Implementation of Ticagrelor Reduced Mortality in Routine Clinical Care: Evidence From a Natural Experiment Including 109 995 Patients With Myocardial Infarction in Sweden.

Background Effectiveness estimates from observational studies on ticagrelor use in routine clinical care are conflicting, with some contrary to the results of the pivotal randomized controlled trial of ticagrelor in acute coronary syndrome. The aim of this study was to estimate the effect of implementing and using ticagrelor in routine clinical care in patients with myocardial infarction using a natural experimental approach. Methods and Results This is a retrospective cohort study including patients hospitalized for myocardial infarction in Sweden between 2009 and 2015. The study exploited differences in the timing and speed of ticagrelor implementation between treatment centers as a source of random treatment assignment. The effect of implementing and using ticagrelor was estimated based on the admitting center's likelihood of treating patients with ticagrelor, measured as the proportion of patients treated in the 90 days before patient admission. The main outcome was 12-month mortality. The study included 109 955 patients, of whom 30 773 were treated with ticagrelor. Being admitted to a treatment center with higher past ticagrelor use was associated with a reduction in 12-month mortality (2.5 percentage points for 100% versus 0% past use [95% CI, 0.2-4.8]). The results are in line with the findings from the ticagrelor pivotal trial. Conclusions Using a natural experiment, this study finds that the implementation and use of ticagrelor in routine clinical care has reduced 12-month mortality in patients admitted to the hospital with myocardial infarction in Sweden and supports the external validity of randomized evidence on ticagrelor effectiveness.

Scaling up quality improvement intervention for perinatal care in Nepal (NePeriQIP); study protocol of a cluster randomised trial.

INTRODUCTION: Nepal Perinatal Quality Improvement Project (NePeriQIP) intends to scale up a quality improvement (QI) intervention for perinatal care according to WHO/National guidelines in hospitals of Nepal using the existing health system structures. The intervention builds on previous research on the implementation of Helping Babies Breathe-quality improvement cycle in a tertiary healthcare setting in Nepal. The objective of this study is to evaluate the effect of this scaled-up intervention on perinatal health outcomes. METHODS/DESIGN: Cluster-randomised controlled trial using a stepped wedged design with 3 months delay between wedges will be conducted in 12 public hospitals with a total annual delivery rate of 60 000. Each wedge will consist of 3 hospitals. Impact will be evaluated on intrapartum-related mortality (primary outcome), overall neonatal mortality and morbidity and health worker's performance on neonatal care (secondary outcomes). A process evaluation and a cost-effectiveness analysis will be performed to understand the functionality of the intervention and to further guide health system investments will also be performed. DISCUSSION: In contexts where resources are limited, there is a need to find scalable and sustainable implementation strategies for improved care delivery. The proposed study will add to the scarce evidence base on how to scale up interventions within existing health systems. If successful, the NePeriQIP model can provide a replicable solution in similar settings where support and investment from the health system is poor, and national governments have made a global pledge to reduce perinatal mortality. TRIAL REGISTRATION NUMBER: ISRCTN30829654.

Development of smooth pursuit eye movements in very preterm born infants: 3. Association with perinatal risk factors.

AIM: To investigate the association between perinatal risk factors and neonatal complications and early oculo-motor development in very preterm infants. METHODS: Perinatal risk factors were identified, and the potential association with early oculo-motor development was evaluated by measuring smooth pursuit eye movements (SP) at 2 and 4 months' corrected age (CA) in a population of very preterm infants born in Uppsala County 2004-2007 (n = 113). RESULTS: Among the 15 tested factors, eight showed significant association in univariate analysis with lower levels of SP at 4 months' CA, namely administration of prenatal corticosteroids, gestational age, birthweight, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, intraventricular haemorrhage >grade 2, and persistent ductus arteriosus. At 2 months' CA, only retinopathy of prematurity >stage 2 was associated with lower levels of SP. When all factors significant in the univariate tests were included in multiple regressions aimed to assess each factor's independent relation to SP, periventricular leukomalacia was the only significant independent factor. When adding 2-5 of the significant factors using multiple regression analysis, the levels of SP became lower. CONCLUSION: Perinatal risk factors were associated with lower levels of SP. This could be interpreted as delayed or disturbed development of normal oculomotor ability.

Development of smooth pursuit eye movements in very preterm infants: 1. General aspects.

AIM: To investigate early oculo-motor development in a population-based cohort of very preterm infants. METHODS: Early oculo-motor development was prospectively studied by measuring smooth pursuit eye movements at 2 and 4 months corrected age in a population of very preterm infants born in Uppsala County 2004-2007. Eighty-one preterm infants were studied, and 32 healthy term infants constituted the control group. RESULTS: The study group consisted of infants with a mean gestational age of 28 + 5 weeks. At 2 and 4 months corrected age, infants born very preterm showed lower gain (p < 0.001) and proportion of smooth pursuit eye movements (p < 0.001) compared to the control group. The boys showed higher gain of smooth pursuit eye movements at both 2 and 4 months corrected age, compared to girls. CONCLUSIONS: Oculo-motor development measured by smooth pursuit eye movements is delayed in very preterm infants at 2 and 4 months corrected age. This might be a risk factor or early indicator of later perceptual and behavioural impairment.