Association between toxic drug events and encephalopathy in British Columbia, Canada: a cross-sectional analysis.

BACKGROUND: Encephalopathy can occur from a non-fatal toxic drug event (overdose) which results in a partial or complete loss of oxygen to the brain, or due to long-term substance use issues. It can be categorized as a non-traumatic acquired brain injury or toxic encephalopathy. In the context of the drug toxicity crisis in British Columbia (BC), Canada, measuring the co-occurrence of encephalopathy and drug toxicity is challenging due to lack of standardized screening. We aimed to estimate the prevalence of encephalopathy among people who experienced a toxic drug event and examine the association between toxic drug events and encephalopathy. METHODS: Using a 20% random sample of BC residents from administrative health data, we conducted a cross-sectional analysis. Toxic drug events were identified using the BC Provincial Overdose Cohort definition and encephalopathy was identified using ICD codes from hospitalization, emergency department, and primary care records between January 1st 2015 and December 31st 2019. Unadjusted and adjusted log-binomial regression models were employed to estimate the risk of encephalopathy among people who had a toxic drug event compared to people who did not experience a toxic drug event. RESULTS: Among people with encephalopathy, 14.6% (n = 54) had one or more drug toxicity events between 2015 and 2019. After adjusting for sex, age, and mental illness, people who experienced drug toxicity were 15.3 times (95% CI = 11.3, 20.7) more likely to have encephalopathy compared to people who did not experience a drug toxicity event. People who were 40 years and older, male, and had a mental illness were at increased risk of encephalopathy. CONCLUSIONS: There is a need for collaboration between community members, health care providers, and key stakeholders to develop a standardized approach to define, screen, and detect neurocognitive injury related to drug toxicity.

Exploring the contextual risk factors and characteristics of individuals who died from the acute toxic effects of opioids and other illegal substances: listening to the coroner and medical examiner voice. / Exploration des facteurs de risque contextuels et des caractéristiques des personnes décédées des effets toxiques aigus d'opioïdes et d'autres substances illégales : prise en compte de l'avis des coroners et des médecins légistes.

INTRODUCTION: Substance-related acute toxicity deaths continue to be a serious public health concern in Canada. This study explored coroner and medical examiner (C/ME)perspectives of contextual risk factors and characteristics associated with deaths from acute toxic effects of opioids and other illegal substances in Canada. METHODS: In-depth interviews were conducted with 36 C/MEs in eight provinces and territories between December 2017 and February 2018. Interview audio recordings were transcribed and coded for key themes using thematic analysis. RESULTS: Four themes described the perspectives of C/MEs: (1) Who is experiencing a substance-related acute toxicity death?; (2) Who is present at the time of death?; (3) Why are people experiencing an acute toxicity death?; (4) What are the social contextual factors contributing to deaths? Deaths crossed demographic and socioeconomic groups and included people who used substances on occasion, chronically, or for the first time. Using alone presents risk, while using in the presence of others can also contribute to risk if others are unable or unprepared to respond. People who died from a substance-related acute toxicity often had one or more contextual risk factors: contaminated substances, history of substance use, history of chronic pain and decreased tolerance. Social contextual factors contributing to deaths included diagnosed or undiagnosed mental illness, stigma, lack of support and lack of follow-up from health care. CONCLUSION: Findings revealed contextual factors and characteristics associated with substance-related acute toxicity deaths that contribute to a better understanding of the circumstances surrounding these deaths across Canada and that can inform targeted prevention and intervention efforts.

Using linked data to identify pathways of reporting overdose events in British Columbia, 2015-2017.

Introduction: Overdose events related to illicit opioids and other substances are a public health crisis in Canada. The BC Provincial Overdose Cohort is a collection of linked datasets identifying drug-related toxicity events, including death, ambulance, emergency room, hospital, and physician records. The datasets were brought together to understand factors associated with drug-related overdose and can also provide information on pathways of care among people who experience an overdose. Objectives: To describe pathways of recorded healthcare use for overdose events in British Columbia, Canada and discrepancies between data sources. Methods: Using the BC Provincial Overdose Cohort spanning 2015 to 2017, we examined pathways of recorded health care use for overdose through the framework of an injury reporting pyramid. We also explored differences in event capture between linked datasets. Results: In the cohort, a total of 34,113 fatal and non-fatal overdose events were identified. A total of 3,056 people died of overdose. Nearly 80% of these deaths occurred among those with no contact with the healthcare system. The majority of events with healthcare records included contact with EHS services (72%), while 39% were seen in the ED and only 7% were hospitalized. Pathways of care from EHS services to ED and hospitalization were generally observed. However, not all ED visits had an associated EHS record and some hospitalizations following an ED visit were for other health issues. Conclusions: These findings emphasize the importance of accessing timely healthcare for people experiencing overdose. These findings can be applied to understanding pathways of care for people who experience overdose events and estimating the total burden of healthcare-attended overdose events. Highlights: In British Columbia, Canada:Multiple sources of linked administrative health data were leveraged to understand recorded healthcare use among people with fatal and non-fatal overdose eventsThe majority of fatal overdose events occurred with no contact with the healthcare system and only appear in mortality dataMany non-fatal overdose events were captured in data from emergency health services, emergency departments, and hospital recordsAccessing timely healthcare services is critical for people experiencing overdose.

Comparing mortality and healthcare utilization in the year following a paramedic-attended non-fatal overdose among people who were and were not transported to hospital: A prospective cohort study using linked administrative health data.

BACKGROUND: As the overdose emergency continues in British Columbia (BC), paramedic-attended overdoses are increasing, as is the proportion of people not transported to hospital following an overdose. This study investigated risk of death and subsequent healthcare utilization for people who were and were not transported to hospital after a paramedic-attended non-fatal overdose. METHODS: Using a linked administrative health data set which includes all overdoses that come into contact with health services in BC, we conducted a prospective cohort study of people who experienced a paramedic-attended non-fatal overdose between 2015 and 2016. People were followed for 365 days after the index event. The primary outcomes assessed were all-cause mortality and overdose-related death. Additionally, we examined healthcare utilization after the index event. RESULTS: In this study, 8659 (84%) people were transported and 1644 (16%) were not transported to hospital at the index overdose event. There were 279 overdose deaths (2.7% of people, 59.4% of deaths) during follow-up. There was no significant difference in risk of overdose-related death, though people not transported had higher odds of a subsequent non-fatal overdose event captured in emergency department and outpatient records within 90 days. People transported to hospital had higher odds of using hospital and outpatient services for any reason within 365 days. CONCLUSIONS: Transport to hospital after a non-fatal overdose is an opportunity to provide care for underlying and chronic conditions. There is a need to better understand factors that contribute to non-transport, particularly among people aged 20-59 and people without chronic conditions.

Known fentanyl use among clients of harm reduction sites in British Columbia, Canada.

BACKGROUND: North America is in the midst of an opioid overdose epidemic and it is commonly suggested that exposure to fentanyl is unknown. Using a provincial survey of harm reduction site clients, we aimed to characterize known and unknown fentanyl use and their correlates among people who use drugs in British Columbia, Canada. METHODS: We recruited 486 clients who were >18 years old and 316 agreed to provide a urine sample for substance use testing. Reported known fentanyl use was defined as a three-level categorical variable assessing recent (i.e., in the previous three days) fentanyl exposure: (i) known exposure; (ii) unknown exposure; and (iii) no exposure. We also assessed any exposure to fentanyl (Yes vs. No) confirmed by urinalysis. Survey data were summarized using descriptive statistics. Multinomial logistic regression and modified Poisson regression models were built to examine different correlates of exposure to fentanyl. RESULTS: Median age of the participants was 40 (IQR: 32-49). Out of the 303 eligible participants, 38.7% (117) reported known fentanyl use, 21.7% (66) had unknown fentanyl use, and 39.6% (120) had no recent fentanyl use. In the adjusted multinomial logistic regression model and in comparison with unknown fentanyl use, recent known fentanyl use was significantly associated with self-report of methadone use (aRRR = 3.18), heroin/morphine use (aRRR = 4.40), and crystal meth use (aRRR = 2.95). Moreover, any recent exposure to fentanyl (i.e., positive urine test for fentanyl) was significantly associated with living in urban settings (aPR = 1.49), and self-reporting recent cannabis use (aPR = 0.73), crystal meth (aPR = 1.45), and heroin/morphine use (aPR = 2.48). CONCLUSION: The landscape of illicit opioid use is changing in BC and more people are using fentanyl knowingly. The increasing prevalence of known fentanyl use is concerning and calls for further investments in public awareness and public policy efforts regarding fentanyl exposure and risks.

Modelling the combined impact of interventions in averting deaths during a synthetic-opioid overdose epidemic.

BACKGROUND AND AIMS: The province of British Columbia (BC) Canada has experienced a rapid increase in illicit drug overdoses and deaths during the last 4 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 AND 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 3030 (2900-3240) death events were averted by all interventions combined. In isolation, 1580 (1480-1740) 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-December 2017). However, the absolute numbers of overdose deaths have not changed.

An evaluation of Take Home Naloxone program implementation in British Columbian correctional facilities.

PURPOSE: To understand how the Take Home Naloxone (THN) program is implemented in two pilot correctional facilities in British Columbia (BC), Canada, in order to identify areas for program improvement and inform the expansion of the program to other Canadian correctional facilities The paper aims to discuss these issues. DESIGN/METHODOLOGY/APPROACH: Two focus groups and one interview were conducted with healthcare staff at two pilot correctional facilities. Sessions were audio recorded, transcribed verbatim and divergent and convergent experiences within and between the facilities were explored in an iterative process. Key themes and lessons learned were identified and later validated by focus group participants. FINDINGS: Key themes that emerged included: challenges and importance of the train-the-trainer program for healthcare staff conducting participant training sessions; potential for improved prison population engagement and awareness of the program; tailoring program resources to the unique needs of an incarcerated population; challenges connecting participants to community harm reduction resources following release; and clarifying and enhancing the role of correctional officers to support the program. RESEARCH LIMITATIONS/IMPLICATIONS: The correctional setting presents unique challenges and opportunities for the THN program that must be considered for program effectiveness. ORIGINALITY/VALUE: This evaluation was conducted to inform program expansion amidst a historic opioid overdose epidemic in BC, and adds to the limited yet growing body of literature on the implementation and evaluation of this program in correctional settings globally.

Correlates of seeking emergency medical help in the event of an overdose in British Columbia, Canada: Findings from the Take Home Naloxone program.

BACKGROUND: British Columbia (BC), Canada, is experiencing an unprecedented number of opioid overdoses mainly due to the contamination of illicit drugs with fentanyl and its analogues. Reluctance to seek emergency medical help (i.e., by calling 9-1-1) has been identified as a barrier to optimal care for overdose victims. This study aimed to identify the correlates of seeking help during an overdose event when naloxone was administered via BC's Take Home Naloxone (THN) program. METHODS: In this cross-sectional study, we reviewed administrative records (from July 2015 to December 2017) about overdose events submitted by THN participants when they received their replacement naloxone kits (n = 2350). The primary outcome of the study was reported calling 9-1-1 and modified Poisson regression models were built to investigate the factors associated with help-seeking during an overdose event. RESULTS: Most overdose victims were men (69.0%) and >30 years old (61.5%). Overall, participants reported calling 9-1-1 in 1310 (55.7%) overdose events. In the multivariable model, the likelihood of calling 9-1-1 was significantly and positively associated with the overdose victim being male and receiving rescue breathing. The likelihood of calling 9-1-1 was significantly and negatively associated with the overdoses occurring in private residences and health regions other than Vancouver Coastal which delivers services to mostly urban residents. CONCLUSION: Overall, medical help was sought for 55.7% of overdoses where naloxone was administered. Overdoses occurring among male victims as well as those receiving higher doses of naloxone and mouth-to-mouth rescue breathing were associated with a higher likelihood of help-seeking by responders. Future interventions need to encourage people who witness an overdose to seek emergency medical help.

Development and characteristics of the Provincial Overdose Cohort in British Columbia, Canada.

INTRODUCTION: British 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. METHODS: Overdose 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. RESULTS: 10,456 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. CONCLUSION: While 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.

Effect of opioid-substitution therapy and mental health counseling on HIV risk among hepatitis C-infected individuals.

BACKGROUND: Understanding differences in HIV incidence among people living with hepatitis C virus (HCV) can help inform strategies to prevent HIV infection. We estimated the time to HIV diagnosis among HCV-positive individuals and evaluated factors that could affect HIV-infection risk in this population. PATIENTS AND METHODS: The British Columbia Hepatitis Testers Cohort includes all BC residents (~1.5 million: about a third of all residents) tested for HCV and HIV from 1990 to 2013 and is linked to administrative health care and mortality data. All HCV-positive and HIV-negative individuals were followed to measure time to HIV acquisition (positive test) and identify factors associated with HIV acquisition. Adjusted HRs (aHRs) were estimated using Cox proportional-hazard regression. RESULTS: Of 36,077 HCV-positive individuals, 2,169 (6%) acquired HIV over 266,883 years of follow-up (overall incidence of 8.1 per 1,000 person years). Overall median (IQR) time to HIV infection was 3.87 (6.06) years. In Cox regression, injection-drug use (aHR 1.47, 95% CI 1.33-1.63), HBV infection (aHR 1.34, 95% CI 1.16-1.55), and being a man who has sex with men (aHR 2.78, 95% CI 2.14-3.61) were associated with higher risk of HIV infection. Opioid-substitution therapy (OST) (aHR 0.59, 95% CI 0.52-0.67) and mental health counseling (aHR 0.48, 95% CI 0.43-0.53) were associated with lower risk of HIV infection. CONCLUSION: Injection-drug use, HBV coinfection, and being a man who has sex with men were associated with increased HIV risk and engagement in OST and mental health counseling were associated with reduced HIV risk among HCV-positive individuals. Improving access to OST and mental health services could prevent transmission of HIV and other blood-borne infections, especially in settings where access is limited.

Identifying injection drug use and estimating population size of people who inject drugs using healthcare administrative datasets.

BACKGROUND: Large linked healthcare administrative datasets could be used to monitor programs providing prevention and treatment services to people who inject drugs (PWID). However, diagnostic codes in administrative datasets do not differentiate non-injection from injection drug use (IDU). We validated algorithms based on diagnostic codes and prescription records representing IDU in administrative datasets against interview-based IDU data. METHODS: The British Columbia Hepatitis Testers Cohort (BC-HTC) includes ∼1.7 million individuals tested for HCV/HIV or reported HBV/HCV/HIV/tuberculosis cases in BC from 1990 to 2015, linked to administrative datasets including physician visit, hospitalization and prescription drug records. IDU, assessed through interviews as part of enhanced surveillance at the time of HIV or HCV/HBV diagnosis from a subset of cases included in the BC-HTC (n = 6559), was used as the gold standard. ICD-9/ICD-10 codes for IDU and injecting-related infections (IRI) were grouped with records of opioid substitution therapy (OST) into multiple IDU algorithms in administrative datasets. We assessed the performance of IDU algorithms through calculation of sensitivity, specificity, positive predictive, and negative predictive values. RESULTS: Sensitivity was highest (90-94%), and specificity was lowest (42-73%) for algorithms based either on IDU or IRI and drug misuse codes. Algorithms requiring both drug misuse and IRI had lower sensitivity (57-60%) and higher specificity (90-92%). An optimal sensitivity and specificity combination was found with two medical visits or a single hospitalization for injectable drugs with (83%/82%) and without OST (78%/83%), respectively. Based on algorithms that included two medical visits, a single hospitalization or OST records, there were 41,358 (1.2% of 11-65 years individuals in BC) recent PWID in BC based on health encounters during 3- year period (2013-2015). CONCLUSION: Algorithms for identifying PWID using diagnostic codes in linked administrative data could be used for tracking the progress of programing aimed at PWID. With population-based datasets, this tool can be used to inform much needed estimates of PWID population size.

A syndemic approach to assess the effect of substance use and social disparities on the evolution of HIV/HCV infections in British Columbia.

BACKGROUND: Co-occurrence of social conditions and infections may affect HIV/HCV disease risk and progression. We examined the changes in relationship of these social conditions and infections on HIV and hepatitis C virus (HCV) infections over time in British Columbia during 1990-2013. METHODS: The BC Hepatitis Testers Cohort (BC-HTC) includes ~1.5 million individuals tested for HIV or HCV, or reported as a case of HCV, HIV, HBV, or tuberculosis linked to administrative healthcare databases. We classified HCV and HIV infection status into five combinations: HIV-/HCV-, HIV+monoinfected, HIV-/HCV+seroconverters, HIV-/HCV+prevalent, and HIV+/HCV+. RESULTS: Of 1.37 million eligible individuals, 4.1% were HIV-/HCV+prevalent, 0.5% HIV+monoinfected, 0.3% HIV+/HCV+ co-infected and 0.5% HIV-/HCV+seroconverters. Overall, HIV+monoinfected individuals lived in urban areas (92%), had low injection drug use (IDU) (4%), problematic alcohol use (4%) and were materially more privileged than other groups. HIV+/HCV+ co-infected and HIV-/HCV+seroconverters were materially most deprived (37%, 32%), had higher IDU (28%, 49%), problematic alcohol use (14%, 17%) and major mental illnesses (12%, 21%). IDU, opioid substitution therapy, and material deprivation increased in HIV-/HCV+seroconverters over time. In multivariable multinomial regression models, over time, the odds of IDU declined among HIV-/HCV+prevalent and HIV+monoinfected individuals but not in HIV-/HCV+seroconverters. Declines in odds of problematic alcohol use were observed in HIV-/HCV+seroconverters and coinfected individuals over time. CONCLUSIONS: These results highlight need for designing prevention, care and support services for HIV and HCV infected populations based on the evolving syndemics of infections and social conditions which vary across groups.

Late hepatitis B and C diagnosis in relation to disease decompensation and hepatocellular carcinoma development.

BACKGROUND & AIMS: We measured the timing of hepatitis B virus (HBV) and hepatitis C virus (HCV) diagnoses relative to the detection of decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC) as an indicator of late hepatitis diagnosis. METHODS: HBV and HCV diagnoses were defined relative to the diagnosis of DC or HCC such that HBV/HCV diagnoses within two years prior, at the time of or after HCC or DC diagnosis were considered late. We performed multivariable logistic regression to assess factors associated with late HBV/HCV diagnoses among those with DC or HCC. RESULTS: From 1990 to 2012, 778/32,664 HBV cases (2.4%) and 3,925/57,866 HCV cases (6.8%) developed DC while 628/32,644 HBV cases (1.9%) and 902/57,866 HCV cases (1.6%) developed HCC. Among HBV and HCV cases with DC, 49% and 40% respectively were late diagnoses, as were 46% and 31% of HBV and HCV cases with HCC, respectively. HBV late diagnosis declined from 100% in 1992 to 11% and 26% in 2011, while HCV late diagnosis declined from 100% in 1992 to 16% and 14% in 2011 for DC and HCC respectively. In multivariable modelling, late HBV diagnosis was associated with mental illness and a fewer number of physician visits in the five years prior to HBV diagnosis. Late HCV diagnosis was also associated with fewer physician visits, while those with illicit drug use were less likely to be diagnosed late. CONCLUSIONS: The proportion of late diagnoses has declined over time. People with better engagement with the healthcare system and with risk activities were diagnosed earlier. Lay summary: Late diagnosis of HBV and HCV represents a missed opportunity to reduce the risk of serious liver disease. Our results identify successes in earlier diagnosis over time using risk-based testing as well as groups that are being missed for screening such as those who do not see a physician regularly and those with serious mental illness.

Long-term effect of sustained virological response on hepatocellular carcinoma in patients with hepatitis C in Canada.

BACKGROUND & AIMS: Evidence is limited on hepatocellular carcinoma (HCC) risk after sustained virological response (SVR) to interferon-based treatment of hepatitis C virus (HCV) infection. We evaluated the effect of SVR on the risk of HCC and estimated its incidence in post-SVR HCV patients from a large population-based Canadian cohort. METHODS: The British Columbia Hepatitis Testers Cohort includes individuals tested for HCV between 1990-2013 linked with data on their medical visits, hospitalizations, cancers, prescription drugs and mortality. Patients receiving interferon-based HCV treatments were followed from the end of treatment to HCC diagnosis, death or December 31, 2012. We examined HCC risk among those who did and did not achieve SVR using multivariable proportional hazard models with the Fine and Gray modification for competing risks. RESULTS: Of 8147 individuals who received HCV treatment and were eligible for analysis, 4663 (57%) achieved SVR and 3484 (43%) did not. Each group was followed for a median of 5.6years (range: 0.5-12.9) for an HCC incidence rate of 1.1/1000 person-years (PY) among the SVR and 7.2/1000 PY among the no SVR group. The HCC incidence rate was higher among those with cirrhosis (SVR: 6.4, no SVR: 21.0/1000 PY). In the multivariable model, SVR was associated with a lower HCC risk (subdistribution hazard ratio [SHR]=0.20, 95% CI: 0.13-0.3), while cirrhosis (SHR=2.61, 95% CI: 1.68-4.04), age ⩾50years, being male and genotype 3 infection were associated with a higher HCC risk. Among those who achieved SVR, cirrhosis, age ⩾50years and being male were associated with a higher HCC risk. CONCLUSION: SVR after interferon-based treatment substantially reduces but does not eliminate HCC risk, which is markedly higher among those with cirrhosis and age ⩾50years at treatment initiation. Treatment of patients at an advanced fibrosis stage with new highly effective drugs will warrant continued surveillance for HCC post-SVR. LAY SUMMARY: We assessed the effect of successful hepatitis C treatment with older interferon-based treatment on the occurrence of liver cancer (hepatocellular carcinoma) and found that successful treatment prevents liver cancer. However, more people with cirrhosis and older age continued to develop liver cancer after successful treatment. Thus, treatment with new drugs among those with cirrhosis will require continued monitoring for liver cancer.

The Population Level Cascade of Care for Hepatitis C in British Columbia, Canada: The BC Hepatitis Testers Cohort (BC-HTC).

BACKGROUND: Population-level monitoring of hepatitis C virus (HCV) infected people across the cascade of care identifies gaps in access and engagement in care and treatment. We characterized a population-level cascade of care for HCV in British Columbia (BC), Canada and identified factors associated with leakage at each stage. METHODS: The BC Hepatitis Testers Cohort (BC-HTC) includes 1.5million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV cascade of care stages: 1) estimated population prevalence; 2) HCV diagnosed; 3) HCV RNA tested; 4) genotyped; 5) initiated treatment; and 6) achieved sustained virologic response (SVR). RESULTS: We estimated that 73,203 people were HCV antibody positive in BC in 2012 (undiagnosed: 18,301, 25%; diagnosed: 54,902, 75%). Of these, 56%(40,656) had HCV RNA testing; 34%(26,300) were genotyped; 12%( 8532 ) had received interferon-based therapy and 7%(5197) had SVR. Males, older birth cohorts, and HBV coinfected were less likely to undergo HCV RNA testing. Among those with chronic HCV infection, 32% had received liver-related care. Retention in liver care was more likely in those with HIV, cirrhosis, and drug/alcohol use and less likely in males and HBV coinfected. CONCLUSIONS: Although there are gaps in HCV RNA testing and genotyping after HCV diagnosis, the major gap in the cascade of care was low treatment initiation. People with comorbidities progressed through the cascade of testing and care but few received treatment.

Twin epidemics of new and prevalent hepatitis C infections in Canada: BC Hepatitis Testers Cohort.

BACKGROUND: We characterized the twin epidemics of new and prevalent hepatitis C virus (HCV) infections in British Columbia, Canada to inform prevention, care and treatment programs. METHODS: The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV, HIV or reported as a case of HBV, HCV, HIV or active TB between 1990-2013 linked with data on their medical visits, hospitalizations, cancers, prescription drugs and mortality. Prevalent infection was defined as being anti-HCV positive at first test. Those with a negative test followed by a positive test were considered seroconverters or new infections. RESULTS: Of 1,132,855 individuals tested for HCV, 64,634 (5.8 %) were positive and an additional 3092 cases tested positive elsewhere for a total of 67,726. Of 55,781 HCV positive individuals alive at the end of 2013, 7064 were seroconverters while 48,717 had prevalent infection at diagnosis. The HCV positivity rate (11.2 %) was highest in birth cohort 1945-1964 which declined over time. New infections were more likely to be male, 15-34 years of age (born 1965-1984), HIV- or HBV-coinfected, socioeconomically disadvantaged, have problematic drug and alcohol use and a mental health illness. The profile was similar for individuals with prevalent infection, except for lower odds of HBV-coinfection, major mental health diagnoses and birth cohort >1975. CONCLUSIONS: The HCV positivity rate is highest in birth cohort 1945-1964 which represents most prevalent infections. New infections occur in younger birth cohorts who are commonly coinfected with HIV and/or HBV, socioeconomically marginalized, and living with mental illness and addictions.

Assessing Hepatitis C Burden and Treatment Effectiveness through the British Columbia Hepatitis Testers Cohort (BC-HTC): Design and Characteristics of Linked and Unlinked Participants.

BACKGROUND: The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. METHODS: The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. RESULTS: Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90-100%). CONCLUSION: Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV.

Decreasing Hepatitis C Incidence Among a Population With Repeated Tests: British Columbia, Canada, 1993-2011.

OBJECTIVES: We estimated HCV incidence among individuals who repeatedly underwent anti-HCV testing. METHODS: We studied HCV-negative individuals who had at least 2 tests between April 1992 and September 2012 in British Columbia, Canada. We calculated incidence as the number of new infections per 100 person-years at risk. RESULTS: From 1992 to 2012, 323 598 individuals who persistently tested negative and 7490 HCV seroconverters contributed 1 774 262 person-years of observation time. Incidence rates ranged from 2.66 infections per 100 person-years (95% confidence interval [CI] = 2.07, 3.35) in 1993 to 0.25 infections per 100 person-years (95% CI = 0.21, 0.29) in 2011. Rates declined sharply in the 1990s and declined more gradually in the 2000s. Incidence declined with age; highest incidence rates were among those aged 15 to 24 years. Incidence among male repeat testers exceeded that of female repeat testers across all years, although the gap narrowed over time. CONCLUSIONS: Addictions treatment, harm reduction, prevention education, and novel initiatives to remove barriers in health infrastructure need to be intensified for those who inject drugs, particularly men and younger persons.

Genetic determinants of cocaine-associated agranulocytosis.

BACKGROUND: Drug-induced agranulocytosis is a recognized adverse drug event associated with serious infectious complications. Levamisole is an antihelminthic and immunomodulator withdrawn from North American markets in 2005 after reports of agranulocytosis. Previous studies of levamisole, suggest that the human leukocyte antigen (HLA)-B27 confers a genetic predisposition to this adverse drug event. Since 2009, emergency room visits due to agranulocytosis in individuals consuming levamisole-adulterated crack-cocaine have increased. METHODS: We performed a case-control study using a genotyping assay and novel gene chip to test the association between cocaine-associated agranulocytosis (CAA) and HLA-B27 and to identify pharmacokinetic and pharmacodynamic gene variants associated with the phenotype. RESULTS: Fifty-one CAA cases were identified through a provincial physician reporting system between 2008 and 2011. We examined eight of these cases and 26 matched controls. Genotyping revealed a significant association between HLA-B27 and CAA (odds ratio [OR] 9.2, 95% confidence interval [CI], 1.54-54.6). We also observed a similar association with the HLA-B27 tag single nucleotide polymorphism rs4349859 (OR 9.2, 95% CI 1.5-54.6) and rs13202464 (OR 6.7, 95% CI 1.1-41). Further associations were identified with variants in the ARBCC12 (OR 10.0, 95% CI 2.7-36.8) and CYP11A1 (OR 7.4, 95% CI 2.1-26.6) genes, while a novel protective association was observed with variants in the ARDB1 gene (OR 0.06, 95% CI 0.007-0.46). CONCLUSIONS: We confirmed the association of HLA-B27 with CAA and identified additional susceptibility variants. Health care providers should inform people who are identified as having CAA that it is genetically determined and can recur with continued cocaine use. The severity of infections and subsequent hospitalization, and the risk of recurrence may prompt health-promoting behaviour changes of the affected individuals. These genetic associations warrant the attention of public health and knowledge translation efforts to highlight the implications for susceptibility to this severe adverse drug event.

Test uptake and case detection of syphilis, HIV, and hepatitis C among women undergoing prenatal screening in British Columbia, 2007 to 2011.

OBJECTIVE: Test uptake and case detection trends for rubella, syphilis, HIV, and hepatitis C (HCV) were compared among the 2007 to 2011 cohort of women undergoing prenatal testing in British Columbia. Analysis involved linkage of provincially centralized laboratory and surveillance data to assess prenatal test uptake and rates of newly diagnosed versus prevalent infections. METHODS: We included prenatal specimens submitted from BC women aged 16 to 45 years in 2007 to 2011. Laboratory records were linked to provincial surveillance systems to identify confirmed maternal syphilis and HIV cases. Previous positive status was determined for HIV and HCV if a prior confirmed case was identified from laboratory records. We determined rates of HIV and HCV newly identified at prenatal screening (new diagnoses per 100 000 per year). Prevalence for HIV and HCV was the sum of all new and prior diagnoses (prevalence per 100 000 per year). RESULTS: Of 233 203 women, 96.9% were screened for rubella, 93.3% for syphilis, 93.8% for HIV, and 21.5% for HCV. From 2007 to 2011, the overall rates of new diagnoses were 15.4, 5.1, and 82.8 cases per 100 000 per year for syphilis, HIV, and HCV, respectively. The overall prevalence was 45.9 and 551.5 cases per 100 000 per year for HIV and HCV, respectively (0.05% and 0.6%). From 2007 to 2011, new diagnoses of HCV decreased 40% from 106.0 to 62.1 cases per 100 000 per year. HCV prevalence did not change and increased with maternal age. CONCLUSION: This study links surveillance and laboratory data to provide a provincial picture of prenatal screening test uptake and case detection, with the advantage of distinguishing new from prior diagnoses. This information can help guide prenatal communicable disease screening policy.

Objectif : La mesure dans laquelle les tests de dépistage de la rubéole, de la syphilis, du VIH et de l'hépatite C (VHC) ont été utilisés et les tendances en ce qui concerne la détection de cas de ces maladies ont été comparées, entre 2007 et 2011, chez les cohortes de femmes faisant l'objet d'un dépistage prénatal en Colombie-Britannique. L'analyse a mis en jeu le croisement de données de surveillance et de laboratoire centralisées à l'échelle provinciale, afin de déterminer la mesure dans laquelle les tests de dépistage prénatal ont été utilisés et de comparer le taux d'infections nouvellement diagnostiquées au taux d'infections prévalentes. Méthodes : Nous avons inclus les prélèvements prénataux, issus de Britanno-colombiennes âgées de 16 à 45 ans, qui ont été soumis au cours de la période allant de 2007 à 2011. Les dossiers de laboratoire ont été liés aux systèmes de surveillance provinciaux en vue d'identifier les cas maternels confirmés de syphilis et de VIH. La présence d'un statut de séropositivité préalable a été établie, pour ce qui est du VIH et du VHC, en ce qui concerne les cas préalablement confirmés ayant été identifiés à partir des dossiers de laboratoire. Nous avons déterminé les taux d'infections au VIH et au VHC nouvellement identifiées au moment du dépistage prénatal (nouveaux diagnostics par 100 000 par année). La prévalence du VIH et du VHC équivalait à la somme de tous les diagnostics, tant nouveaux que préalables (prévalence par 100 000 par année). Résultats : Chez 233 203 femmes, 96,9 % ont fait l'objet d'un dépistage visant la rubéole, 93,3 % ont fait l'objet d'un dépistage visant la syphilis, 93,8 % ont fait l'objet d'un dépistage visant le VIH et 21,5 % ont fait l'objet d'un dépistage visant le VHC. Entre 2007 et 2011, les taux globaux de nouveaux diagnostics ont été de 15,4, de 5,1 et de 82,8 cas par 100 000 par année pour ce qui est de la syphilis, du VIH et du VHC, respectivement. La prévalence globale était de 45,9 et de 551,5 cas par 100 000 par année pour ce qui est du VIH et du VCH, respectivement (0,05 % et 0,6 %). Entre 2007 et 2011, les nouveaux diagnostics de VHC ont connu une baisse de 40 % en passant de 106,0 à 62,1 cas par 100 000 par année. La prévalence du VHC n'a pas connu de fluctuation et nous avons constaté que celle des anticorps anti-VHC augmentait en fonction de l'âge maternel. Conclusion : Cette étude a procédé au croisement des données de surveillance et de laboratoire afin de pouvoir brosser un tableau provincial de la mesure dans laquelle les tests de dépistage prénatal ont été utilisés et de la détection de cas qui s'en est suivie, le tout s'accompagnant de l'avantage de pouvoir distinguer les nouveaux diagnostics des diagnostics préalables. Ces renseignements pourront contribuer à orienter la politique de dépistage prénatal des maladies transmissibles.