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Background: Universal infant morbidity risk factors (poor birth outcomes, suboptimal breastfeeding, poverty) occur more frequently in HIV exposed uninfected (HEU) than HIV unexposed uninfected (HUU) infants. HEU infants’ unique exposures, including in utero exposure to HIV products and maternal immune compromise, may potentiate HEU infants’ infectious morbidity risk. The primary objective was to determine whether HEU infants experience greater infectious morbidity than HUU infants through HIV exposure-specific pathways beyond universal infant morbidity risk factors. Methods: This prospective cohort study identified low risk HIV-infected and HIV-uninfected mothers and their term newborns from a single community midwife unit in Kraaifontein, South Africa. The primary outcome, at least one infectious cause hospitalization or death before six months of age, was classified according to modified WHO case-definitions and compared between HEU and HUU infants. Complete outcome determination on all infants was possible through linkage with the electronic provincial hospital administration system and mortality registry. Adjusted odds ratios (aOR) were calculated by multivariable logistic regression including stratified analyses conditioned on breastfeeding. Results: One hundred and seventy six (94 HEU, 82 HUU) mother-infant pairs were included. HIV-infected mothers were older (median 27.8 vs. 24.7 years, p
Background and objectives:The fourth Millennium Development Goal to reduce childhood mortality by two-thirds will not be achieved in most countries of sub-Saharan Africa. Infectious diseases are the most common cause of death in these children. A significant period of vulnerability occurs in the weeks and months following discharge. We sought to characterize mortality both in-hospital and post-discharge in children admitted with infectious diseases and develop prediction models for these outcomes. Methods:The primary study was a cohort study of children 6 months to 5 years of age admitted with proven or suspected infections. Children were followed throughout hospitalization and until six months post-discharge. Prediction models for in-hospital and post-discharge mortality were developed using standard logistic regression techniques. A further prospective cohort study was conducted to determine morbidity, mortality and health seeking following pediatric outpatient department visits in a rural health facility.Results:The primary cohort study enrolled 1307 subjects who were admitted with a proven or suspected infection. Sixty five (5.0%) children died in hospital and 61 (4.9%) of children died during the six month post-discharge period. Parsimonious models were developed for both in-hospital and post-discharge mortality. Variables for in-hospital prediction included Blantyre coma score, weight for age z-score, and HIV status. Variables for post-discharge prediction included Blantyre coma score, mid-upper arm circumference, HIV status, oxygen saturation and time since last hospitalization. Both models performed well with areas under of receiver operating characteristics curve of 0.85 and 0.80, respectively. Most (65%) post-discharge deaths occurred outside of a hospital. The secondary study of out-patient department visits included 717 sick-child visits and found that mortality and subsequent admission over 30 days occurs after approximately 2% of visits. Health seeking occurred in 7% of sick-child visits. No baseline clinical factors were associated with outcomes following these visits.Interpretation:The derived models can be used to develop effective interventions to improve in-hospital care, referral of admitted subjects to higher levels of care, and post-discharge care. Further research is required to better understand health seeking following out-patient department visits.
Transplantation is the preferred treatment for patients with kidney failure, but the need for transplantation exceeds the organ supply. Strategies to address the organ shortage include: preventing end-organ failure, increasing the number of deceased donor kidneys (DDK) for transplantation, and ensuring appropriate allocation to avoid organ waste. This thesis: develops an improved metric for deceased donation activity; describes an age-matching allocation strategy to reduce organ waste; and examines the impact of selected wait-list policies on disparities in access to DDK transplantation.Using national administrative databases, we: Estimated and validated the number of potential deceased organ donors among in-hospital deaths using diagnostic codes; Calculated differences in DDK and transplant candidate survival by age using Cox regression to determine the area between survival curves (ABSC), and combined these measures with information on DDK and candidate ages to define age cut-points for DDK allocation; Described the use and outcomes of older DDKs (≥ 65 years) in countries with different allocation systems using Cox regression and ABSC, and identified patients that achieved a lifetime of transplant function from older DDKs; and Examined longitudinal use and outcomes of wait-listing candidates at multiple transplant centres using logistic and Cox regression.Three percent of Canadians who die in-hospital were identified as potential organ donors, suggesting significant potential to increase deceased donation. We determined DDK and candidate age cut-points for Canadian allocation, and estimated that implementation of these cut-points could have eliminated 500 years of wasted donor kidney function, and prevented 800 years of post-transplant dialysis compared to the current allocation strategy. We found that older DDKs provided a lifetime of kidney function for patients aged >60 years, suggesting targeted use of these organs could safely increase transplantation. Finally, we determined that multiple wait-listing helped minimize geographic disparities in accessing transplantation and may be an important policy consideration in countries that do not currently allow multiple listing.As transplantation wait-lists grow at unprecedented rates, the potential to increase deceased donation, implement allocation policies to decrease organ wastage, safely expand the use of older deceased donors and promulgate wait-list policies to increase access to transplantation will become more important.
Background and objectives: Pediatric emergency department (PED) utilization has increased, resulting in long waiting times for children and families. Extending PED physician coverage as a solution may not be cost effective or sustainable. Physician assistants (PAs), clinicians with roles tailored to assist physicians, have skills best suited to provide care in high volume and low complexity environments. As a large proportion of PED visits are for non-emergent problems, PAs are an alternative solution to increasing PED demand given constrained healthcare resources. Despite the growing acceptance of PAs, there are few studies evaluating their roles or cost-effeciency in PEDs. We assessed PA acceptance by Canadian healthcare users and providers, and estimated the impact of PAs on patient flow compared to extending physician coverage. Methods: The range and frequency of clinical complaints managed at a tertiary care PED was ascertained from an administrative database. Surveys of Canadian PED physicians defined a clinical scope of practice for PAs and estimated the proportion of PED visits a PA could manage, with varying degrees of physician supervision. Healthcare users were surveyed regarding their willingness to receive PA care. A discrete event simulation model of a PED was built to assess the impact of extending physician coverage versus adding PAs at equal incremental cost to the system, on waiting time, length of stay (LOS) and rate of patients leaving without being seen (LWBS).Results and interpretation: Provided that their waiting time was shortened, Canadians were willing to have their children receive care from PAs for minor injuries and non-emergent ailments. Although few Canadian PED physicians were familiar with PAs, most supported the concept of PA utilization for a large proportion of non-emergent visits. However, physicians wanted to remain directly involved thereby limiting PA autonomy. The simulation found important reductions in waiting time, LOS and LWBS rates for both scenarios: the extended physician model benefited all acuity levels, while the PA model with restricted PA autonomy favoured only highest acuity patients. Increasing the level of PA autonomy was critical in broadening the impact of PAs to all acuity levels.
Background: Younger adults have been identified as an emerging ‘at-risk’ population with a rising prevalence of cardiac risk factors and hospitalization for acute myocardial infarction (AMI). Coupled with this is an unexplained excess early AMI mortality risk in younger women compared to younger men. Self-perceived health status (symptoms, physical function and disease perception) has been proposed as a contributing factor; however, not much is known about sex differences in health status outcomes of younger adults post AMI. The overarching goal of this thesis is to enhance our understanding of AMI in younger adults (20-55 years). The main objectives are: 1) to examine sex differences and 10-year trends in AMI hospitalization and early AMI mortality, and to determine whether the sex gap in early AMI mortality has changed in recent years, and 2) to examine the sex differences and changes in health status during the first year following AMI. Methods: The age- and sex-specific 10-year trends in AMI hospitalization and 30-day AMI mortality were based on population-based, administrative data in British Columbia (BC) and assessed using negative binomial and logistic regression, respectively. Sex differences and changes in health status were assessed using prospectively collected data on 286 younger AMI patients, in BC. Linear and generalized linear mixed models were used to assess health status changes. Results: Between 2000-2009, younger adults, particularly women, did not experience the same declining AMI hospitalization rates as older adults. Furthermore, for early AMI mortality, the observed sex differences among younger adults persisted, even after adjusting for comorbidities. While health status in both men and women diminished in the first month following AMI, driven by worse angina and physical function, it improved thereafter. Younger women consistently had significantly worse cardiac-related physical function, disease perception, and overall physical and mental health than younger men during the first year; however, the changes in health status were similar in men and women.Conclusions: The findings highlight a persistent sex difference in early mortality and health status following AMI among younger adults. The first month after AMI is a critical period to intensify support and treatment in order to improve outcomes.