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Background Cryptococcosis due to Cryptococcus neoformans and Cryptococcus gattii varies with geographic region, populations affected, disease manifestations, and severity of infection, which impact treatment. Methods We developed a retrospective cohort of patients diagnosed with culture-proven cryptococcosis during 1995–2013 from 5 centers in North America and Australia. We compared underlying diseases, clinical manifestations, treatment, and outcomes in patients with C. gattii or C. neoformans infection. Results A total of 709 patients (452 C. neoformans; 257 C. gattii) were identified. Mean age was 50.2 years; 61.4% were male; and 52.3% were white. Time to diagnosis was prolonged in C. gattii patients compared with C. neoformans (mean, 52.2 vs 36.0 days; P Conclusions This study emphasizes differences in species-specific epidemiology and outcomes of patients with cryptococcosis, including underlying diseases, site of infection, and mortality. Species identification in patients with cryptococcosis is necessary to discern epidemiologic patterns, guide treatment regimens, and predict clinical progression and outcomes.

BACKGROUND & AIMS: The province of British Columbia (BC), Canada has experienced a rapid increase in illicit drug overdoses and deaths during the last four years, with a provincial emergency declared in April 2016. These deaths have been driven primarily by the introduction of synthetic opioids into the illicit opioid supply. This study aimed to measure the combined impact of large-scale opioid overdose interventions implemented in BC between April 2016 and December 2017 on the number of deaths averted. DESIGN: We expanded on the mathematical modelling methodology of our previous study to construct a Bayesian hierarchical latent Markov process model to estimate monthly overdose and overdose-death risk, along with the impact of interventions. SETTING/CASES: Overdose events and overdose-related deaths in BC from January 2012 to December 2017. INTERVENTIONS: The interventions considered were take-home naloxone kits, overdose prevention/supervised consumption sites and opioid agonist therapy MEASUREMENTS: Counterfactual simulations were performed with the fitted model to estimate the number of death events averted for each intervention, and in combination. FINDINGS: Between April 2016 and December 2017, BC observed 2177 overdose deaths (77% fentanyl-detected). During the same period, an estimated 3 030 (2 900 – 3 240) death events were averted by all interventions combined. In isolation, 1 580 (1 480 – 1 740) were averted by take-home naloxone, 230 (160 – 350) by overdose prevention services, and 590 (510 – 720) were averted by opioid agonist therapy. CONCLUSIONS: A combined intervention approach has been effective in averting overdose deaths during British Columbia’s opioid overdose crisis in the period since declaration of a public health emergency (April 2016 to December 2017). However, the absolute numbers of overdose deaths have not changed.

IntroductionBritish Columbia has the highest rate of opioid overdose in Canada, driven by the use of illegal opioids such as fentanyl. In addition to ongoing surveillance, there is a need for more comprehensive data to identify risk factors, inform the development of interventions, and evaluate the public health emergency response. Objectives and ApproachThe Provincial Overdose Cohort is a linked administrative dataset based on information from hospital admissions, physician visits, prescription dispensations, poison centre calls, ambulance, emergency department, coroner’s data, and First Nations Client File. Overdoses in the province were identified for the period January 2015-November 2016. Overdoses occurring within a 24 hour period across data sources were grouped as a single episode. For identified cases and for a control population (a 20% random sample of the BC residents), health care and prescribing history was appended dating back to 2010. Initial analyses were conducted based on a prioritization process with knowledge users. ResultsIntegration of distinct data sources about overdose events provided a more complete understanding of the extent of the opioid crisis than use of a single dataset alone. Between January 1, 2015 and November 30, 2016 10,456 overdoses occurred in BC. Overdose deaths represented only 13% of individuals overdosing; 54% of all overdoses were captured through ambulance records and 46\% through emergency and hospital records, with some overlap between the datasets. Most cases had contact with the health care system in the year before overdose suggesting opportunities for intervention. Some demographic differences were noted when comparing fatal and non-fatal overdoses, but few differences in health or prescribing histories were identifiable using administrative data. Conclusion/ImplicationsThe Provincial Overdose Cohort is a uniquely comprehensive dataset in a jurisdiction at the forefront of the opioid overdose response. Jurisdictions developing surveillance systems should consider the inclusion of ambulance, emergency room and hospital data in order to more completely characterize the population at risk.

IntroductionBritish Columbia (BC), Canada declared a public health emergency in April 2016 for opioid overdose. Comprehensive data was needed to identify risk factors, inform interventions, and evaluate response actions. We describe the development of an overdose cohort, including linkage strategy, case definitions, and data governance model, and present the resulting characteristics, including data linkage yields and case overlap among data sources.MethodsOverdose events from hospital admissions, physician visits, poison centre and ambulance calls, emergency department visits, and coroner's data were grouped into episodes if records were present in multiple sources. A minimum of five years of universal health care records (all prescription dispensations, fee-for-service physician billings, emergency department visits and hospitalizations) were appended for each individual. A 20% random sample of BC residents and a 1:5 matched case-control set were generated. Consultation and prioritization ensured analysts worked to address questions to directly inform public health actions.Results10,456 individuals suffered 14,292 overdoses from January 1, 2015 to Nov 30, 2016. Only 28% of overdose events were found in more than one dataset with the unique contribution of cases highest from ambulance records (32%). Compared with fatal overdoses, non-fatal events more often involved females, younger individuals (20 to 29 years) and those 60 or older. In 78% of illegal drug deaths, there was no associated ambulance response. In the year prior to first recorded overdose, 60% of individuals had at least one ED visit, 31% at least one hospital admission, 80% at least one physician visit, and 87% had filled at least one prescription in a community pharmacy.ConclusionWhile resource-intensive to establish, a linked cohort is useful for characterizing the full extent of the epidemic, defining sub-populations at risk, and patterns of contact with the health system. Overdose studies in other jurisdictions should consider the inclusion of multiple data sources.

It has been over a decade since Cryptococcus gattii was first recognized as the causative organism of an outbreak of cryptococcosis on Vancouver Island, British Columbia. A number of novel observations have been associated with the study of this emergent pathogen. A novel genotype of C. gattii, VGIIa was described as the major genotype associated with clinical disease. Minor genotypes, VGIIb and VGI, are also responsible for disease in British Columbians, in both human and animal populations. The clinical major genotype VGIIa and minor genotype VGIIb are identical to C. gattii isolated from the environment of Vancouver Island. There is more heterogeneity in VGI, and a clear association with the environment is not apparent. Between 1999 and 2010, there have been 281 cases of C. gattii cryptococcosis. Risk factors for infection are reported to be age greater than 50 years, history of smoking, corticosteroid use, HIV infection, and history of cancer or chronic lung disease. The major C. gattii genotype VGIIa is as virulent in mice as the model Cryptococcus, H99 C. neoformans, although the outbreak strain produces a less protective inflammatory response in C57BL/6 mice. The minor genotype VGIIb is significantly less virulent in mouse models. Cryptococcus gattii is found associated with native trees and soil on Vancouver Island. Transiently positive isolations have been made from air and water. An ecological niche for this organism is associated within a limited biogeoclimatic zone characterized by daily average winter temperatures above freezing.

To determine whether particular environmental, medical, or behavioral risk factors existed among Cryptcoccus gattii-infected persons compared with the general population, we conducted a sex-matched case-control study on a subset of case-patients in British Columbia (1999-2001). Exposures and underlying medical conditions among all case-patients (1999-2007) were also compared with results of provincial population-based surveys and studies. In case-control analyses, oral steroids (matched odds ratio [MOR] 8.11, 95% confidence interval [CI] 1.74-37.80), pneumonia (MOR 2.71, 95% CI 1.05-6.98), and other lung conditions (MOR 3.21, 95% CI 1.08-9.52) were associated with infection. In population comparisons, case-patients were more likely to be ≥50 years of age (p

Incidence is high, but the predominant strain does not seem to cause greater illness or death than do other strains., British Columbia, Canada, has the largest reported population of Cryptococcus gattii–infected persons worldwide. To assess the impact of illness, we retrospectively analyzed demographic and clinical features of reported cases, hospitalizations, and deaths during 1999–2007. A total of 218 cases were reported (average annual incidence 5.8 per million persons). Most persons who sought treatment had respiratory illness (76.6%) or lung cryptococcoma (75.4%). Persons without HIV/AIDS hospitalized with cryptococcosis were more likely than those with HIV/AIDS to be older and admitted for pulmonary cryptococcosis. The 19 (8.7%) persons who died were more likely to be older and to have central nervous system disease and infection from the VGIIb strain. Although incidence in British Columbia is high, the predominant strain (VGIIa) does not seem to cause greater illness or death than do other strains. Further studies are needed to explain host and strain characteristics for regional differences in populations affected and disease outcomes.

This organism should be recognized as an emerging pathogen in the United States., Cryptococcus gattii has emerged as a human and animal pathogen in the Pacific Northwest. First recognized on Vancouver Island, British Columbia, Canada, it now involves mainland British Columbia, and Washington and Oregon in the United States. In Canada, the incidence of disease has been one of the highest worldwide. In the United States, lack of cryptococcal species identification and case surveillance limit our knowledge of C. gattii epidemiology. Infections in the Pacific Northwest are caused by multiple genotypes, but the major strain is genetically novel and may have emerged recently in association with unique mating or environmental changes. C. gattii disease affects immunocompromised and immunocompetent persons, causing substantial illness and death. Successful management requires an aggressive medical and surgical approach and consideration of potentially variable antifungal drug susceptibilities. We summarize the study results of a group of investigators and review current knowledge with the goal of increasing awareness and highlighting areas where further knowledge is required.

Background Cryptococcus gattii (Cg) infection emerged in British Columbia in 1999. A longitudinal, clinical description of patients has not been reported. Methods Medical records were reviewed for Cg patients identified through surveillance (1999-2007). Risk factors for Cg mortality were explored using multivariate Cox regression; longitudinal patterns in serum cryptococcal antigen (SCrAg) titers and the probability of chest cryptococcomas over time were estimated using cubic B-splines in mixed-effects regression models. Results Among 152 patients, 111 (73.0%) were culture confirmed. Isolated lung infection was present in 105 (69.1%) patients; 47 (30.9%) had central nervous system infection, with or without lung involvement. Malignancy was the provisional diagnosis in 64 (42.1%) patients. Underlying diseases were present in 91 (59.9%) patients; 23 (15.1%) were immunocompromised, and 23 (15.1%) had asymptomatic disease. There were only 2 (1.8%) culture positive relapses, both within 12 months of follow-up. The estimated median time to resolution of lung cryptococcomas and decline in SCrAg titer to 50 years (hazard ratio [HR], 15.6; 95% confidence interval [CI], 1.9-130.5) and immunocompromise (HR, 5.8; CI, 1.5-21.6). All Cg-related mortality occurred among culture-positive cases within 1 year of diagnosis. Conclusions Cryptococcomas and serum antigenemia were slow to resolve. However, late onset of failed therapy or relapse was uncommon, suggesting that delayed resolution of these findings does not require prolongation of treatment beyond that recommended by guidelines.

A total of 184 methicillin-resistant Staphylococcus aureus (MRSA) strains were collected from patients who sought treatment primarily for skin and soft tissue infections from January 1, 1999, to March 31, 2002, in east-central Saskatchewan, Canada. Molecular subtyping analysis using pulsed-field gel electrophoresis showed 2 major clusters. Cluster A (n = 55) was composed of a multidrug-resistant MRSA strain associated with a long-term care facility and was similar to the previously reported nosocomial Canadian epidemic strain labeled CMRSA-2. Cluster B (n = 125) was associated with cases identified at community health centers and was indistinguishable from a community-associated (CA)-MRSA strain identified previously in the United States (USA400). Cluster B remained susceptible to a number of classes of antimicrobial agents and harbored the lukF-PV and lukS-PV toxin genes. Over 50% of both clonal groups displayed high-level resistance to mupirocin. This is the first report of the USA400 strain harboring the lukF-PV and lukS-PV toxin genes in Canada.

Cryptococcus gattii causes life-threatening infection of the pulmonary and central nervous systems in hosts with normal immunity and traditionally has been considered to be restricted geographically to tropical and subtropical climates. The recent outbreak of C. gattii in the temperate climate of Vancouver Island, BC, Canada, led to a collaborative investigation. The objectives of the current study were to ascertain the environmental source of the outbreak infections, survey the molecular types of the outbreak and environmental cryptococcal isolates, and determine the extent of genetic diversity among the isolates. PCR-fingerprinting and amplified fragment length polymorphism (AFLP) were used to examine the genotypes, and mating assays were performed to determine the mating type of the isolates. All outbreak and environmental isolates belonged to C. gattii . Concordant results were obtained by using PCR-fingerprinting and AFLP analysis. The vast majority of clinical and veterinary infections were caused by isolates of the molecular type VGII/AFLP6, but two were caused by molecular type VGI/AFLP4. All environmental isolates belonged to molecular type VGII/AFLP6. Two or three subtypes were observed within VGII/AFLP6 among outbreak and environmental isolates. All mating-competent isolates were of the α-mating type. The emergence of this usually tropical pathogen on Vancouver Island highlights the changing distribution of this genotype and emphasizes the importance of an ongoing collaborative effort to monitor the global epidemiology of this yeast.

This chapter outlines issues that were quickly explored, starting with the realization in 2001 that Vancouver Island was a hot spot for a pathogen not previously described as endemic and not restricted to tropical and subtropical climates. The picture of the outbreak that has developed has implications for global travel, climate change, land use patterns, and environmental colonization. Importantly, cryptococcosis caused by Cryptococcus gattii now serves as an excellent illustration of the impact of pathogen spread into a clement ecological niche, in this case, one that happened to be in a major population center of western Canada and the Pacific Northwest. Symptoms and clinicopathological changes in animals on Vancouver Island were consistent with disease reported elsewhere. The most common primary system involved was respiratory, followed by the central nervous system (CNS), in both cats and dogs. Animal cryptococcosis due to C. gattii is a nonregulated disease in Canada. Molecular typing of C. gattii environmental isolates from Vancouver Island using PCR fingerprinting and/or restriction fragment length polymorphism methodologies revealed that the majority of isolates belonged to the VGII molecular type and a small number belonged to the VGI molecular type. A number of solid culture media, biochemical tests, and stains can confirm the diagnosis of Cryptococcus to the genus level. Ecological niche modeling was employed to identify geographical areas in British Columbia with suitable environmental conditions to support the permanent colonization of C. gattii in the environment.

We compared travel histories of case-patients with Cryptococcus gattii infection during 1999–2006 to travel destinations of the general public on Vancouver Island, British Columbia, Canada. Findings validated and refined estimates of risk on the basis of place of residence and showed no spatial progression of risk areas on this island over time.

Lyme disease (LD) is rare in British Columbia (BC) and, despite being a reportable condition since 1994, may be underreported. Here we review all provincial laboratory and clinical databases to determine the number of LD cases reported in BC from 1997 to 2008. We analyzed demographic characteristics of LD cases and used capture-recapture methodology to estimate the true number of cases in BC for this period. From 1997 to 2008, 93 confirmed cases of LD were reported in BC. Conservative capture-recapture estimates place the true number of LD cases in BC during this period at 142 (95% confidence interval: 111-224), indicating up to 40% underreporting of this rare disease. Despite this underreporting, BC continues to have low endemic risk of LD. Strategies are needed to increase both physician awareness and the use of preventive measures in the BC population, including for those traveling to other endemic areas.

159 Background: The goal of the collaborative is to improve the quality and consistency of physical and emotional symptom management across the cancer journey. Objectives are to promote the adoption of electronic symptom assessment using a standardized tool and to increase the clinical use of evidence based guidelines to effectively manage patient identified symptoms. Methods: The actions taken for this initiative are (a) manage cancer symptoms through a patient reported measurement tool; (b) improve the quality of symptom management through the uptake of symptom management guides and algorithms for care; and (c) drive improvement through the adoption of an electronic symptom assessment platform. The following aims were established for this work: (1) aim for symptom screening and assessment (70% of ambulatory cancer clinic patients are screened for symptom severity using ESAS at least once/month); (2) aim for symptom management (evidence from chart audits show intervention as per evidence based guidelines for patients reported symptom scores); (3) aim for patient satisfaction (90% of target population indicates that their health care team took their scores into consideration when developing a care plan); and (4)aim for evidence of use (90% of patients state that their doctor or nurse spoke with them about their symptom screen). Results: 60% of cancer patients are screened each month representing over 28,000 people. Six of fourteen cancer regions are above the provincial target of 70%, with some close to 90%. 92% of patients felt ESAS was important to complete to help health care providers know how they are feeling. Conclusions: Cancer Care Ontario has been able to drive improvements in symptom management through the implementation of system wide electronic symptom assessment. For other jurisdictions interested in adopting this approach, the following areas are critical for success: a) leadership at all levels of the system; b) clinical tools at the point of care; c) engagement of patients in the design of care; d) communications support to spread information to all stakeholders; and e) using to data to drive performance improvement and accountability.

56 Background: The goal of the collaborative is to improve the quality and consistency of physical and emotional symptom management across the cancer journey. Objectives are: (a) promote the adoption of electronic symptom assessment using a standardized tool and (b) increase the clinical use of evidence based guidelines to effectively manage patient identified symptoms. Methods: The actions taken for this initiative are to manage cancer symptoms through a patient reported measurement tool; improve the quality of symptom management through the uptake of symptom management guides and algorithms for care; and drive improvement through the adoption of an electronic symptom assessment platform The following aims were established for this work: (1) Aim for symptom screening and assessment (70% of ambulatory cancer clinic patients are screened for symptom severity using ESAS at least once/month) (2) aim for symptom management (evidence from chart audits show intervention as per evidence based guidelines for patients reported symptom scores) (3) aim for patient satisfaction (90% of target population indicates that their health care team took their scores into consideration when developing a care plan) and (4) aim for evidence of use (90% of patients state that their doctor or nurse spoke with them about their symptom screen). Results: 60% of cancer patients are screened each month representing over 28,000 people. Six of fourteen cancer regions are above the provincial target of 70%, with some close to 90%. 92% of patients felt ESAS was important to complete to help health care providers know how they are feeling. Conclusions: Cancer Care Ontario has been able to drive improvements in symptom management through the implementation of system wide electronic symptom assessment. For other jurisdictions interested in adopting this approach, the following areas are critical for success. (a.) Leadership at all levels of the system; (b.) clinical tools at the point of care; (c) engagement of patients in the design of care; (d) communications support to spread information to all stakeholders; and (e) using to data to drive performance improvement and accountability.

70 Background: Cancer Care Ontario (CCO) is an Ontario government agency which drives quality and improvement for the Ontario cancer system. Person-Centred Care (PCC) has been an identified goal both from the recent Institute of Medicine (IOM) report and as a corporate strategic priority at CCO. CCO is assessing the degree of PCC practiced in Ontario’s Cancer system to design interventions to improve this aspect of care delivery and design. Currently no established or validated indicators for PCC have been tested and evaluation methodology of PCC is unclear. A baseline of the system’s focus on PCC is required to establish a provincial plan to drive quality improvement. Methods: A series of 14 semi-structured interviews were conducted at Ontario’s regional cancer centers (RCCs) to determine the degree of development of a PCC culture in Ontario’s cancer system. Interviews were conducted with all 14 Regional Cancer Programs (RCPs) including: - 10 Patient and Family Advisors (PFAs); and - 56 RCPs and hospital leaders (Directors, Managers, Physicians, Nursing, Psychosocial Oncology providers). Sixty-six participants (direct interviews/questionnaires) were interviewed; questionnaires were received from 28 organizations (hospitals/RCCs). Results: Although 86% of interviewed organizations reported having a PCC corporate strategy, 41% of hospitals and 73% of RCCs do not have dedicated staff to support the strategy. 53% of organizations work with a Patient and Family Advisory Council (PFAC) and only 43% engage PFAs in decision-making tables with 94% of RCPs expressing a need for guidance on PFA engagement. Key facilitators to promote PCC are: strong and committed leadership and continuous staff engagement/education. Primary barriers include: equity in PFA recruitment, cultural resistance to PCC, and lack of evaluation frameworks. Conclusions: Advancing PCC requires strong provincial direction, training to foster PFA engagement, and measurement and accountability frameworks for cultural change. Clear definitions on accountabilities for PCC roles and expectations for PFAs and staff are also key to supporting PCC regionally.

240 Background: Cancer Care Ontario (CCO) is an Ontario government agency that drives system wide quality improvement in disease prevention and screening, the delivery of care and the patient experience (PE), for cancer, chronic kidney disease and access to care for key health services. CCO partners with 14 Regional Cancer Programs across the province. CCO measures the cancer PE retrospectively through a paper-based Ambulatory Oncology Patient Satisfaction Survey but there are limitations such as the delay in reporting of results. CCO is developing and implementing a province-wide electronic real-time PE survey to measure PE. An electronic survey tool will enable the collection, analysis and reporting of PE data more quickly to drive quality improvement. Methods: A current state assessment was undertaken in fall 2013 to understand support for and readiness of CCO’s Regional Cancer Centres (RCCs) to move forward with measuring PE in real-time, at point of care. 14 semi-structured interviews were conducted with RCCs Regional Vice Presidents (RVP); over 800 patients participated in focus groups in 11 of 14 regions; a targeted online survey was completed by 16 administrators in 14 regions. Results: Interest in a real-time measurement (RTM) approach was overwhelmingly positive – 94% of patients and 100% of RVPs thought that measuring PE in real-time is important. Patients want the real-time survey to be short - 61% of patients reported that the number of questions they are willing to answer is 5-10, with 18% indicating 15 questions. 62% of patients reported that they were willing to spend 2-6 minutes answering a survey, with 24% reporting 10 minutes. 36% of the RCCs have ad hoc RTM strategies and 21% have utilized an electronic tool. There was no co-ordination or data sharing between RCPs. Conclusions: CCO is implementing a province-wide RTM strategy which includes the validation of a RTM PE survey and procurement of an electronic solution to capture, analyze and report PE data. CCO will initially pilot the survey and electronic tool with the intention of a provincial rollout to cancer centres upon a post-pilot evaluation.

5 Background: Patients frequently have a difficult time finding their way through the process of diagnostic testing for cancer; the uncertainty is stressful and anxiety can impede effective communication and decision-making. Patient navigation is an ideal approach to supporting patients during the diagnostic phase of cancer care. Methods: Between 2010 and 2011, 14 Patient Navigators were trained and introduced into Diagnostic Assessment Programs (DAPs) across Ontario. DAPs are designed to provide coordination and supportive care to patients undergoing diagnostic testing and assessment. A patient survey served to evaluate the impact of patient navigation on the patient experience. Standardized tools were introduced to measure symptom severity and symptom management. Interviews were done to gauge provider and team perspectives on the role. Results: During the pilot, patient symptoms improved in the areas of well-being, tiredness, anxiety and shortness of breath, each by 30% or more. The patient survey indicated that through the program, patients got the information and support they needed; 91% of patients surveyed said that they were either satisfied or very satisfied with their experience with the patient navigator. The navigation pilot sites saw their diagnostic wait times fall by 55%. The Patient Navigators have found their work to be highly satisfying and rewarding, enjoying the opportunity it provides to use their full scope of practice in a multidisciplinary environment. Physicians expressed a high degree of satisfaction with the support provided by the Patient Navigators, reporting that patients were better prepared and informed when they arrived for their clinic appointments. Conclusions: This work has shown that patient navigation enhances the experience of patients as they move along the diagnostic continuum. Patient Navigators assist patients with managing their physical and psychosocial symptoms and play a critical role in providing the information and support patients need during a time that is full of uncertainty and distress. The diagnostic phase is a prime example of where navigation can have an impact on both the quality of patient care and the effectiveness of the health care team.

Cryptococcus gattii, emergent on Vancouver Island, British Columbia (BC), Canada, in 1999, was detected during 2003-2005 in 3 persons and 8 animals that did not travel to Vancouver Island during the incubation period; positive environmental samples were detected in areas outside Vancouver Island. All clinical and environmental isolates found in BC were genotypically consistent with Vancouver Island strains. In addition, local acquisition was detected in 3 cats in Washington and 2 persons in Oregon. The molecular profiles of Oregon isolates differed from those found in BC and Washington. Although some microclimates of the Pacific Northwest are similar to those on Vancouver Island, C. gattii concentrations in off-island environments were typically lower, and human cases without Vancouver Island contact have not continued to occur. This suggests that C. gattii may not be permanently colonized in off-island locations.