K.S. Joseph

Out-of-hospital cardiac arrest (OHCA) resuscitation is guided by a set of published guidelines that includes several interventions based on the organizing framework known as the chain-of-survival. The aim of the studies in this dissertation was to examine the effects of these interventions in improving survival following non-traumatic adult OHCA. Data for this purpose was obtained from two multi-centre studies carried out in the United States and Canada. Analysis methods included multivariable logistic regression and matched propensity score analysis. The first study was an analysis of a cohort of 12,821 OHCA cases that showed that younger age, public location, shorter response time, initial rhythm of ventricular fibrillation/tachycardia, and advanced airway management were associated with improved survival, while epinephrine administration was associated with a reduction in survival. Specialized post-arrest care appeared to be associated with improved survival but the magnitude of this was attenuated in analyses of cases transported to hospital. There was a non-significant association between advanced airway management and reduced survival (adjusted odds ratio (AOR) 0.82, 95% confidence interval (CI) 0.59–1.14) and a substantial reduction in survival among those who received epinephrine (AOR 0.13, 95% CI 0.10–0.17). The second study was based on a cohort of 14,673 non-traumatic OHCA cases and showed that initial rhythm modified the effect of prehospital epinephrine administration: asystole was associated with a 14-fold decrease in the adjusted odds of survival if epinephrine was administered, while ventricular fibrillation/tachycardia was associated with a 5.8-fold decrease in the adjusted odds of survival if epinephrine was administered (p-value for interaction
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Increased operative vaginal delivery, using obstetric forceps and/or vacuum, has been recommended in an effort to curb the rising rate of cesarean delivery. However, the comparative perinatal and maternal safety of operative vaginal delivery and cesarean delivery is not clear. This dissertation aimed to quantify rates of severe perinatal and maternal morbidity and mortality following operative vaginal delivery and cesarean delivery. The studies in this dissertation were based on information from Canadian national and provincial population-based health databases and included women who delivered a singleton term infant by operative vaginal or cesarean delivery between 2003 and 2014. Study sizes varied from 10,901 to 1,938,913. Logistic regression, propensity score analysis and ecological Poisson regression were used to estimate adjusted rate ratios (ARR) with 95% confidence intervals (CI).Midpelvic operative vaginal delivery was associated with an increased risk of severe perinatal morbidity/mortality compared with cesarean delivery, although this association varied based on instrument applied and indication for operative delivery. For example, among deliveries with dystocia, midpelvic operative vaginal delivery was associated with higher rates of severe perinatal morbidity/mortality compared with cesarean delivery (forceps ARR 2.11, 95% CI 1.46-3.07; vacuum ARR 2.17, 95% CI 1.49-3.15). Among deliveries with fetal distress, the risk of severe maternal morbidity/mortality was higher with midpelvic forceps and lower with midpelvic vacuum. However, rates of obstetric trauma were high following operative vaginal delivery, irrespective of instrument or indication.Rates of birth trauma and obstetric trauma were significantly increased after operative vaginal delivery at all pelvic stations. Further, the population (ecological) rate of operative vaginal delivery was positively associated with the rate of obstetric trauma and the rate of severe birth trauma: a one percent increase in the operative vaginal delivery rate resulted in over 700 additional cases of obstetric trauma per year among nulliparous women. Encouraging higher rates of operative vaginal delivery as a strategy to prevent cesarean delivery may result in higher rates of perinatal and maternal morbidity/mortality, especially birth trauma and obstetric trauma. The risks and benefits of both operative vaginal and cesarean delivery should be clearly communicated to women, ideally in the antepartum period.

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Approximately 10% of children live in households where a parent has a chronic illness and many children are exposed to a parent coping with a potentially disabling chronic condition, such as multiple sclerosis (MS). However, few methodologically rigorous studies have evaluated the impact of parental MS on child development. The purpose of this thesis was to fill this knowledge gap by studying the association between parental MS and child and adolescent development. The studies in this dissertation were based on population-based health databases from Manitoba and British Columbia. The cohorts followed in these population-based studies included all individuals with MS who had a child with a completed Early Development Instrument (EDI) school readiness assessment, and matched parent-child dyads of unaffected parents. Parents with MS were identified using a validated algorithm, as those with ≥3 records related to MS in hospital admission, physician visit or prescription claims. Mental and physical morbidity in parents and children were also identified through a combination of hospital, physician and drug claims. In Manitoba, children in kindergarten with an MS parent were similar to matched children of unaffected parents on all developmental domains as assessed by the EDI. However, in the larger population-based cohort from British Columbia, children of mothers with MS had lower rates of vulnerability on the social competence domain (odds ratio 0.62, 95% confidence interval [CI] 0.44-0.87). Overall, mental health morbidity, such as anxiety and depression, was significantly more common among MS parents compared with MS-unaffected parents. Additionally, such parental mental health morbidity mediated the association between maternal MS and mood and/or anxiety disorders in children. Incidence rates of psychiatric disorders were significantly higher in children and adolescents with an MS parent who were exposed to parental MS since birth, compared with children and adolescents of MS-unaffected parents (hazard ratio 1.37, 95% CI 1.05-1.78). In summary, the presence of parental MS was not independently associated with adverse developmental health in kindergarten-aged children. However, MS was associated with substantially higher levels of mental health morbidity in parents and such morbidity was associated with adverse child and adolescent psychiatric morbidity.

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Increases in postpartum hemorrhage have been reported in several high income countries between 1991 and 2004. The purpose of this thesis was to investigate possible causes of recent increases in postpartum hemorrhage.Data sources included a population-based database of deliveries in British Columbia, Canada, between 2000 and 2009 (n=371,193), and a hospitalization database of deliveries in Canada (excluding Quebec) between 2003 and 2010 (n=2,193,425). Postpartum hemorrhage was defined as a blood loss of ≥500 mL for a vaginal delivery or ≥1000 mL for cesarean delivery or as a diagnosis noted by a health care provider. The influence of changes in risk factors on temporal trends in postpartum hemorrhage was studied using logistic regression.There was a significant increase in atonic postpartum hemorrhage in British Columbia from 4.8% in 2001 to 6.3% in 2009 (34% increase, 95% confidence interval [CI] 26-42%). This increase was not be explained by changes in the maternal, fetal and obstetric factors studied, including previously understudied factors such as maternal pre-pregnancy body mass index and labour augmentation with oxytocin. In Canada, rates of postpartum hemorrhage increased from 5.1% in 2003 to 6.2% in 2010 (22% increase, 95% CI 20% to 25%), driven by an increase in atonic postpartum hemorrhage. Placenta accreta was responsible for only a negligible fraction of postpartum hemorrhage. Temporal trends in severe postpartum hemorrhage in Canada showed a similar pattern; postpartum hemorrhage with blood transfusion increased from 36.7 in 2003 to 50.4 per 10,000 deliveries in 2010, while postpartum hemorrhage with hysterectomy increased from 4.9 to 5.8 per 10,000 deliveries over the same period. The temporal increase in postpartum hemorrhage did not explain a concurrent rise in obstetric acute renal failure in Canada. The increase in obstetric acute renal failure was restricted to women with hypertensive disorders of pregnancy. In summary, postpartum hemorrhage and severe postpartum hemorrhage continued to increase in Canada in recent years, and the maternal, fetal and obstetric factors studied did not explain the rise. Further studies are required to identify the role of other risk factors that may explain the observed increase in postpartum hemorrhage.

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