Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial.

Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to alveolar simplification, impaired alveolar-capillary development, interstitial fibrosis, and often pulmonary hypertension. BPD is the most common pulmonary sequela of prematurity and is often fatal; however, there remains no FDA-approved therapies to treat or prevent BPD. Sildenafil is increasingly used off-label in premature infants despite scant safety and efficacy data. Sildenafil reduces lung injury and preserves normal vasculature in preclinical models, and improves outcomes in children with pulmonary hypertension, and thus is a promising candidate for BPD. Following phase I studies, we developed the phase II SIL02 trial to describe the safety, pharmacokinetics and preliminary effectiveness of intravenous and enteral sildenafil in premature infants at risk for BPD. SIL02 is a randomized, double-blind, placebo-controlled, 3-cohort, sequential dose-escalating trial of enteral or intravenous (IV) sildenafil dosed every 8 h for up to 34 days. The target IV doses were 0.125, 0.5 and 1 mg/kg/dose in cohorts 1, 2 and 3, respectively; while the enteral doses will be double the IV doses. Eligible infants must be < 29 weeks' gestation at birth and requiring respiratory support at 7-28 days' postnatal age. Adverse events and preliminary effectiveness will be compared by treatment group. Using the final population PK model, empirical Bayesian estimates will be generated for each patient. Preliminary effectiveness will be measured by the incidence of moderate to severe BPD or death at 36 weeks and change in the BPD risk estimation.

Giving parents support: a randomized trial of peer support for parents after NICU discharge.

BACKGROUND: Peer support during inpatient hospitalization has been recommended for NICU parents and can improve maternal mental health. Less is known about the impact of peer support after NICU discharge on parental mental health and infant healthcare utilization. METHODS: Three hundred families of infants approaching discharge from a Level IV NICU were randomized to receive a care notebook (control) or care notebook plus peer support for 12 months (intervention). Participants reported on measures of stress, depression, anxiety, self-efficacy, and infant healthcare utilization. Analysis compared outcomes between control and treatment groups. RESULTS: Parental depression, anxiety, stress, and self-efficacy improved significantly for all participants, yet there were no differences between control and intervention groups. Infant ED visits, hospitalizations, immunization status, and developmental status at 12 months did not differ between groups. CONCLUSIONS: Peer support after NICU discharge did not improve self-reported parental mental health measures or infant healthcare utilization. CLINICAL TRIAL REGISTRATION: NCT02643472.

Adolescent Substance Use & Psychopathology: Interactive Effects of Cortisol Reactivity and Emotion Regulation.

How are emotional processes associated with the increased rates of substance use and psychological disorders commonly observed during adolescence? An index of emotion-related physiological arousal-cortisol reactivity-and subjective emotion regulation have both been independently linked to substance use and psychological difficulties among youth. The current study (N = 134 adolescents) sought to elucidate the interactive effects of cortisol reactivity following a stressful parent-child interaction task and self-reported emotion regulation ability on adolescents' substance use and externalizing and internalizing behavior problems. Results revealed that adolescents with low levels of cortisol reactivity and high emotion regulation difficulties were more likely to use substances, and also had the highest parent-reported symptoms of oppositional defiant disorder. With respect to internalizing symptoms, high emotion-related physiological reactivity coupled with high emotion regulation difficulties were associated with higher self-reported major depression symptoms among youth. Findings reveal that different profiles of HPA axis arousal and emotion regulation are associated with substance use and symptoms of psychopathology among adolescents.