BACKGROUND:

In recent years, the proportion of patients attending tertiary care HIV clinics who are recent immigrants to Canada has increased dramatically.

METHODS:

Among patients first seen at the Toronto Hospital Immunodeficiency Clinic (Toronto, Ontario) between January 1, 2000 and August 31, 2009, the time to death from the first positive HIV test was compared between individuals who had immigrated to Canada within 10 years of their first visit and individuals who were either Canadian-born or who had immigrated more than 10 years before their first clinic visit. In addition, for the antiretroviral-naive patients in these two groups who initiated combination antiretroviral therapy, the time to and the duration of virologic suppression were compared.

RESULTS:

In a multivariable proportional hazards (PH) model, recent immigrant status was associated with decreased mortality (HR 0.11, P=0.03) after adjusting for age, CD4 count and the risk factor for men having sex with men. In multivariable PH models, recent female immigrants achieved virologic suppression more quickly (HR 1.51, P=0.02), while male immigrants (HR 1.14, P=0.44) and female nonimmigrants (HR 0.90, P=0.61) had similar times to virologic suppression as male nonimmigrants, respectively, after adjusting for the year of and viral load at combination antiretroviral therapy initiation. When pregnant women were removed from the analysis, there were no significant differences in the rates of virologic rebound according to sex or immigration status.

DISCUSSION:

Despite the perceived barriers of newcomers to Canada, mortality was lower among recent immigrants and virologic suppression was achieved more quickly in recent female immigrants.

This study aimed to understand gender and ethnicity differences in HIV-related stigma experienced by 1026 HIV-positive individuals living in Ontario, Canada that were enrolled in the OHTN Cohort Study. Total and subscale HIV-related stigma scores were measured using the revised HIV-related Stigma Scale. Correlates of total stigma scores were assessed in univariate and multivariate linear regression. Women had significantly higher total and subscale stigma scores than men (total, median = 56.0 vs. 48.0, p<0.0001). Among men and women, Black individuals had the highest, Aboriginal and Asian/Latin-American/Unspecified people intermediate, and White individuals the lowest total stigma scores. The gender-ethnicity interaction term was significant in multivariate analysis: Black women and Asian/Latin-American/Unspecified men reported the highest HIV-related stigma scores. Gender and ethnicity differences in HIV-related stigma were identified in our cohort. Findings suggest differing approaches may be required to address HIV-related stigma based on gender and ethnicity; and such strategies should challenge racist and sexist stereotypes.

The purpose of this cross-sectional study is to assess the desire, need, perceptions, and knowledge of assisted reproductive technologies (ARTs) for women living with HIV (WLWHIV) and determine correlates of ART knowledge desire. WLWHIV of reproductive age were surveyed using the survey instrument “The HIV Pregnancy Planning Questionnaire” at HIV/AIDS service organizations across Ontario, Canada. Of our cohort of 500 WLWHIV, median age was 38, 88% were previously pregnant, 78% desired more information regarding ART, 59% were open to the idea of receiving ART, 39% felt they could access a sperm bank, and 17% had difficulties conceiving (self-reported). Age, African ethnicity, and residence in an urban center were correlated with desire for more ART information. Of participants, 50% wanted to speak to an obstetrician/gynecologist regarding pregnancy planning, and 74% regarded physicians as a main source of fertility service information. While the majority of participants in our cohort desire access to ART information, most do not perceive these services as readily accessible. Healthcare practitioners were viewed as main sources of information regarding fertility services and need to provide accurate information regarding access. Fertility service professionals need to be aware of the increasing demand for ART among WLWHIV.

Objective

Because effective antiretroviral therapy (ART) reduces immune activation, we hypothesize that early changes in immune activation are associated with subsequent virologic response to therapy.

Design

Observational cohort study.

Setting

Institutional HIV clinic.

Subjects

Thirty-four adult HIV patients with virologic failure on their current antiretroviral regimen.

Intervention

Change to salvage regimen selected by patient’s physician.

Main Outcome Measures

Measures of immune activation at baseline and at 2, 4, 8, and 24 weeks after enrollment. Data were analyzed by proportional hazards (PH) models.

Results

PH models showed that reductions between baseline and week 2 in expression of CD38 (P = 0.02) or CD95 (P = 0.02) on CD4+ T cells were associated with increased likelihood of achieving virologic suppression. Kaplan-Meier analysis demonstrated that patients who had reductions within the first 2 weeks of therapy in CD4+ T-cell expression of CD38 (P = 0.003) or CD95 (P = 0.08) were more likely to achieve viral suppression than those who did not.

Conclusions

Reduced CD4+ T-cell expression of CD38 and CD95 occurring within 2 weeks of salvage therapy is associated with subsequent viral suppression. Monitoring CD38 and CD95 may allow earlier assessment of the response to ART.

Background

Although highly active antiretroviral therapy (HAART) has dramatically decreased HIV-related morbidity and mortality, the associated costs, toxicities, and resistance risks make the potential delay of HAART initiation an attractive goal. Suppression of herpes simplex virus type 2 (HSV-2) may be a novel strategy for achieving this goal because HSV-2 is associated with clinically significant increases in HIV viral load, the primary driver of HIV disease progression.

Methods/Design

The VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial is a multicentre, randomized, fully blinded, clinical trial of twice daily valacyclovir 500 mg versus placebo for delaying the need for initiating HAART among HIV-1, HSV-2 co-infected HAART-naïve adults. 480 participants from Canada, Brazil and Argentina will undergo quarterly clinical follow-up until reaching the composite primary endpoint of having a CD4+ T-cell count ≤ 350 cells/mm3 or initiation of HAART for any reason, whichever occurs first. The primary analysis will use a proportional hazards model, stratified by site, to estimate the relative risk of progression to this endpoint associated with valacyclovir. Secondary analyses will compare the rates of change in CD4 count, median log10 HIV viral load, drug-related adverse events, frequency of HSV reactivations, rate of acyclovir-resistant HSV, and quality of life between study arms.

Discussion

Although HIV treatment guidelines continue to evolve, with some authorities recommending earlier HAART among asymptomatic individuals, the potential delay of HAART remains a clinically relevant goal for many. If shown to be of benefit, implementation of the VALIDATE intervention will require careful consideration of both individual patient-level and public health implications.

Trial Registration

Current Controlled Trials ISRCTN66756285

ClinicalTrials.gov NCT00860977

Background

In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission.

Methods

A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission.

Results

45 laboratory-confirmed intubated SARS patients were identified. Of the 697 HCWs involved in their care, 624 (90%) participated in the study. SARS-CoV was transmitted to 26 HCWs from 7 patients; 21 HCWs were infected by 3 patients. In multivariate GEE logistic regression models, presence in the room during fiberoptic intubation (OR = 2.79, p = .004) or ECG (OR = 3.52, p = .002), unprotected eye contact with secretions (OR = 7.34, p = .001), patient APACHE II score ≥20 (OR = 17.05, p = .009) and patient Pa02/Fi02 ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients.

Conclusion

Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients.

Beate Sander and colleagues assess the cost-effectiveness of the program that provides free seasonal influenza vaccines to the entire population of Ontario, Canada.

Background

In July 2000, the province of Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free seasonal influenza vaccines for the entire population. This is the first large-scale program of its kind worldwide. The objective of this study was to conduct an economic appraisal of Ontario's UIIP compared to a targeted influenza immunization program (TIIP).

Methods and Findings

A cost-utility analysis using Ontario health administrative data was performed. The study was informed by a companion ecological study comparing physician visits, emergency department visits, hospitalizations, and deaths between 1997 and 2004 in Ontario and nine other Canadian provinces offering targeted immunization programs. The relative change estimates from pre-2000 to post-2000 as observed in other provinces were applied to pre-UIIP Ontario event rates to calculate the expected number of events had Ontario continued to offer targeted immunization. Main outcome measures were quality-adjusted life years (QALYs), costs in 2006 Canadian dollars, and incremental cost-utility ratios (incremental cost per QALY gained). Program and other costs were drawn from Ontario sources. Utility weights were obtained from the literature. The incremental cost of the program per QALY gained was calculated from the health care payer perspective. Ontario's UIIP costs approximately twice as much as a targeted program but reduces influenza cases by 61% and mortality by 28%, saving an estimated 1,134 QALYs per season overall. Reducing influenza cases decreases health care services cost by 52%. Most cost savings can be attributed to hospitalizations avoided. The incremental cost-effectiveness ratio is Can$10,797/QALY gained. Results are most sensitive to immunization cost and number of deaths averted.

Conclusions

Universal immunization against seasonal influenza was estimated to be an economically attractive intervention.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Annual outbreaks (epidemics) of influenza—a viral disease of the nose, throat, and airways—make millions of people ill and kill about 500,000 individuals every year. In doing so, they impose a considerable economic burden on society in terms of health care costs and lost productivity. Influenza epidemics occur because small but frequent changes in the viral proteins to which the immune system responds mean that an immune response produced one year by exposure to an influenza virus provides only partial protection against influenza the next year. Annual immunization with a vaccine that contains killed influenza viruses of the major circulating strains can boost this natural immunity and greatly reduce a person's chances of catching influenza. Consequently, many countries run seasonal influenza vaccine programs. These programs usually target people at high risk of complications from influenza and individuals likely to come into close contact with them, and people who provide essential community services. So, for example, in most Canadian provinces, targeted influenza immunization programs (TIIPs) offer free influenza vaccinations to people aged 65 years or older, to people with chronic medical conditions, and to health care workers.

Why Was This Study Done?

Some experts argue, however, that universal vaccination might provide populations with better protection from influenza. In 2000, the province of Ontario in Canada decided, therefore, to introduce a universal influenza immunization program (UIIP) to provide free influenza vaccination to everyone older than 6 months, the first large program of this kind in the world. A study published in 2008 showed that, following the introduction of the UIIP, vaccination rates in Ontario increased more than in other Canadian provinces. In addition, deaths from influenza and influenza-related use of health care facilities decreased more in Ontario than in provinces that continued to offer a TIIP. But is universal influenza vaccination good value for money? In this study, the researchers evaluate the cost-effectiveness of the Ontario UIIP by comparing the health outcomes and costs associated with its introduction with the health outcomes and costs associated with a hypothetical continuation of targeted influenza immunization.

What Did the Researchers Do and Find?

The researchers used data on TIIP and UIIP vaccine uptake, physician visits, emergency department visits, hospitalizations for influenza, and deaths from influenza between 1997 and 2004 in Ontario and in nine Canadian states offering TIIPs, and Ontario cost data, in their “cost-utility” analysis. This type of analysis estimates the additional cost required to generate a year of perfect health (a quality-adjusted life-year or QALY) through the introduction of an intervention. QALYs are calculated by multiplying the time spent in a certain health state by a measure of the quality of that health state. The researchers report that the cost of Ontario's UIIP was about twice as much as the cost of a TIIP for the province. However, the introduction of the UIIP reduced the number of influenza cases by nearly two-thirds and reduced deaths from influenza by more than a quarter compared with what would have been expected had the province continued to offer a TIIP, an overall saving of 1,134 QALYs. Furthermore, the reduction in influenza cases halved influenza-related health care costs, mainly because of reductions in hospitalization. Overall, this means that the additional cost to Ontario of saving one QALY through the introduction of the UIIP was Can$10,797, an “incremental cost-effectiveness ratio” of $10,797 per QALY gained.

What Do These Findings Mean?

In Canada, an intervention is considered cost-effective from the point of view of a health care purchaser if it costs less than Canadian $50,000 to gain one QALY. These findings indicate, therefore, that for Ontario the introduction of the UIIP is economically attractive. Indeed, the researchers calculate that even if the costs of the UIIP were to double, the additional cost of saving one QALY by introducing universal immunization would remain below $50,000. Other “sensitivity” analyses undertaken by the researchers also indicate that universal immunization is likely to be effective and cost-effective in Ontario if other key assumptions and/or data included in the calculations are varied within reasonable limits. Given these findings, the researchers suggest that a UIIP might be an appealing intervention in other Canadian provinces and in other high-income countries where influenza transmission and health-care costs are broadly similar to those in Ontario.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000256.

A PLoS Medicine Research Article by Kwong and colleagues describes how the introduction of universal influenza immunization in Ontario altered influenza-related health care use and deaths in the province

Wikipedia pages are available on QALYs and on cost-utility analysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)

Bandolier, an independent online journal about evidence-based health-care, provides information about QALYs and their use in cost-utility analysis

The UK National Institute for Health and Clinical Excellence has a webpage on Measuring effectiveness and cost-effectiveness: the QALY

Background

Viral load (VL) monitoring is an essential component of the care of HIV positive individuals. Rates of VL monitoring have been shown to vary by HIV risk factor and clinical characteristics. The objective of this study was to determine whether there are differences among regions in Canada in the rates of VL testing of HIV-positive individuals on combination antiretroviral therapy (cART), where the testing is available without financial barriers under the coverage of provincial health insurance programs.

Methods

The Canadian Observational Cohort (CANOC) is a collaboration of nine Canadian cohorts of HIV-positive individuals who initiated cART after January 1, 2000. The study included participants with at least one year of follow-up. Generalized Estimating Equation (GEE) regression models were used to determine the effect of geographic region on (1) the occurrence of an interval of 9 months or more between two consecutive recorded VL tests and (2) the number of days between VL tests, after adjusting for demographic and clinical covariates. Overall and regional annual rates of VL testing were also reported.

Results

3,648 individuals were included in the analysis with a median follow-up of 42.9 months and a median of 15 VL tests. In multivariable GEE logistic regression models, gaps in VL testing >9 months were more likely in Quebec (Odds Ratio (OR) = 1.72, p < 0.0001) and Ontario (OR = 1.78, p < 0.0001) than in British Columbia and among injection drug users (OR = 1.68, p < 0.0001) and were less likely among older individuals (OR = 0.77 per 10 years, p < 0.0001), among men having sex with men (OR = 0.62, p < 0.0001), within the first year of cART (OR = 0.15, p < 0.0001), among individuals on cART at the time of the blood draw (OR = 0.34, p < 0.0001) and among individuals with VL < 50 copies/ml at the previous visit (OR = 0.56, p < .0001).

Conclusions

Significant variation in rates of VL testing and the probability of a significant gap in testing were related to geographic region, HIV risk factor, age, year of cART initiation, type of cART regimen, being in the first year of cART, AIDS-defining illness and whether or not the previous VL was below the limit of detection.

Background

Improvements in life expectancy and quality of life for HIV-positive women coupled with reduced vertical transmission will likely lead numerous HIV-positive women to consider becoming pregnant. In order to clarify the demand, and aid with appropriate health services planning for this population, our study aims to assess the fertility desires and intentions of HIV-positive women of reproductive age living in Ontario, Canada.

Methodology/Principal Findings

A cross-sectional study with recruitment stratified to match the geographic distribution of HIV-positive women of reproductive age (18–52) living in Ontario was carried out. Women were recruited from 38 sites between October 2007 and April 2009 and invited to complete a 189-item self-administered survey entitled “The HIV Pregnancy Planning Questionnaire” designed to assess fertility desires, intentions and actions. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios of significant predictors of fertility intentions. The median age of the 490 participating HIV-positive women was 38 (IQR, 32–43) and 61%, 52%, 47% and 74% were born outside of Canada, living in Toronto, of African ethnicity and currently on antiretroviral therapy, respectively. Of total respondents, 69% (95% CI, 64%–73%) desired to give birth and 57% (95% CI, 53%–62%) intended to give birth in the future. In the multivariable model, the significant predictors of fertility intentions were: younger age (age<40) (p<0.0001), African ethnicity (p<0.0001), living in Toronto (p = 0.002), and a lower number of lifetime births (p = 0.02).

Conclusions/Significance

The proportions of HIV-positive women of reproductive age living in Ontario desiring and intending pregnancy were higher than reported in earlier North American studies. Proportions were more similar to those reported from African populations. Healthcare providers and policy makers need to consider increasing services and support for pregnancy planning for HIV-positive women. This may be particularly significant in jurisdictions with high levels of African immigration.

BACKGROUND

Provider-caregiver communication is a key ingredient in quality health care and patient safety, and effective communication has been shown to affect compliance and outcomes.

OBJECTIVES

To identify and compare communication issues among three paediatric outpatient clinics.

METHODS

In this prospective, qualitative study, a questionnaire was used to survey physicians, nurse practitioners and caregivers at three different infectious diseases clinics.

RESULTS

There was a statistically significant preponderance of families in the tuberculosis clinic for whom English was not the mother tongue and who were not fluent in English. Patients in the HIV clinic were less likely to be at their first appointment than were patients attending the other clinics. Patients in the general clinic were less likely to have been seen by the same physician on the previous visit. Parents from all three clinics were satisfied with the care they received, with communication and with rapport with their child. There was a trend toward parents in the tuberculosis clinic being happier with their clinic visit and less likely to complain about the wait time.

CONCLUSIONS

Language proficiency and lack of continuity of provider care were identified as potential risks for patient safety in the ambulatory setting. Further studies are necessary to identify language and cultural issues that may affect patient care in a tertiary paediatric hospital servicing a multiethnic population.

BACKGROUND:

Increasing rates of trimethoprim-sulfamethoxazole (TMP-SMX) resistance among uropathogens have raised concerns about its continued role in empirical treatment of acute uncomplicated cystitis in adult women.

OBJECTIVE:

To determine current rates of antibiotic resistance among uropathogens in the community.

METHODS:

Urine culture reports from adult women with symptoms of cystitis attending the offices of family physicians from across Canada were examined. Antibiotic sensitivities and the total number of antibiotics an organism was resistant to was determined.

RESULTS:

In 446 women, 235 (61.4%) positive urine cultures were identified. Of these, 38.2% were resistant to at least one antibiotic and 21.5% were resistant to two or more antibiotics. The rate of ampicillin resistance was 34.1%. For TMP-SMX, resistance was reported in 10.8% of samples. Antibiotic resistance was higher in British Columbia (55%) and western provinces (48%), compared with Ontario (33.3%) and the eastern provinces (26.3%, P=0.04, Fisher's exact test). Multidrug resistance was also higher in western Canada (33.9%) than in eastern Canada (16.6%, P=0.007).

CONCLUSIONS:

TMP-SMX resistance in Canada remains within current recommended guidelines, allowing for its continued use as a first line empirical treatment for acute cystitis in adult women. The reasons for higher rates of antibiotic resistance in western Canada merit further study.