Longitudinal DNA methylation in parent-infant pairs impacted by intergenerational social adversity: An RCT of the Michigan Model of Infant Mental Health Home Visiting.

INTRODUCTION: Early childhood development is a strong predictor of long-term health outcomes, potentially mediated via epigenetics (DNA methylation). The aim of the current study was to examine how childhood experiences, punitive parenting, and an intergenerational psychotherapeutic intervention may impact DNA methylation in young children and their mothers. METHODS: Mothers and their infants/toddlers between 0 and 24 months were recruited at baseline (n = 146, 73 pairs) to participate in a randomized control trial evaluating the effectiveness of The Michigan Model of Infant Mental Health Home Visiting (IMH-HV) parent-infant psychotherapy compared to treatment as usual. Baseline and 12-month post-enrollment data were collected in the family's home and included self-report questionnaires, biological saliva samples, home environment observation, video-taped parent-child interaction, and audio-recorded interviews. Saliva DNA methylation was measured at the genes, nuclear receptor subfamily 3 group C member 1 (NR3C1), solute carrier family 6 member 4 (SLC6A4), brain-derived neurotrophic factor (BDNF), and the genetic element, long interspersed nuclear element-1 (LINE1). RESULTS: For mothers, baseline methylation of BDNF, SLC6A4, NR3C1, or LINE1 was largely not associated with baseline measures of their childhood adversity, adverse life experiences, demographic characteristics related to structurally driven inequities, or to IMH-HV treatment effect. In infants, there were suggestions that methylation in SLC6A4 and LINE1 was associated with parenting attitudes. Infant BDNF methylation suggested an overall decrease in response to IMH-HV psychotherapy over 12 months. CONCLUSIONS: Overall, our findings suggest that the epigenome in infants and young children may be sensitive to both early life experiences and parent-infant psychotherapy.

Nine months of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine chemotherapy for rifampicin/multidrug-resistant tuberculosis: a multicenter, randomized, open-label non-inferiority trial in China.

BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Study protocol for a randomized trial on timely delivery versus expectant management in late preterm small for gestational age pregnancies with an abnormal umbilicocerebral ratio (UCR): the DRIGITAT study.

BACKGROUND: The clinical inability to correctly identify late fetal growth restriction (FGR) within a group of fetuses who are identified as small for gestational age (SGA) is an everyday problem for all obstetrician-gynecologists. This leads to substantial overtreatment of healthy small fetuses but also inadequate detection of the growth-restricted fetuses that may benefit from timely delivery. Redistribution of the fetal circulation, signaled by an abnormal ratio of the Doppler velocity flow profiles of the umbilical artery and the middle cerebral artery, more specifically an increased umbilicocerebral ratio (UCR) (or its inverse: a decreased cerebroplacental ratio (CPR)), is an adaptation to chronic hypoxemia and nutritional scarcity with long-term consequences in survivors. The relevance of an abnormal UCR has been signaled extensively, and there is a general consensus that it is a signal of FGR, independent of size, with a strong association with poor outcomes. Yet, in the current literature, no comparisons of a monitoring-delivery strategy based on unfavorable UCR have been published. The objective of the Doppler Ratio In fetal Growth restriction Intervention Trial At (near) Term (DRIGITAT) is to evaluate if the timing of the delivery based on an abnormal UCR in late preterm fetuses identified as SGA improves neurodevelopmental outcomes at 2 years of age. METHODS: The DRIGITAT study is a national multicenter cohort study of women with singleton pregnancies between 32 and 37 weeks of gestation identified as SGA, with a nested randomized controlled trial (RCT) in case of an abnormal UCR (> 0.8). Recruiting centers are in The Netherlands. In the nested RCT, women are randomized to either immediate induction of labor or expectant management from 34 weeks in case of severely abnormal size (EFW or FAC < p3) and from 36 weeks in case of mildly abnormal size (EFW or FAC p3-p10). The primary outcome measure is the 7-point average difference in the composite cognitive score (CCS) and composite motor score (CMS) on the Bayley-3 at 2 years. Secondary outcome measures include a composite outcome of neonatal morbidity, perinatal mortality, mode of delivery, maternal quality of life, costs, and predictive value of serum biomarkers. Analyses will be by intention to treat. The required sample size is determined for the nested RCT as 185 patients. DISCUSSION: This study will provide insight into the diagnostic efficacy of UCR measurement in the evaluation of SGA fetuses in order to differentiate the healthy SGA fetus from the growth-restricted fetus and to determine if a fetus with abnormal UCR benefits from early delivery. TRIAL REGISTRATION: Healthcare Evaluation Netherlands NTR6663 . Registered on 14 August 2017.

Prevention of Metamphetamine Use Relapse Through Improving Effective Information, Education and Communication (IEC): An Open Cluster-Randomized-Controlled Trial / Lao Medical Journal

Background and Rational@#In Lao PDR, relapse of metamphetamine use following discharge from rehabilitation center is unacceptably high (~50%). Good preparedness and IEC provision to the rehabilitated addicts before discharge from the rehabilitation center is likely to be vital to prevent relapse. Effective IEC would probably help to reduce the rate of relapse.@*Methodology@#This was an open cluster-randomized-controlled trial to assess the newly developed IEC package among metamphetamine users. The intervention group received new IEC package (education message + brochure + telephone contact number + follow-up) while the conventional advice was given to control group. The study participants were followed up for 6 months by telephone (at 1, 3, 6 months). The primary endpoint was the relapse rate.@*Result@#One hundred and eighty-one addicts were enrolled in the trial (93 in intervention and 88 in control groups). Ninety-six subjects were male. The overall mean (SD) age of the participants was 26.5 (6.1) years and the overall median (range) duration of drug use was 5 (0.5 – 26) years and these figures were not significantly different between the groups (P=0.50 and P=0.97), respectively). The proportion of the participants who were lost to follow-up was 8%. Sixty percents of the study subjects completed 6-months follow up and this was not statistically different between the groups (P=0.93). The overall percentage of relapse was 39% (65/166) [36% (31/85) in intervention and 42% (34/81) in control groups, P=0.38). The median (range) duration of relapse was 30 (1 – 160) days and this was not significantly different between the groups (P=0.38). In a multiple logistic regression model, contact with drug users following discharge from the rehabilitation center was significantly associated with relapse [AOR = 73, 95%CI = 39 – 405, P<0.001] while having a permanent job following discharge was a protective factor for relapse [AOR = 0.03 (0.004 – 0.27), P=0.002].@*Conclusion@#The relapse rate of metamphetamine use was lower in the group with new IEC package than in control group but this was not statistically significant. Further study with a larger scale is strongly recommended

Slow movement resistance training using body weight improves muscle mass in the elderly: A randomized controlled trial.

To examine the effect of a 12-week slow movement resistance training using body weight as a load (SRT-BW) on muscle mass, strength, and fat distribution in healthy elderly people. Fifty-three men and 35 women aged 70 years old or older without experience in resistance training participated, and they were randomly assigned to a SRT-BW group or control group. The control group did not receive any intervention, but participants in this group underwent a repeat measurement 12 weeks later. The SRT-BW program consisted of 3 different exercises (squat, tabletop push-up, and sit-up), which were designed to stimulate anterior major muscles. Initially, these exercises were performed by 2 sets of 10 repetitions, and subsequently, the number of repetitions was increased progressively by 2 repetitions every 4 weeks. Participants were instructed to perform each eccentric and concentric phase of movement slowly (spending 4 seconds on each movement), covering the full range of motion. We evaluated muscle mass, strength, and fat distribution at baseline and after 12 weeks of training. Changes over 12 weeks were significantly greater in the SRT-BW group than in the control group, with a decrease in waist circumference, hip circumference, and abdominal preperitoneal and subcutaneous fat thickness, and an increase in thigh muscle thickness, knee extension strength, and hip flexion strength. In conclusion, relatively short-term SRT-BW was effective in improving muscle mass, strength, and fat distribution in healthy elderly people.