item response. CONCLUSIONS: The present results have the potential to estimate the distribution of depressive symptoms in the general population. While the degree of depressive symptoms varies from individual to individual, an entire population may show a certain mathematical distribution.

[A Case of Fulminant Hepatitis after Administration of Abiraterone Acetate].

A 77-year-old man with castration-resistant prostate cancer (CRPC) received abiraterone acetate in October 2014. He visited our outpatient clinic because of general malaise and anorexia 27 days after starting abiraterone acetate. The lab test showed hepatic dysfunction (aspartate transaminase, AST 440 U/l, alanine transaminase, ALT 420 U/l) and the elevation of liver enzymes continued on the next day even after stopping abiraterone acetate. Three days later, he was hospitalized due to severe elevation of liver enzymes (AST 1,171 U/l, ALT 1,487 U/l) , and the decreased prothrombin activity (60.5%). The result of the lab test were negative for viral and autoimmune hepatitis. Three days after admission, he entered hepatic coma (grade III) and prothrombin activity decreased (23.2%) , compatible with fulminant hepatitis. Plasma exchange and steroid pulse therapy were started the next day, but he died 39 days after starting abiraterone acetate. In addition, the result of drug-induced lymphocyte stimulation test performed 3 days before his death was possibly positive.

[A Case of Castration-Resistant Prostate Cancer with Fatal Convulsive Seizure after Administration of Enzalutamide].

Enzalutamide, an androgen receptor antagonist, is a standard drug for the treatment of castrationresistant prostate cancer. A 77-year-old man developed a seizure after administration of enzalutamide. The patient presented with general fatigue and high fever approximately 5 weeks after oral administration of enzalutamide. Several days later, a seizure attack occurred at home, resulting in cardiopulmonary arrest. The patient was taken to the hospital emergency room but could not be resuscitated. We described a 63-year-old man who was diagnosed with clinical T1c prostate cancer, with a Gleason score of 6 (3＋3), and a preoperative prostate-specific antigen (PSA) level of 5. 27 ng/ml. Radical prostatectomy(RP) was performed and final pathologyshowed Gleason score 3＋4, pT2c with negative surgical margin. In spite of suggested surgical radicality, PSA was 3.32, 4.78, 5.93 ng/ml, at 1, 2, and 3 months after RP, respectively. However, radiological investigation revealed no metastasis. Because of this clinical discrepancy, we checked the PSA-α1-antichemotrypsin level and found it to be ≦0.1 ng/ml. From these results, false PSA elevation caused byinterference of positive heterophilic antibodies was suggested and demonstrated byseveral immunoassays.

Japan Unified Protocol Clinical Trial for Depressive and Anxiety Disorders (JUNP study): study protocol for a randomized controlled trial.

BACKGROUND: The unified protocol for the transdiagnostic treatment of emotional disorders is a promising treatment approach that could be applicable to a broad range of mental disorders, including depressive, anxiety, trauma-related, and obsessive-compulsive disorders. However, no randomized controlled trial has been conducted to verify the efficacy of the unified protocol on the heterogeneous clinical population with depressive and anxiety disorders. METHODS/DESIGN: The trial was designed as a single-center, assessor-blinded, randomized, 20-week, parallel-group superiority study in order to compare the efficacy of the combination of unified protocol and treatment-as-usual versus waiting-list with treatment-as-usual for patients with depressive and/or anxiety disorders. The primary outcome was depression at 21 weeks, assessed by the 17-item version of the GRID-Hamilton Rating Scale for Depression. Estimated minimum sample size was 27 participants in each group. We will also examine the treatment mechanisms, treatment processes, and neuropsychological correlates. DISCUSSION: The results of this study will clarify the efficacy of the unified protocol for depressive and anxiety disorders, and the treatment mechanism, process, and neurological correlates for the effectiveness of the unified protocol. If its efficacy can be confirmed, the unified protocol may be of high clinical value for Japan, a country in which cognitive behavioral treatment has not yet been widely adopted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02003261 (registered on December 2, 2013).

[Cognitive Behavioral Therapy for Depression].

Cognitive behavioral therapy (CBT) is a form of psychotherapy that improves dysfunc- tional cognition, and enhances the ability to manage problems in daily life. Not only CBT tech- niques, such as behavior activation, cognitive restructuring, and problem solving, but also case formulation and therapeutic relationships are important in CBT, which are useful for psychia- trists who work at a general hospital.

[Supervision in Psychiatric Training].

Psychotherapy is an essential component of psychiatric treatment. Although appropriate training including supervision is essential to become able to conduct psychotherapy skillfully, supervision has not been performed in the training of Japanese psychiatrists. In this article, we explain how to utilize supervision in psychiatric training.

Proportion of patients without mental disorders being treated in mental health services worldwide.

BACKGROUND: Previous research suggests that many people receiving mental health treatment do not meet criteria for a mental disorder but are rather 'the worried well'. AIMS: To examine the association of past-year mental health treatment with DSM-IV disorders. METHOD: The World Health Organization's World Mental Health (WMH) Surveys interviewed community samples of adults in 23 countries (n = 62 305) about DSM-IV disorders and treatment in the past 12 months for problems with emotions, alcohol or drugs. RESULTS: Roughly half (52%) of people who received treatment met criteria for a past-year DSM-IV disorder, an additional 18% for a lifetime disorder and an additional 13% for other indicators of need (multiple subthreshold disorders, recent stressors or suicidal behaviours). Dose-response associations were found between number of indicators of need and treatment. CONCLUSIONS: The vast majority of treatment in the WMH countries goes to patients with mental disorders or other problems expected to benefit from treatment.

[Adverse Events and Precautions Regarding Cognitive Behavioral Therapy].

Adverse events of cognitive behavioral therapy (CBT) can be used to identify two types depending on whether or not CBT is practiced appropriately. The results of a randomized control trial (RCT) when CBT is performed effectively show that the rate of adverse events is as low as, or lower than, that on using a pill placebo. Many adverse events are associated with a low quality of CBT caused by inappropriate practice due to therapists' lack of knowledge, skills, and experience. In order to achieve effective CBT for RCT, it is considered important to frequently assess the status of patients before and during CBT sessions, utilize the Cognitive Therapy Rating Scale after the session, and conduct supervision based on audio recordings of the session.

Irritable mood in adult major depressive disorder: results from the world mental health surveys.

BACKGROUND: Although irritability is a core symptom of DSM-IV major depressive disorder (MDD) for youth but not adults, clinical studies find comparable rates of irritability between nonbipolar depressed adults and youth. Including irritability as a core symptom of adult MDD would allow detection of depression-equivalent syndromes with primary irritability hypothesized to be more common among males than females. We carried out a preliminary examination of this issue using cross-national community-based survey data from 21 countries in the World Mental Health (WMH) Surveys (n = 110,729). METHODS: The assessment of MDD in the WHO Composite International Diagnostic Interview includes one question about persistent irritability. We examined two expansions of the definition of MDD involving this question: (1) cases with dysphoria and/or anhedonia and exactly four of nine Criterion A symptoms plus irritability; and (2) cases with two or more weeks of irritability plus four or more other Criterion A MDD symptoms in the absence of dysphoria or anhedonia. RESULTS: Adding irritability as a tenth Criterion A symptom increased lifetime prevalence by 0.4% (from 11.2 to 11.6%). Adding episodes of persistent irritability increased prevalence by an additional 0.2%. Proportional prevalence increases were significantly higher, but nonetheless small, among males compared to females. Rates of severe role impairment were significantly lower among respondents with this irritable depression who did not meet conventional DSM-IV criteria than those with DSM-IV MDD. CONCLUSION: Although limited by the superficial assessment in this single question on irritability, results do not support expanding adult MDD criteria to include irritable mood.

Two cohort and three independent anonymous twin projects at the Keio Twin Research Center (KoTReC).

The Keio Twin Research Center has conducted two longitudinal twin cohort projects and has collected three independent and anonymous twin data sets for studies of phenotypes related to psychological, socio-economic, and mental health factors. The Keio Twin Study has examined adolescent and adult cohorts, with a total of over 2,400 pairs of twins and their parents. DNA samples are available for approximately 600 of these twin pairs. The Tokyo Twin Cohort Project has followed a total of 1,600 twin pairs from infancy to early childhood. The large-scale cross-sectional twin study (CROSS) has collected data from over 4,000 twin pairs, from 3 to 26 years of age, and from two high school twin cohorts containing a total of 1,000 pairs of twins. These data sets of anonymous twin studies have mainly targeted academic performance, attitude, and social environment. The present article introduces the research designs and major findings of our center, such as genetic structures of cognitive abilities, personality traits, and academic performances, developmental effects of genes and environment on attitude, socio-cognitive ability and parenting, genes x environment interaction on attitude and conduct problem, and statistical methodological challenges and so on. We discuss the challenges in conducting twin research in Japan.

[Cognitive therapy/cognitive behavior therapy for depression].

Cognitive behavior therapy (CBT) is a structured short-term therapy designed to change the patient's negatively distorted cognition. The effectiveness of cognitive therapy/cognitive behavior therapy has been increasingly recognized not only by professionals and academics but also by the public, and in April, 2010, this therapy started to be covered by the national health insurance in Japan. In this article, the author described the high-intensity and low-intensity CBT from the practical point of view.

The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study.

PURPOSE: To determine through the analysis of our multi-institutional database whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma (UUTC) is beneficial. METHODS: A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study. Clinical features evaluated were sex, tumor location, adjuvant chemotherapy status, tumor pathology (histology, grade, infiltrating growth, lymphovascular invasion (LVI)), and cause of death. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis. RESULTS: In pT3 patients, overall 5-year CSS rate was 68.4% and median CSS time was 31 months (range 3-114 months). In the adjuvant chemotherapy group, 5-year CSS rate was 80.8%, whereas 5-year CSS rate was 64.4% in the non-adjuvant chemotherapy group. By multivariate analysis, adjuvant chemotherapy status was significantly associated with CSS (P = 0.008) were sex, tumor grade, tumor histology, and LVI presence. CONCLUSIONS: This study, although it was retrospective study, revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis. Prospective studies evaluating adjuvant therapy regimens for UTTC are required.

[Developing effectively therapeutic relationships].

For good therapeutic relationship, adequate case conceptualization is essential, and clinicians should try to understand both symptoms and resilience of patients. Furthermore, clinicians should displays a satisfactory degree of warmth, concern, confidence, genuineness, and professionalism, organize a session and use time adequately, collaborate with a patient, ask enough questions to help a patient widen his/her points of view, and elicit and respond verbal and non-verbal feedback from patients during a session.