Clonal Hematopoiesis and Cardiovascular Disease in Patients With Multiple Myeloma Undergoing Hematopoietic Cell Transplant.

Importance: There is a paucity of information on the association between clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular disease (CVD) in patients with cancer, including those with multiple myeloma (MM) undergoing hematopoietic cell transplant (HCT), a population at high risk of developing CVD after HCT. Objective: To examine the association between CHIP and CVD in patients with MM and to describe modifiers of CVD risk among those with CHIP. Design, Setting, and Participants: This was a retrospective cohort study of patients with MM who underwent HCT between 2010 and 2016 at City of Hope Comprehensive Cancer Center in Duarte, California, and had pre-HCT mobilized peripheral blood stem cell (PBSC) products cryopreserved and accessible for CHIP analyses. The study team performed targeted panel DNA sequencing to detect the presence of CHIP (variant allele frequency 2% or more). Main Outcomes and Measures: The primary end point was the 5-year cumulative incidence and risk for developing de novo CVD (heart failure, coronary artery disease, or stroke) after HCT. Results: Of 1036 consecutive patients with MM (580 male [56%]; median age, 60.0 years) who underwent a first autologous HCT, 201 patients had at least 1 CHIP variant (19.4%) and 35 patients had 2 or more variants (3.4%). The 5-year incidence of CVD was significantly higher in patients with CHIP (21.1% vs 8.4%; P < .001) compared with those without CHIP; the 5-year incidence among those with 2 or more variants was 25.6%. In the multivariable model, CHIP was associated with increased risk of CVD (hazard ratio [HR], 2.72; 95% CI, 1.70-4.39), as well as of individual outcomes of interest, including heart failure (HR, 4.02; 95% CI, 2.32-6.98), coronary artery disease (HR, 2.22; 95% CI, 1.06-4.63), and stroke (HR, 3.02; 95% CI, 1.07-8.52). Patients who had both CHIP and preexisting hypertension or dyslipidemia were at nearly 7-fold and 4-fold increased risk of CVD, respectively (reference: no CHIP, no hypertension, or dyslipidemia). Conclusion and Relevance: CHIP was significantly and independently associated with risk of CVD in patients with MM undergoing HCT and may serve as a novel biologically plausible biomarker for CVD in this cohort. Patients with MM and both CHIP and cardiovascular risk factors had an exceptionally high risk of CVD. Additional studies are warranted to determine if cardiovascular preventive measures can reduce CHIP-associated CVD risk.

Neurophysiological markers of depression detection and severity prediction in first-episode major depressive disorder.

OBJECTIVE: Deviant γ auditory steady-state responses (γ-ASSRs) have been documented in some psychiatric disorders. Nevertheless, the role of γ-ASSR in drug-naïve first-episode major depressive disorder (FEMD) patients remains equivocal. This study aimed to examine whether γ-ASSRs are impaired in FEMD patients and predict depression severity. METHODS: Cortical reactivity was assessed in a cohort of 28 FEMD patients relative to 30 healthy control (HC) subjects during an ASSR paradigm randomly presented at 40 and 60 Hz. Event-related spectral perturbation and inter-trial phase coherence (ITC) were calculated to quantify dynamic changes of the γ-ASSR. Receiver operating characteristic curve combined with binary logistic regression were then employed to summarize ASSR variables that maximally differentiated groups. RESULTS: FEMD patients exhibited significantly inferior 40 Hz-ASSR-ITC in the right hemisphere versus HC subjects (p = 0.007), along with attenuated θ-ITC that reflected underlying impairments in θ responses during 60 Hz clicks (p < 0.05). Moreover, the 40 Hz-ASSR-ITC and θ-ITC in the right hemisphere can be used as a combinational marker to detect FEMD patients with 84.0 % sensitivity and 81.5 % specificity (area under the curve was 0.868, 95 % CI: 0.768-0.968). Pearson's correlations between the depression severity and ASSR variables were further conducted. The symptom severity of FEMD patients was negatively correlated with 60 Hz-ASSR-ITC in the midline and right hemisphere, possibly indicating that depression severity mediated high γ neural synchrony. CONCLUSIONS: Our findings provide critical insight into the pathological mechanism of FEMD, suggesting first that 40 Hz-ASSR-ITC and θ-ITC in right hemisphere constitute potential neurophysiological markers for early depression detection, and second, that high γ entrainment deficits may contribute to underlying symptom severity in FEMD patients.

The Psychometric Properties and Cutoff Score of the Child and Adolescent Mindfulness Measure (CAMM) in Chinese Primary School Students.

To date, the Child and Adolescent Mindfulness Measure (CAMM) has been translated into several languages, including Chinese. This study aimed to explore the reliability and validity of the Chinese version of the CAMM and to identify the appropriate cutoff score among Chinese primary school students. A total of 1283 participants (52.2% males; 11.52 ± 0.78 years of age) completed a series of questionnaires to evaluate their mental health, including mindfulness, subjective well-being, positive youth development (PYD), depression, and anxiety. Item analysis, Confirmatory Factor Analysis (CFA), Exploratory Structural Equation Modeling (ESEM), criterion-related validity analysis, Receiver Operating Characteristic (ROC) analysis, and reliability analysis were performed. The results show that the Chinese version of the CAMM had acceptable item−scale correlation (r = 0.405−0.775, p < 0.001) and was the best fit for the two-factor ESEM model (χ2 = 168.251, p < 0.001, df = 26, TLI = 0.910, CFI = 0.948, RMSEA = 0.065, SRMR = 0.033) among Chinese primary school students. Additionally, the total score of the Chinese version of the CAMM was significantly associated with subjective well-being and PYD (r = 0.287−0.381, p < 0.001), and negatively associated with depression, and anxiety (r = −0.612−−0.542, p < 0.001). Moreover, a cutoff score of 22 or higher revealed a significant predictive power for all the included criteria. Finally, the Chinese version of the CAMM had good internal consistency (Cronbach's α = 0.826, McDonald's ω = 0.826). Altogether, the Chinese version of the CAMM had satisfactory psychometric properties, and it can be applied to Chinese children.

YinQiSanHuang Jiedu decoction for the treatment of hepatitis B-related compensated liver cirrhosis: study protocol for a multi-center randomized controlled trial.

INTRODUCTION: Hepatitis B-related compensated liver cirrhosis is related to a higher risk of hepatocellular carcinoma, and antiviral therapy is the preferred method. As the pathological mechanisms of liver fibrosis are complex, drugs developed for a single target are difficult to be effective in clinical practice, so there are no chemical drugs or biological drugs with clear efficacy available for clinical application at present. Traditional Chinese medicine is a kind of medical science that has been gradually formed during thousands of years and continuously enriched by the people of all ethnic groups in China. Traditional Chinese medicine shows curative effects in the treatment of liver diseases, especially in the field of liver fibrosis prevention and treatment. This study aims to test the integrative medicine (Chinese medicine plus antiviral therapy) effective on lowing hepatocellular carcinoma risk among patients with hepatitis-related compensated liver cirrhosis. METHODS AND ANALYSIS: This is a multi-center randomized controlled trial, and a total of 5 hospitals and 802 patients will be involved in. All the subjects are randomly allocated to the YinQiSanHuang Jiedu decoction (YQSHD) group (n = 401) or the placebo group (n = 401). The YQSHD group receives YQSHD granule with entecavir (ETV), and the placebo group receives YQSHD placebo with ETV. The treatment period will last for 52 weeks, and the follow-up period for 52 ± 2 weeks. The primary outcome measure is the annual incidence of HCC. Outcomes will be assessed at baseline and after treatment. The objective of this trial is "the integrative of YQSHD with ETV reduce the annual incidence of HCC to 1%." ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Committee of Guang'anmen Hospital, China (No.2019-006-KY), and the other centers in the trial will not begin recruiting until the local ethical approval has been obtained. Trial final results will be disseminated via publication. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900021532 . Registered on February 26, 2019.

Move More, Sit Less and Sleep Well: An analysis of WHO movement guidelines for children under 5 years of age.

Insufficient physical activity (PA), prolonged sedentary behavior (SB) and inadequate sleep (SLP) are detrimental factors to population health. To address health issues caused by insufficient PA, excessive SB and poor SLP, the World Health Organization (WHO) updated PA and SB guidelines for all populations aged from 5 years to 65 years and older in 2020. For children under 5 years old, the WHO issued the first global guidelines for PA, SB and SLP (collectively refer to movement behaviors) in April 2019. The guidelines applied a holistic approach to promote health behaviors, filling the gap of no comprehensive global movement guidelines for young children. Although the guidelines for young children offer guidance for health promotion, some research and practice implications and other issues should be mentioned. This commentary includes considerations for the importance of the WHO guidelines for younger children, critical analysis of evidence for developing the guidelines, and recommendations for future research and practice. The aim of this paper is to further advance health research in younger populations.

Efficacy and safety of YinQiSanHuang-antiviral decoction in chronic hepatitis B: study protocol for a randomized, placebo-controlled, double-blinded trial.

INTRODUCTION: Chronic hepatitis B (CHB) is a global public health problem. Antiviral therapy is the primary treatment. Studies have shown that a combined therapy of traditional Chinese medicine (TCM) and conventional antiviral drugs has better efficacy than conventional antiviral for treatment of CHB. YinQiSanHuang-antiviral decoction (YQSH) is a TCM compound preparation that has shown an effect on anti-hepatitis B virus and on slowing progression of hepatitis B-related liver diseases. To evaluate the efficacy and safety of YQSH combined with entecavir and its preventive effect on hepatitis B cirrhosis, we designed this randomized, double-blind and placebo-controlled trial. The objective is that the combination of YinQiSanHuang-antiviral decoction with entecavir will reduce the annual incidence of liver fibrosis/cirrhosis to 1%. METHODS: This is a multicenter, randomized, placebo-controlled, double-blinded trial involving five hospitals. A total of 802 patients are randomly allocated to two groups: the YQSH group (n = 401) or the placebo group (n = 401). The YQSH group receives YQSH with entecavir; the placebo group receives granules of placebo with entecavir. Patients receive treatment for 52 weeks and then are followed up for 52 ± 2 weeks. The primary outcome measure is the annual incidence of cirrhosis. The secondary outcome measures are hepatitis B virus DNA negative rate, hepatitis B surface antigen negative rate, hepatitis B e antigen seroconversion rate, liver function (alanine aminotransferase, aspartate aminotransferase , gamma-glutamyl transferase , alkaline phosphatase , serum albumin, and total bilirubin), spleen thickness, evaluation scores of patients' clinical symptoms, and safety assessment. Outcomes will be assessed at baseline and after treatment. DISCUSSION: Combination therapy could become a trend for treatment of CHB, and this trial expects to provide credible clinical evidence for the future combination of TCM and conventional antiviral drugs for the treatment of CHB. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900021521. Registered on 25 February 2019.