Cohort study of team-based care among marginalized people who use drugs in Ottawa.

OBJECTIVE: To describe team-based care use among a cohort of people who use drugs (PWUD) and to determine factors associated with receipt of team-based care. DESIGN: A cohort study using survey data collected between March and December 2013. These data were then linked to provincial-level health administrative databases to assess patterns of primary care among PWUD in the 2 years before survey completion. SETTING: Ottawa, Ont. PARTICIPANTS: Marginalized PWUD 16 years of age or older. MAIN OUTCOME MEASURES: Patients were assigned to primary care models based on survey responses and then were categorized as attached to team-based medical homes, attached to non-team-based medical homes, not attached to a medical home, and no primary care. Descriptive statistics and multinomial logistic regression were used to determine associations between PWUD and medical home models. RESULTS: Of 663 total participants, only 162 (24.4%) received team-based care, which was associated with high school level of education (adjusted odds ratio [AOR] = 2.18; 95% CI 1.13 to 4.20), receipt of disability benefits (AOR = 2.47; 95% CI 1.22 to 5.02), and HIV infection (AOR = 2.88; 95% CI 1.28 to 6.52), and was inversely associated with recent overdose (AOR = 0.49; 95% CI 0.25 to 0.94). In comparison, 125 (18.8%) received non-team-based medical care, which was associated with university or college education (AOR = 2.31; 95% CI 1.04 to 5.15) and mental health comorbidity (AOR = 4.18; 95% CI 2.33 to 7.50), and was inversely associated with being detained in jail in the previous 12 months (AOR = 0.51; 95% CI 0.28 to 0.90). CONCLUSION: Although team-based, integrated models of care will benefit disadvantaged groups the most, few PWUD receive such care. Policy makers should mitigate barriers to physician care and improve integration across health and social services.

Eliminating Structural Barriers: The Impact of Unrestricted Access on Hepatitis C Treatment Uptake Among People Living With Human Immunodeficiency Virus.

BACKGROUND: High costs of direct-acting antivirals (DAAs) have led health-care insurers to limit access worldwide. Using a natural experiment, we evaluated the impact of removing fibrosis stage restrictions on hepatitis C (HCV) treatment initiation rates among people living with human immunodeficiency virus (HIV), and then examined who was left to be treated. METHODS: Using data from the Canadian HIV-HCV Coinfection Cohort, we applied a difference-in-differences approach. Changes in treatment initiation rates following the removal of fibrosis stage restrictions were assessed using a negative binomial regression with generalized estimating equations. The policy change was then specifically assessed among people who inject drugs (PWID). We then identified the characteristics of participants who remained to be treated using a modified Poisson regression. RESULTS: Between 2010-2018, there were a total of 585 HCV initiations among 1130 eligible participants. After removing fibrosis stage restrictions, DAA initiations increased by 1.8-fold (95% confidence interval [CI] 1.3-2.4) controlling for time-invariant differences and secular trends. Among PWID the impact appeared even stronger, with an adjusted incidence rate ratio of 3.6 (95% CI 1.8-7.4). However, this increased treatment uptake was not sustained. At 1 year following universal access, treatment rates declined to 0.8 (95% CI .5-1.1). Marginalized participants (PWID and those of indigenous ethnicity) and those disengaged from care were more likely to remain HCV RNA positive. CONCLUSIONS: After the removal of fibrosis restrictions, HCV treatment initiations nearly doubled immediately, but this treatment rate was not sustained. To meet the World Health Organization elimination targets, the minimization of structural barriers and adoption of tailored interventions are needed to engage and treat all vulnerable populations.

Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies.

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.

Antibiotic use among twelve Canadian First Nations communities: a retrospective chart review of skin and soft tissue infections.

BACKGROUND: Previous publications indicated an emerging issue with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), particularly skin and soft tissue infections (SSTIs), in Indigenous communities in Canada. The objectives of this analysis were to explore the prevalence of SSTIs due to CA-MRSA and patterns of antimicrobial use in the community setting. METHODS: A retrospective chart review was conducted as part of an environmental scan to assess antibiotic prescriptions in 12 First Nations communities across five provinces in Canada including Alberta, Saskatchewan, Manitoba, Ontario, and Québec. Charts were randomly selected from nursing stations and patients who had accessed care in the previous 12 months and were ≥ 18 years were included in the review. Data was collected from September to December, 2013 on antibiotic prescriptions, including SSTIs, clinical symptoms, diagnostic information including presence of CA-MRSA infection, and treatment. RESULTS: A total of 372 charts were reviewed, 60 from Alberta, 70 from Saskatchewan, 120 from Manitoba, 100 from Ontario, and 22 from Québec. Among 372 patients, 224 (60.2%) patients had at least one antibiotic prescription in the previous 12 months and 569 prescriptions were written in total. The prevalence of SSTIs was estimated at 36.8% (137 cases of SSTIs in 372 charts reviewed). In 137 cases of SSTIs, 34 (24.8%) were purulent infections, and 55 (40.2%) were due to CA-MRSA. CONCLUSIONS: This study has identified a high prevalence of antibiotic use and SSTIs due to CA-MRSA in remote and isolated Indigenous communities across Canada. This population is currently hard to reach and under-represented in standard surveillance system and randomized retrospective chart reviews can offer complimentary methodology for monitoring disease burden, treatment and prevention.

Applying principles of injury and infectious disease control to the opioid mortality epidemic in North America: critical intervention gaps.

North America has been experiencing an acute and unprecedented public health crisis involving excessive and increasing levels of opioid-related overdose mortality. In the present commentary, we examine current interventions (as existent mainly in Canada) to date and compare them against established intervention frameworks and practices in other areas of public health, specifically injury and infectious disease control. We observe that current interventions focusing on opioid drug safety or exposure-specifically those that focus on distinctly potent and toxic opioid products driving major increases in overdose mortality-may be considered the equivalent of 'agent-' or 'vector'-based interventions. Such interventions have been largely neglected in favor of 'host' (e.g., drug user-oriented) or 'environmental' measures among strategies to reduce opioid-related overdose, likely contributing to the limited efficacy of current measures. We explore potential reasons, implications and remedies for these gaps in the overall public health strategy employed towards improved interventions to reduce opioid-related health harms.

Correlations between opioid mortality increases related to illicit/synthetic opioids and reductions of medical opioid dispensing - exploratory analyses from Canada.

BACKGROUND: North America has been experiencing a persistent epidemic of opioid-related overdose mortality, which has increasingly been driven by fatalities from illicit, toxic opioids in most recent years. Patterns of synthetic opioid availability and related mortality are heterogeneous across Canada, and differing explanations exist as to their differentiated proliferation. We examined the perspective that heterogeneous province-based variations in prescription opioid availability, facilitated by various control strategies, post-2010 may have created regionally differential supply gaps for non-medical opioid use substituted by synthetic opioid products with differential impacts on mortality risks and outcomes in Canada. METHODS: We examined annual, prescription opioid dispensing rates and changes in the ten Canadian provinces (for the periods of 1) 2011-2018, 2) 'peak-year'-to-2018) in Defined Daily Doses/1000 population/day, derived from data from a large representative, stratified sample of community pharmacies projected to a Canada total. Annual, provincial opioid-related mortality rates and changes for years 2016-2018 were calculated from federal data. We computed correlation values (Pearson's R) between respective province-based change rates for prescription opioid dispensing and opioid-related mortality for the two over-time scenarios. RESULTS: All but one province featured reductions in prescription opioid dispensing 2011-2018; seven of the ten provinces had increases in opioid mortality 2016-2018. The correlation between changes in opioid dispensing (2011-2018) and in opioid-mortality (2016-2018) was r = 0.63 (df = 8, p-value: 0.05); the correlation was r = 0.57 (df = 8, p-value: 0.09) for changes in opioid dispensing 'peak year'-to-2018, respectively. CONCLUSIONS: Quasi-significant results indicate that recent increases in opioid-related deaths driven by illicit, synthetic opioids tended to be larger in provinces where reductions in prescription opioid availability have been more extensive. It is a plausible explanation that these reductions created supply gaps for non-medical opioid use increasingly filled by illicit, synthetic opioids differentially contributing to opioid-related deaths, generating un-intended adverse effects for previous interventions. General prevention measures to reduce opioid availability, and targeted prevention for at-risk opioid users exposed to toxic drug supply may be include counteractive effects and require coordinated reconciliation.

Engagement in primary health care among marginalized people who use drugs in Ottawa, Canada.

BACKGROUND: There may be less primary health care engagement among people who use drugs (PWUD) than among the general population, even though the former have greater comorbidity and more frequent use of emergency department care. We investigated factors associated with primary care engagement among PWUD. METHODS: The Participatory Research in Ottawa: Understanding Drugs (PROUD) cohort study meaningfully engaged and trained people with lived experience to recruit and survey marginalized PWUD between March-December 2013. We linked this survey data to provincial-level administrative databases held at ICES. We categorized engagement in primary care over the 2 years prior to survey completion as: not engaged (< 3 outpatient visits to the same family physician) versus engaged in care (3+ visits to the same family physician). We used multivariable logistic regression to determine factors associated with engagement in primary care. RESULTS: Characteristics of 663 participants included a median age of 43 years, 76% men, and 67% living in the two lowest income quintile neighborhoods. Despite high comorbidity and a median of 4 (interquartile range 0-10) primary care visits in the year prior to survey completion, only 372 (56.1%) were engaged in primary care. Engagement was most strongly associated with the following factors: receiving provincial benefits, including disability payments (adjusted odds ratio [AOR] 4.14 (95% confidence interval [CI] 2.30 to 7.43)) or income assistance (AOR 3.69 (95% CI 2.00 to 6.81)), having ever taken methadone (AOR 3.82 (95% CI 2.28 to 6.41)), mental health comorbidity (AOR 3.43 (95% CI 2.19 to 5.38)), and having stable housing (AOR 2.09 (95% CI 1.29 to 3.38)). CONCLUSIONS: Despite high comorbidity, engagement in primary care among PWUD was low. Our findings suggest that social care (housing, disability, and income support) and mental health care are associated with improved primary care continuity; integration of these care systems with primary care and opioid substitution therapy may lessen the significant morbidity and acute care use among PWUD.

The Consensus Hepatitis C Cascade of Care: Standardized Reporting to Monitor Progress Toward Elimination.

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate, in simple terms, the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of individuals with HCV to diagnosis, treatment, and cure. The value of reporting would be enhanced if a standardized approach were used for generating CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway, and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and for ensuring accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets.

Sustained virological response from interferon-based hepatitis C regimens is associated with reduced risk of extrahepatic manifestations.

BACKGROUND & AIMS: HCV infection is associated with several extrahepatic manifestations (EHMs). We evaluated the impact of sustained virological response (SVR) on the risk of 7 EHMs that contribute to the burden of extrahepatic disease: type 2 diabetes mellitus, chronic kidney disease or end-stage renal disease, stroke, ischemic heart disease, major adverse cardiac events, mood and anxiety disorders, and rheumatoid arthritis. METHODS: A longitudinal cohort study was conducted using data from the British Columbia Hepatitis Testers Cohort, which included ~1.3 million individuals screened for HCV. We identified all HCV-infected individuals who were treated with interferon-based therapies between 1999 and 2014. SVR was defined as a negative HCV RNA test ≥24 weeks post-treatment or after end-of-treatment, if unavailable. We computed adjusted subdistribution hazard ratios (asHR) for the effect of SVR on each EHM using competing risk proportional hazard models. Subgroup analyses by birth cohort, sex, injection drug exposure and genotype were also performed. RESULTS: Overall, 10,264 HCV-infected individuals were treated with interferon, of whom 6,023 (59%) achieved SVR. Compared to those that failed treatment, EHM risk was significantly reduced among patients with SVR for type 2 diabetes mellitus (asHR 0.65; 95%CI 0.55-0.77), chronic kidney disease or end-stage renal disease (asHR 0.53; 95% CI 0.43-0.65), ischemic or hemorrhagic stroke (asHR 0.73; 95%CI 0.49-1.09), and mood and anxiety disorders (asHR 0.82; 95%CI 0.71-0.95), but not for ischemic heart disease (asHR 1.23; 95%CI 1.03-1.47), major adverse cardiac events (asHR 0.93; 95%CI 0.79-1.11) or rheumatoid arthritis (asHR 1.09; 95% CI 0.73-1.64). CONCLUSIONS: SVR was associated with a reduction in the risk of several EHMs. Increased uptake of antiviral therapy may reduce the growing burden of EHMs in this population. LAY SUMMARY: We estimated the rates of chronic comorbidities other than liver disease between those who were cured and those who failed treatment for hepatitis C virus (HCV) infection. Our findings showed that the rates of these non-liver diseases were largely reduced for those who were cured with interferon-based treatments. Early HCV treatments could provide many benefits in the prevention of various HCV complications beyond liver disease.

Applying core theory and spatial analysis to identify hepatitis C virus infection "core areas" in British Columbia, Canada.

"Core areas" of transmission for bacterial sexually transmitted infections have been identified. However, it is unclear whether core areas apply to viral infections, such as hepatitis C virus (HCV). We used geographic mapping and spatial analysis to identify distinct core areas of HCV infection in British Columbia (BC) using the BC Hepatitis Testers Cohort (BC-HTC), 1990-2013. The BC-HTC includes all BC residents tested for HCV (~1.5 million; 1990-2013). Core HCV infection areas were identified spatially and temporally for five time periods (1990-1993, 1994-1998, 1999-2003, 2004-2008 and 2009-2013) through thematic mapping, Kernel Density Estimation, Hotspot analysis and cluster analysis at the Census dissemination area level in ArcGIS and SatScan. HCV infection core areas were consistently identified. HCV core areas expanded from the downtown of major cities in different regions of BC (Metro Vancouver, Vancouver Island, and Northern BC; 1990-1998), to smaller cities in Metro Vancouver and Interior BC (2000 onwards). Statistically significant clusters, or hotspots, were also observed for downtown Vancouver, Northern BC (Prince George) and Vancouver Island from 1990 to 2008 with expansion to other urban areas in Metro Vancouver from 1990-2013. Statistically significant clusters persisted after adjustment for injection drug use, number of HCV tests, age, sex, material and social deprivation. Persistence of areas with high HCV diagnoses rates in Vancouver and Prince George supports the theory of core areas of HCV transmission. Identification of core areas can inform prevention, care and treatment programme interventions and evaluate their impact over time.

Characteristics of Gay, Bisexual and Other Men Who Have Sex With Men With Multiple Diagnoses of Infectious Syphilis in British Columbia, Canada, 2005-2014.

BACKGROUND: Infectious syphilis has increased substantially over the past decade. Targeting limited public health resources toward subpopulations with multiple reinfections may have a large impact in reducing onward transmission within a community. METHODS: A chart review was conducted for individuals with 4 or more infectious syphilis diagnoses between 2005 and 2014 (the top 1% of all syphilis diagnoses in British Columbia, Canada). We characterized the sociodemographics, partner notification outcomes and social network. RESULTS: Between 2005 and 2014, there were 30 individuals with 4 or more syphilis diagnoses, accounting for 139 diagnoses. All were men who have sex with men and 29 (96%) were human immunodeficiency virus-positive. Of the 139 diagnoses, 65% occurred in the early latent stage of infection, 22% in the secondary stage, and 14% in the primary stage. The median number of sexual partners per diagnosis was 5 (range, 1-50). Among the 838 partners reported, 79% were notifiable, 53% were notified, and 23% were reported to be tested or treated. Sexual network mapping showed that almost half of the members of this group could be linked to one another either directly or indirectly via partners over 10 years. Social network mapping demonstrated high connectivity, with 4 venues associated with almost two thirds of the study population. CONCLUSIONS: The connectivity and recurrent diagnoses in this study population suggest potential benefits of targeted interventions to individuals with multiple diagnoses and their partners. Our study highlights the need for enhanced care, increased syphilis testing frequency, and exploring alternative preventative methods among individuals with syphilis rediagnoses to reduce syphilis incidence.

The population level care cascade for hepatitis C in British Columbia, Canada as of 2018: Impact of direct acting antivirals.

BACKGROUND: Population-level monitoring of hepatitis C virus (HCV) infected people across cascades of care identifies gaps in access and engagement in care and treatment. We characterized the population-level care cascade for HCV in British Columbia (BC), Canada before and after introduction of Direct Acting Antiviral (DAA) treatment. METHODS: BC Hepatitis Testers Cohort (BC-HTC) includes 1.7 million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2018 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV care cascade stages: (a) antibody diagnosed; (b) RNA tested; (c) RNA positive; (d) genotyped; (e) initiated treatment; and (f) achieved sustained virologic response (SVR). RESULTS: We estimated 61 127 people were HCV antibody positive in BC in 2018 (undiagnosed: 7686, 13%; diagnosed: 53 441, 87%). Of those diagnosed, 83% (44 507) had HCV RNA testing, and of those RNA positive, 90% (28 716) were genotyped. Of those genotyped, 61% (17 441) received therapy, with 90% (15 672) reaching SVR. Individuals from older birth cohorts had lower progression to HCV RNA testing. While people who currently inject drugs had the highest proportional progression to RNA testing, this group had the lowest proportional treatment uptake. CONCLUSIONS: Although gaps in HCV RNA and genotype testing after antibody diagnosis exist, the largest gap in the care cascade is treatment initiation, despite introduction of DAA treatment and removal of treatment eligibility restrictions. Further interventions are required to ensure testing and treatment is equitably accessible in BC.

Hepatitis C Testing, Status and Treatment among Marginalized People Who Use Drugs in an Inner City Setting: An Observational Cohort Study.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is common among people who inject drugs (PWID) and is associated with morbidity and premature death. Although HCV can be cured, treatment may be inaccessible. We studied HCV testing, status and treatment among marginalized people who use drugs in Ottawa, Canada, a setting with universal insurance coverage for physician services. METHODS: We analyzed data from the Participatory Research in Ottawa: Understanding Drugs study, a cross-sectional, peer-administered survey of people who use drugs from 2012 to 2013. We linked responses to population-based health administrative databases and used multivariable Poisson regression to identify factors independently associated with self-reported HCV testing, self-reported positive HCV status, and database-determined engagement in HCV treatment. RESULTS: Among 663 participants, 562 (84.8%) reported testing for HCV and 258 (45.9%) reported HCV-positive status. In multivariable analysis, HCV-positive status was associated with female gender (RR 1.27; 95%CI 1.04 to 1.55), advancing age (RR 1.03/year; 95%CI 1.02 to 1.04), receiving disability payments (RR 1.42; 95%CI 1.06 to 1.91), injecting drugs (RR 5.11; 95%CI 2.64 to 9.91), ever injecting with a used needle (RR 1.30; 95%CI 1.12 to 1.52), and ever having taken methadone (RR 1.26; 95%CI 1.05 to 1.52). Of HCV positive participants, 196 (76%) were engaged in primary care but only 23 (8.9%) had received HCV therapy. Conclusions/Importance: Although HCV testing and positive status rates are high among PWID in our study, few have received HCV treatment. Innovative initiatives to increase access to HCV treatment for PWID are urgently needed.

Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort.

BACKGROUND & AIMS: Direct-acting antiviral therapies (DAA) are an important tool for hepatitis C virus (HCV) elimination. However, reinfection among people who inject drugs (PWID) may hamper elimination targets. Therefore, we estimated HCV reinfection rates among DAA-treated individuals, including PWID. METHODS: We analyzed data from the British Columbia Hepatitis Testers Cohort which included ∼1.7 million individuals screened for HCV in British Columbia, Canada. We followed HCV-infected individuals treated with DAAs who achieved a sustained virologic response (SVR) and had ≥1 subsequent HCV RNA measurement to April 22nd, 2018. Reinfection was defined as a positive RNA measurement after SVR. PWID were identified using a validated algorithm and classified based on recent (<3 years) or former (≥3 years before SVR) use. Crude reinfection rates per 100 person-years (PYs) were calculated. Poisson regression was used to model adjusted incidence rate ratios (IRRs) and 95% CIs. RESULTS: Of 4,114 individuals who met the inclusion criteria, most were male (n = 2,692, 65%), born before 1965 (n = 3,411, 83%) and were either recent (n = 875, 21%) or former PWID (n = 1,793, 44%). Opioid-agonist therapy (OAT) was received by 19% of PWID. We identified 40 reinfections during 2,767 PYs. Reinfection rates were higher among recent (3.1/100 PYs; IRR 6.7; 95% CI 1.9-23.5) and former PWID (1.4/100 PYs; IRR 3.7; 95% CI 1.1-12.9) than non-PWID (0.3/100 PYs). Among recent PWID, reinfection rates were higher among individuals born after 1975 (10.2/100 PYs) and those co-infected with HIV (5.7/100 PYs). Only one PWID receiving daily OAT developed reinfection. CONCLUSIONS: Population-level reinfection rates remain elevated after DAA therapy among PWID because of ongoing exposure risk. Engagement of PWID in harm-reduction and support services is needed to prevent reinfections. LAY SUMMARY: Direct-acting antivirals are an effective tool for the treatment of hepatitis C virus, enabling the elimination of the virus. However, some patients who have been successfully treated with direct-acting antivirals are at risk of reinfection. Our findings showed that the risk of reinfection was highest among people with recent injection drug use. Among people who inject drugs, daily use of opioid-agonist therapy was associated with a lower risk of reinfection.

Estimating the impact of early hepatitis C virus clearance on hepatocellular carcinoma risk.

Although achieving sustained virological response (SVR) through antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) attributable to hepatitis C virus (HCV) infection, the impact of early viral clearance on HCC is not well defined. In this study, we compared the risk of HCC among individuals who spontaneously cleared HCV (SC), the referent population, with the risk in untreated chronic HCV (UCHC), those achieved SVR, and those who failed interferon-based treatment (TF). The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV between 1990-2013, integrated with medical visits, hospitalizations, cancers, prescription drugs and mortality data. This analysis included all HCV-positive patients with at least one valid HCV RNA by PCR on or after HCV diagnosis. Of 46 666 HCV-infected individuals, there were 12 527 (26.8%) SC; 24 794 (53.1%) UCHC; 5355 (11.5%) SVR and 3990 (8.5%) TF. HCC incidence was lowest (0.3/1000 person-years (PY)) in the SC group and highest in the TF group (7.7/1000 PY). In a multivariable model, compared to SC, TF had the highest HCC risk (hazard ratio (HR):14.52, 95% confidence interval (CI): 9.83-21.47), followed by UCHC (HR: 5.85; 95% CI: 4.07-8.41). Earlier treatment-based viral clearance similar to SC could decrease HCC incidence by 69.4% (95% CI: 57.5-78.0), 30% (95% CI: 10.8-45.1) and 77.5% (95% CI: 69.4-83.5) among UCHC, SVR and TF patients, respectively. In conclusion, using SC as a real-world comparator group, it showed that substantial reduction in HCC risk could be achieved with earlier treatment initiation. These analyses should be replicated in patients who have been treated with direct acting antiviral therapies.

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.

Cocaine/crack use is not associated with fibrosis progression measured by AST-to-Platelet Ratio Index in HIV-HCV co-infected patients: a cohort study.

BACKGROUND: Cocaine and crack use has been associated with HIV and HCV infections, but its consequences on HCV progression have not been well established. We analyzed the impact of cocaine/crack use on liver fibrosis progression in a cohort of HIV-HCV co-infected patients. METHODS: A Canadian multicenter prospective cohort study followed 1238 HIV-HCV co-infected persons every 6 months between 2003 and 2013. Data were analyzed from 573 patients with positive HCV RNA, not on HCV treatment, without significant liver fibrosis (AST-to-Platelet Ratio Index (APRI) <1.5) or history of end-stage liver disease at baseline, and having at least two study visits. Recent cocaine/crack use was defined as use within 6 months of cohort entry. Incidence rates of progression to significant fibrosis (APRI ≥ 1.5) were determined according to recent cocaine/crack use. Cox Proportional Hazards models were used to assess the association between time-updated cocaine/crack use and progression to APRI ≥ 1.5 adjusting for age, sex, HCV duration, baseline ln(APRI), and time-updated alcohol abuse, history of other drug use and CD4+ cell count. RESULTS: At baseline, 211 persons (37%) were recent cocaine/crack users and 501 (87%) ever used cocaine/crack. Recent users did not differ from non-recent users on gender, age, and CD4+ T-cell count. Over 1599 person-years of follow up (522 PY in recent users, 887 PY in previous users and 190 PY in never users),158 (28%) persons developed significant fibrosis (9.9/100 PY; 95% CI, 8.3-11.4); 56 (27%) recent users (10.7/100 PY; 7.9-13.5), 81 (28%) previous users (9.1/100 PY; 7.1-11.1), and 21 (29%) never users (11.1/100 PY; 6.3-15.8). There was no association between ever having used or time-updated cocaine/crack use and progression to APRI ≥ 1.5 (adjusted HR (95%CI): 0.96 (0.58, 1.57) and 0.88;(0.63-1.25), respectively). CONCLUSIONS: We could not find evidence that cocaine/crack use is associated with progression to advanced liver fibrosis in our prospective study of HIV-HCV co-infected patients.

Use of GetCheckedOnline, a Comprehensive Web-based Testing Service for Sexually Transmitted and Blood-Borne Infections.

BACKGROUND: The British Columbia Centre for Disease Control implemented a comprehensive Web-based testing service GetCheckedOnline (GCO) in September 2014 in Vancouver, Canada. GCO's objectives are to increase testing for sexually transmitted and blood-borne infections (STBBIs), reach high-prevalence populations facing testing barriers, and increase clinical STI service capacity. GCO was promoted through email invitations to provincial STI clinic clients, access codes to clients unable to access immediate clinic-based testing (deferred testers), and a campaign to gay, bisexual, and other men who have sex with men (MSM). OBJECTIVE: The objective of the study was to report on characteristics of GCO users, use and test outcomes (overall and by promotional strategy) during this pilot phase. METHODS: We used GCO program data, website metrics, and provincial STI clinic records to describe temporal trends, progression through the service pathway, and demographic, risk, and testing outcomes for individuals creating GCO accounts during the first 15 months of implementation. RESULTS: Of 868 clients creating accounts, 318 (36.6%) submitted specimens, of whom 96 (30.2%) tested more than once and 10 (3.1%) had a positive STI diagnosis. The proportion of clients submitting specimens increased steadily over the course of the pilot phase following introduction of deferred tester codes. Clients were diverse with respect to age, gender, and ethnicity, although youth and individuals of nonwhite ethnicity were underrepresented. Of the 506 clients completing risk assessments, 215 (42.5%) were MSM, 89 (17.6%) were symptomatic, 47 (9.3%) were STI contacts, 232 (45.8%) reported condomless sex, 146 (28.9%) reported ≥4 partners in the past 3 months, and 76 (15.0%) reported a recent STI. A total of 63 (12.5%) GCO clients were testing for the first time. For 868 accounts created, 337 (38.8%) were by clinic invitations (0 diagnoses), 298 (34.3%) were by deferred testers (6 diagnoses), 194 (22.4%) were by promotional campaign (3 diagnoses), and 39 (4.5%) were by other means (1 diagnosis). CONCLUSIONS: Our evaluation suggests that GCO is an acceptable and feasible approach to engage individuals in testing. Use by first-time testers, repeated use, and STI diagnosis of individuals unable to access immediate clinic-based testing suggest GCO may facilitate uptake of STBBI testing and earlier diagnosis. Use by MSM and individuals reporting sexual risk suggests GCO may reach populations with a higher risk of STI. Motivation to test (eg, unable to access clinical services immediately) appears a key factor underlying GCO use. These findings identify areas for refinement of the testing model, further promotion, and future research (including understanding reasons for drop-off through the service pathway and more comprehensive evaluation of effectiveness). Increased uptake and diagnosis corresponding with expansion of the service within British Columbia will permit future evaluation of this service across varying populations and settings.

A cohort study examining emergency department visits and hospital admissions among people who use drugs in Ottawa, Canada.

BACKGROUND: The health of people who use drugs (PWUD) is characterized by multimorbidity and chronicity of health conditions, necessitating an understanding of their health care utilization. The objective of this study was to evaluate emergency department (ED) visits and hospital admissions among a cohort of PWUD. METHODS: We used a retrospective observational design between 2012 and 2013. The population was a marginalized cohort of PWUD (the PROUD study) for whom survey data was linked (n = 663) to provincial health administrative data housed at the Institute for Clinical Evaluative Sciences. We constructed a 5:1 comparison group matched by age, sex, income quintile, and region. The main outcomes were defined as having two or more ED visits, or one or more hospital admissions, in the year prior to survey completion. We used multivariable logistic regression analyses to identify factors associated with these outcomes. RESULTS: Compared to the matched cohort, PWUD had higher rates of ED visits (rate ratio [RR] 7.0; 95% confidence interval [95% CI] 6.5-7.6) and hospitalization (RR 7.7; 95% CI 5.9-10.0). After adjustment, factors predicting more ED visits were receiving disability (adjusted odds ratio [AOR] 3.0; 95% CI 1.7-5.5) or income assistance (AOR 2.7; 95% CI 1.5-5.0), injection drug use (AOR 2.1; 95% CI 1.3-3.4), incarceration within 12 months (AOR 1.6; 95% CI 1.1-2.4), mental health comorbidity (AOR 2.1; 95% CI 1.4-3.1), and a suicide attempt within 12 months (AOR 2.1; 95% CI 1.1-3.4). Receiving methadone (AOR 0.5; 95% CI 0.3-0.9) and having a regular family physician (AOR 0.5; 95% CI 0.2-0.9) were associated with lower odds of having more ED visits. Factors associated with more hospital admissions included Aboriginal identity (AOR 2.4; 95% CI 1.4-4.1), receiving disability (AOR 2.4; 95% CI 1.1-5.4), non-injection drug use (opioids and non-opioids) (AOR 2.2; 95% CI 1.1-4.4), comorbid HIV (AOR 2.4; 95% CI 1.2-5.6), mental health comorbidity (AOR 2.4; 95% CI 1.3-4.2), and unstable housing (AOR 1.9; 95% CI 1.0-3.4); there were no protective factors for hospitalization. CONCLUSIONS: Improved post-incarceration support, housing services, and access to integrated primary care services including opioid replacement therapy may be effective interventions to decrease acute care use among PWUD, including targeted approaches for people receiving social assistance or with mental health concerns.