Janet Raboud

Antiviral Therapy and Outcomes of Influenza Requiring Hospitalization in Ontario, Canada

BACKGROUNDnWe conducted a prospective cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario, Canada.nnnMETHODSnPatients admitted to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study. Demographic and medical data were collected by patient and physician interview and chart review. The main outcome evaluated was death within 15 days after symptom onset.nnnRESULTSnData were available for 512 of 541 eligible patients. There were 185 children (<15 years of age), none of whom died and none of whom were treated with antiviral drugs. The median age of the 327 adults was 77 years (range, 15-98 years), 166 (51%) were male, 245 (75%) had a chronic underlying illness, and 216 (71%) had been vaccinated against influenza. Of the 327 adult patients, 184 (59%) presented to the emergency department within 48 h after symptom onset, 52 (16%) required intensive care unit admission, and 27 (8.3%) died within 15 days after symptom onset. Most patients (292 patients; 89%) received antibacterial therapy; 106 (32%) were prescribed antiviral drugs. Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality (odds ratio, 0.21; 95% confidence interval, 0.06-0.80; n=100, 260). There was no apparent impact of antiviral therapy on length of stay in survivors.nnnCONCLUSIONSnThere is a significant burden of illness attributable to influenza in this highly vaccinated population. Treatment with antiviral drugs was associated with a significant reduction in mortality.

Gender and Ethnicity Differences in HIV-related Stigma Experienced by People Living with HIV in Ontario, Canada

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, medianu200a=u200a56.0 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.

Association of Hematological Parameters with Insulin Resistance and β-Cell Dysfunction in Nondiabetic Subjects

OBJECTIVEnPrevious studies reported independent associations of hematological parameters with risk of incident type 2 diabetes, although limited data are available on associations of these parameters with insulin resistance (IR) and (especially) pancreatic beta-cell dysfunction in large epidemiological studies. Our objective was to evaluate the associations of hematological parameters, including hematocrit (HCT), hemoglobin (Hgb), red blood cell count (RBC), and white blood cell count with IR and beta-cell dysfunction in a cohort of nondiabetic subjects at high metabolic risk.nnnMETHODSnNondiabetic subjects (n = 712) were recruited in Toronto and London, Ontario, Canada, between 2004 and 2006, based on the presence of one or more risk factors for type 2 diabetes mellitus including obesity, hypertension, a family history of diabetes, and/or a history of gestational diabetes. Fasting blood samples were collected and oral glucose tolerance tests administered, with additional samples for glucose and insulin drawn at 30 and 120 min. Measures of IR included the homeostasis model assessment (HOMA-IR) and Matsudas insulin sensitivity index, whereas measures of beta-cell dysfunction included the insulinogenic index divided by HOMA-IR as well as the insulin secretion-sensitivity index-2. Associations of hematological parameters with IR and beta-cell dysfunction were assessed using multiple linear regression and analysis of covariance with adjustments for age, gender, ethnicity, smoking, cardiovascular disease, systolic and diastolic blood pressure, and waist circumference.nnnRESULTSnHOMA-IR increased across quartiles of HCT, Hgb, RBC, and white blood cell count after adjustment for age, gender, ethnicity, and smoking (all P (trend) <0.0001). Similarly, there was a strong stepwise decrease in the Matsudas insulin sensitivity index across increasing quartiles of these hematological measures (all P (trend) <0.0001). The associations remained significant after further adjustment for previous cardiovascular disease, blood pressure, and waist circumference (all P (trend) <0.0001). Similarly, there was a strong pattern of decreasing beta-cell function across increasing quartiles of all hematological patterns (all P (trend) <0.0001). The findings for HCT, Hgb, and RBC were attenuated slightly after full multivariate adjustment, although the trend across quartiles remained highly significant.nnnCONCLUSIONnThese findings suggest that standard, clinically relevant hematological variables may be related to the underlying pathophysiological changes associated with type 2 diabetes mellitus.

Cohort Profile: The Ontario HIV Treatment Network Cohort Study (OCS)

The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27,720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy.ca).

Risk of cardiovascular disease associated with HCV and HBV coinfection among antiretroviral-treated HIV-infected individuals.

BACKGROUNDnThe increased risk for cardiovascular disease (CVD) in HIV is well established. Despite high prevalence of viral hepatitis coinfection with HIV, there are few studies on the risk of CVD amongst antiretroviral therapy (ART)-treated coinfected patients.nnnMETHODSnOntario HIV Treatment Network Cohort Study participants who initiated ART without prior CVD events were analysed. HBV and HCV coinfection were identified by serology and RNA test results. CVD was defined as any of: coronary artery disease including atherosclerosis, chronic ischaemic heart disease and arteriosclerotic vascular disease; myocardial infarction; congestive heart failure; cerebrovascular accident or stroke; coronary bypass; angioplasty; and sudden cardiac death. The impact of HBV and HCV coinfection on time to CVD was assessed using multivariable competing risk models accounting for left truncation between ART initiation and study enrolment.nnnRESULTSnA total of 3,416 HIV-monoinfected, 432 HIV-HBV- and 736 HIV-HCV-coinfected individuals were followed for a median (IQR) of 2.32 years (1.36-8.02). Over the study period, 167 CVD events and 613 deaths were documented. After adjustment for age, gender, race, year initiating ART, weight and smoking status, HBV was not associated with time to CVD onset (aHR=1.05, 95% CI [0.63, 1.74]; P=0.86). There was an elevated risk of CVD for HCV-coinfected individuals, which approached statistical significance (aHR=1.44, 95% CI [0.97, 2.13]; P=0.07).nnnCONCLUSIONSnOur results are consistent with a moderate increase of CVD among individuals with HIV-HCV coinfection relative to those with HIV infection alone, lending support to consideration of initiation of HCV antiviral treatment.

Patterns of handwashing behavior and visits to patients on a general medical ward of healthcare workers.

OBJECTIVEnTo obtain accurate data regarding the handwashing behavior and patterns of visits to patients by healthcare workers (HCWs).nnnMETHODSnAll visits by HCWs to selected patient rooms were recorded for 3 days and 2 nights. Additionally, 5 nurses were observed for 1 day each and 2 nurses were observed for 1 night each. Nurses were observed for their entire shifts and all of their activities were recorded.nnnSETTINGnA general medical ward in a tertiary-care hospital.nnnPARTICIPANTSnConvenience samples of HCWs and patients.nnnRESULTSnPatients were visited every 25 minutes on average. Monitoring rooms and observing nurses resulted in similar rates of patient visits. The highest level of risk was contact with body fluids in 11% of visits and skin in 40% of visits. The overall rate of handwashing was 46%; however, the rate was higher for visits involving contact with body fluids (81%) and skin (61%). Nurses returned immediately to the same patient 45% of the time. The rate of handwashing was higher for the last of a series of visits to a patients room (53% vs 30%, P < .0001).nnnCONCLUSIONSnNurses adjusted their handwashing rates in accordance with the risk level of each visit. Monitoring patient rooms and observing nurses yielded similar estimates of patient visits and proportions of visits involving contact with skin or body fluids. Education programs about hand hygiene may be more effective if patterns of care and levels of risk are incorporated into recommendations.

Preventing type 2 diabetes using combination therapy: design and methods of the CAnadian Normoglycaemia Outcomes Evaluation (CANOE) trial

Several studies have demonstrated that type 2 diabetes mellitus (DM) can be prevented/delayed in subjects with impaired glucose tolerance (IGT) by using pharmacologic agents and/or lifestyle interventions. However, a number of challenges remain, including the translation of lifestyle programmes to the general population and the need to achieve greater risk reductions by using pharmacologic approaches. IGT, like DM, is characterized by insulin resistance, β‐cell dysfunction and increased hepatic glucose production. We believe that the use of combination diabetes therapy would be a particularly effective diabetes prevention strategy. In this context, we initiated the Canadian Normoglycemia Outcomes Evaluation (CANOE) study, a moderately sized, randomized, double‐blind, controlled trial. The primary objective of CANOE is to determine whether treatment with metformin plus rosiglitazone, in addition to a healthy living lifestyle programme, will prevent the development of DM. The secondary objective of CANOE is to determine whether this treatment approach will improve cardiovascular risk factors associated with IGT. A total of 200 patients will be recruited in Toronto and London, Ontario, and followed for an average of 4 years (range 3–5 years). Active treatment with metformin (500u2003mg) plus rosiglitazone (2u2003mg), administered as one capsule twice daily, will be compared to matched placebo. Subjects will be eligible for randomization if they have IGT and are between the ages of 30–75 years. The primary outcome will be the development of new‐onset DM, diagnosed by either two fasting plasma glucose values of ≥7u2003mmol/l or one positive oral glucose tolerance test with a 2‐h plasma glucose value of >11.0u2003mmol/l during the active drug phase of the trial. With a sample size of 100 participants per group, we will be able to detect a relative risk reduction of 45%, with a two‐sided log‐rank test with a significance level of 0.05 and 80% power, assuming that the median time to progression is 8 years in the control group and that participants will be recruited over 2 years and followed for an average of 4 years. In conclusion, the CANOE study will determine whether combination pharmacological therapy combined with a lifestyle intervention programme can significantly modify the development of diabetes in high‐risk Canadians.

Ethnicity and gender differences in lipodystrophy of HIV-positive individuals taking antiretroviral therapy in Ontario, Canada.

Abstract Purpose: This study assessed ethnicity and gender differences in prevalence, type, and severity of antiretroviral-associated lipodystrophy in HIV-positive individuals in Ontario. Methods: This was a cross-sectional analysis of the Ontario Cohort Study (OCS), a prospective study of HIV-positive patients in Ontario. Lipodystrophy was defined as at least 1 major or 2 minor self-reported changes of peripheral lipoatrophy and/or central lipohypertrophy. Prevalence, type, and severity were compared by ethnicity (Black, White, or Other) and gender. Univariate and multivariate logistic regression analyses identified predictors of lipodystrophy. Results: Data were available for 778 participants (659 men, 119 women). There were 517 Whites, 121 Blacks, and 140 patients of Other ethnicities. In univariate analyses, Whites reported more peripheral lipoatrophy (P = .004) and abdominal lipohypertrophy (P = .04); these ethnic differences were observed in males (P = .05 and P = .03, respectively) but not females. Males reported more peripheral lipoatrophy (P = .01), whereas females had more central lipohypertrophy (P < .0001) and mixed fat redistribution (P < .0001). Multivariable regression analyses revealed Black women to be most vulnerable to lipodystrophy (P = .02), particularly lipohypertrophy (P < .0001). Conclusions: Ethnicity and gender are important factors influencing lipodystrophy. Combining lipoatrophy and lipohypertrophy into a single entity is not appropriate. Black women were most vulnerable to lipohypertrophy, which has important implications for antiretroviral therapy roll-out in Africa.

Factors Associated With Critical-Care Healthcare Workers' Adherence to Recommended Barrier Precautions During the Toronto Severe Acute Respiratory Syndrome Outbreak

OBJECTIVEnTo assess factors associated with adherence to recommended barrier precautions among healthcare workers (HCWs) providing care to critically ill patients with severe acute respiratory syndrome (SARS).nnnSETTINGnFifteen acute care hospitals in Ontario, Canada.nnnDESIGNnRetrospective cohort study.nnnPATIENTSnAll patients with SARS who required intubation during the Toronto SARS outbreak in 2003.nnnPARTICIPANTSnHCWs who provided care to or entered the room of a SARS patient during the period from 24 hours before intubation until 4 hours after intubation.nnnMETHODSnStandardized interviews were conducted with eligible HCWs to assess their interactions with the SARS patient, their use of barrier precautions, their practices for removing personal protective equipment, and the infection control training they received.nnnRESULTSnOf 879 eligible HCWs, 795 (90%) participated. In multivariate analysis, the following predictors of consistent adherence to recommended barrier precautions were identified: recognition of the patient as a SARS case (odds ratio [OR], 2.5 [95% confidence interval {CI}, 1.5-4.5); recent infection control training (OR for interactive training, 2.7 [95% CI, 1.7-4.4]; OR for passive training, 1.7 [95% CI, 1.0-3.0]), and working in a SARS unit (OR, 4.0 [95% CI, 1.8-8.9]) or intensive care unit (OR, 4.3 [95% CI, 2.0-9.0]). Two factors were associated with significantly lower rates of consistent adherence: the provision of care for patients with higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR for score APACHE II of 20 or greater, 0.4 [95% CI, 0.28-0.68]) and work on shifts that required more frequent room entry (OR for 6 or more entries per shift, 0.5 [95% CI, 0.32-0.86]).nnnCONCLUSIONSnThere were significant deficits in knowledge about self-protection that were partially corrected by education programs during the SARS outbreak. HCWs adherence to self-protection guidelines was most closely associated with whether they provided care to patients who had received a definite diagnosis of SARS.

Symptomatic primary HIV infection or risk experiences? Circumstances surrounding HIV testing and diagnosis among recent seroconverters

Our objective was to understand the circumstances surrounding HIV testing among recent HIV seroconverters (n = 80) compared to HIV-negative controls (n = 106) in Ontario, Canada using self-reported interview data. Diagnosis of symptomatic primary HIV infection (SPHI) was defined as diagnosis by the participants physician. Testing in response to symptoms was reported by 42% of seroconverters vs 12% of controls. More controls than seroconverters tested in response to risk behaviour (70% vs 50%) or from a desire to know their status (34% vs 12%). Among seroconverters, 76% reported flu-like illness during the time period of infection, 66% had symptoms consistent with SPHI, and 35% reported a physicians diagnosis of SPHI. Compared to seroconverters with undiagnosed SPHI, more of those diagnosed with SPHI had rash (odds ratio = 4.5). SPHI plays a significant role in HIV testing and subsequent early diagnosis in this population. More seroconversions could be diagnosed with better patient and physician awareness of its symptoms.