Clozapine and Long-Term Mortality Risk in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Studies Lasting 1.1-12.5 Years

INTRODUCTION: Patients with schizophrenia have an elevated mortality risk compared to the general population, with cardiovascular-related deaths being the leading cause. The role of clozapine use in the long-term mortality risk is unclear. While clozapine treatment may increase the risk for cardiovascular mortality, it may have protective effects regarding suicidal behavior. METHODS: We systematically searched EMBASE, MEDLINE, and PsycINFO and reviewed studies that used a long-term follow-up (ie, >52 weeks) and reported on mortality in adults diagnosed with schizophrenia-spectrum disorders who had received clozapine treatment. RESULTS: Altogether, 24 studies reported on 1327 deaths from any causes during 217691 patient years in patients treated with clozapine. The unadjusted mortality rate in 22 unique samples during a follow-up of 1.1-12.5 (median = 5.4) years was 6.7 (95% confidence interval [CI] = 5.4-7.9) per 1000 patient years. Long-term, crude mortality rate ratios were not significantly lower in patients ever treated with clozapine during follow-up, but significantly lower in patients continuously treated with clozapine compared to patients with other antipsychotics (mortality rate ratio = 0.56, 95% CI = 0.36-0.85, P-value = .007). Few studies reported on rates of long-term cause-specific mortality (suicide and ischemic heart disease), which showed no significant difference in patients using clozapine compared to patients using other antipsychotics. Statistical heterogeneity was high in all analyses. DISCUSSION: Continuous clozapine treatment in schizophrenia patients was associated with a significantly lower long-term all-cause mortality rate compared to other antipsychotic use. These findings, combined with the known efficacy of clozapine, give reason to re-evaluate the hesitancy to prescribe clozapine in regular care settings. TRIAL REGISTRATION: PROSPERO CRD42017069390

Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants The Early Nutrition Study Randomized Clinical Trial

IMPORTANCE Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother's milk when compared with formula. When own mother's milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear. OBJECTIVE To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality. DESIGN, SETTINGS, AND PARTICIPANTS The Early Nutrition Studywas a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight <1500 g) admitted to 1 of 6 neonatal intensive care units in the Netherlands from March 30, 2012, through August 17, 2014. Intent-to-treat analysis was performed. INTERVENTIONS Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother's milk was not (sufficiently) available. MAIN OUTCOMES AND MEASURES The primary end point was cumulative occurrence of serious infection (sepsis or meningitis), necrotizing enterocolitis, or mortality during the first 60 days of life. RESULTS A total of 930 infants were screened for inclusion; 557 were excluded, resulting in 373 infants (183 receiving donor milk and 190 receiving formula) who were evaluated by intent-to-treat analysis (median birth weight, 1066 g; mean gestational age, 28.4 weeks). Own mother's milk comprised 89.1% and 84.5% of total mean intake during the intervention period for the donor milk and formula groups, respectively. The incidence of the combined outcome was not different (85 [44.7%] [formula] vs 77 [42.1%] [donor milk]; mean difference, 2.6%; 95% CI, -12.7% to 7.4%). The adjusted hazard ratio was 0.87 (95% CI, 0.63-1.19; P =.37). CONCLUSIONS AND RELEVANCE In the current study, pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother's milk availability was insufficient. Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary

Process Evaluation of the BOOST-A™ Transition Planning Program for Adolescents on the Autism Spectrum: A Strengths-Based Approach

© 2017 Springer Science+Business Media, LLC A process evaluation was conducted to determine the effectiveness, usability, and barriers and facilitators related to the Better OutcOmes & Successful Transitions for Autism (BOOST-A™), an online transition planning program. Adolescents on the autism spectrum (n = 33) and their parents (n = 39) provided feedback via an online questionnaire. Of these, 13 participants were interviewed to gain in-depth information about their experiences. Data were analyzed using descriptive statistics and thematic analysis. Four themes were identified: (i) taking action to overcome inertia, (ii) new insights that led to clear plans for the future, (iii) adolescent empowerment through strengths focus, and (iv) having a champion to guide the way. The process evaluation revealed why BOOST-A™ was beneficial to some participants more than others. Trial registration #ACTRN1261500011959