Guided parent-delivered cognitive behavioural therapy for Japanese children and parents: a single-arm uncontrolled study

Background: Guided parent-delivered cognitive behavioural therapy (GPD-CBT) is an effective low-intensity treatment for childhood anxiety disorder in Western countries and can increase access to evidence-based psychological therapies. Aim: This study aimed to examine its feasibility in a Japanese sample. Method: Twelve children with anxiety disorders and their parents participated in the study, and ten children and parents completed the program. Participants were assessed at pre-, post- and one-month follow-up using a diagnostic interview for anxiety disorders, self- and parent-report measures for anxiety, depression, parental behaviour, and parental anxiety. Results: Four children (40% of completers) were free from their primary diagnoses immediately following the brief treatment, and seven children (70%) at the one-month follow-up. Changes in disorder severity, child and parent reported anxiety symptoms, and child reported depression symptoms were consistent with those found in Western trials of GPD-CBT and of Japanese trials of more intensive CBT for child anxiety disorders that involves both the child and the parent. Moderate increases were also found in child reported parental autonomy behaviours; however, there were only small changes in parent self-reported anxiety. Conclusion: These results support the potential of GPD-CBT to increase access to evidence-based treatments for anxiety disorders in Japanese children

A multicenter randomized controlled trial to evaluate the efficacy and safety of nelfinavir in patients with mild COVID-19

Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were randomly assigned (1:1) to receive oral nelfinavir (750 mg; thrice daily for 14 days) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to viral clearance, confirmed using quantitative reverse-transcription PCR by assessors blinded to the assigned treatment. A total of 123 patients (63 in the nelfinavir group and 60 in the control group) were included. The median time to viral clearance was 8.0 (95% confidence interval [CI], 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI, 7.0 to 10.0) days in the control group, with no significant difference between the treatment groups (hazard ratio, 0.815; 95% CI, 0.563 to 1.182; P = 0.1870). Adverse events were reported in 47 (74.6%) and 20 (33.3%) patients in the nelfinavir and control groups, respectively. The most common adverse event in the nelfinavir group was diarrhea (49.2%). Nelfinavir did not reduce the time to viral clearance in this setting. Our findings indicate that nelfinavir should not be recommended in asymptomatic or mildly symptomatic patients infected with SARS-CoV-2. The study is registered with the Japan Registry of Clinical Trials (jRCT2071200023). IMPORTANCE The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. However, its efficacy in patients with COVID-19 has not been studied. We conducted a multicenter, randomized controlled trial to evaluate the efficacy and safety of orally administered nelfinavir in patients with asymptomatic or mildly symptomatic COVID-19. Compared to standard-of-care alone, nelfinavir (750 mg, thrice daily) did not reduce the time to viral clearance, viral load, or the time to resolution of symptoms. More patients had adverse events in the nelfinavir group than in the control group (74.6% [47/63 patients] versus 33.3% [20/60 patients]). Our clinical study provides evidence that nelfinavir, despite its antiviral effects on SARS-CoV-2 in vitro, should not be recommended for the treatment of patients with COVID-19 having no or mild symptoms

Correction: Comparison of short-term clinical outcomes between low-dose prasugrel and clopidogrel as part of triple antithrombotic therapy in patients requiring oral anticoagulant therapy and percutaneous coronary intervention.

[This corrects the article DOI: 10.1371/journal.pone.0272140.]

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

Lateral meniscal injury without medial meniscal injury indicates the existence of the Segond fracture in ACL-deficient knees

Background/Objective: The purpose of this study was to find factors indicating the occurrence of the Segond fracture, a specific type of anterolateral ligament injury. Methods: From January 2015 to December 2017, we retrospectively reviewed the medical records of patients diagnosed with acute anterior cruciate ligament (ACL) injury who underwent reconstruction within 90 days of injury. Diagnosis of the Segond fracture was determined either by magnetic resonance imaging or plain radiographs. Factors examined were: age at surgery, sex, body mass index (kg/m2), status of menisci, and activities led to ACL injury. After univariate screening, multivariate logistic regression analyses were performed. Patients were divided into four groups based on the presence of lateral meniscal (LM) and/or medial meniscal (MM) injuries and compared with respect to the occurrence of Segond fractures. Results: A total of 375 patients were included (163 males, 212 females), with mean age 25.8 years old. Among them, 22 of 375 (5.9 %) had a Segond fracture. We identified injured lateral menisci (adjusted odds ratio (aOR), 3.029; 95 % Confidence Interval (CI), 1.206–7.609; P = 0.018), intact medial menisci (aOR, 0.229; 95 % CI, 0.065–0.810; P = 0.022), and higher body mass index (aOR, 1.102; 95 % CI, 1.008–1.205; P = 0.034) as factors indicative of the occurrence of Segond fracture. LM injury without MM injury suggested the existence of a Segond fracture. Conclusion: LM injury without a MM injury indicated the occurrence of a Segond fracture. Higher body mass index also increased the risk for Segond fracture occurrence

Feasibility of guided internet-based cognitive behavioral therapy for patients with anorexia nervosa

Objective: The objective of the present study was to investigate the feasibility of guided internet cognitive behavioral therapy (ICBT) for anorexia nervosa. Methods: We conducted a prospective single-arm study between January 2020 and March 2021. The intervention was built using videos, web programs, and chat tools. The intervention program was largely based on metacognitive training. Participants performed the self-help program once a week for 12 consecutive weeks. The primary outcome was the global Eating Disorder Examination Questionnaire (EDE-Q) score. Secondary outcomes included clinical symptoms of eating disorders, metacognitive function, body mass index, depression, and generalized anxiety. The main statistical analysis examined whether the EDE-Q score and other outcomes at the end of the intervention differed from the baseline. Results: Fourteen participants underwent the trial treatment, and 13 completed the intervention. There was a significant reduction in the global EDE-Q score from 3.48 (SD = 1.4) to 2.54 (SD = 1.5, p = 0.02, Cohens d = 0.75) from baseline to post-intervention. Some EDE-Q subscales and body checking questionnaire scale demonstrated statistically significant improvements, with moderate to large effect sizes. Although there was no significant improvement in body mass index, metacognitive function, or depressive symptoms, there was a significant improvement in the severity of generalized anxiety (M = -4.0, p = 0.01, Cohens d = 0.95). No adverse events were observed. Discussion: Our findings suggest that guided ICBT for anorexia nervosa is well accepted by female patients and practical as a telemedicine approach that improves symptoms. In the future, tightly controlled randomized controlled trials should be conducted for efficacy verification.Funding Agencies|Japan Society for the Promotion of Science (JSPS) KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [18K17313, 19J00227]</p

Bevacizumab in First-Line Chemotherapy Improves Progression-Free Survival for Advanced Ovarian Clear Cell Carcinoma

(1) Background: We investigated survival outcomes following first-line chemotherapy before and after approval of bevacizumab (Bev) for ovarian cancer in Japan to evaluate the efficacy of Bev for advanced clear cell carcinoma (CCC). (2) Methods: We investigated 28 consecutive patients diagnosed with CCC (stages III/IV) at our hospital between 2008 and 2018. Bev was administered for treatment of advanced CCC after approval in Japan in November 2013. Progression-free survival (PFS) was compared between 10 patients treated before Bev approval (2008–2013, Bev- group) and 18 patients treated after Bev approval (2014–2018, Bev+ group) for first-line chemotherapy. (3) Results: No intergroup difference was observed in patient characteristics. The rate of completeness of resection was higher in the Bev − group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev + group received ≥ 21 cycles of Bev. The median PFS increased from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis showed that performance status (p = 0.049), Bev administration (p = 0.023) and completeness of resection (p = 0.023) were independent prognostic factors for PFS. (4) Conclusions: Bev incorporated into first-line chemotherapy might improve PFS in patients with advanced CCC. We hope that our findings will be confirmed in adequate clinical trials

Comparison of 30 Cytokines in Human Breast Milk between 1989 and 2013 in Japan

Milk cytokines play a vital role in mucosal immunity during infancy by supporting immune development and functions. Although the maternal background characteristics influence milk cytokines, changes in cytokine levels across generations remain unclear. Colostrum (C, n = 48) and mature milk (MM, n = 49) samples were collected from lactating Japanese women in 1989 (2727 samples) and 2013 (1408 samples). Milk cytokines were comprehensively measured using a suspension array and immunosorbent assays. The positive rates and cytokine concentrations were compared between the two generations using logistic and multiple regression analyses. Twenty-eight cytokines tested positive in all sample groups (1989-C, 1989-MM, 2013-C, and 2013-MM). The median osteopontin (OPN) level was significantly higher in the 1989-C group than in the 2013-C group (318.1 vs. 137.5 μg/mL; p = 0.0016) but did not differ between the MM groups. The median TGF-β1 level was significantly lower in the 1989-MM group than in the 2013-MM group (1056.2 vs. 1330.8 pg/mL; p = 0.008) but did not differ between the C groups. Most cytokines were comparable between generations, except for potential variation in the C-OPN and TGF-β1 levels. Milk cytokine secretion may reflect temporal changes in maternal background characteristics; however, the results from the analysis of 30-year-old samples may have influenced the milk cytokine levels. Further studies are needed with a larger number of milk samples collected from the same individuals at multiple time points over a wide lactation period, with detailed data on the maternal and infant background characteristics and diets

Sodium-Glucose Co-Transporter 2 Inhibitors Reduce Macular Edema in Patients with <i>Diabetes mellitus</i>

Purpose: To determine the efficacy of systemic sodium-glucose co-transporter 2 inhibitors (SGLT2i) on diabetic macular edema (DME). Methods: The medical records of patients with DME with a central retinal thickness (CRT) ≥320 µm in men and 305 µm in women, more than 6 months after the initiation of diabetes mellitus treatment, were reviewed. The CRT and best-corrected visual acuity (BCVA) were evaluated before and after the initiation of systemic SGLT2i and non-SGLT2i treatments. Results: There were 24 eyes of 19 patients with DME that were treatment naïve or had not received treatments for the DME within four months before the initiation of SGLT2i. In these patients, the BCVA had a 0.31 ± 0.39 logarithm of the minimum angle of resolution (logMAR) units at the baseline, and it did not improve significantly at 0.26 ± 0.29 logMAR units after the initiation of SGLT2i (p = 0.56). However, the SGLT2i treatment significantly reduced the CRT from 423.3 ± 79.8 µm to 379.6 ± 69.5 µm (p = 0.0001). In the same evaluation of 19 eyes of 14 patients with DME that were initiated with non-SGLT2i agents, there was no significant difference between the baseline BCVA and the BCVA after the initiation of non-SGLT2i (p = 0.47). The CRT increased significantly after the initiation of non-SGLT2i (p = 0.0011). In three eyes in which the SGLT2i treatments were administered at the time of anti-vascular endothelial growth factor (VEGF) treatments, the anti-VEGF treatment alone had only a limited effect on the DME, but the reduction in the DME was enhanced after the addition of SGLT2i. Conclusions: These findings indicate that systemic SGLT2i can reduce DMEs, and they suggest that SGLT2i may be an additional treatment option to anti-VEGF treatments for eyes with DMEs

Mixed venous oxygen tension is a crucial prognostic factor in pulmonary hypertension: a retrospective cohort study

Abstract Background The prognostic value of mixed venous oxygen tension (PvO2) at pulmonary hypertension diagnosis treated with selective pulmonary vasodilators remains unclear. This study sought to investigate the association of PvO2 with long-term prognosis in pulmonary arterial hypertension (PAH) and medically treated chronic thromboembolic pulmonary hypertension (CTEPH) and to identify the distinct mechanisms influencing tissue hypoxia in patients with CTEPH or PAH. Methods We retrospectively analyzed data from 138 (age: 50.2 ± 16.6 years, 81.9% women) and 268 (age: 57.4 ± 13.1 years, 72.8% women) patients with PAH and CTEPH, respectively, diagnosed at our institution from 1983 to 2018. We analyzed the survival rates of patients with/without tissue hypoxia (PvO2 < 35 mmHg) and identified their prognostic factors based on the pulmonary hypertension risk stratification guidelines. Results Survival was significantly poorer in patients with tissue hypoxia than in those without it for PAH (P = 0.001) and CTEPH (P = 0.017) treated with selective pulmonary vasodilators. In patients with PAH, PvO2 more strongly correlated with prognosis than other hemodynamic prognostic factors regardless of selective pulmonary vasodilators usage. PvO2 was the only significant prognostic factor in patients with CTEPH treated with pulmonary hypertension medication. Patients with CTEPH experiencing tissue hypoxia exhibited significantly poorer survival than those in the intervention group (P < 0.001). PvO2 more strongly correlated with the cardiac index (CI) than the alveolar-arterial oxygen gradient (A-aDO2) in PAH; whereas in CTEPH, PvO2 was more strongly correlated with A-aDO2 than with CI. Conclusions PvO2 may represent a crucial prognostic factor for pulmonary hypertension. The prognostic impact of tissue hypoxia affects different aspects of PAH and CTEPH, thereby reflecting their distinct pathogenesis