Publications by authors named "James Wilton"

32 Publications

The impact of current opioid agonist therapy on hepatitis C virus treatment initiation among people who use drugs from in the DAA era: A population-based study.

Clin Infect Dis 2021 Jun 14. Epub 2021 Jun 14.

British Columbia Centre for Disease Control, Vancouver, BC, Canada.

Background: Evidence that opioid agonist therapy (OAT) is associated with increased odds of hepatitis C virus (HCV) treatment initiation among people who use drugs (PWUD) is emerging. The objective of this study was to determine the association between current OAT and HCV treatment initiation among PWUD in a population-level linked administrative dataset.

Methods: The British Columbia (BC) Hepatitis Testers Cohort was used for this study, which includes all people tested for or diagnosed with HCV in BC, linked to medical visits, hospitalizations, laboratory, prescription drug, and mortality data from 1992 until 2019. PWUD with injecting drug use or opioid use disorder and chronic HCV infection were identified for inclusion in this study. HCV treatment initiation was the main outcome, and subdistribution proportional hazards modeling was used to assess the relationship with current OAT.

Results: 13,803 PWUD with chronic HCV were included in this study. Among those currently on OAT at the end of the study period, 47% (2,704/5,770) had started HCV treatment, whereas 22% (1778/8033) of those not currently on OAT has started HCV treatment .. Among PWUD with chronic HCV infection, current OAT was associated with higher likelihood of HCV treatment initiation in time to event analysis (adjusted hazard ratio 1.84 [95%CI, 1.50, 2.26]).

Conclusions: Current OAT was associated with a higher likelihood of HCV treatment initiation. However, many PWUD with HCV currently receiving OAT have yet to receive HCV treatment. Enhanced integration between substance use care and HCV treatment is needed to improve the overall health of PWUD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab546DOI Listing
June 2021

Impact of HCV infection and ethnicity on incident type 2 diabetes: findings from a large population-based cohort in British Columbia.

BMJ Open Diabetes Res Care 2021 06;9(1)

School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada

Introduction: Increasing evidence indicates that chronic hepatitis C virus (HCV) infection is associated with higher risk of diabetes. Previous studies showed ethnic disparities in the disease burden of diabetes, with increased risk in Asian population. We described the incidence of type 2 diabetes related to HCV infection and assessed the concurrent impact of HCV infection and ethnicity on the risk of diabetes.

Research Design And Methods: In British Columbia Hepatitis Testers Cohort, individuals were followed from HCV diagnosis to the earliest of (1) incident type 2 diabetes, (2) death or (3) end of the study (December 31, 2015). Study population included 847 021 people. Diabetes incidence rates in people with and without HCV were computed. Propensity scores (PS) analysis was used to assess the impact of HCV infection on newly acquired diabetes. PS-matched dataset included 117 184 people. We used Fine and Gray multivariable subdistributional hazards models to assess the effect of HCV and ethnicity on diabetes while adjusting for confounders and competing risks.

Results: Diabetes incidence rates were higher among people with HCV infection than those without. The highest diabetes incidence rate was in South Asians with HCV (14.7/1000 person-years, 95% CI 12.87 to 16.78). Compared with Others, South Asians with and without HCV and East Asians with HCV had a greater risk of diabetes. In the multivariable stratified analysis, HCV infection was associated with increased diabetes risk in all subgroups: East Asians, adjusted HR (aHR) 3.07 (95% CI 2.43 to 3.88); South Asians, aHR 2.62 (95% CI 2.10 to 3.26); and Others, aHR 2.28 (95% CI 2.15 to 2.42).

Conclusions: In a large population-based linked administrative health data, HCV infection was associated with higher diabetes risk, with a greater relative impact in East Asians. South Asians had the highest risk of diabetes. These findings highlight the need for care and screening for HCV-related chronic diseases such as type 2 diabetes among people affected by HCV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjdrc-2021-002145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186745PMC
June 2021

Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study.

J Hepatol 2021 Jun 4. Epub 2021 Jun 4.

British Columbia Centre for Disease Control, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

Background: We evaluated the effect of sustained virologic response(SVR) from direct acting antiviral(DAA) treatments on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia(BC), Canada.

Methods: We used data from the BC Hepatitis Testers Cohort, which includes people tested for hepatitis C virus(HCV) since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting(IPTW) to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modeling to assess effect of DAAs on mortality.

Findings: There were 10,855 people treated with DAAs (SVR: 10,426 [96%], no-SVR: 425) and 10,855 untreated individuals. Median follow-up time was 2.2 years (interquartile range: 1.3-3.6; maximum: 6.2). The all-cause mortality rate was 19.5/1000 person-years (PY) among the SVR group(deaths=552), 86.5/1000 PY among the no-SVR group (deaths=96), and 99.2/1000 PY among the untreated group (deaths=2133). In the multivariable model, SVR was associated with significant reduction in all-cause(adjusted hazard ratio[aHR]:0.19, 95%CI:0.17-0.21), liver-(subdistribution HR[asHR]:0.22, 95%CI: 0.18-0.27) and drug-related mortality(asHR: 0.26, 95%CI:0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use(IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality.

Conclusions: DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people with IDU.

Lay Summary: We assessed the effect of treatment of hepatitis C virus infection with direct acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.05.028DOI Listing
June 2021

Cohort profile: development and characteristics of a retrospective cohort of individuals dispensed prescription opioids for non-cancer pain in British Columbia, Canada.

BMJ Open 2021 04 13;11(4):e043586. Epub 2021 Apr 13.

BC Centre for Disease Control, Vancouver, British Columbia, Canada.

Purpose: Prescription opioids (POs) are widely prescribed for chronic non-cancer pain but are associated with several risks and limited long-term benefit. Large, linked data sources are needed to monitor their harmful effects. We developed and characterised a retrospective cohort of people dispensed POs.

Participants: We used a large linked administrative database to create the Opioid Prescribing Evaluation and Research Activities cohort of individuals dispensed POs for non-cancer pain in British Columbia (BC), Canada (1996-2015). We created definitions to categorise episodes of PO use based on a review of the literature (acute, episodic, chronic), developed an algorithm for inferring clinical indication and assessed patterns of PO use across a range of characteristics.

Findings To Date: The current cohort includes 1.1 million individuals and 3.4 million PO episodes (estimated to capture 40%-50% of PO use in BC). The majority of episodes were acute (81%), with most prescribed for dental or surgical pain. Chronic use made up 3% of episodes but 88% of morphine equivalents (MEQ). Across the acute to episodic to chronic episode gradient, there was an increasing prevalence of higher potency POs (hydromorphone, oxycodone, fentanyl, morphine), long-acting formulations and chronic pain related indications (eg, back, neck, joint pain). Average daily dose (MEQ) was similar for acute/episodic but higher for chronic episodes. Approximately 7% of the cohort had a chronic episode and chronic pain was the characteristic most strongly associated with chronic PO use. Individuals initiating a chronic episode were also more likely to have higher social/material deprivation and previous experience with a mental health condition or a problem related to alcohol or opioid use. Overall, these findings suggest our episode definitions have face validity and also provide insight into characteristics of people initiating chronic PO therapy.

Future Plans: The cohort will be refreshed every 2 years. Future analyses will explore the association between POs and adverse outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-043586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051385PMC
April 2021

Decentralizing PrEP delivery: Implementation and dissemination strategies to increase PrEP uptake among MSM in Toronto, Canada.

PLoS One 2021 18;16(3):e0248626. Epub 2021 Mar 18.

Division of Infectious Diseases, St. Michael's Hospital, Toronto, Ontario, Canada.

Pre-exposure prophylaxis (PrEP) is traditionally prescribed by HIV specialist physicians. Given finite specialist resources, there is a need to scale up PrEP delivery by decentralizing services via other healthcare professionals. We aimed to assess the feasibility of delivering PrEP to men who have sex with men (MSM) through primary care physicians and sexual health clinic nurses. We piloted a multi-component, implementation and dissemination research program to increase provision of PrEP through primary care physicians and sexual health clinic nurses in Toronto, Canada. Community-based organizations (CBOs) provided prospective participants with information cards that contained links to an online module on engaging providers in a conversation about PrEP. In our patient-initiated continuing medical education (PICME) strategy, participants saw their family doctors and gave them the card, which also contained a link to a Continuing Medical Education module. In the nurse-led strategy, participants visited one of two participating clinics to obtain PrEP. We administered an optional online questionnaire to patients and providers at baseline and six months. CBOs distributed 3043 cards. At least 339 men accessed the online module and 196 completed baseline questionnaires. Most (55%) intended to visit nurses while 21% intended to consult their physicians. Among 45 men completing follow-up questionnaires at 6 months, 31% reported bringing cards to their physicians and obtaining PrEP through them; sexual health clinics delivered PrEP to 244 patients. Participants who went through the PICME approach reported no changes in relationships with their providers. Nurses showed fidelity to PrEP prescribing guidelines. Nurse-led PrEP and patient-initiated continuing medical education (PICME) for primary care physicians are feasible strategies to increase PrEP uptake. Nurse-led PrEP delivery was preferred by most patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248626PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971529PMC
March 2021

Prenatal hepatitis C screening, diagnoses, and follow-up testing in British Columbia, 2008-2019.

PLoS One 2020 31;15(12):e0244575. Epub 2020 Dec 31.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Objective: Current guidelines in British Columbia recommend prenatal screening for hepatitis C antibodies (anti-HCV) if risk factors are present. We aimed to estimate frequency of prenatal anti-HCV testing, new diagnoses, repeated and follow-up testing among BC women.

Methods: BC Centre for Disease Control Public Health Laboratory data estimated the number of BC women (assigned female at birth or unknown sex) aged 13-49 who received routine prenatal serological screening (HIV, hepatitis B, syphilis and rubella) from 2008-2019. Anti-HCV tests ordered the same day as routine prenatal screens were considered prenatal anti-HCV tests. Assessment of follow-up was based on HCV RNA and/or genotype testing within one year of new prenatal anti-HCV diagnoses.

Results: In 2019, 55,202 routine prenatal screens were carried out for 50,392 BC women. Prenatal anti-HCV tests increased significantly, from 19.6% (9,704/49,515) in 2008 to 54.6% (27,516/50,392) in 2019 (p<0.001). New prenatal anti-HCV diagnoses (HCV positive diagnoses at first test or seroconversions) declined from 14.3% in 2008 to 10.1% in 2019. The proportion of women with new prenatal anti-HCV diagnoses that were a result of a first HCV test declined from 0.3% (29/9,701) in 2008 to 0.03% (8/27,500) in 2019. For women known to be anti-HCV positive at the time of prenatal screening, the proportion who had a prenatal anti-HCV test increased from 35.6% in 2008 to 50.8% in 2019.

Conclusion: Prenatal anti-HCV testing increased substantially over the study period. However, new HCV diagnoses remained relatively stable, suggesting that a considerable proportion of BC women with low or no risk are being screened as part of prenatal care. The vast majority of women with new HCV diagnoses receive appropriate follow-up HCV RNA and genotype testing, which may indicate interest in HCV treatment. These findings contribute to the discussion around potential for prenatal anti-HCV screening in an effort to eliminate HCV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775094PMC
March 2021

HCV reinfection rates after cure or spontaneous clearance among HIV-infected and uninfected men who have sex with men.

Liver Int 2021 03 22;41(3):482-493. Epub 2020 Dec 22.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Background & Aims: Hepatitis C virus (HCV) reinfection among high-risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada.

Methods: We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018.

Results: Of 1349 HCV-positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person-years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003-2.92), injection drug use (aHR 2.60, 95% CI 1.57-4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29-3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13-0.46) was associated with reduced HCV reinfection risk.

Conclusions: There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14762DOI Listing
March 2021

Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada.

Int J Drug Policy 2020 Oct 19;86:102989. Epub 2020 Oct 19.

British Columbia Centre for Disease Control, 655 West 12(th) Avenue, Vancouver, British Columbia, Canada, V5Z 4R4; School of Population and Public Health, University of British Columbia, 2206 E Mall, Vancouver, British Columbia, Canada, V6T 1Z3.

Background: The majority of new HCV infections in Canada occur in people who inject drugs. Thus, while curative direct antiviral agents (DAAs) herald a promising new era in hepatitis C virus (HCV) treatment, improving the lives and wellbeing of people living with HCV (PLHCV) must be considered in the context of reducing overdose-related harms and with a syndemic lens. We measure drug-related deaths (DRDs) among HCV-negative people and PLHCV in British Columbia (BC), Canada, and the impact of potent contaminants like fentanyl on deaths.

Methods: We identified DRDs among PLHCV and HCV-negative individuals from 2010 to 2018 in the BC Hepatitis Testers Cohort, a population-based dataset of ~1.7 million British Columbians comprising comprehensive administrative and clinical data. We estimated annual standardized liver- and drug-related mortality rates per 100,000 person-years (PY) and described the contribution of specific drugs, including fentanyl and its analogues, implicated in DRDs over time.

Results: DRDs constituted 20.1% of deaths among PLHCV and 4.7% of deaths among HCV-negative individuals; a 4.3-fold (95% confidence interval: 4.0-4.5) difference. Drug-related mortality overtook liver-related mortality for PLHCV in 2015 and HCV-negative individuals in 2016 and rose from 241.7 to 436.5 per 100,000 PY from 2010 to 2018 amongPLHCV and from 20.0 to 57.1 per 100,000 PY for HCV-negative individuals over the same period. The proportion of deaths attributable to drugs among PLHCV and HCV-negative individuals increased from 15.1% to 26.1% and 3.1% to 8.0%, in 2010 and 2018, respectively. The proportion of DRDs attributed solely to synthetic opioids such as fentanyl averaged across both groups increased from 2.1% in 2010 to 69.6% in 2017.

Conclusion: Steep drug-related mortality increases among PLHCV and HCV-negative individuals over the last decade highlight the urgent need to address overdose-related drivers and harms in these populations using an integrated care approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.drugpo.2020.102989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569420PMC
October 2020

Syndemic profiles of people living with hepatitis C virus using population-level latent class analysis to optimize health services.

Int J Infect Dis 2020 Nov 15;100:27-33. Epub 2020 Aug 15.

School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; BC Centre for Disease Control, Vancouver, BC, Canada; Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada. Electronic address:

Background: Hepatitis C (HCV) affects diverse populations such as people who inject drugs (PWID), 'baby boomers,' gay/bisexual men who have sex with men (gbMSM), and people from HCV endemic regions. Assessing HCV syndemics (i.e.relationships with mental health/chronic diseases) among subpopulations using Latent Class Analysis (LCA) may facilitate targeted program planning.

Methods: The BC Hepatitis Testers Cohort(BC-HTC) includes all HCV cases identified in BC between 1990 and 2015, integrated with medical administrative data. LCA grouped all BC-HTC HCV diagnosed people(n = 73,665) by socio-demographic/clinical indicators previously determined to be relevant for HCV outcomes. The final model was chosen based on fit statistics, epidemiological meaningfulness, and posterior probability. Classes were named by most defining characteristics.

Results: The six-class model was the best fit and had the following names and characteristics: 'Younger PWID'(n =11,563): recent IDU (67%), people born >1974 (48%), mental illness (62%), material deprivation (59%). 'Older PWID'(n =15,266): past IDU (78%), HIV (17%), HBV (17%) coinfections, alcohol misuse(68%). 'Other Middle-Aged People'(n = 9019): gbMSM (26%), material privilege (31%), people born between 1965-1974 (47%). 'People of Asian backgrounds' (n = 4718): East/South Asians (92%), no alcohol misuse (97%) or mental illness (93%), people born <1945 (26%), social privilege (66%). 'Rural baby boomers' (n = 20,401): rural dwellers (32%), baby boomers (79%), heterosexuals (99%), no HIV (100%). 'Urban socially deprived baby boomers' (n = 12,698): urban dwellers (99%), no IDU (100%), liver disease (22%), social deprivation (94%).

Conclusions: Differences between classes suggest variability in patients' service needs. Further analysis of health service utilization patterns may inform optimal service layout.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2020.08.035DOI Listing
November 2020

Trends in HIV pre-exposure prophylaxis uptake in Ontario, Canada, and impact of policy changes: a population-based analysis of projected pharmacy data (2015-2018).

Can J Public Health 2021 02 11;112(1):89-96. Epub 2020 Jun 11.

Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.

Objectives: HIV pre-exposure prophylaxis (PrEP) is a proven tool for HIV prevention, but PrEP use in Ontario, Canada, and the effects of recent policies are unknown. We estimated the number and characteristics of PrEP users in Ontario and evaluated the impacts of policy changes between July 2015 and June 2018.

Methods: We obtained tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) dispensation data for Ontario from IQVIA, and applied an algorithm to identify use for PrEP. We report prevalent PrEP use for the second quarter of 2018 according to age, sex, region, prescriber specialty, and payer type, and generate "PrEP-to-need ratios" (PNR) by dividing these numbers by the estimated numbers of new HIV diagnoses. We used interventional autoregressive integrated moving average models to examine the impact of three policy changes on PrEP use: Health Canada approval (February 2016), availability of generic TDF/FTC and partial public drug coverage (September 2017), and public drug coverage for individuals aged < 25 years (January 2018).

Results: The estimated number of individuals receiving PrEP increased 713%, from 374 in 2015 Q3 to 3041 in 2018 Q2. Among PrEP users in 2018 Q2, 97.5% were male, 60.4% were < 40 years, 67.7% obtained PrEP from a family physician, 77.2% used private insurance, and 67.0% were in Toronto. PNRs were highest in 30-39-year-olds, males, Toronto and the Central East and West regions. Time series analyses found that Health Canada approval (p = 0.0001) and introducing generics/partial public drug coverage (p = 0.002) led to significantly increased use.

Conclusions: PrEP use has risen in Ontario in association with favourable policy changes, but remains far below guideline recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17269/s41997-020-00332-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851246PMC
February 2021

Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study.

Open Forum Infect Dis 2020 Mar 29;7(3):ofaa055. Epub 2020 Feb 29.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Background: Clinical trials show high efficacy of sofosbuvir/velpatasvir (SOF/VEL), but there are limited data from "real-world" settings. We aimed to evaluate SOF/VEL effectiveness for all hepatitis C virus (HCV) genotypes (GTs) in British Columbia (BC), Canada.

Methods: We used the BC Hepatitis Testers Cohort, which includes all HCV cases in the province (1990-2015) linked to administrative databases, including prescriptions to end of 2018. We measured sustained virologic response (SVR; negative RNA ≥10 weeks after treatment end) and identified characteristics associated with non-SVR. Conservatively, we excluded individuals with no assessment for SVR if their last RNA test after treatment initiation was negative (but included if positive).

Results: Of 2821 eligible participants, most were infected with GT1 (1076, 38.1%) or GT3 (1072, 38.0%), and a minority (278, 9.9%) were treated with RBV. SVR was 94.6% (2670/2821) overall and 94.5% (1017/1076) for GT1, 96.4% (512/531) for GT2, and 93.7% (1004/1072) for GT3. When disaggregated by GT, treatment regimen, and cirrhosis/treatment experience, SVR was lowest (30/40, 75.0%) among treatment-experienced GT3 individuals treated with RBV. Characteristics associated with non-SVR in multivariable analysis included younger age, RBV addition, and being a person with HIV (PWH) or who injects/injected drugs (PWID). When treatment regimen (±RBV) was removed from multivariable model, treatment experience was associated with non-SVR for GT3. Of 151 non-SVR individuals, 56.3% were nonvirological failures (treatment incomplete/no assessment for SVR) and 43.7% were virological failures (nonresponse/relapse). A disproportionately high percentage of non-SVR among PWID was due to nonvirological failure.

Conclusions: SOF/VEL was highly effective in this "real-world" population-based cohort. Additional support is required for PWID/PWH to reach SVR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052750PMC
March 2020

Reply to: "Pitfalls in measuring temporal trends for late diagnosis of viral hepatitis".

J Hepatol 2019 12 23;71(6):1256-1258. Epub 2019 Oct 23.

British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2019.09.015DOI Listing
December 2019

Cohort profile: Development and profile of a population-based, retrospective cohort of diagnosed people living with HIV in Ontario, Canada (Ontario HIV Laboratory Cohort).

BMJ Open 2019 05 27;9(5):e027325. Epub 2019 May 27.

Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Purpose: Population-based cohorts of diagnosed people living with HIV (PLWH) are limited worldwide. In Ontario, linked HIV diagnostic and viral load (VL) test databases are centralised and contain laboratory data commonly used to measure engagement in HIV care. We used these linked databases to create a population-based, retrospective cohort of diagnosed PLWH in Ontario, Canada.

Participants: A datamart was created by integrating diagnostic and VL databases and linking records at the individual level. These databases contain information on laboratory test results and sociodemographic/clinical information collected on requisition/surveillance forms. Datamart individuals enter our cohort with the first record of a nominal HIV-positive diagnostic test (1985-2015) or VL test (1996-2015), and remain unless administratively lost to follow-up (LTFU; no VL test for >2 years and no VL test in later years). Non-nominal diagnostic tests are excluded as they lack identifying information to permit linkage to other tests. However, individuals diagnosed non-nominally are included in the cohort with record of a VL test. The LTFU rule is applied to indirectly censor for death/out-migration.

Findings To Date: As of the end of 2015, the datamart contained 40 372 HIV-positive diagnostic tests and 23 851 individuals with ≥1 VL test. Almost half (46.3%) of the diagnostic tests were non-nominal and excluded, although this was lower (~15%) in recent years. Overall, 29 587 individuals have entered the cohort-contributing 229 302 person-years of follow-up since 1996. Between 2000 and 2015, the number of diagnosed PLWH (cohort individuals not LTFU) increased from 8859 to 16 110, and the percent who were aged ≥45 years increased from 29.1% to 62.6%. The percent of diagnosed PLWH who were virally suppressed (<200 copies/mL) increased from 40.7% in 2000 to 79.5% in 2015.

Future Plans: We plan to conduct further analyses of HIV care engagement and link to administrative databases with information on death, migration, physician billing claims and prescriptions. Linkage to other data sources will address cohort limitations and expand research opportunities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-027325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537973PMC
May 2019

Trends in HIV care cascade engagement among diagnosed people living with HIV in Ontario, Canada: A retrospective, population-based cohort study.

PLoS One 2019 4;14(1):e0210096. Epub 2019 Jan 4.

Data and Applied Science Impact, Ontario HIV Treatment Network, Toronto, Canada.

Background: The HIV cascade is an important framework for assessing systems of care, but population-based assessment is lacking for most jurisdictions worldwide. We measured cascade indicators over time in a population-based cohort of diagnosed people living with HIV (PLWH) in Ontario, Canada.

Methods: We created a retrospective cohort of diagnosed PLWH using a centralized laboratory database with HIV diagnostic and viral load (VL) test records linked at the individual-level. Individuals enter the cohort with record of a nominal HIV-positive diagnostic test or VL test, and remain unless administratively lost to follow-up (LTFU, >2 consecutive years with no VL test and no VL test in later years). We calculated the annual percent of diagnosed PLWH (cohort individuals not LTFU) between 2000 and 2015 who were in care (≥1 VL test), on ART (as documented on VL test requisition) or virally suppressed (<200 copies/ml). We also calculated time from diagnosis to linkage to care and viral suppression among individuals newly diagnosed with HIV. Analyses were stratified by sex and age. Upper/lower bounds were calculated using alternative indicator definitions.

Results: The number of diagnosed PLWH increased from 8,859 (8,859-11,389) in 2000 to 16,110 (16,110-17,423) in 2015. Over this 16-year period, the percent of diagnosed PLWH who were: in care increased from 81% (63-81%) to 87% (81-87%), on ART increased from 55% (34-60%) to 81% (70-82%) and virally suppressed increased from 41% (23-46%) to 80% (67-81%). Between 2000 and 2014, the percent of newly diagnosed individuals who linked to care within three months of diagnosis or achieved viral suppression within six months of diagnosis increased from 67% to 82% and from 22% to 42%, respectively. Estimates were generally lower for females and younger individuals.

Discussion: HIV cascade indicators among diagnosed PLWH in Ontario improved between 2000 and 2015, but gaps still remain-particularly for younger individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210096PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319701PMC
September 2019

Trends in HIV care cascade engagement among diagnosed people living with HIV in Ontario, Canada: A retrospective, population-based cohort study.

PLoS One 2019 4;14(1):e0210096. Epub 2019 Jan 4.

Data and Applied Science Impact, Ontario HIV Treatment Network, Toronto, Canada.

Background: The HIV cascade is an important framework for assessing systems of care, but population-based assessment is lacking for most jurisdictions worldwide. We measured cascade indicators over time in a population-based cohort of diagnosed people living with HIV (PLWH) in Ontario, Canada.

Methods: We created a retrospective cohort of diagnosed PLWH using a centralized laboratory database with HIV diagnostic and viral load (VL) test records linked at the individual-level. Individuals enter the cohort with record of a nominal HIV-positive diagnostic test or VL test, and remain unless administratively lost to follow-up (LTFU, >2 consecutive years with no VL test and no VL test in later years). We calculated the annual percent of diagnosed PLWH (cohort individuals not LTFU) between 2000 and 2015 who were in care (≥1 VL test), on ART (as documented on VL test requisition) or virally suppressed (<200 copies/ml). We also calculated time from diagnosis to linkage to care and viral suppression among individuals newly diagnosed with HIV. Analyses were stratified by sex and age. Upper/lower bounds were calculated using alternative indicator definitions.

Results: The number of diagnosed PLWH increased from 8,859 (8,859-11,389) in 2000 to 16,110 (16,110-17,423) in 2015. Over this 16-year period, the percent of diagnosed PLWH who were: in care increased from 81% (63-81%) to 87% (81-87%), on ART increased from 55% (34-60%) to 81% (70-82%) and virally suppressed increased from 41% (23-46%) to 80% (67-81%). Between 2000 and 2014, the percent of newly diagnosed individuals who linked to care within three months of diagnosis or achieved viral suppression within six months of diagnosis increased from 67% to 82% and from 22% to 42%, respectively. Estimates were generally lower for females and younger individuals.

Discussion: HIV cascade indicators among diagnosed PLWH in Ontario improved between 2000 and 2015, but gaps still remain-particularly for younger individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210096PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319701PMC
September 2019

Outcome measures of disease activity for rare autoimmune rheumatic diseases.

Br J Hosp Med (Lond) 2018 Jul;79(7):396-401

Consultant, Department of Rheumatology, University College London Hospital NHS Trust, London.

Systemic lupus erythematosus, scleroderma, myositis and Sjögren's syndrome are rare, complex, multi-systemic rheumatic diseases associated with significant morbidity and mortality. Thorough assessments of disease activity are required to guide clinical management and assess response to new therapies in clinical trials. This article reviews the commonly used outcome measures to assess this group of diseases and discusses the limitations of their use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12968/hmed.2018.79.7.396DOI Listing
July 2018

Awareness of, interest in, and willingness to pay for HIV pre-exposure prophylaxis among Canadian gay, bisexual, and other men who have sex with men.

Can J Public Health 2018 12 5;109(5-6):791-799. Epub 2018 Jun 5.

British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.

Objectives: Pre-exposure prophylaxis (PrEP) is a highly effective, HIV prevention strategy increasingly being accessed by gay, bisexual, and other men who have sex with men (GBMSM). GBMSM face structural and individual-level barriers accessing PrEP, including awareness and cost. This paper assesses socio-demographic factors associated with awareness, interest, and willingness to pay for PrEP in a sample of Canadian GBMSM.

Methods: Data were derived from the 2015 Sex Now survey, a cross-sectional, online survey of GBMSM. Respondents were recruited through social media, sex-seeking "apps," and by word of mouth. We used univariable and multivariable logistic regression models to estimate associations between socio-demographic factors and three primary outcomes.

Results: Our sample consisted of 7176 HIV-negative Canadian GBMSM. Of respondents, 54.7% were aware of PrEP, 47.4% were interested in PrEP, and 27.9% of PrEP-interested respondents reported they would pay for PrEP out-of-pocket. Awareness and interest varied between provinces, while GBMSM outside urban areas were less likely to be PrEP aware. Bisexual-identified men, and men over 50, were less likely to be aware and interested in PrEP in multivariable models. Only annual income and educational attainment were associated with willingness to pay for PrEP.

Conclusion: This study identifies important disparities in awareness, interest, and willingness to pay for PrEP. Future interventions and educational efforts should target non-gay-identified and older GBMSM, as well as GBMSM outside urban areas. PrEP implementation may risk further perpetuating existing health inequities based on socio-economic status if PrEP continues to be accessed primarily through private insurance or paid for out-of-pocket.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17269/s41997-018-0090-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964486PMC
December 2018

Trends in the awareness, acceptability, and usage of HIV pre-exposure prophylaxis among at-risk men who have sex with men in Toronto.

Can J Public Health 2018 06 26;109(3):342-352. Epub 2018 Apr 26.

Centre for Urban Health Solutions, St. Michael's Hospital, Toronto, Canada.

Objectives: Pre-exposure prophylaxis (PrEP) with daily oral tenofovir/emtricitabine dramatically reduces HIV risk in men who have sex with men (MSM). However, uptake is slow worldwide.

Methods: We administered anonymous cross-sectional questionnaires to MSM presenting for anonymous HIV testing at a Toronto sexual health clinic at four successive time points during the period 2013-2016. We assessed trends in PrEP awareness, acceptability, and use over time using the Cochran-Armitage Trend Test, and identified barriers to using PrEP by constructing "PrEP cascades" using 2016 data. We assumed that to use PrEP, MSM must (a) be at risk for HIV, (b) be at objectively high risk (HIRI-MSM score ≥ 10), (c) perceive themselves to be at medium-to-high risk, (d) be aware of PrEP, (e) be willing to use PrEP, (f) have a family doctor, (g) be comfortable discussing sexual health with that doctor, and (h) have drug coverage/be willing to pay out of pocket.

Results: MSM participants were mostly white (54-59.5%), with median age 31 years (IQR = 26-38). PrEP awareness and use increased significantly over time (both p < 0.0001), reaching 91.3% and 5.0%, respectively, in the most recent wave. Willingness to use PrEP rose to 56.5%, but this increase did not reach statistical significance (p = 0.06). The full cascade, ABCDEFGH, suggested few could readily use PrEP under current conditions (11/400 = 2.8%). The largest barriers, in descending order, were low self-perceived HIV risk, unwillingness to use PrEP, and access to PrEP providers.

Conclusion: To maximize its potential public health benefits, PrEP scale-up strategies must address self-perceived HIV risk and increase access to PrEP providers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17269/s41997-018-0064-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153704PMC
June 2018

Decentralizing the delivery of HIV pre-exposure prophylaxis (PrEP) through family physicians and sexual health clinic nurses: a dissemination and implementation study protocol.

BMC Health Serv Res 2018 Jul 3;18(1):513. Epub 2018 Jul 3.

Division of Infectious Diseases, St. Michael's Hospital, Toronto, Canada.

Background: Gay, bisexual and other men who have sex with men (gbMSM) in Canada continue to experience high rates of incident HIV. Pre-exposure prophylaxis (PrEP, the regular use of anti-HIV medication) reduces HIV acquisition and could reduce incidence. However, there are too few physicians with expertise in HIV care to meet the projected demand for PrEP. To meet demand and achieve greater public health impact, PrEP delivery could be 'decentralized' by incorporating it into front-line prevention services provided by family physicians (FPs) and sexual health clinic nurses.

Methods: This PrEP decentralization project will use two strategies. The first is an innovative knowledge dissemination approach called 'Patient-Initiated CME' (PICME), which aims to empower individuals to connect their family doctors with online, evidence-based, continuing medical education (CME) on PrEP. After learning about the project through community agencies or social/sexual networking applications, gbMSM interested in PrEP will use a uniquely coded card to access an online information module that includes coaching on how to discuss their HIV risk with their FP. They can provide their physician a link to the accredited CME module using the same card. The second strategy involves a pilot implementation program, in which gbMSM who do not have a FP may bring the card to designated sexual health clinics where trained nurses can deliver PrEP under a medical directive. These approaches will be evaluated through quantitative and qualitative methods, including: questionnaires administered to patients and physicians at baseline and at six months; focus groups with patients, FPs, and sexual health clinic staff; and review of sexual health clinic charts. The primary objective is to quantify the uptake of PrEP achieved using each decentralization strategy. Secondary objectives include a) characterizing barriers and facilitators to PrEP uptake for each strategy, b) assessing fidelity to core components of PrEP delivery within each strategy, c) measuring patient-reported outcomes including satisfaction with clinician-patient relationships, and d) conducting a preliminary costing analysis.

Discussion: This study will assess the feasibility of a novel strategy for disseminating knowledge about evidence-based clinical interventions, and inform future strategies for scale-up of an underutilized HIV prevention tool.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12913-018-3324-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029110PMC
July 2018

High HIV risk and syndemic burden regardless of referral source among MSM screening for a PrEP demonstration project in Toronto, Canada.

BMC Public Health 2018 02 27;18(1):292. Epub 2018 Feb 27.

Division of Infectious Diseases, St. Michael's Hospital, 30 Bond St, 4CC - Room 4-179, Toronto, ON, M5B 1W8, Canada.

Background: To maximize public health impact and cost-effectiveness, HIV pre-exposure prophylaxis (PrEP) must reach individuals at high HIV risk. Referrals for PrEP can be self- or provider-initiated, but there are several challenges to both. We assessed whether HIV risk differed by referral source among gay, bisexual and other men who have sex (gbMSM) screening for an HIV PrEP demonstration project.

Methods: PREPARATORY-5 was an open-label PrEP demonstration project enrolling gbMSM at high risk of HIV acquisition in Toronto, Canada. Study eligibility criteria related to high risk was defined as scoring ≥10 on the HIV Incidence Risk Index for MSM (HIRI-MSM) and engaging in at least 1 act of condomless receptive anal sex within the past 6 months. Recruitment was promoted through self-referrals (ads in a sexual networking app and gay newspaper/website) and provider-referrals (10 community-based organizations, CBOs). HIV risk score (HIRI-MSM) and syndemic health burden were measured among gbMSM screened for study participation and compared according to referral source.

Results: Between October 16 and December 30, 2014, online ads generated 1518 click-throughs and CBOs referred 115 individuals. Overall, 165 men inquired about the trial, of which 86 underwent screening. The majority of screened men were self-referrals (60.5%), scored ≥10 on HIRI-MSM (96.5%), and reported condomless receptive anal sex in the past 6 months (74.2%). Self- and provider-referrals had similarly high HIV risk profiles, with a median (IQR) HIRI-MSM score of 26.0 (19.0-32.5) and 28.5 (20.0-34.0) (p = 0.3), and 75.0% and 73.5% reporting condomless receptive anal sex (p = 0.9), respectively. The overall burden of syndemic health problems was also high, with approximately one-third overall identified as having depressive symptoms (39.5%), alcohol-related problems (39.5%), multiple drug use (31.4%), or sexual compulsivity (31.4%). There were no significant differences in syndemic health problems by referral source.

Conclusions: HIV risk and syndemic burden were high among gbMSM presenting for this PrEP demonstration project regardless of referral source. Self-referral may be a useful and efficient strategy for identifying individuals suitable for PrEP use. Online strategies and CBOs working in gay men's health may play important roles in connecting individuals at high HIV risk to PrEP services.

Trial Registration: ClinicalTrials.gov NCT02149888 . Registered May 12th 2014.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-018-5180-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830065PMC
February 2018

Considerations for Using the HIRI-MSM Screening Tool to Identify MSM Who Would Benefit Most From PrEP.

J Acquir Immune Defic Syndr 2017 10;76(2):e58-e61

*Applied Epidemiology Unit, Ontario HIV Treatment Network, Toronto, Ontario, Canada†Division of Infectious Diseases, St. Michael's Hospital, Toronto, Ontario, Canada‡Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000001472DOI Listing
October 2017

Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale-up among men who have sex with men in Toronto, Canada: disconnect between objective and subjective HIV risk.

J Int AIDS Soc 2016 3;19(1):20777. Epub 2016 Jun 3.

Department of Medicine, University of Toronto, Toronto, Canada.

Introduction: Identifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify "optimal" candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada.

Methods: Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify "optimal" candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses.

Results: Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were "optimal" candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3-2.2) and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2-2.3). The proportion of men who were "optimal" candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (≥26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate-to-high HIV risk, 23.6% were unaware of PrEP, 40.1% were not willing to use PrEP, 47.6% lacked a family physician with whom they felt comfortable discussing sexual health, and 31.6% had no means to cover the cost of PrEP.

Conclusions: A higher HIRI-MSM cut-off may be helpful for identifying candidates for PrEP scale-up. Improving engagement in the PrEP cascade will require interventions to simultaneously address multiple barriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911732PMC
http://dx.doi.org/10.7448/IAS.19.1.20777DOI Listing
August 2017

Lower Extremity Focused Neurologic Examination.

Authors:
James P Wilton

Clin Podiatr Med Surg 2016 Apr 28;33(2):191-202. Epub 2016 Jan 28.

Department of Orthopedics, New England Peripheral Nerve Center, Valley Regional Hospital, 241 Elm Street, Claremont, NH 03743, USA. Electronic address:

A focused lower extremity neurologic evaluation aids in the diagnosis of lower extremity nerve pathology. Injuries to the peripheral neural infrastructure can result in chronic neuropathic pain and discomfort. The most common etiologies of chronic neuropathic pain are from peripheral distal pathologies. A complete lower extremity neurologic evaluation includes sensory, motor, and deep tendon reflexes. Additional specific attention to the geographic anatomic testing of peripheral sensory and motor nerves is essential in eliciting a correct etiologic diagnosis for peripheral neural pain and dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cpm.2015.12.008DOI Listing
April 2016

Preparing for pre-exposure prophylaxis: perceptions and readiness of Canadian pharmacists for the implementation of HIV pre-exposure prophylaxis.

Int J STD AIDS 2016 07 29;27(8):608-16. Epub 2015 May 29.

Division of Infectious Diseases, St. Michael's Hospital; University of Toronto; Hassle Free Clinic, Toronto, ON, Canada.

Pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV transmission but has the potential to cause harm if not used properly. Pharmacists are well-positioned to foster PrEP's efficacy but little is known whether they would endorse it as an HIV prevention tool. The objective of the study was to determine Canadian HIV pharmacists' support for PrEP and to identify current barriers to promoting PrEP. Canadian pharmacists with experience in HIV care were invited to complete an online survey about their experiences, opinions, and learning needs regarding PrEP from December 2012 to January 2013. Among the 59 surveys received, 48 met criteria for final analysis. Overall, 33 (69%) respondents would provide education positively supporting the use of PrEP and 26 (54%) believed Health Canada should approve PrEP for use in Canada. Familiarity with the concept of PrEP and practice characteristics examined did not appear to be significantly associated with support for PrEP in univariable analyses. The principal barriers to promoting PrEP included inadequate drug coverage and insufficient knowledge to educate others. Many Canadian HIV pharmacists would endorse PrEP for high-risk patients; however, wider dissemination of information and lower drug costs may be needed to make PrEP more widely promoted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0956462415589896DOI Listing
July 2016

Pre-exposure prophylaxis for sexually-acquired HIV risk management: a review.

HIV AIDS (Auckl) 2015 28;7:125-36. Epub 2015 Apr 28.

Division of Infectious Diseases, St Michael's Hospital, University of Toronto, Toronto, ON, Canada ; Department of Medicine, University of Toronto, Toronto, ON, Canada.

Despite significant efforts, the rate of new HIV infections worldwide remains unacceptably high, highlighting the need for new HIV prevention strategies. HIV pre-exposure prophylaxis (PrEP) is a new approach that involves the ongoing use of antiretroviral medications by HIV-negative individuals to reduce the risk of HIV infection. The use of daily tenofovir/emtricitabine as oral PrEP was found to be effective in multiple placebo-controlled clinical trials and approved by the United States Food and Drug Administration. In addition, the Centers for Disease Control and Prevention in the United States and the World Health Organization have both released guidelines recommending the offer of oral PrEP to high-risk populations. The scale-up of PrEP is underway, but several implementation questions remain unanswered. Demonstration projects and open-label extensions of placebo-controlled trials are ongoing and hope to contribute to our understanding of PrEP use and delivery outside the randomized controlled trial setting. Evidence is beginning to emerge from these open-label studies and will be critical for guiding PrEP scale-up. Outside of such studies, PrEP uptake has been slow and several client- and provider-related barriers are limiting uptake. Maximizing the public health impact of PrEP will require rollout to be combined with interventions to promote uptake, support adherence, and prevent increases in risk behavior. Additional PrEP strategies are currently under investigation in placebo-controlled clinical trials and may be available in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/HIV.S50025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422285PMC
May 2015

The Drosophila TIPE family member Sigmar interacts with the Ste20-like kinase Misshapen and modulates JNK signaling, cytoskeletal remodeling and autophagy.

Biol Open 2015 Apr 2;4(5):672-84. Epub 2015 Apr 2.

The Genome Sciences Centre, BC Cancer Agency, 675 West 10 Avenue, Vancouver, BC V5Z 1L3, Canada Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada

TNFAIP8 and other mammalian TIPE family proteins have attracted increased interest due to their associations with disease-related processes including oncogenic transformation, metastasis, and inflammation. The molecular and cellular functions of TIPE family proteins are still not well understood. Here we report the molecular and genetic characterization of the Drosophila TNFAIP8 homolog, CG4091/sigmar. Previous gene expression studies revealed dynamic expression of sigmar in larval salivary glands prior to histolysis. Here we demonstrate that in sigmar loss-of-function mutants, the salivary glands are morphologically abnormal with defects in the tubulin network and decreased autophagic flux. Sigmar localizes subcellularly to microtubule-containing projections in Drosophila S2 cells, and co-immunoprecipitates with the Ste20-like kinase Misshapen, a regulator of the JNK pathway. Further, the Drosophila TNF ligand Eiger can induce sigmar expression, and sigmar loss-of-function leads to altered localization of pDJNK in salivary glands. Together, these findings link Sigmar to the JNK pathway, cytoskeletal remodeling and autophagy activity during salivary gland development, and provide new insights into TIPE family member function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/bio.20148417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434819PMC
April 2015

Entrapment neuropathy about the foot and ankle: an update.

J Am Acad Orthop Surg 2015 Jan;23(1):58-66

Occurrences of entrapment neuropathies of the lower extremity are relatively infrequent; therefore, these conditions may be underappreciated and difficult to diagnose. Understanding the anatomy of the peripheral nerves and their potential entrapment sites is essential. A detailed physical examination and judicious use of imaging modalities are also vital when establishing a diagnosis. Once an accurate diagnosis is obtained, treatment is aimed at reducing external pressure, minimizing inflammation, correcting any causative foot and ankle deformities, and ultimately releasing any constrictive tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5435/JAAOS-23-01-58DOI Listing
January 2015

Preparing for PrEP: perceptions and readiness of canadian physicians for the implementation of HIV pre-exposure prophylaxis.

PLoS One 2014 18;9(8):e105283. Epub 2014 Aug 18.

Division of Infectious Diseases, University of Toronto, Toronto, Ontario, Canada; Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Hassle Free Clinic, Toronto, Ontario, Canada; Division of Infectious Diseases, St Michael's Hospital, Toronto, Ontario, Canada.

Recent evidence has demonstrated the efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention, but concerns persist around its use. Little is known about Canadian physicians' knowledge of and willingness to prescribe PrEP. We disseminated an online survey to Canadian family, infectious disease, internal medicine, and public health physicians between September 2012-June 2013 to determine willingness to prescribe PrEP. Criteria for analysis were met by 86 surveys. 45.9% of participants felt "very familiar" with PrEP, 49.4% felt that PrEP should be approved by Health Canada, and 45.4% of respondents were willing to prescribe PrEP. Self-identifying as an HIV expert (odds ratio, OR = 4.1, 95% confidence interval, CI = 1.6-10.2), familiarity with PrEP (OR = 5.0, 95%CI = 1.3-19.0) and having been asked by patients about PrEP (OR = 4.0, 95%CI = 1.5-10.5) were positively associated with willingness to prescribe PrEP on univariable analysis. The latter two were the strongest predictors on multivariate analysis. Participants cited cost and efficacy as major concerns. 75.3% did not feel that information had been adequately disseminated among physicians. In summary, Canadian physicians demonstrate varying levels of support for PrEP and express concerns about its implementation. Further research on real-world effectiveness, continuing medical education, and clinical support is needed to prepare physicians for this prevention strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0105283PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136811PMC
April 2015

Knowledge of and opinions on HIV preexposure prophylaxis among front-line service providers at Canadian AIDS service organizations.

AIDS Res Hum Retroviruses 2013 Sep 22;29(9):1183-9. Epub 2013 Jun 22.

Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Oral daily tenofovir/emtricitabine (Truvada) is approved in the United States for HIV preexposure prophylaxis (PrEP) but has generated controversy in the media and within HIV-affected communities. We conducted an online survey about PrEP-related knowledge, experience, opinions, and learning needs, and received 160 responses from service providers at Canadian AIDS Service Organizations. Respondents were cautiously optimistic about PrEP and 48.8% believed that PrEP warranted Health Canada approval. In multivariable logistic regression, support for PrEP approval was associated with more years working in HIV (odds ratio=1.89 per decade, 95% CI=1.10, 3.25), low baseline familiarity with PrEP (OR=3.24, 95% CI=1.01, 14.41), and knowing someone who had used PrEP (OR=4.39, 95% CI=1.28,15.08). Participants major concerns about PrEP were similar to those highlighted in other publications, and some issues specific to certain target populations were raised. Several participants (26.2%) had been asked about PrEP in the past year and 10.6% knew of one or more Canadian who had used PrEP. Despite clients' interest, most participants thought that they (60.6%) or their organization (63.1%) did not have enough current knowledge about PrEP, highlighting the need for further education on this novel HIV prevention strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/aid.2013.0090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749697PMC
September 2013

Detection of neuropathy due to Mycobacterium leprae using noninvasive neurosensory testing of susceptible peripheral nerves.

Ann Plast Surg 2005 Dec;55(6):633-7

Institute for Peripheral Nerve Surgery, Baltimore, MD, USA.

The prevalence of disability in patients with Hansen disease is related to peripheral nerve dysfunction. This dysfunction, which is due to chronic nerve compression, is the result of invasion of the peripheral nerve by Mycobacteria leprae. This suggests that early identification of M. leprae would be aided by detection of early stages of peripheral nerve compression. Traditional evaluation of peripheral nerve function with monofilaments, electrodiagnostic testing, or by observing motor palsy or digital ulcers unfortunately identifies only late sequelae of peripheral nerve dysfunction. The cutaneous pressure threshold required to identify 1 from 2 static-touch stimuli was obtained with the Pressure-Specified Sensory Device in upper and lower extremities of 51 patients who completed multidrug therapy for Hansen disease. Abnormal peripheral nerve function was identified in each patient and in each of the 120 bilateral nerves that were evaluated. The degree of nerve dysfunction included the range from early to late stages of nerve compression, suggesting that this method of neurosensory testing offers the possibility for early detection of peripheral nerve problems in Hansen disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.sap.0000185888.44243.d5DOI Listing
December 2005
-->