IMPORTANCE Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI.OBJECTIVE To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. INTERVENTIONS Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). MAIN OUTCOMES AND MEASURESThe primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. RESULTS Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month followup. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, −0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, −2.9% [95% CI, −7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, −0.9 [95% CI, −2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, −5.4% [95% CI, −12.8% to 2.1%]; P = .16).CONCLUSIONS AND RELEVANCE Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Ou...

BackgroundThe relationship between population trends in delaying childbirth and rising rates of primary cesarean delivery is unclear. The aims of the present study were (1) to characterize the association between maternal age and the outcome of labor, (2) to determine the proportion of the increase in primary cesarean rates that could be attributed to changes in maternal age distribution, and (3) to determine whether the contractility of uterine smooth muscle (myometrium) varied with maternal age.Methods and FindingsWe utilized nationally collected data from Scotland, from 1980 to 2005, and modeled the risk of emergency cesarean section among women delivering a liveborn infant in a cephalic presentation at term. We also studied isolated myometrial strips obtained from 62 women attending for planned cesarean delivery in Cambridge, England, from 2005 to 2007. Among 583,843 eligible nulliparous women, there was a linear increase in the log odds of cesarean delivery with advancing maternal age from 16 y upwards, and this increase was unaffected by adjustment for a range of maternal characteristics (adjusted odds ratio for a 5-y increase 1.49, 95% confidence interval [CI] 1.48–1.51). Increasing maternal age was also associated with a longer duration of labor (0.49 h longer for a 5-y increase in age, 95% CI 0.46–0.51) and an increased risk of operative vaginal birth (adjusted odds ratio for a 5-y increase 1.49, 95% CI 1.48–1.50). Over the period from 1980 to 2005, the cesarean delivery rate among nulliparous women more than doubled and the proportion of women aged 30–34 y increased 3-fold, the proportion aged 35–39 y increased 7-fold, and the proportion aged ≥40 y increased 10-fold. Modeling indicated that if the age distribution had stayed the same over the period of study, 38% of the additional cesarean deliveries would have been avoided. Similar associations were observed in multiparous women. When studied in vitro, increasing maternal age was associated with reduced spontaneous activity and increased likelihood of multiphasic spontaneous myometrial contractions.ConclusionsDelaying childbirth has significantly contributed to rising rates of intrapartum primary cesarean delivery. The association between increasing maternal age and the risk of intrapartum cesarean delivery is likely to have a biological basis.

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ObjectiveTo evaluate the risk of childhood hospitalization associated with infant feeding patterns at 6-8 weeks of age in Scotland.Study designA retrospective population level study based on the linkage of birth, death, maternity, infant health, child health surveillance, and admission records for children born as single births in Scotland between 1997 and 2009 (n = 502 948) followed up to March 2012. Descriptive analyses, Kaplan Meier tests, and Cox regression were used to quantify the association between the mode of infant feeding and risk of childhood hospitalization for respiratory, gastrointestinal, and urinary tract infections, and other common childhood ailments during the study period.ResultsWithin the first 6 months of life, there was a greater hazard ratio (HR) of hospitalization for common childhood illnesses among formula-fed infants (HR 1.40; 95% CI 1.35-1.45) and mixed-fed infants (HR 1.18; 95% CI 1.11-1.25) compared with infants exclusively breastfed after adjustment for parental, maternal, and infant health characteristics. Within the first year of life and beyond, a greater relative risk of hospitalization was observed among formula-fed infants for a range of individual illnesses reported in childhood including gastrointestinal, respiratory, and urinary tract infections, otitis media, fever, asthma, diabetes, and dental caries.ConclusionsUsing linked administrative data, we found greater risks of hospitalization in early childhood for a range of common childhood illnesses among Scottish infants who were not exclusively breastfed at 6-8 weeks of age.

Objective To determine the effect of time and day of birth on the risk of neonatal death at term.

IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) affects 39 million people worldwide; in isolation, it doubles annual health care costs and, when associated with comorbid mental health problems, it quadruples the costs.OBJECTIVE To compare the education and health outcomes of schoolchildren treated for ADHD with their peers. DESIGN, SETTING, AND PARTICIPANTSIn this population-based cohort study, individual-level record linkage was performed of 8 Scotland-wide administrative databases covering dispensed prescriptions, admissions to acute and psychiatric hospitals, maternity records, annual pupil census, examinations, school absences and exclusions, and unemployment. The study cohort comprised 766 244 children attending Scottish primary, secondary, and special schools at any point between

ObjectivesTo investigate mortality rates and causes in children and young people with intellectual disabilities.DesignRetrospective cohort; individual record linkage between Scotland’s annual pupil census and National Records of Scotland death register.SettingGeneral community.ParticipantsPupils receiving local authority-funded schooling in Scotland, 2008 to 2013, with an Additional Support Need due to intellectual disabilities, compared with other pupils.Main outcome measuresDeaths up to 2015: age of death, age-standardised mortality ratios (age-SMRs); causes of death including cause-specific age-SMRs; avoidable deaths as defined by the UK Office of National Statistics.Results18 278/947 922 (1.9%) pupils had intellectual disabilities. 106 died over 67 342 person-years (crude mortality rate=157/100 000 person-years), compared with 458 controls over 3 672 224 person-years (crude mortality rate=12/100 000 person-years). Age-SMR was 11.6 (95% CI 9.6 to 14.0); 16.6 (95% CI 12.2 to 22.6) for female pupils and 9.8 (95% CI 7.7 to 12.5) for male pupils. Most common main underlying causes were diseases of the nervous system, followed by congenital anomalies; most common all-contributing causes were diseases of the nervous system, followed by respiratory system; most common specific contributing causes were cerebral palsy, pneumonia, respiratory failure and epilepsy. For all contributing causes, SMR was 98.8 (95% CI 69.9 to 139.7) for congenital anomalies, 76.5 (95% CI 58.9 to 99.4) for nervous system, 63.7 (95% CI 37.0 to 109.7) for digestive system, 55.3 (95% CI 42.5 to 72.1) for respiratory system, 32.1 (95% CI 17.8 to 57.9) for endocrine and 14.8 (95% CI 8.9 to 24.5) for circulatory system. External causes accounted for 46% of control deaths, but the SMR for external-related deaths was still higher (3.6 (95% CI 2.2 to 5.8)) for pupils with intellectual disabilities. Deaths amenable to good care were common.ConclusionPupils with intellectual disabilities were much more likely to die than their peers, and had a different pattern of causes, including amenable deaths across a wide range of disease categories. Improvements are needed to reduce amenable deaths, for example, epilepsy-related and dysphagia, and to support families of children with life-limiting conditions.

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