Increasing Treatment Rates for Hepatitis C in Primary Care.

BACKGROUND: Despite antiviral agents that can cure the disease, many individuals with Hepatitis C Virus (HCV) remain untreated. Primary care clinicians can play an important role in HCV treatment but often feel they do not have the requisite skills. METHODS: We implemented a population-based improvement intervention over 10 months to support treatment of HCV in a primary care setting. The intervention included a decision-support tool, education for clinicians, enhanced interprofessional team supports, mentorship, and proactive patient outreach. We used process and outcome measures to understand the impact on the proportion of patients who initiated treatment and achieved Sustained Virologic Response (SVR). We used physician focus groups and pharmacist interviews to understand the context and mechanisms influencing the impact of the intervention. RESULTS: Between December 2018 and June 2020, the percentage of HCV RNA positive patients who started treatment rose from 66.0% (354/536) to 75.5% (401/531) with 92.5% (371/401) of those starting treatment achieving SVR. Qualitative findings highlighted that the intervention helped raise awareness and confidence among physicians for treating HCV in primary care. A collaborative team environment, education, mentorship, and a decision-support tool integrated into the electronic record were all enablers of success although patient psychosocial complexity remained a barrier to engagement in treatment. CONCLUSION: A multifaceted primary care improvement initiative increased clinician confidence and was associated with an increase in the proportion of HCV RNA positive patients who initiated curative treatment.

Requiring help injecting among people who inject drugs in Toronto, Canada: Characterising the need to address sociodemographic disparities and substance-use specific patterns.

INTRODUCTION: Those requiring help injecting are at an elevated risk of injection-related injury and blood-borne infections and are thus a priority group for harm reduction programs. As supervised consumption services (SCS) are scaled-up across Canada, information on those who require help injecting is necessary to inform equitable service uptake. We characterised the sociodemographic, structural and drug use correlates of needing help injecting among a cohort of people who inject drugs in Toronto, Canada. METHODS: A cross-sectional baseline survey was administered between November 2018 and March 2020. Unadjusted and multivariable logistic regression models examined associations with requiring help injecting in the past 6 months. A gender-stratified sub-analysis described characteristics of receiving help among those requiring it. RESULTS: Of 701 participants (31.0% cisgender women), 294 (41.9%) needed recent help injecting. In unadjusted analyses, being a racialised, non-Indigenous person (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.13-2.86) or a cisgender woman (OR 1.72, 95% CI 1.24-2.39) were associated with needing help. In multivariable analyses, requiring assistance was associated with needing frequent help preparing drugs (adjusted OR [AOR] 9.52, 95% CI 4.78-21.28), fewer years since first injection (AOR for 1 year increase: 0.97, 95% CI 0.95-0.99) and injecting stimulants. Among those who required help, cisgender women reported needing assistance more often than cisgender men (P = 0.009). DISCUSSION AND CONCLUSIONS: Over two-fifths of the sample required help injecting; requiring assistance was associated with sociodemographic indicators and substance use-specific patterns. Findings highlight the need to scale-up educational resources for those who receive or provide help injecting, as well as SCS that accommodate onsite injection assistance.

Prognostic and predictive effects of TP53 co-mutation in patients with EGFR-mutated non-small cell lung cancer (NSCLC).

INTRODUCTION: TP53 mutations are common in non-small cell lung cancer (NSCLC) and have been reported as prognostic of poor outcome. The impact of TP53 co-mutations in epidermal growth factor receptor (EGFR)-mutated NSCLC is unclear. MATERIALS AND METHODS: Tissue from 105 patients with EGFR-mutated NSCLC at Princess Margaret Cancer Centre was analyzed by next-generation or Sanger sequencing to determine TP53 mutational status. Associations between TP53 status and baseline patient and tumor characteristics, treatments and outcomes (relapse-free survival [RFS] after surgical resection, overall survival [OS], overall response rate [ORR] and progression-free survival [PFS] on EGFR tyrosine kinase inhibitors [TKIs]), were investigated. RESULTS: Dual TP53/EGFR mutations were found in 43/105 patients (41%). Among 76 patients who underwent surgical resection, neither RFS (HR 0.99, CI 0.56-1.75, p=0.96) nor OS (HR 1.39, CI 0.70-2.77; p=0.35) was associated with TP53 status. Sixty patients (24 TP53 MUT; 36 TP53 WT) received first-generation EGFR TKIs for advanced disease. ORR was not significantly different (TP53 MUT 54%, WT 66%, p=0.42). There was a non-significant trend towards shorter PFS on EGFR TKIs with TP53 mutation (HR 1.74, CI 0.98-3.10, p=0.06). When limited to TP53 missense mutations (n=17), PFS was significantly shorter (HR 1.91, CI 1.01-3.60, p=0.04). Among 11 evaluable patients treated with T790M inhibitors, ORR was not significantly different (TP53 MUT 3/3 [100%], WT 7/8 [88%]). CONCLUSIONS: Patients with dual TP53/EGFR mutations, especially missense mutations, had marginally lower response rates and shorter PFS when treated with EGFR TKI therapy. Larger datasets are required to validate these observations.