David Patrick


Research Interests

Antibiotics and Resistance
Responding to the Threat of Antimicrobial Resistance at Population Level
Response to Emerging Infectious Diseases

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Graduate Student Supervision

Doctoral Student Supervision

Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.

Health and economic impact of the 13-valent pneumococcal conjugate vaccination program in British Columbia, Canada (2022)

BACKGROUND: Streptococcus pneumoniae causes substantial health and economic burden. Two vaccines available to combat pneumococcal disease are the 23-valent pneumococcal polysaccharide vaccine (PPV23) for adults and the 13-valent pneumococcal conjugate vaccine (PCV13) for children. This thesis evaluated changes in health and economic burden from pneumococcal disease following the PCV13 introduction in the infant immunization program in British Columbia (BC), Canada.METHODS: A literature search and meta-analyses determined the indirect effect of the PCV13 childhood immunization on invasive pneumococcal disease (IPD) among adults worldwide. Then, pneumococcal disease, i.e., IPD, and acute otitis media (AOM), acute sinusitis (AS), and community-acquired pneumonia (CAP) cases and associated healthcare costs were identified using administrative databases for the years 2000-2018. Costs were adjusted to 2018 Canadian dollars. Changes in the incidence, annual healthcare utilization, and associated costs for pneumococcal disease were evaluated across vaccine eras (pre-PCV13 era: 2000-2010, PCV13 era: 2011-2018) using generalized linear models and adjusted for the PCV7 program (2004-2010). RESULTS: A substantial decline in overall IPD (18%), PCV7 (55%), and PCV13 (40%) serotype IPD were observed among adults following the PCV13 vaccine use in the infant immunization program globally. However, a concurrent 112% increase in non-vaccine serotype IPD occurred during the PCV13 period. Similar declines in overall IPD (18%), PCV7-related (70%), and PCV13-related (24%) vaccine serotype IPD among adults and increase in non-vaccine serotype (NVT) IPD (154%) were noted in BC. A substantial rate reduction in AOM (30%) and AS (15%) across all ages was recorded. Although CAP incidence decreased among young children aged 0-2 years (9%), there was a modest increase in the older age groups: 50-64 years (7%), and ≥65 years (5%). As such, temporal declines in total annual cost were observed in the PCV13 era for IPD (27%), AOM (30%), and AS (32%) compared to the pre-PCV13 era, but not CAP, where an increase of 4% in total costs was seen across all ages. CONCLUSIONS: Increasing NVT IPD and pneumonia rates in the post-PCV13 necessitates a need for newer vaccines and stresses the importance of improving public health messaging to increase the PPV23 uptake rates.

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Determinants of West Nile Virus (WNV) incidence in select regions of Canada: an examination of climate and ecological drivers in British Columbia and Saskatchewan (2018)

Background: West Nile Virus (WNV) is a zoonotic arbovirus that has caused significant diseasein Canada, yet remains rare in British Columbia (BC). WNV is spread between avian reservoirsby Culex mosquitoes, and incidental transmission to humans can occur. Understanding temporal and spatial changes in WNV risk is di cult because of the complexity of the transmissioncycle. Nonetheless, public health agencies require decision support in order to guide resourceallocation. Understanding the climate and ecological drivers of WNV disease can help with thedevelopment of such tools.Methods: Descriptive analyses were used to compare ecological and climate conditions in yearswith and without WNV transmission in BC from 2009 to 2015. Generalized linear mixed modelswere used to evaluate associations between WNV incidence in Saskatchewan (2003-2007) and:1) total irrigated landscape, and 2) avian community structure. Results were combined witha literature review to develop a WNV decision-support tool for BC which was evaluated via auser survey.Results: WNV activity in BC between 2009-2015 was limited to select locations during hot summers when temperatures remained above key temperature thresholds during the amplificationperiod. In Saskatchewan, human incidence was positively associated with irrigated landscapesin 2003 but not 2007. Non-passerine species richness and abundance was positively associatedwith incidence from 2003-2007, and the dilution hypothesis was not supported. Heat was consistently associated with incidence, but other predictors had varying effects between years andmodels. The resulting decision support tool contained seven surveillance inputs and three hazard levels. Survey results supported the choice of surveillance inputs and the recommendedprevention measures.Discussion: Ecological complexity challenges quantitative risk prediction for WNV and necessitates the use of simpler tools for public health decision support. Public health agenciesin low-incidence areas should invest public health resources in improving situational awarenessand preparedness instead of risk prediction. The decision support tool created here provides ageneral estimate of WNV amplification as a proxy of WNV hazard. Continued refinement ofthe tool as more is learned about the ecology of WNV would increase its utility

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In search of improved approaches to antibiotic stewardship: can we explain variations in physician practice patterns related to outpatient infection management? (2017)

The discovery of antibiotics was one of the most significant advances in modern medicine; however, our reliance on antibiotics is threatened by the spread of resistance. Antibiotic resistance is a natural phenomenon that is exacerbated by selection pressure from antibiotic use. Where prescriptions are required for antibiotics, understanding prescribing behaviour is paramount. Guidelines recommend antibiotics for respiratory tract infections (RTIs) only when pneumonia or other serious complications are suspected. Urine cultures are recommended for complicated, but not uncomplicated, urinary tract infections (UTIs). The objectives of this thesis were to identify factors related to patients, physicians, and geographic regions associated with antibiotic use for RTIs, and urine culturing for UTI; and to explore the extent of variations in these practices across physicians.A systematic review of the literature was conducted to assess factors that have previously been empirically associated with antibiotic prescribing. Then, using linked administrative datasets, factors associated with antibiotic prescriptions for paediatric respiratory tract infection were analyzed. Urine culture data was subsequently linked in, to explore urine culturing practices. These analyses demonstrated that observed physician characteristics had a stronger influence on practice patterns that did differences in patient characteristics. In particular, physicians who had been in practice for longer tended to be more likely to prescribe antibiotics, and to order urine cultures. Physicians trained outside of Canada were more likely to prescribe, but less likely to order a urine culture. Female physicians were less likely to prescribe antibiotics, and more likely to order urine cultures. The variation between physicians that remained after accounting for observed characteristics was substantial. This research demonstrates some common features of physicians that are associated with antibiotic prescribing and urine culture use. However, the variation between physicians in practice styles is greater than the effects of these characteristics. These findings have implications for the design and implementation of antibiotic stewardship efforts to improve antibiotic use. For example, audit and feedback interventions and academic detailing have shown some promise, and may be particularly effective if targeted to physicians with higher prescribing or culturing practices. This thesis demonstrates the utility of administrative datasets in identifying such physicians.

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Secondary complications of spinal cord injury: risk, inter-relationships, and effects on neurological outcomes (2015)

Background: Although there have been major advances in acute care following spinal cord injury (SCI), individuals surviving the acute period experience a reduced life expectancy. Historically, acute respiratory and renal dysfunction were the most prevalent complications, and remain important contributors to mortality. However, all-cause cardiovascular disease (CVD) has now emerged as the leading cause of mortality in chronic SCI. Although it has been long speculated that individuals with SCI may be at a higher risk of complications such as CVD, quantitative data are currently limited. Furthermore, the inter-relationships among secondary complications are currently unknown, as is the relationship with changes in neurological function.Objectives: to examine the risk of secondary complications among individuals with SCI; to examine the relationships among secondary complications in individuals with SCI; to examine the relationship among secondary complications and neurological outcomes. Methods: Data were compiled from the Canadian Community Health Survey, the SCI Community Health Survey, the European Multi-Centre Study on Spinal Cord Injury dataset, and the Simon Fraser University SCI dataset. Several methods were employed for analysis of these data, including: multivariable logistic and linear regression, mixed effects models, and unbiased recursive partitioning.Results: Findings identified elevated odds of heart disease, stroke, Type 2 diabetes, chronic respiratory conditions, and chronic pain among individuals with SCI when compared with non-SCI individuals. Complex correlations were also identified among secondary complications following SCI. These include positive associations between neuropathic pain and CVD, and between blood pressure fluctuations and CVD. Lastly, secondary complications (specifically neuropathic pain) following SCI were positively correlated with neurological decline in chronic phases of injury, and neurological motor recovery in acute phases. These relationships may be partly related through treatments for the secondary complications rather than the secondary complications themselves. Implications: These novel findings update current knowledge of secondary complications among individuals with SCI. These data are useful in guiding the prospective collection of data elements within SCI-specific registries, as well as the design/analysis of studies (i.e., issues of confounding in multivariable analyses). These epidemiological data will also be useful for refined, hypothesis-driven physiological studies exploring precise biological mechanisms.

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Could Rats Pose a Health Risk for People Living in Vancouver's Downtown Eastside? Understanding the Ecology of Rats and Rat Associated Zoonoses in an Inner-City Neighbourhood (2014)

Urban rats (Rattus spp.) are an important source of zoonotic pathogens, yet there is a paucity of integrated, interdisciplinary, ecosystem-based research on rat-associated zoonoses (RAZ). The goal of this project was to begin to characterize the public health risks associated with rats by studying the ecology of rat populations and the zoonotic pathogens that they carry in an inner-city neighbourhood of Vancouver, Canada. By characterizing rat populations within our study area, we were able to identify a number of factors which could influence the ecology of RAZ. We were also able to design a tool to predict rat abundance based on characteristics of the urban microenvironment, which may be useful for predicting RAZ prevalence in the future. Although we found that L. interrogans (a common RAZ) was present in our study area, other zoonoses thought to be endemic in rat populations worldwide (Seoul hantavirus, Rickettsia typhi, and Bartonella spp.) were conspicuously absent. However, rats were found to carry other potentially zoonotic organisms (Clostridium difficile and methicillin-resistant Staphylococcus aureus) for which they are not the ‘traditional’ reservoir. Finally, we found that by integrating data regarding rat ecology and RAZ, we were able to gain a more comprehensive picture of how these pathogens circulate within rat populations. Overall, this research illustrates the importance of a comprehensive and holistic approach for obtaining a better understanding of RAZ, and highlights the need for ongoing research and surveillance.

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Use of animal data in public health surveillance for emerging zoonotic diseases (2013)

Infectious agents transmitted between animals and humans (zoonoses) are important causes of emerging infectious diseases with major societal, economic, and public health implications. In order to prevent and control emerging zoonotic diseases (EZDs), they should ideally be identified in animals before they affect the human population. The utility of animal data for public health EZD surveillance was investigated in this thesis in four studies: a systematic literature review of current EZD surveillance systems and three critical examinations of pilot agricultural animal health surveillance systems. The first critical examination used expert-elicited criteria of EZD surveillance needs to evaluate a sentinel clinical pre-diagnostic system. The other two studies used statistical modeling to assess the ability of a laboratory-based system and an integrated system with both human and animal data to detect known patterns and outbreaks. The systematic review identified few evaluated surveillance systems, hence an evidence base for successful systems could not be obtained. Experts identified diagnostic data from laboratories and information on potential human exposures as important for public health action. While the sentinel animal surveillance system was not deemed useful on its own, identified gaps and biases in laboratory submissions suggest that sentinel veterinarians could inform animal laboratory surveillance. Seasonal trends and expected events of public health importance were identified in animal diagnostic laboratory data, however, statistical surveillance in either pre-diagnostic or diagnostic data streams did not provide adequate early warning signals for action. While the integrated surveillance for Salmonella bacteria allowed for the examination of the relationship between human and animal data, statistical alerts did not correlate with expert-identified investigations. Laboratory surveillance is likely the best candidate for EZD surveillance in animals, however, this information needs to be supplemented with potential human exposure information, as well as knowledge of data gaps and biases inherent in the data. Without this additional risk information to convert the animal data into risk for humans, the best use of animal laboratory data at this time is to help generate hypotheses in epidemiological investigations and in helping evaluate programs by examining longer-term trends.

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Master's Student Supervision

Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.

Evaluating BC Provincial Academic Detailing Service's intervention on antibiotic prescribing for suspected urinary tract infections in British Columbia's nursing homes (2019)

Background: From June 2016, an academic detailing (AD) intervention took place in 115 nursing homes (NHs) in British Columbia. Physicians, nurses, and NH staff received AD to reduce unnecessary antibiotic treatment. We hypothesized that local health areas (LHAs) with NHs visited by academic detailers experienced a decreasing trend in UTI-linked and overall antibiotic prescribing. Methods: We used population-based administrative datasets of services provided to NH residents from June 2015 till March 2017, aggregated by month for LHA intervention and control groups. Ecologic change in the UTI-linked and overall prescribing trend was evaluated with linear segmented regression. Sensitivity analysis to evaluate potential bias from linking antibiotic use to the occurrence of UTI-related diagnoses by fee-for-service provider’s billings was undertaken. Results: In the study period, there were 93,327 antibiotic prescriptions and 24,081 prescriptions linked to UTI diagnostic codes. For the UTI-linked analysis, the control’s antibiotic prescribing pre-intervention trend was a monthly decrease of -0.15 DDD/1,000 residents/day per month versus -0.09 after start of the intervention – a slope change of 0.06 (95% CI: -0.16 to 0.29) DDD/1,000 residents/day per month. The intervention group’s pre-intervention trend was almost identical to the controls’, a monthly decrease of -0.14 DDD/1,000 residents/day vs -0.27 after start of the intervention – a slope change of -0.13 (95% CI: -0.32 to -0.07) DDD/1,000 residents/day per month. The difference in slope changes was -0.19 (95% CI: -0.29 to 0.80) DDD/1,000 residents/day per month. The sensitivity analysis indicated that linkage bias was unlikely to bias the UTI-linked analysis’ trends. Conclusions: This ecologic study found that a population-level AD intervention was associated with decreases in UTI-linked prescribing trends but not overall prescribing trends.

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The multiple sclerosis prodrome: a systematic review and an evaluation of fatigue, sleep disorders, anemia and body pain (2019)

Background: Findings from several studies suggest that the first symptoms of Multiple Sclerosis (MS) predate onset by years, consistent with the presence of an MS prodromal phase. This thesis aims to evaluate evidence of an MS prodromal syndrome and to determine whether fatigue, sleep disorders, anemia or body pain are elevated preceding MS onset. Methods: A systematic review was undertaken of studies assessing symptoms or conditions prior to, or at, MS onset or diagnosis. A population-based matched cohort study using linked health care and MS-specific clinical databases in British Columbia, Canada, was conducted to compare the prevalence of fatigue, sleep disorders, anemia and body pain between MS cases in the five years preceding a first demyelinating claim or MS symptom onset and general population controls. Using random effects zero-inflated negative binomial models, the frequency of physician visits for these same conditions was similarly compared prior to a first demyelinating claim only. Results: Among the 28 studies identified in the systematic review, several conditions, including anxiety, depression, migraine and cognitive impairment, were more frequently observed prior to, or at, MS onset or diagnosis. However, comparative population-based studies were largely lacking. The prevalence of fatigue, sleep disorders, anemia and body pain over the 5 year period preceding the first demyelinating event, as well as sleep disorders and body pain over the 5 year period preceding MS onset, was higher among MS cases than general population controls. Sex and age modified findings, with a stronger positive association observed between MS and anemia among men, and between MS and body pain among individuals aged 30 years and older, prior to a first demyelinating event. Approaching the first demyelinating event, the frequency of physician visits for fatigue, sleep disorders, anemia and body pain increased among MS cases relative to controls. Conclusion: This dissertation reveals a paucity of population-based studies investigating the suspected MS prodrome and provides evidence that fatigue, sleep disorders, anemia and body pain are elevated in the MS prodrome.

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The impacts of kill-trapping on carriage of Leptospira interrogans and methicillin-resistant Staphylococcus aureus by wild rats in Vancouver's Downtown Eastside (2017)

The ecology of wild urban rats is an important determinant of the transmission and carriage ofrat-associated zoonoses (RAZ). For example, previous research has shown that RAZ areclustered in rat populations at the level of the city-block, possibly because rats, which rarelymove beyond a single city-block, live in colonies that do not interact with rats from othercolonies. It may therefore be the case that rat colonies self-limit the spread of RAZ to within theinfected colony. Because anthropogenic disturbances can disrupt animal ecology, I hypothesizedthat human disruptions of typical rat ecology, such as pest-control, can also disrupt theepidemiology of RAZ within the disturbed rat population. This dissertation tests the hypothesisthat kill-trapping wild urban rat populations can lead to unpredictable changes in RAZepidemiology, even leading to increases in the transmission and/or spread amongst ratpopulations. This work tested rats for Methicillin-resistant Staphylococcus aureus (MRSA) andLeptospira interrogans both before and after enacting a kill-trapping intervention at the level ofthe city-block in Vancouver Canada’s Downtown Eastside (DTES). Study blocks werecategorized as either intervention blocks (in which kill-trapping was enacted), non-kill flankingblocks (blocks immediately next to intervention blocks in which no kill-trapping was enacted),and control blocks (in which no kill-trapping was enacted). Rats caught after kill-trapping inintervention blocks had 9.55 (95% CI 1.75-78.31) times the odds of carrying Leptospirainterrogans than did rats that were caught in any block type before the intervention. This effectwas not observed in any other block type for Leptospira interrogans or for carriage of MRSA.These results indicate that kill-trapping may impact the odds that rats that survive the killtrappingcarry some RAZ.

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