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F Xie,
Y Hu,
S E Turvey,
L A Magee,
R M Brunham,
K-C Choi,
M Krajden,
P C K Leung,
D M Money, D M Patrick,
E Thomas,
P von Dadelszen
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ABSTRACT: Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-kappaB (NF-kappaB) subunit and interleukin-1beta (IL-1beta), and inflammatory cytokine profiles in women with pre-eclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls.
A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1beta, NF-kappaB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays.
A single tertiary maternity hospital in Vancouver, Canada.
Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia (>or=34(+0) weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls.
Women with pre-eclampsia (as a single combined group of early- and late-onset, and particularly in women with early-onset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-kappaB subunit, and IL-1beta mRNA expression, and TNF-alpha:IL-10 and IL-6:IL-10 ratios compared with other groups.
These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.
BJOG An International Journal of Obstetrics & Gynaecology 01/2010; 117(1):99-108. · 3.41 Impact Factor
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ABSTRACT: HIV vaccine development remains an urgent priority. This article is a systematic review of HIV vaccine preparedness studies in the high-income 30 Organization for Economic Co-operation and Development countries, to identify factors important for HIV vaccine trial development in injection drug users (IDU), men who have sex with men (MSM), and women at heterosexual risk (WAHR) across these countries. Of 27 articles we identified, willingness to participate (WTP) was assessed in eight studies involving IDU, 11 involving MSM, and one involving WAHR. WTP ranged in IDU at 41-86%, MSM at 23-94%, and in WAHR, it was at 81%. Studies reported recruitment of high-risk individuals. Retention was assessed in eight studies involving IDU, five involving MSM, and three involving WAHR. IDU were retained at a range of 3-98%, MSM at 70-95% and WAHR at 67-92%. This review provides an in-depth summary of HIV vaccine preparedness studies that were conducted in the Organization for Economic Co-operation and Development countries.
AIDS Care 11/2007; 19(9):1118-27. · 1.60 Impact Factor
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ABSTRACT: Contacts of tuberculosis (TB) cases identified from eight Provincial databases in British Columbia, Canada, between 1990 and 2000.
To assess the risk of developing TB based on tuberculin skin test (TST) sizes in contacts of TB cases who did not receive treatment for latent TB infection.
Retrospective, population-based cohort study with a 12-year follow-up.
Among 26,542 contacts, 180 individuals developed TB (TB rate 678/100,000). Household contacts with a TST size 0-4 mm had a TB rate of 1014/100,000, those with 5-9 mm a TB rate of 2162/100,000 and those with 10-14 mm a rate of 4478/100,000. Children aged 0-10 years with 0-4 mm had a TB rate of 806/100,000, those with 5-9 mm a TB rate of 5556/100,000 and those with 10-14 mm a rate of 42,424/100,000. Immunosuppressed contacts with TST sizes 0-4 mm had a TB rate of 630/100,000, those with 5-9 mm a TB rate of 1923/100,000, and those with 10-14 mm a rate of 1770/100,000.
TB rates were high for all TST sizes in household contacts, 0-10 year old contacts and immunosuppressed contacts. These contacts may benefit from treatment for latent TB infection, regardless of the size of their TST.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 10/2007; 11(9):1014-20. · 2.73 Impact Factor
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ABSTRACT: Providing summary recommendations regarding self collection of vaginal specimens for human papillomavirus (HPV) testing is difficult owing to the wide range of published estimates for the diagnostic accuracy of this approach. To determine summary estimates from analyses of reported findings of the sensitivity, specificity and summary receiver operating characteristic curves (SROC) for self collected vaginal specimens for HPV testing compared to the reference standard, clinician collected HPV specimens.
Standard search criteria for a diagnostic systematic review were employed. Eligible studies were combined using a random effects model and summary ROC curves were derived for overall and for specific subgroups.
Summary measures were determined from 12 studies. Six studies where patients used Dacron or cotton swabs or cytobrushes to obtain samples were pooled and had an overall sensitivity of 0.74 (95% CI 0.61 to 0.84) and specificity of 0.88 (95% CI 0.83 to 0.92), with diagnostic odds ratio of 22.3 and an area under the curve of 0.91. Self specimens using Dacron or cotton swabs or cytobrushes collected by women enrolled at referral clinics had an overall sensitivity of 0.81 (95% CI 0.65 to 0.91) and specificity of 0.90 (95% CI 0.80 to 0.95). Sensitivity and specificity of tampons ranged from 0.67-0.94 and 0.80-0.85 respectively.
Our findings indicate that the combined sensitivity for HPV-DNA is more than 70% when patients use Dacron swabs, cotton swabs, or cytobrushes to obtain their own vaginal specimens for HPV-DNA evaluation. Self collected HPV-DNA swabs may be an appropriate alternative for low resource settings or in patients reluctant to undergo pelvic examinations.
Sexually Transmitted Infections 07/2005; 81(3):207-12. · 2.85 Impact Factor
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ABSTRACT: To describe patient experiences and views regarding genital herpes management.
Between February 2002 and January 2003, subjects with genital herpes were recruited via the International Herpes Alliance website and through banners on additional sites. Surveys were available in English, French, Spanish, Italian, and German and assessed views on access to care, diagnosis, related emotional experiences, educational resources, counselling, pharmacotherapy, and satisfaction with care.
2075 patient responses from 78 countries were analysed. 49% reported their diagnosis was by culture (or other direct detection) and 9% by antibody test, while 34% reported they had been diagnosed by examination alone. 65% used a prescription antiviral therapy, 18% a topical antiviral therapy, and 17% an alternative therapy. Of 901 subjects who reported on frequency of antiviral use, only 30% reported a frequency consistent with a suppressive regimen while 59% of respondents said they would be likely to take daily therapy if it reduced the frequency of outbreaks. Patient satisfaction with management of physical symptoms was independently associated with duration of initial visit >or=15 minutes (adjusted odds ratio (OR) = 4.52), receiving a prescription (adj OR = 2.34) and receipt of a brochure/fact sheet (adj OR = 2.14). Satisfaction with attention to emotional issues also correlated with the first two of these factors.
Genital herpes management may be improved by including the use of confirmatory laboratory testing, employing a full range of antiviral therapy options, providing educational materials, and committing more time to counselling at the initial visit.
Sexually Transmitted Infections 06/2004; 80(3):192-7. · 2.85 Impact Factor
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D M Patrick,
M L Rekart,
A Jolly,
S Mak,
M Tyndall,
J Maginley,
E Wong,
T Wong,
H Jones,
C Montgomery,
R C Brunham
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ABSTRACT: This study describes the epidemiology and ethnography of an outbreak of infectious syphilis in Vancouver, British Columbia. Between 1996 and 1999, British Columbias's rate of infectious syphilis rose from 0.5 to 3.4 per 100,000, with a dense concentration of cases among sex trade workers, their clients, and street-involved people in the downtown eastside area of Vancouver. Sexual networks were imported cases with secondary spread (dyads and triads), large densely connected dendritic networks of sex trade workers and clients, or occasional starburst networks among gay men. Only 232 of 429 partners were documented as having been treated (54% of those named, or 0.9 per case). The geographical and demographic concentration of this outbreak led to consideration of a programme of focused mass treatment with single dose azithromycin.
Sexually Transmitted Infections 05/2002; 78 Suppl 1:i164-9. · 2.85 Impact Factor
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Canada communicable disease report = Relevé des maladies transmissibles au Canada 04/2002; 28(6):45-9.
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ABSTRACT: Beginning in 1994, Vancouver experienced an explosive outbreak of HIV infection among injection drug users (IDUs). The objectives of this study were to measure the prevalence and incidence of hepatitis C virus (HCV) infection in this context and to examine factors associated with HCV seroconversion among IDUs.
IDUs recruited through a study site and street outreach completed interviewer-administered questionnaires covering subjects' characteristics, behaviour, health status and service utilization and underwent serologic testing for HIV and HCV at baseline and semiannually thereafter. A Cox proportional hazards model was used to identify independent correlates of HCV seroconversion.
As of Nov. 30, 1999, 1345 subjects had been recruited into the study cohort. The prevalence of anti-HCV antibodies was 81.6% (95% confidence interval [CI] 79.6% to 83.6%) at enrollment. Sixty-two HCV seroconversions occurred among 155 IDUs who were initially HCV negative and who returned for follow-up, for an overall incidence density rate of 29.1 per 100 person-years (95% CI 22.3 to 37.3). The HCV incidence remained above 16 per 100 person-years over 3 years of observation (December 1996 to November 1999), whereas HIV incidence declined from more than 19 to less than 5 per 100 person-years. Independent correlates of HCV seroconversion included female sex, cocaine use, injecting at least daily and frequent attendance at a needle exchange program.
Because of high transmissibility of HCV among those injecting frequently and using cocaine, the harm reduction initiatives deployed in Vancouver during the study period proved insufficient to eliminate hepatitis C transmission in this population.
Canadian Medical Association Journal 11/2001; 165(7):889-95. · 8.22 Impact Factor
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ABSTRACT: This study sought to provide the first population estimates of herpes simplex type 2 (HSV-2) seroprevalence in Canada.
To measure the antenatal seroprevalence of HSV-2 antibodies in reproductive age women.
An anonymous unlinked seroprevalence study used stored sera collected from pregnant women in British Columbia during 1999. Randomized sampling within age strata selected a total of 1215 subjects, ages 15 to 44 years. Serologic testing used the Gull Meridian Test. Overall prevalence was directly standardized to the 1999 Canadian female population.
The age-adjusted prevalence for HSV-2 was 17.3% (95% CI, 15.2-19.4). Prevalence ranged from 7.1% (ages, 15-19 years) to 28.1% (ages, 40-44 years), with the largest increases after the age of 24 years.
The HSV-2 seroprevalence among pregnant women in British Columbia is similar to that in the United States and other countries. Seroprevalence continues to rise through the later reproductive years. This observation may relate to continued transmission, an age cohort effect, or both.
Sex Transm Dis 08/2001; 28(7):424-8. · 2.87 Impact Factor
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ABSTRACT: To estimate population size of hard-to-reach groups such as injecting drug users and men who have sex with men.
Several different methods were used to estimate the size of these populations in Canada's three largest cities (Toronto, Montreal and Vancouver).
A novel method (referred to as the indirect method) was developed for use in Toronto and Vancouver that combines HIV serodiagnostic information with data on HIV testing behavior. Population size estimates were obtained by dividing the number of injecting drug users or men who have sex with men recorded in HIV serodiagnostic databases in a given year by the proportion of the corresponding group that reported being tested in a 1-year period. Results of this method were compared with four other methods: (1) population surveys; (2) capture-recapture (for injecting drug users only); (3) a modified Delphi technique; and (4) a method based on the proportion of never-married men aged 45 and over (for men who have sex with men only). Only these other methods were used in Montreal.
The survey method gave the lowest estimates which are best viewed as minimum estimates given the relative inability of surveys to access these populations and the reluctance of participants to admit to sensitive behaviors. The indirect method produced results more closely comparable with those obtained by other methods, but they are probably slight overestimates, at least for injecting drug users, due to possible underestimation of the proportion tested for HIV. Point estimates using the indirect method were 17,700 and 17,500 for injecting drug users in Toronto and Vancouver, respectively, and 39,100 and 15,900 for men who have sex with men. In Toronto, results for the other methods ranged from 12,300-13,360 for injecting drug users and 18,800-35,000 for men who have sex with men. For Vancouver, these ranges were 6400-11,670 and 7000-26,500, respectively. In Montreal, ranges were 4300-12,500 for injecting drug users and 18,500-40,000 for men who have sex with men.
This novel method provides estimates of population size of hard-to-reach groups such as injecting drug users and men who have sex with men that are comparable with results derived by other methods. These estimates may be useful for the purposes of planning, implementing and evaluating prevention and care services, especially when they are combined with the results of other estimation methods to improve the degree of confidence in the resulting estimates.
AIDS 05/2001; 15 Suppl 3:S41-8. · 6.24 Impact Factor
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Canada communicable disease report = Relevé des maladies transmissibles au Canada 02/2001; 27(2):13-8.
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ABSTRACT: The aim of this study was to describe the relationship between sociodemographic characteristics and human immunodeficiency (HIV) status of a cohort of injection drug users (IDUs) on their self-reported health service utilization.
Interviewer-administered questionnaire.
IDUs who had injected illicit drugs within the previous month were recruited through street outreach. They underwent serology for HIV-1 and questionnaires on demographics, drug using behaviors, housing status, and health service utilization (hospitalization overnight and emergency department visits) in the previous 6 months. Logistic regression analysis was used to identify independent associations with the use of health services.
Of 1,103 cohort participants, 65% were male, 63% were white, and 23% were HIV positive. Cocaine was the most frequently injected drug used. Almost half (47%) had used health services in the previous 6 months. The following variables were associated independently with health service utilization (adjusted odds ratio; 95% confidence interval): unstable housing, defined as living primarily in a hotel, boarding room, or transition house or on the street in the past 6 months (1.44; 1.11-1.86); female gender (1.45; 1.11-1.89); HIV-positive status (1.43; 1.06-1.92); injection of cocaine (1.50; 1.12-2.02); and primary care I physician visit in past 6 months (1.91; 1.39-2.64).
IDUs with unstable housing were more likely to report emergency department and hospital use, which may be a reflection of their disorganized lifestyle or poorer health status. Further studies are required to assess the effect on the health status and health care use of IDUs of interventions that increase the availability of safe, affordable housing.
Journal of Urban Health 12/1999; 76(4):409-18. · 2.13 Impact Factor
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ABSTRACT: An association between needle exchange attendance and higher HIV prevalence rates among injecting drug users (IDU) in Vancouver has been interpreted by some to suggest that needle exchange programmes (NEP) may exacerbate HIV spread. We investigated this observed association to determine whether needle exchange was causally associated with the spread of HIV.
Prospective cohort study of 694 IDU recruited in the downtown eastside of Vancouver. Subjects were HIV-negative at the time of recruitment and had injected illicit drugs within the previous month.
Of 694 subjects, the 15-month cumulative HIV incidence was significantly elevated in frequent NEP attendees (11.8+/-1.7 versus 6.2+/-1.5%; log-rank P = 0.012). Frequent attendees (one or more visits per week) were younger and were more likely to report: unstable housing and hotel living, the downtown eastside as their primary injecting site, frequent cocaine injection, sex trade involvement, injecting in 'shooting galleries', and incarceration within the previous 6 months. The Cox regression model predicted 48 seroconversions among frequent attendees; 47 were observed. Although significant proportions of subjects reported obtaining needles, swabs, water and bleach from the NEP, only five (0.7%) reported meeting new friends or people there. When asked where subjects had met their new sharing partners, only one out of 498 respondents cited the needle exchange. Paired analysis of risk variables at baseline and the first follow-up visit did not reveal any increase in risk behaviours among frequent attendees, regardless of whether they had initiated drug injection after establishment of the NEP.
We found no evidence that this NEP is causally associated with HIV transmission. The observed association should not be cited as evidence that NEP may promote the spread of HIV. By attracting higher risk users, NEP may furnish a valuable opportunity to provide additional preventive/support services to these difficult-to-reach individuals.
AIDS 05/1999; 13(6):F45-51. · 6.24 Impact Factor
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ABSTRACT: Intravenous drug users (IDUs) represent a high risk group for dual human immunodeficiency virus (HIV) and tuberculosis (TB) infection. Screening with TB skin testing has therefore been suggested in this group. Subjects' compliance for returning to have TB skin test results read is a major problem. In the setting of a needle exchange program we evaluated the role of financial incentives to increase compliance.
We evaluated the role of giving a small financial incentive of Can $5 to subjects if they returned to have their purified protein derivative (PPD) skin test read. IDUs who had previously been skin-tested were compared with IDUs drawn from a similar population who, prospectively, were offered a financial incentive.
During the initial period 558 subjects were evaluated and no incentive was offered. During the second phase of the study 549 IDUs were assessed but were also offered Can $5 if they returned to have their skin test read. Use of incentives increased compliance from 43% to 78% (P = 0.001). During the same period three active cases of TB were also diagnosed.
We suggest that use of financial incentives can increase the return of IDUs to have their skin tests read. Further studies are required to assess the efficacy of follow-up interventions, especially the use of isoniazid chemoprophylaxis.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 03/1999; 3(2):153-5. · 2.73 Impact Factor
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ABSTRACT: SETTING: Intravenous drug users (IDUs) represent a high risk group for dual human immunodeficiency virus (HIV) and tuberculosis (TB) infection. Screening with TB skin testing has therefore been suggested in this group. Subjects' compliance for returning to have TB skin test results read is a major problem. In the setting of a needle exchange program we evaluated the role of financial incentives to increase compliance.METHODS: We evaluated the role of giving a small financial incentive of Can $5 to subjects if they returned to have their purified protein derivative (PPD) skin test read. IDUs who had previously been skin-tested were compared with IDUs drawn from a similar population who, prospectively, were offered a financial incentive.RESULTS: During the initial period 558 subjects were evaluated and no incentive was offered. During the second phase of the study 549 IDUs were assessed but were also offered Can $5 if they returned to have their skin test read. Use of incentives increased compliance from 43% to 78% (P = 0.001). During the same period three active cases of TB were also diagnosed.CONCLUSIONS: We suggest that use of financial incentives can increase the return of IDUs to have their skin tests read. Further studies are required to assess the efficacy of follow-up interventions, especially the use of isoniazid chemoprophylaxis.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 01/1999; 3(2):153-155. · 2.73 Impact Factor
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ABSTRACT: The objectives of this study were to assess the effect of British Columbia's June 1994 guidelines for prenatal HIV screening on the rate of maternal-fetal HIV transmission and to estimate the cost-effectiveness of such screening.
The authors conducted a retrospective review of pregnancy and delivery statistics, HIV screening practices, laboratory testing volume, prenatal and labour management decisions of HIV-positive women, maternal-fetal transmission rates and associated costs.
Over 1995 and 1996, 135,681 women were pregnant and 92,645 carried to term. The rate of HIV testing increased from 55% to 76% of pregnancies on chart review at one hospital between November 1995 and November 1996. On the basis of seroprevalence studies, an estimated 50.2 pregnancies and 34.3 (95% confidence interval 17.6 to 51.0) live births to HIV-positive women were expected. Of 42 identified mother-infant pairs with an estimated date of delivery during 1995 or 1996, 25 were known only through screening. Of these 25 cases, there were 10 terminations, 1 spontaneous abortion and 14 cases in which the woman elected to carry the pregnancy to term with antiretroviral therapy. There was one stillbirth. One instance of maternal-fetal HIV transmission occurred among the 13 live births. The net savings attributable to prevented infections among babies carried to term were $165,586, with a saving per prevented case of $75,266.
A routine offer of pregnancy screening for HIV in a low-prevalence setting reduces the rate of maternal-fetal HIV transmission and may rival other widely accepted health care expenditures in terms of cost-effectiveness.
Canadian Medical Association Journal 11/1998; 159(8):942-7. · 8.22 Impact Factor
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ABSTRACT: The proportion of injection drug users (IDUs) testing positive for Human Immunodeficiency Virus (HIV) in British Columbia has increased from 3 to 7% since January 1993 (Patrick et al., 1997). We conducted a qualitative study as a first step in a case control investigation aimed at identifying risk factors associated with HIV seroconversion. Sixteen subjects participated in in-depth interviews which were transcribed and analysed using grounded theory methods. Three dominant themes emerged: Addiction, Prevention, and Social Determinants. The results suggest that prevention efforts such as the availability of clean needles and condoms are not adequate to combat the complex social determinants of addiction--be they causal or consequential--which in turn contribute to unsafe injection practices.
AIDS Care 07/1998; 10(3):313-21. · 1.60 Impact Factor
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ABSTRACT: The aim of this article is to provide an overview of the epidemiology, diagnosis, screening and pharmacotherapy of Chlamydia trachomatis infections in adolescents and adults, together with a critical review of economic studies published on this topic. C. trachomatis continues to produce enormous social and economic consequences despite advances in prevention, screening and treatment. Both infected men and women are at risk of developing sequelae, although women tend to have more serious complications. Several strategies are available for diagnosis and screening. In populations with a high prevalence of disease, DNA-amplification assays may be the most cost-effective approach for diagnosis and screening. Empirical treatment of all patients is also cost effective; however, it may not be feasible for all health systems. A single dose of azithromycin is the most cost-effective antimicrobial agent for treatment of C. trachomatis infection.
PharmacoEconomics 03/1998; 13(2):191-222. · 2.66 Impact Factor
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ABSTRACT: The objective of this study was to identify factors associated with frequent needle exchange program (NEP) attendance by injection drug users (IDUs) in Vancouver, Canada. Data were examined from a case control study of recent HIV infection. IDUs with documented HIV seroconversion after January 1, 1994 (n = 89) and seronegative controls with two documented HIV-negative test results in the same period (n = 192) were asked about demographic and social information, drug injection and sexual behavior, and NEP attendance. Logistic regression was used to examine the effect of multiple variables on NEP attendance while adjusting for HIV status and other potential confounders. Frequent (> 1 time/week) versus nonfrequent (< or = 1 time/week) NEP attenders did not differ with respect to gender, age, ethnicity, education, or HIV serostatus. For men, multivariate analysis showed that frequent cocaine injection was the only variable independently associated with NEP attendance (adjusted odds ratio [AOR] = 3.9; 95% confidence interval [CI] = 1.8-8.3); for women, independently associated variables were frequency of any drug injection (AOR = 5.5; 95% CI = 1.7-17), shooting gallery attendance (AOR = 11.5; 95% CI = 2.2-66), and having a nonlegal source of income (AOR = 3.4; 95% CI = 1.0-12). Borrowing used needles was associated with frequent NEP attendance in the univariate analysis. The NEP in Vancouver attracts IDUs who are frequent injectors (especially men using cocaine) and who have high-risk behaviors or an unstable lifestyle. This finding reinforces the role of NEPs as potential focal points for intervention in this hard-to-reach population.
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 02/1998; 17(2):160-6.
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ABSTRACT: Despite the fact that needle exchange was introduced in Vancouver as early as 1988, needle sharing remains common. An analysis was conducted to identify determinants of borrowing used needles among subjects participating in a case-control study. IDUs had a documented HIV seroconversion after 1 January, 1994 (n = 89), or repeatedly tested HIV-seronegative after this date (n = 192). Interviewer-administered questionnaires focused on drug use, sexual behaviours, source of needles and depression. Subjects were asked if they had "ever been forced to have sex" as a child, youth or adult. Logistic regression identified determinants of borrowing needles. After controlling for HIV serostatus, factors independently associated with borrowing were injecting > 4 times/day, polydrug use, and ever experiencing non-consensual sex (AOR = 3.4, 95% CI: 1.8, 6.5). Depression was associated with borrowing, although not independently so. Homosexual activity was independently associated with borrowing among males, whereas living with a sexual partner was an independent predictor for females. Access or barriers to clean needle use were not associated with borrowing. Social determinants, particularly a history of sexual abuse, are among the most significant predictors of needle borrowing among Vancouver's IDUs. Early identification of these factors should be a component of HIV prevention programmes.
Addiction 10/1997; 92(10):1339-47. · 4.31 Impact Factor
