Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can do access to CBT via the Internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time. Objective: The present study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, and SAD. Methods: A total of 29 Japanese participants (mean age = 35.4 years, SD=9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of therapist using tablet PC (iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety and Working Alliance Inventory (WAI-SF). All primary outcomes were assessed at baseline, and at weeks 1 (baseline), 8 (mid-intervention), and 16 (post-intervention) by face-to-face during therapy. The occurrence of adverse events were observed after each session. For the primary analysis comparing between pre- and post- treatments, the participants’ points and 95% CIs were estimated by the paired t-tests with the change between pre- and post-treatment. Results: A significant reductions in symptom of obsession-compulsion (Y-BOCS; -6.2, Cohen’s d=0.74, 95% CI -9.4 to -3.0, P=.002), panic (PDSS; -5.6, Cohen’s d=0.89, 95% CI –9.83 to –1.37, P=.015), social anxiety (LSAS; -33.56, Cohen’s d=1.10, 95% CI –59.62 to –7.49, P=.018) were observed. In addition, depression (PHQ-9; -1.72, Cohen’s d=0.27, 95% CI –3.26 to –0.19, P=.029) and general anxiety (GAD-7; -3.03, Cohen’s d=0.61, 95% CI –4.57 to -1.49, P<.001) were significantly improved. Although there were no significant changes at 16 weeks from baseline in EQ-5D (0.0336, Cohen’s d=-0.202, 95% CI –0.0198 to 0.00869, P=.208), there were high therapeutic alliance (i.e., WAI-SF) scores (from 68.0 to 73.7) throughout treatment, which significantly increased (4.14, 95% CI 1.24 to 7.04, P=.007). Of the participants, 86% (25/29) were satisfied with videoconference-delivered CBT, and 83% (24/29) preferred videoconference-delivered CBT to face to face CBT. An adverse event occurred to a patient with SAD; the incidence was 3% (1/30). Conclusions: Videoconference-delivered CBT for patients with OCD, SAD, and SAD may be feasible and acceptable. Clinical Trial: Trial Regsitration system: University Hospital Medical Information Network(UMIN) Center URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000030495 Trial ID: UMIN000026609 Official scientific title of the study: A single-arm pilot study of videoconference cognitive-behavioral therapy for obsessive-compulsive disorder, social anxiety, and panic disorder

This randomized, double‐blind, placebo‐controlled trial evaluated dexamethasone efficacy at preventing fever, anorexia, and nausea/vomiting, the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Child‐Pugh class A/B patients with HCC and no macrovascular invasion/extrahepatic metastases were randomly assigned to either a dexamethasone regimen (day 1, intravenous dexamethasone [20 mg] and granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg]) or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg]; days 2 and 3, intravenous placebo). The primary endpoint was complete response, defined as the absence of grade ≥1 fever, anorexia, or nausea/vomiting according to the Common Terminology Criteria for Adverse Events (version 4.0) and no use of rescue therapy for 120 hours after TACE. A total of 120 patients between October 2010 and June 2013 were randomly assigned to treatment groups. Overall the complete response rate was greater with the dexamethasone regimen than with the control regimen (47.5%, 95% confidence interval 34.3%‐60.9%, versus 10.2%, 95% confidence interval 3.8%‐20.8%; P < 0.001). Cumulative incidences of fever, anorexia, and nausea/vomiting were higher in the control regimen group compared with the dexamethasone group (P < 0.001, P < 0.001, and P = 0.095, respectively). The dexamethasone regimen was generally well tolerated by HCC patients including those with well‐controlled diabetes mellitus and those with hepatitis B virus infection. Conclusion: The dexamethasone regimen was more effective than the control regimen at preventing TACE‐induced fever, anorexia, and nausea/vomiting in patients with HCC. (Hepatology 2018;67:575‐585).

Objective To classify diseases based on age at peak incidence to identify risk factors for later disease in women's life course. Design A cross-sectional baseline survey of participants in the Japan Nurses’ Health Study. Setting A nationwide prospective cohort study on the health of Japanese nurses. The baseline survey was conducted between 2001 and 2007 (n=49 927). Main outcome measures Age at peak incidence for 20 diseases from a survey of Japanese women was estimated using the Kaplan-Meier method with the Kernel smoothing technique. The incidence rate and peak incidence for diseases whose peak incidence occurred before the age of 45 years or before the perimenopausal period were selected as early-onset diseases. The OR and 95% CI were estimated to examine the risk of comorbidity between early-onset and other diseases. Results Four early-onset diseases (endometriosis, anaemia, migraine headache and uterine myoma) were significantly correlated with one another. Late-onset diseases significantly associated (OR>2) with early-onset diseases included comorbid endometriosis with ovarian cancer (3.65 (2.16 to 6.19)), endometrial cancer (2.40 (1.14 to 5.04)) and cerebral infarction (2.10 (1.15 to 3.85)); comorbid anaemia with gastric cancer (3.69 (2.68 to 5.08)); comorbid migraine with transient ischaemic attack (3.06 (2.29 to 4.09)), osteoporosis (2.11 (1.71 to 2.62)), cerebral infarction (2.04 (1.26 to 3.30)) and angina pectoris (2.00 (1.49 to 2.67)); and comorbid uterine myoma with colorectal cancer (2.31 (1.48 to 3.61)). Conclusions While there were significant associations between four early-onset diseases, women with a history of one or more of the early-onset diseases had a higher risk of other diseases later in their life course. Understanding the history of early-onset diseases in women may help reduce the subsequent risk of chronic diseases in later life.

Background: Face-to-face individual cognitive behavioral therapy (CBT) and internet-based CBT (ICBT) without videoconferencing are known to have long-term effectiveness for obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). However, videoconference-delivered CBT (VCBT) has not been investigated regarding its long-term effectiveness and cost-effectiveness. Objective: The purpose of this study was to investigate the long-term effectiveness and cost-effectiveness of VCBT for patients with OCD, PD, or SAD in Japan via a 1-year follow-up to our previous 16-week single-arm study. Methods: Written informed consent was obtained from 25 of 29 eligible patients with OCD, PD, and SAD who had completed VCBT in our clinical trial. Participants were assessed at baseline, end of treatment, and at the follow-up end points of 3, 6, and 12 months. Outcomes were the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Panic Disorder Severity Scale (PDSS), Liebowitz Social Anxiety Scale (LSAS), Patient Health Questionnaire–9 (PHQ-9), General Anxiety Disorder–7 (GAD-7), and EuroQol-5D-5L (EQ-5D-5L). To analyze long-term effectiveness, we used mixed-model analysis of variance. To analyze cost-effectiveness, we employed relevant public data and derived data on VCBT implementation costs from Japanese national health insurance data. Results: Four males and 21 females with an average age of 35.1 (SD 8.6) years participated in the 1-year follow-up study. Principal diagnoses were OCD (n=10), PD (n=7), and SAD (n=8). The change at 12 months on the Y-BOCS was −4.1 (F1=4.45, P=.04), the change in PDSS was −4.4 (F1=6.83, P=.001), and the change in LSAS was −30.9 (F1=6.73, P=.01). The change in the PHQ-9 at 12 months was −2.7 (F1=7.72, P=.007), and the change in the GAD-7 was −3.0 (F1=7.09, P=.009). QALY at 12 months was 0.7469 (SE 0.0353, 95% Cl 0.6728-0.821), and the change was a significant increase of 0.0379 (P=.01). Total costs to provide the VCBT were ¥60,800 to ¥81,960 per patient. The set threshold was ¥189,500 ($1723, €1579, and £1354) calculated based on willingness to pay in Japan. Conclusions: VCBT was a cost-effective way to effectively treat Japanese patients with OCD, PD, or SAD. Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000026609; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030495

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: In reality, pharmacotherapy still remains the most common treatment for insomnia. This study aimed to examine the effectiveness of our internet delivered computerized cognitive behavioral therapy (ICBT) program as an adjunct to usual care (UC) compared with UC alone in patients with insomnia, who remain symptomatic following hypnotics. Objective: We examined the effectiveness of our ICBT program as an adjunct to UC compared with UC alone in patients with insomnia who remain symptomatic following hypnotics. Methods: We recruited 23 patients with insomnia who remain symptomatic following pharmacologic treatment including benzodiazepines, and we conducted a exploratory randomized controlled trial. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) at week 6 of treatment. Secondary outcomes were the sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE), number of awakenings (NA), refreshment and soundness of sleep, anxiety by Hospital Anxiety and Depression Scale (HADS), depression measured by the Center for Epidemiologic Studies Depression Scale (CES-D), and quality of life measured by the EuroQol-5D (EQ-5D). All parameters were measured at weeks 0 (baseline), 6 (post-intervention), and 12 (follow-up). Results: The adjusted mean reduction (−6.11) in PSQI at week 6 from baseline in the ICBT+UC group was significantly (p<0.001) larger than that (0.40) in the UC group. Significant differences were also found in favor of ICBT+UC for PSQI, SOL, SE, NA and depression at all assessment points. Refreshment, soundness of sleep, anxiety, and quality of life improved by week 6 in ICBT+UC compared with UC. There were no reports of adverse events in either group during the study. Conclusions: These results indicate that our 6-week ICBT program is an effective treatment adjunct to UC for improving insomnia and related symptoms even after unsuccessful pharmacotherapy. Clinical Trial: UMIN000021509. Trial name: Effectiveness study of internet-based cognitive behavioral therapy for insomnia: A pilot randomized controlled trial. URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000023545