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Simon R M Dobson,
Shelly McNeil,
Marc Dionne,
Meena Dawar,
Gina Ogilvie, Mel Krajden,
Chantal Sauvageau,
David W Scheifele,
Tobias R Kollmann,
Scott A Halperin,
Joanne M Langley,
Julie A Bettinger,
Joel Singer,
Deborah Money,
Dianne Miller,
Monika Naus,
Fawziah Marra,
Eric Young
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ABSTRACT: Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible.
To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses.
Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%).
Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. MAIN OUTCOMES AND MEASURES: Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months.
The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36.
Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended.
clinicaltrials.gov Identifier: NCT00501137.
JAMA The Journal of the American Medical Association 05/2013; 309(17):1793-802. · 30.03 Impact Factor
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ABSTRACT: BACKGROUND: Hepatitis C virus (HCV) infection is a major preventable and treatable cause of morbidity and mortality. The ability to link population based centralized laboratory HCV testing data with administrative databases provided a unique opportunity to compare mortality between HCV seronegative and seropositive individuals. Through the use of laboratory testing patterns and results, the objective of this study was to differentiate the viral effects of mortality due to HCV infection from risk behaviours/activities that are associated with acquisition of HCV infection. METHODS: Serological testing data from the British Columbia (BC) Centre for Disease Control Public Health Microbiology and Reference Laboratory from 1992--2004 were linked to the BC Vital Statistics Agency death registry. Four groups of HCV testers were defined by their HCV antibody (anti-HCV) testing patterns: single non-reactive (SNR); serial multiple tested non-reactive (MNR); reactive at initial testing (REAC); and seroconverter (SERO) (previously seronegative followed by reactive, a marker for incident infection). Standardized mortality ratios (SMRs) were calculated to compare the relative risk of all cause and disease specific mortality to that of the BC population for each serological group. Time dependent Cox proportional hazard regression was used to compare hazard ratios (HRs) among HCV serological groups. RESULTS: All anti-HCV testers had higher SMRs than the BC population. Referent to the SNR group, the REAC group had higher risks for liver (HR: 9.62; 95% CI=8.55-10.87) and drug related mortality (HR: 13.70; 95% CI=11.76-16.13). Compared to the REAC group, the SERO group had a lower risk for liver (HR: 0.53; 95% CI=0.24-0.99), but a higher risk for drug related mortality (HR: 1.54; 95% CI=1.12-2.05). CONCLUSIONS: These findings confirm that individuals who test anti-HCV positive have increased mortality related to progressive liver disease, and that a substantial proportion of the mortality is attributable to drug use and risk behaviours/activities associated with HCV acquisition. Mortality reduction in HCV infected individuals will require comprehensive prevention programming to reduce the harms due to behaviours/activities which relate to HCV acquisition, as well as HCV treatment to prevent progression of chronic liver disease.
BMC Public Health 04/2013; 13(1):291. · 2.00 Impact Factor
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Manon Ragonnet-Cronin,
Stéphane Aris-Brosou,
Isabelle Joanisse,
Harriet Merks,
Dominic Vallée,
Kyna Caminiti,
Michael Rekart, Mel Krajden,
Darrel Cook,
John Kim,
Laurie Malloch,
Paul Sandstrom,
James Brooks
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ABSTRACT: It has been reported that the increase in human immunodeficiency virus (HIV) sequence diversity in drug resistance surveillance specimens may be used to classify the duration of HIV infection as <1 or >1 year. We describe a mixed base classifier (MBC) optimized to categorize the duration of subtype B infections as <6 or >6 months on the basis of sequences for drug resistance surveillance specimens and compared MBC findings with those of serologic methods.
The behavior of the MBC was examined across a range of thresholds for calling mixed bases. MBC performance was then evaluated using either complete pol sequences or sites reflecting evolutionary pressures (HLA selection sites, sites that increased in entropy over the course of infection, and codon positions).
The MBC performance was optimal when secondary peaks on the sequencing chromatogram accounted for at least 15% of the area of primary peaks. A cutoff of <0.45% mixed bases in the pol region best identified recent infections (sensitivity = 82.7%, specificity = 78.8%), with improvement achieved by analyzing only sites that increased in entropy.
In an extended data set of 1354 specimens classified by BED, the optimized MBC performed significantly better than a simple MBC (agreement, 68.98% vs 67.13%). If further validated, the MBC may prove beneficial for detecting recent infection and estimating the incidence of HIV infection.
The Journal of Infectious Diseases 07/2012; 206(5):756-64. · 6.41 Impact Factor
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Danuta M Skowronski,
Naveed Z Janjua,
Gaston De Serres,
Anne-Luise Winter,
James A Dickinson,
Jennifer L Gardy,
Jonathan Gubbay,
Kevin Fonseca,
Hugues Charest,
Natasha S Crowcroft,
Monique Douville Fradet,
Nathalie Bastien,
Yan Li, Mel Krajden,
Suzana Sabaiduc,
Martin Petric
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ABSTRACT: During the 2010-2011 winter, a large number of outbreaks due to influenza A/H3N2 at long-term care facilities, including higher-than-expected attack rates among vaccinated staff, were reported in some regions of Canada. Interim analysis from the community-based sentinel surveillance system showed circulating H3N2 variants and suboptimal vaccine effectiveness (VE), assessed here for the entire season's data set.
Nasal/nasopharyngeal swabs and epidemiologic details were collected from patients presenting to sentinel sites within 7 days of onset of influenza-like illness. Cases tested positive for influenza by real-time reverse-transcription polymerase chain reaction; controls tested negative. Odds ratios for medically attended, laboratory-confirmed influenza in vaccinated vs nonvaccinated participants were used to derive adjusted VE. Viruses were characterized by hemagglutination inhibition (HI), and the hemagglutinin genes of a subset were sequenced to explore vaccine relatedness.
Final 2010-2011 VE analysis included 1718 participants (half aged 20-49 years), 93 with A(H1N1)pdm09, 408 with A/H3N2, and 199 with influenza B. Among adults aged 20-49 years, adjusted VE was 65% (95% confidence interval [CI], 8%-87%) for A(H1N1)pdm09 and 66% (95% CI, 10%-87%) for influenza B. Vaccine effectiveness was substantially lower for A/H3N2, at 39% (95% CI, 0%-63%). Phylogenetic analysis identified 2 circulating H3N2 variant clades, A/HongKong/2121/2010 (87%) and A/Victoria/208/2009 (11%), bearing multiple amino acid substitutions at antigenic sites (12 and 8, respectively) compared with the H3N2 vaccine component used in Canada (A/Victoria/210/2009[NYMC X-187]). However, HI characterized all H3N2 isolates as well matched to the vaccine.
Public health observations of increased facility H3N2 outbreaks were consistent with the sentinel network's detection of genetic variants and suboptimal VE but not with conventional HI characterization. We highlight the utility of a multicomponent sentinel surveillance platform that incorporates genotypic, phenotypic, and epidemiologic indicators into the assessment of influenza virus, new variant circulation, vaccine relatedness, and VE.
Clinical Infectious Diseases 04/2012; 55(3):332-42. · 9.15 Impact Factor
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ABSTRACT: Vaccination is one of the most effective medical interventions. However, optimization of existing as well as design of new vaccines is still mostly conducted empirically; a rational approach to vaccine design is largely prohibited by the lack of insight into the relevant mechanisms underlying immune-mediated protection. To delineate the impact of variables on immune memory formation following vaccination, we took advantage of a trial assessing the role of the age of the recipient and the number of administered doses of the quadrivalent HPV vaccine in a well-characterized longitudinal cohort of girls and young women. We found that age of the recipient and the number of doses administered differentially impact the development of B and T cell memory. Specifically, age of the recipient significantly impacted generation of HPV 18-specific B cell memory, while the number of vaccine doses displayed a significant effect on the development of HPV-specific T cell memory. Our data indicate that rational design of vaccines has to be tailored according to the desired induction of B and/or T cell memory.
Vaccine 03/2012; 30(24):3572-9. · 3.77 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) infection is associated with substantial costs to patients, their caregivers and society.
We evaluated time costs (time spent seeking healthcare) and out-of-pocket (OOP) costs for patients with HCV and their caregivers.
We measured costs for 738 HCV outpatients in a tertiary-care clinic using a patient-completed questionnaire. Time and OOP costs were compared across disease stages and sociodemographic categories. We examined the association between cost and disease stage using linear regression adjusting for age, gender, marital status, education, income and Index of Coexistent Disease (ICED) comorbidity score. Costs were expressed in 2007 Canadian dollars.
The mean annual time cost per patient was $2136 (98 h), and ranged from $281 (18 h) in individuals who had cleared the virus to $9416 in transplant recipients (420 h). Caregiver costs were reported in 10% of patients. The mean annual OOP cost per patient was $1326. Patients receiving active treatment and those with late-stage disease spent $2500-2800 per year on HCV-related healthcare, approximately 7% of their annual income. Patients who had cleared the virus had the lowest time and OOP costs. Low income and unemployed patients had higher costs.
In HCV-infected individuals, OOP and time costs represent a significant economic burden and fall disproportionately upon those least able to afford them. The lower cost burden among those who were successfully treated suggests that wider use of antiviral therapy may reduce economic burden in addition to improving health outcomes.
Liver international: official journal of the International Association for the Study of the Liver 01/2012; 32(5):815-25. · 3.82 Impact Factor
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ABSTRACT: Our objective was to describe the characteristics of acute and established HIV infections diagnosed in the Canadian province of British Columbia. Province-wide HIV testing and surveillance data were analyzed to inform recommendations for targeted use of screening algorithms to detect acute HIV infections.
Acute HIV infection was defined as a confirmed reactive HIV p24 antigen test (or HIV nucleic acid test), a non-reactive or reactive HIV EIA screening test and a non-reactive or indeterminate Western Blot. Characteristics of unique individuals were identified from the British Columbia HIV/AIDS Surveillance System. Primary drug resistance and HIV subtypes were identified by analyzing HIV pol sequences from residual sera from newly infected individuals.
From February 2006 to October 2008, 61 individuals met the acute HIV infection case definition, representing 6.2% of the 987 newly diagnosed HIV infections during the analysis period. Acute HIV infection cases were more likely to be men who have sex with men (crude OR 1.71; 95% CI 1.01-2.89], to have had a documented previous negative HIV test result (crude OR 2.89; 95% CI 1.52-5.51), and to have reported a reason for testing due to suspected seroconversion symptoms (crude OR 5.16; 95% CI 2.88-9.23). HIV subtypes and rates of transmitted drug resistance across all classes of drugs were similar in persons with both acute and established HIV infections.
Targeted screening to detect acute HIV infection is a logical public health response to the HIV epidemic. Our findings suggest that acute HIV infection screening strategies, in our setting, are helpful for early diagnosis in men who have sex with men, in persons with seroconversion symptoms and in previously negative repeat testers.
Journal of the International AIDS Society 08/2011; 14:39. · 3.26 Impact Factor
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ABSTRACT: Crack use is prevalent amongst street drug users in Canadian cities, and associated with severe drug use, health and social problems. Whilst few targeted interventions are available for crack use, the common use and sharing of hazardous makeshift paraphernalia are a key concern, as these risks may be associated with oral injury and blood-borne virus (BBV)--e.g., hepatitis C virus (HCV)--transmission amongst users. Recently, distribution programmes of so-called 'safer crack use kits' (SCUKs) have been initiated in select Canadian cities, primarily to reduce the use of unsafe materials and paraphernalia sharing amongst crack users. This study explored uptake and benefits of, barriers to, and possible improvements to two recently implemented SCUK distribution programme in Victoria, Canada.
N=31 regular crack smokers were recruited through community-based efforts between June and August 2010, and assessed via an interviewer-administered protocol involving quantitative and qualitative data items. Descriptive analyses were completed with the quantitative data, and thematic content analyses were conducted with the qualitative data in order to identify and extract prominent themes and issues.
The sample indicated high levels of socio-economic marginalization, poly-substance use, health problems, lengthy crack use histories and common crack paraphernalia sharing. Most participants exclusively utilized the SCUK programme including glass-stems in addition to other paraphernalia materials. Participants described: lesser need to share--or to commit property crimes to obtain resources for--crack to paraphernalia, increased health awareness, and increased personal and community safety as benefits experienced from SCUK use. Limitations in SCUK resources and distribution, shortcomings in materials, and police interference were cited as barriers to current SCUK program delivery.
SCUK distribution in Victoria appears to result in a variety of individual and community health benefits. These benefits could be solidified by addressing current programme limitations, including better resourcing, expanding geographic distributions and eliminating police interference.
The International journal on drug policy 06/2011; 22(4):292-300. · 2.54 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) infection is associated with impairment in health-related quality of life (HRQOL). The purpose of this study was to evaluate HRQOL across the HCV disease spectrum using preference-based (utility) and non-preference-based (psychometric) methods, adjusting for sociodemographic factors and co-morbidity.
Hepatitis C virus patients (n = 751) were recruited from several tertiary care settings in Vancouver, Canada for this observational, cross-sectional cohort study. Patients completed the Health Utilities Index Mark 2/3, a self-administered time trade-off utility instrument, and the Hepatitis Quality of Life Questionnaire (SF-36 with HCV-specific items). We examined the association between HRQOL and disease stage using linear regression adjusting for age, education, marital status, income, and co-morbidities.
Utility scores were low across disease stage and instrument, ranging from 0.51 to 0.80. On the SF-36, the mean Physical Component Summary score ranged from 37.2 to 49.2 across disease stage, and the Mental Component Summary score ranged from 39.7 to 45.7 (United States norms = 50). In general, patients with viral clearance had the highest scores, and those with late-stage disease (cirrhosis, liver cancer) had the lowest. Multivariable linear regression showed that the effect of disease stage was modest overall. Increasing age, lower income, unattached marital status, and high comorbidity were strongly associated with impairment in HRQOL.
The effect of stage of disease on HRQOL is modest, although viral clearance is associated with higher HRQOL. HCV patients' HRQOL is strongly associated with concomitant illness and sociodemographic factors.
Journal of Gastroenterology and Hepatology 06/2011; 27(1):149-57. · 2.87 Impact Factor
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ABSTRACT: Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 but not for genotype-2/3; this is based on expert opinion, not on published evidence.
In retrospective analysis of a large trial database prior to the publication of recent guidelines, we compared outcomes in 985 treatment-naïve patients with hepatitis C who did or did not undergo liver biopsy before starting peginterferon alfa-2a plus ribavirin.
Physicians elected to treat 141/654 (21.6%) genotype-1 patients and 126/331 (38.1%) genotype-2/3 patients without liver biopsy. There were no differences in baseline characteristics among those with or without pre-treatment liver biopsy, except for female preponderance in genotype-1 patients with liver biopsy. The sustained viral response (SVR) rate was no different amongst genotype-2/3 patients who had a biopsy before treatment with 66.3% SVR vs. 69.8% of those treated without biopsy (p = 0.546), but significantly higher among genotype-1 patients with pre-treatment liver biopsy at 54.6 vs. 44.0% for those treated without a liver biopsy (p = 0.029). In genotype-1 patients with liver biopsy, more patients with cirrhosis had dose adjustments (p = 0.0057) rather than drug discontinuation. There was tendency for earlier discontinuation among patients without pre-treatment liver biopsy.
Pre-treatment liver biopsy was associated with better SVR amongst genotype-1 patients. This improvement may reflect ongoing commitment to completing the treatment course by both patient and physician. In genotype-2/3 patients, pre-treatment liver biopsy may not be essential to maximize SVR rates. This study validates the recommendations of the most recent treatment guidelines for hepatitis C.
Annals of hepatology: official journal of the Mexican Association of Hepatology 06/2011; 10(3):260-9. · 1.81 Impact Factor
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Mel Krajden,
Darrel Cook,
Amanda Yu,
Ron Chow,
Wendy Mei,
Shelly McNeil,
Deborah Money,
Marc Dionne,
Karuna P Karunakaran,
Joel M Palefsky,
Simon Dobson,
Gina Ogilvie,
Martin Petric
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ABSTRACT: Human papillomavirus 16 (HPV 16) and HPV 18 antibody responses in a 2- versus 3-dose HPV vaccine (Gardasil) trial were measured by a pseudovirus neutralizing antibody (PsV NAb) assay and by the Merck competitive Luminex immunoassay (cLIA). Eight hundred twenty-four female subjects assigned to three dosing regimens (group 1, 9 to 13 years old; 2 doses, months 0 and 6 [n = 259]; group 2, 9 to 13 years old; 3 doses, months 0, 2, and 6 [n = 260]; group 3, 16 to 26 years old; 3 doses, months 0, 2, and 6 [n = 305]) had postvaccine responses assessed 1 month after the last dose. Of 791 subjects with baseline and 7-month sera, 15 (1.9%) and 9 (1.1%) were baseline seropositive for HPV 16 and HPV 18, respectively. All baseline-seronegative vaccinees seroconverted to both HPV 16 and HPV 18. Mean anti-HPV 16 levels were similar for groups 1 and 2 (for PsV NAb, P = 0.675; for cLIA, P = 0.874), and levels for both groups 1 and 2 were approximately 2-fold higher than that for group 3 (for PsV NAb and cLIA, P < 0.001). Mean anti-HPV 18 levels were approximately 1.4-fold lower in group 1 than in group 2 (for PsV, NAb P = 0.013; for cLIA, P = 0.001), and levels for both groups 1 and 2 were approximately 2.0- to 2.5-fold higher than that for group 3 (for PsV NAb and cLIA, P < 0.001). Pearson correlation coefficients for the assays were 0.672 for HPV 16 and 0.905 for HPV 18. Most of the discordant results were observed at lower cLIA signals. These results suggest that the PsV NAb assay could be a suitable alternative to cLIA for the measurement of postvaccine antibody responses.
Clinical and vaccine immunology: CVI 01/2011; 18(3):418-23. · 2.37 Impact Factor
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ABSTRACT: Disease-specific estimates of medical costs are important for health policy decision making.
To identify predictors of health care costs associated with hepatitis C virus (HCV) seropositivity across disease phases.
HCV laboratory tests from the BC Centre for Disease Control were linked to administrative data pertaining to health services and drugs dispensed to estimate costs among case subjects and controls. The case group comprised HCV seropositive individuals (n=20,001), and the control group comprised single-tested, HCV seronegative persons (n=70,752) identified between January 1997 and December 2004. Subject observation time was assigned to the three following disease phases: initial phase (after diagnosis), late phase (late-stage liver disease) and predeath phase (12 months before death). Case subjects and controls were matched for age, sex and a propensity score within each phase to determine the net cost attributable to HCV seropositivity, and were adjusted for demographic and clinical factors.
Costs increased with disease progression, with hospitalization being the highest cost component in all phases. Initial and late phase net costs (2005 Canadian dollars) were $1,850 and $6,000 per patient per year, respectively. Costs among case subjects were driven by age, comorbidities, mental illness, illicit drug use and HIV coinfection. While predeath case subject and control costs were virtually the same, costs were high and case subjects died at a younger age.
HCV seropositivity is associated with increased medical costs driven by viral sequelae and medicosocial vulnerabilities (ie, mental illness, illicit drug use and HIV coinfection). Cost mitigation and health outcome improvements will require broad-based prevention programming to reduce vulnerabilities and HCV treatment to prevent disease progression, respectively.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 12/2010; 24(12):717-26. · 1.21 Impact Factor
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International Journal of Cancer 11/2010; 128(12):3012 - 3012. · 5.44 Impact Factor
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ABSTRACT: Since its first detection in New York (1999), West Nile virus (WNv) has spread across the United States and Canada with the first activity reported in Canada in 2001. By 2004, WNv had been detected almost in every province of Canada and the contiguous regions of the United States with the exception of British Columbia (BC), this despite being detected in Alberta in 2003 and Washington as early as 2002. In August 2009, two human cases were serologically found to have WNv infection. They reported mosquito bites and had only traveled in the South and Central Okanagan areas of BC before their presentation. On the basis of clinical, laboratory, and epidemiological data, these two human cases have been confirmed as the first locally acquired WNv cases in BC. Various factors may have contributed to the 10-year delay in the spread of WNv to BC, including regional weather conditions and unique topography.
Vector borne and zoonotic diseases (Larchmont, N.Y.) 10/2010; 11(8):1221-4. · 2.61 Impact Factor
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ABSTRACT: Pre-eclampsia shares several similarities with atherosclerotic heart disease. We explored whether, like atherosclerosis, there is a potential link between cytomegalovirus (CMV) infection and pre-eclampsia.
CMV IgG, IgM and IgA antibodies were determined by enzyme-linked immunosorbent assays in serums from pre-eclampsia (n = 78), normotensive intrauterine growth restriction (nIUGR) (n = 30) and normal pregnancy controls (n = 109). Data were analyzed by chi-squared, Kruskal-Wallis ANOVA and Mann-Whitney U-tests. Further, we conducted a comprehensive review of published studies on the relation between CMV infection and pre-eclampsia. Risk ratios (RRs) and 95% confidence interval (CI), according to CMV infection status, were calculated using Review Manager.
Women with pre-eclampsia had increased CMV IgG seropositivity compared with nIUGR (p < 0.01) and normal pregnancy controls (p < 0.01). In addition, CMV IgG antibody level was higher in pre-eclampsia than normal pregnancy controls (p < 0.001). No difference was observed in CMV IgM or IgA among study groups. Data synthesis revealed that women with CMV infection were at higher risk in the development of pre-eclampsia, compared with women without CMV infection. Combined results for six studies yielded a RR of 1.5 (95% CI 1.2-1.9).
CMV infection seems to affect the occurrence of pre-eclampsia. Evaluation of the relation between CMV infection and pre-eclampsia may provide mechanistic insights into pre-eclampsia-related inflammation.
Acta Obstetricia Et Gynecologica Scandinavica 09/2010; 89(9):1162-7. · 1.77 Impact Factor
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International Journal of Cancer 08/2010; · 5.44 Impact Factor
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Jason Grebely,
Elizabeth Knight,
Tyler Ngai,
Krista A Genoway,
Jesse D Raffa,
Michelle Storms,
Lesley Gallagher, Mel Krajden,
Gregory J Dore,
Fiona Duncan,
Brian Conway
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ABSTRACT: Despite that 60-90% of injection drug users (IDUs) are infected with hepatitis C virus (HCV) infection, IDUs are often denied therapy based on concerns of reinfection following treatment. However, there are little data in this regard. We evaluated HCV re-infection following sustained virologic response (SVR) among HCV-infected IDUs having received HCV treatment in a multidisciplinary program.
Following treatment, participants were encouraged to return at follow-up intervals of 1 year and illicit drug use histories were obtained. In those with SVR, HCV RNA testing by PCR was performed to determine if relapse or reinfection occurred.
Among 58 receiving HCV treatment between January 2002 and December 2006, 60% (35 of 58) achieved an SVR. Patients were followed for a median of 2.0 years following SVR (range, 0.4-5.0 years), with ongoing illicit and injection drug use reported in 54% (19 of 35) and 46% (16 of 35). Of the 35 with SVR, 28 remained HCV RNA negative during follow-up (80%), with four lost to follow-up and one dying of hepatocellular carcinoma and two cases of reinfection were observed (2 of 35). The rates of reinfection were 3.2 per 100 p-y (95% CI:0.4, 11.5) overall and 5.3 per 100 p-y (95% CI:0.6, 19.0) among those reporting injecting following SVR (n = 16). One of two participants with HCV re-infection spontaneously cleared virus following reinfection.
The rate of reinfection following treatment for HCV infection among current and former IDUs engaged in a multidisciplinary program is low.
Journal of Gastroenterology and Hepatology 07/2010; 25(7):1281-4. · 2.87 Impact Factor
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ABSTRACT: Aims: Despite the increased prevalence of crack use, research on street drug use in Canada currently focusses mainly on injection drug use and/or use in large urban centres. This study's objective was to assess the distinct socio-demographic characteristics, drug-use patterns, health profiles and risk behaviours as well as intervention needs of primary crack users in three mid-sized communities in British Columbia, Canada. Methods: Study participants were recruited with the help of local service agencies and peer recruiters, and assessed between July and November 2008 based on a protocol involving quantitative, qualitative and biological measures. Findings: The majority of the samples: reported unstable housing/homelessness; relied on social benefit payments for income generation; were under current criminal justice supervision; were poly-drug users, using other drugs like alcohol, cannabis or opioids; reported physical and mental health problems; were hepatitis C virus positive; had numerous crack-use episodes per day; frequently shared crack-use paraphernalia; and obtained crack pipe paraphernalia from makeshift items. Conclusions: This study documents crack use as a prevalent street drug use activity associated with extensive social and health risks and harms, which currently are not sufficiently addressed by the existing interventions in the study sites. Concerted attention to, and delivery of, targeted prevention and treatment interventions for the public health problem of crack use in Canada is urgently required.
06/2010; 17(4):333-353.
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Marc Deschênes,
Vincent G Bain,
Samuel S Lee,
Morris Sherman,
Curtis L Cooper,
Eric M Yoshida,
Paul J Marotta, Mel Krajden,
Christopher Usaty,
Robert Balshaw,
Kevork M Peltekian
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ABSTRACT: The objective of this analysis was to identify predictors of relapse in genotype 1 patients after 48 weeks of treatment with peginterferon plus ribavirin.
Retrospective analysis of data from treatment-naive genotype 1 patients with an end-of-treatment response after 48 weeks of treatment with peginterferon alpha-2a plus ribavirin 1000/1200 mg/day in the Canadian Pegasys Expanded Access Program.
Among treatment-naive genotype 1 patients with an end-of-treatment response (n = 432), the sustained virological response status was known for 405 individuals (sustained virological response n = 328, 81%; relapse n = 77, 19%). Early virological response rates at week 12 were similar in relapsers (98.7%) and sustained responders (98.5%). More relapsers (12 of 77, 15.6%) than sustained responders (15 of 328, 4.6%) had quantifiable hepatitis C virus (HCV) RNA (>or=600 IU/ml) at week 12 and, among these patients, mean and maximum HCV RNA levels were higher in relapsers, although the median values were similar. Factors significantly associated with relapse in the multiple logistic regression analysis include older age (odds ratio: 1.48 per decade, 95% confidence interval: 1.06-2.07; P = 0.023), Caucasian ethnicity (odds ratio: 3.23, confidence interval: 1.25-8.33; P = 0.016), higher baseline serum HCV RNA level (P = 0.005), the drop in HCV RNA between baseline and week 12 (P = 0.026), and the interaction between baseline HCV RNA level and the decrease in HCV RNA between baseline and week 12 (P = 0.032).
Older age, Caucasian ethnicity, and high baseline HCV RNA level, and a smaller decrease in HCV RNA between baseline and week 12 predict a relapse in genotype 1 patients.
European journal of gastroenterology & hepatology 03/2010; 22(5):546-51. · 1.66 Impact Factor
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Gina S Ogilvie,
Dirk J van Niekerk, Mel Krajden,
Ruth E Martin,
Thomas G Ehlen,
Kathy Ceballos,
Stuart J Peacock,
Laurie W Smith,
Lisa Kan,
Darrel A Cook,
Wendy Mei,
Gavin C E Stuart,
Eduardo L Franco,
Andrew J Coldman
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ABSTRACT: In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with > or = CIN3 as the outcome.
HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases
To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program.
International Standard Randomised Controlled Trial Number Register, ISRCTN79347302.
BMC Cancer 03/2010; 10:111. · 3.01 Impact Factor
