Development, Implementation, and Meta-Evaluation of a National Approach to Programmatic Assessment in Canadian Family Medicine Residency Training.

The growing international adoption of competency-based medical education has created a desire for descriptions of innovative assessment approaches that generate appropriate and sufficient information to allow for informed, defensible decisions about learner progress. In this article, the authors provide an overview of the development and implementation of the approach to programmatic assessment in postgraduate family medicine training programs in Canada, called Continuous Reflective Assessment for Training (CRAFT). CRAFT is a principles-guided, high-level approach to workplace-based assessment that was intentionally designed to be adaptable to local contexts, including size of program, resources available, and structural enablers and barriers. CRAFT has been implemented in all 17 Canadian family medicine residency programs, with each program taking advantage of the high-level nature of the CRAFT guidelines to create bespoke assessment processes and tools appropriate for their local contexts. Similarities and differences in CRAFT implementation between 5 different family medicine residency training programs, representing both English- and French-language programs from both Western and Eastern Canada, are described. Despite the intentional flexibility of the CRAFT guidelines, notable similarities in assessment processes and procedures across the 5 programs were seen. A meta-evaluation of findings from programs that have published evaluation information supports the value of CRAFT as an effective approach to programmatic assessment. While CRAFT is currently in place in family medicine residency programs in Canada, given its adaptability to different contexts as well as promising evaluation data, the CRAFT approach shows promise for application in other training environments.

Will a quadruple multiplexed point-of-care screening strategy for HIV-related co-infections be feasible and impact detection of new co-infections in at-risk populations? Results from cross-sectional studies.

OBJECTIVES: Multiplexed point-of-care (POC) devices can rapidly screen for HIV-related co-infections (eg, hepatitis C (HCV), hepatitis B (HBV), syphilis) in one patient visit, but global evidence for this approach remains limited. This study aimed to evaluate a multiplex POC testing strategy to expedite screening for HIV-related co-infections in at-risk populations. METHODS: A multiplex strategy was developed with two subsequent versions of an investigational device Miriad. It was evaluated in two non-comparable settings and populations in two countries for feasibility of conduct, detection of new infections, preference and accuracy. Version 1 was evaluated in 375 sexually transmitted disease clinic attendees in Mumbai, India; version 2 was evaluated in 119 injection drug users in Montreal, Canada. RESULTS: Feasibility (completion rate) of the multiplex strategy was high (86.1% Mumbai; 92.4% Montreal). A total of 170 new infections were detected in Mumbai (56 HIV, 75 HBV, 37 syphilis, 2 HCV) versus 2 in Montreal. Preference was 60% in Mumbai and 97% in Montreal. Miriad version 1 specificities were high: HIV 99.7% (98.3% to 100%), HBV 99.3% (97.6% to 99.9%), HCV 99.7% (98.5% to 99.9%), syphilis 85.2% (80.9% to 88.8%); sensitivities were as follows: HIV 100% (94.8% to 100%), HBV 13.3% (6.6% to 23.2%), HCV 50% (1.3% to 98.7%), syphilis 86.1% (70.5% to 95.3%). With version 2, specificities improved: HIV 100% (97.2% to 100%), HBV 100% (97.3% to 100%), HCV 85.3% (73.8% to 93.0%), syphilis 98.1% (93.3% to 99.8%); sensitivities were: HIV 100% (47.3% to 100%), HCV 80.4% (66.1% to 90.6%), syphilis 100% (22.4% to 100%). CONCLUSIONS: A quad multiplex POC strategy for HIV and co-infections was feasible to operationalise and preferred by patients in both settings. Many new infections were identified in Mumbai and accuracy improved with version 2 of the assay. Such a strategy will help expedite screening for co-infections, particularly where baseline screening is low. These findings are valuable to practitioners, researchers, policymakers and funders involved in initiatives for all four diseases with implications for scale-up.

HIV-1 transmission patterns in antiretroviral therapy-naïve, HIV-infected North Americans based on phylogenetic analysis by population level and ultra-deep DNA sequencing.

Factors that contribute to the transmission of human immunodeficiency virus type 1 (HIV-1), especially drug-resistant HIV-1 variants remain a significant public health concern. In-depth phylogenetic analyses of viral sequences obtained in the screening phase from antiretroviral-naïve HIV-infected patients seeking enrollment in EPZ108859, a large open-label study in the USA, Canada and Puerto Rico (ClinicalTrials.gov NCT00440947) were examined for insights into the roles of drug resistance and epidemiological factors that could impact disease dissemination. Viral transmission clusters (VTCs) were initially predicted from a phylogenetic analysis of population level HIV-1 pol sequences obtained from 690 antiretroviral-naïve subjects in 2007. Subsequently, the predicted VTCs were tested for robustness by ultra deep sequencing (UDS) using pyrosequencing technology and further phylogenetic analyses. The demographic characteristics of clustered and non-clustered subjects were then compared. From 690 subjects, 69 were assigned to 1 of 30 VTCs, each containing 2 to 5 subjects. Race composition of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04). VTCs had fewer reverse transcriptase and major PI resistance mutations (9% vs. 24%; p = 0.002) than non-clustered sequences. Both men-who-have-sex-with-men (MSM) (68% vs. 48%; p = 0.001) and Canadians (29% vs. 14%; p = 0.03) were significantly more frequent in VTCs than non-clustered sequences. Of the 515 subjects who initiated antiretroviral therapy, 33 experienced confirmed virologic failure through 144 weeks while only 3/33 were from VTCs. Fewer VTCs subjects (as compared to those with non-clustering virus) had HIV-1 with resistance-associated mutations or experienced virologic failure during the course of the study. Our analysis shows specific geographical and drug resistance trends that correlate well with transmission clusters defined by HIV sequences of similarity. Furthermore, our study demonstrates the utility of molecular and epidemiological analysis of VTCs for identifying population-specific risks associated with HIV-1 transmission and developing effective local healthcare strategies.

Correlates of drug use cessation among participants in the Canadian HIV-HCV Co-infection Cohort.

BACKGROUND: Ongoing drug use remains a barrier to HIV and HCV treatment. We examined the occurrence and correlates of drug use cessation among HIV-HCV co-infected drug users participating in HIV care. METHODS: Participants from the Canadian Co-infection Cohort reporting drug use (injecting drugs and/or smoking crack) with at least two follow-up visits were included (n=521 (43%), 1832 visits). Socio-demographics, behavioural, and health information were collected at each six-month visit. Associations with cessation (no drug use since last visit) were examined using non-linear mixed effects logistic regression models with random intercepts. RESULTS: During follow-up, 361 (69%) participants ceased using drugs. Having a fixed address (aOR [adjusted odds ratio] 1.73, CI [95% confidence interval] 1.02-2.96) and smoking crack without injecting drugs (aOR 3.10, CI 2.05-4.71) were positively associated. Living alone (aOR 0.47, CI 0.35-0.63), current tobacco use (aOR 0.41, CI 0.26-0.64), hazardous alcohol drinking (aOR 0.67, CI 0.49-0.91), snorting drugs (aOR 0.52, CI 0.37-0.74), having a greater exposure to addiction programmes (aOR 0.88, CI 0.81-0.94), having been recruited in Quebec or Nova Scotia (aOR 0.41, CI 0.25-0.66), and British Columbia or Alberta (aOR 0.51, CI 0.32-0.82) were negatively associated. Various socio-demographic (age, education) and health-related (HIV duration, care adherence) factors were not associated. CONCLUSION: Drug use cessation among HIV-HCV co-infected persons is relatively common in this cohort. Stable housing and supportive living situations seem to be important facilitators for drug use cessation in this population. Greater efforts should be made to retain patients in addiction treatment programmes.

Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis.

BACKGROUND: Marijuana smoking is common and believed to relieve many symptoms, but daily use has been associated with liver fibrosis in cross-sectional studies. We aimed to estimate the effect of marijuana smoking on liver disease progression in a Canadian prospective multicenter cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected persons. METHODS: Data were analyzed for 690 HCV polymerase chain reaction positive (PCR-positive) individuals without significant fibrosis or end-stage liver disease (ESLD) at baseline. Time-updated Cox Proportional Hazards models were used to assess the association between the average number of joints smoked/week and progression to significant liver fibrosis (APRI ≥ 1.5), cirrhosis (APRI ≥ 2) or ESLD. RESULTS: At baseline, 53% had smoked marijuana in the past 6 months, consuming a median of 7 joints/week (IQR, 1-21); 40% smoked daily. There was no evidence that marijuana smoking accelerates progression to significant liver fibrosis (APRI ≥ 1.5) or cirrhosis (APRI ≥ 2; hazard ratio [HR]: 1.02 [0.93-1.12] and 0.99 [0.88-1.12], respectively). Each 10 additional joints/week smoked slightly increased the risk of progression to a clinical diagnosis of cirrhosis and ESLD combined (HR, 1.13 [1.01-1.28]). However, when exposure was lagged to 6-12 months before the diagnosis, marijuana was no longer associated with clinical disease progression (HR, 1.10 [0.95-1.26]). CONCLUSIONS: In this prospective analysis we found no evidence for an association between marijuana smoking and significant liver fibrosis progression in HIV/HCV coinfection. A slight increase in the hazard of cirrhosis and ESLD with higher intensity of marijuana smoking was attenuated after lagging marijuana exposure, suggesting that reverse causation due to self-medication could explain previous results.

Variation between Canadian centres in the uptake of treatment for hepatitis C by patients coinfected with HIV: a prospective cohort study.

BACKGROUND: Uptake of treatment for hepatitis C virus (HCV) is low in Canada despite its publicly funded health care system. We explored the uptake of HCV treatment within the Canadian Co-infection Cohort to determine if some treatment centres have been more successful than others at starting patients with HIV-HCV coinfection on HCV treatment. METHODS: We estimated the variation between 16 centres in the uptake of HCV treatment using a Weibull time-to-event model with adjustment for patient characteristics that are thought likely to influence the uptake of treatment. We asked the principal investigator at each centre about access to hepatitis-related specialists and services and the importance of various criteria when determining if a patient with HIV-HCV coinfection should receive treatment for HCV. RESULTS: Among 681 untreated patients in the Canadian Co-infection Cohort, 163 patients with HIV-HCV coinfection started HCV treatment over a period of 1827 patient-years (9 per 100 patient-years). Even after adjustment for case mix, there was still appreciable variation in treatment uptake between centres, with mean hazard ratios of 0.43 (95% credible interval 0.11-1.3) and 3.6 (95% credible interval 1.7-8.4) for the centres least and most likely to start an average patient with HIV-HCV coinfection on HCV treatment. The most important criteria reported by principal investigators for determining eligibility for treatment were severity of fibrosis, current psychiatric comorbidities, current alcohol intake, past HCV treatment and a history of reinfection with HCV. However, the opinions were wide-ranging: 8 of the 15 criteria elicited both the responses "less important" and "very important." INTERPRETATION: The magnitude of the centre effects and diverse opinions about the importance of treatment eligibility criteria suggest that provider-related barriers to HCV treatment uptake are as important as patient-related barriers.

Insulin resistance is associated with progression to hepatic fibrosis in a cohort of HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: Hepatitis C virus (HCV) infection is associated with higher insulin levels and insulin resistance. We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the effect of insulin resistance on the development of hepatic fibrosis. METHODS: Data were analysed from 158 nondiabetic participants in a prospective Canadian cohort of HIV/HCV-coinfected patients. Patients were defined as having insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR) index. Factors associated with a high index (HOMA-IR ≥ 2) were identified using multivariate logistic regression. Incidence rates of liver fibrosis [aspartate aminotransferase- to-platelet ratio index (APRI) ≥ 1.5] were calculated, and multivariate time-dependent Cox regression models used to assess the effect of baseline insulin resistance on the risk of developing an APRI score of at least 1.5 during follow-up. RESULTS: Overall, 56% had baseline HOMA-IR of at least 2. In the adjusted multivariate logistic analysis, only baseline BMI of more than 25 kg/m2 remained associated with insulin resistance [adjusted odds ratio 3.66, 95% confidence interval (CI) 1.70-7.92]. Rates of progression to significant hepatic fibrosis (APRI ≥ 1.5) were higher in those with HOMA-IR of at least 2 (16.32 per 100 person-years, 95% CI 6.68-25.97) compared with those with HOMA-IR less than 2 (7.95 per 100 person-years, 95% CI 0.16-15.75). Baseline HOMA-IR of at least 2 was associated with the development of significant fibrosis (adjusted hazard ratio 7.71, 95% CI 2.55-23.36).

Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in patients coinfected with HIV and hepatitis C virus.

BACKGROUND: Liver cirrhosis has been associated with decreased absolute CD4 cell counts but preserved CD4 cell percentage in human immunodeficiency virus (HIV)-negative persons. We evaluated factors associated with discordance between the absolute CD4 cell count and the CD4 cell percentage in a cohort of patients coinfected with HIV and hepatitis C virus (HCV). METHODS: Baseline data from 908 participants in a prospective, Canadian, multisite cohort of individuals with HIV-HCV coinfection were analyzed. Absolute CD4 cell count and CD4 cell percentage relationships were evaluated. We defined low and high discordance between absolute CD4 cell count/CD4 cell percentage relationships as CD4 cell percentages that differed from the expected CD4 cell percentage, given the observed absolute CD4 cell count, by ±7 percentage points; we defined very low and very high discordance as differences of ±14 percentage points. Factors associated with high or very high discordance, including either end-stage liver disease or aspartate transaminase to platelet ratio index (APRI) of >1.5, were analyzed using multivariate logistic regression models and compared to groups with concordant and low discordant results. RESULTS: High/very high discordance was seen in 31% (n = 286), while 35% (n = 321) had concordant values. Factors associated with very high discordance at baseline included history of end-stage liver disease (adjusted odds ratio [aOR], 6.52; 95% confidence interval [CI], 2.27-18.67) and APRI of >1.5 (aOR 4.69; 95% CI, 1.64-13.35). Compared with those with detectable HCV RNA, those who cleared HCV spontaneously were less likely to have very high discordance. CONCLUSIONS: Discordance between absolute CD4 cell count and CD4 cell percentage is common in an HIV/HCV-coinfected population and is associated with advanced liver disease and ongoing HCV replication.

New directions in HIV healthcare.

The Canadian Association for HIV Research (CAHR) is the professional organization for HIV and AIDS research in Canada or by Canadians. The theme of CAHR 2011 was "Honoring our history, embracing our diversity", and highlighted the strengths that our diverse communities bring to the fight against HIV/AIDS, and more specifically, the important research data presented that reflect the new direction in which HIV research is focused: to regularize the daily life of the HIV-infected patients. Clinical research in the field of HIV has evolved from developing medication to ensure the patients' survival, to the present where survival is assumed and life events are investigated. This article will cover the research presented in the clinical track and will focus on two issues that are going to impact the future of HIV-infected individuals: cognitive health and child conception.

Impact of hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV-HCV coinfection before and after antiretroviral therapy.

OBJECTIVE: HIV is known to have a negative impact on the progression of hepatitis C virus (HCV) infection, whereas the reverse remains unclear. We examined the impact of spontaneous clearance of HCV on CD4(+) T-lymphocyte count progression before and after initiation of antiretroviral therapy (ART) in HIV-HCV coinfected adults. METHODS: Data were analysed from participants in a Canadian, multisite prospective cohort of HIV-infected adults with serologic evidence of HCV infection. The rate of CD4(+) T-lymphocyte change was determined using multivariate mixed linear regression comparing chronically HCV RNA+ with spontaneous clearers (persistently HCV RNA- without HCV therapy). RESULTS: Baseline characteristics of the 271 participants analysed did not differ between individuals whose HCV RNA cleared (n = 35) and those whose HCV RNA persisted (n = 236) except with respect to markers of liver disease. HCV RNA+ individuals had on average seven-times slower recovery of CD4(+) T-cells on chronic ART compared with HCV RNA-: (adjusted change in absolute CD4 cell T-lymphocyte count per year: 4 (95% confidence interval, -0.6 to 8) cells/microl vs. 26 (95% confidence interval, 12 to 41) cells/microl; P < 0.001. Analyses restricted to individuals initiating ART showed similar results. There was also a trend to greater CD4 decline prior to ART initiation among those HCV RNA+, although this did not reach statistical significance. CONCLUSION: We found that CD4 cell progression is negatively affected by the presence of ongoing HCV replication in coinfected individuals initiating ART which persisted throughout stable ART suggesting active HCV infection affects immune restoration even after years of ART exposure.