24 results on '"Szadkowski, Leah"'
Search Results
2. COVID-19 breakthrough infections in vaccinated participants of the Safety and Efficacy of Preventative COVID Vaccines sub-study.
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Walmsley, Sharon, Ravindran, Rizani, Clarke, Rosemarie, Wouters, Bradly, Silva, Amanda, Gingras, Anne-Claude, and Szadkowski, Leah
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- 2022
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3. Risk factors for unplanned paediatric intensive care unit admission after anaesthesia—an international multicentre study.
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Taylor, Katherine L, Frndova, Helena, Szadkowski, Leah, Joffe, Ari R, and Parshuram, Christopher S
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INTENSIVE care units ,EVALUATION of medical care ,RESEARCH ,ANESTHESIA ,MORTALITY ,PEDIATRICS ,PATIENTS ,FISHER exact test ,MANN Whitney U Test ,DISEASES ,CASE-control method ,HOSPITAL admission & discharge ,RISK assessment ,MEDICAL care use ,MEDICAL errors ,DESCRIPTIVE statistics ,CHI-squared test ,DATA analysis software ,LOGISTIC regression analysis ,HOSPITAL care of children ,SECONDARY analysis - Abstract
Objectives Unplanned intensive care unit (ICU) admissions are associated with near-miss events, morbidity, and mortality. We describe the rate, resource utilization, and outcomes of paediatric patients urgently admitted directly to ICU post-anaesthesia compared to other sources of unplanned ICU admissions. Methods We performed a secondary analysis of data from specialist paediatric hospitals in 7 countries. Patients urgently admitted to the ICU post-anaesthesia were combined and matched with 1 to 3 unique controls from unplanned ICU admissions from other locations by age and hospital. Demographic, clinical, and outcome variables were compared using the Wilcoxon rank-sum test for continuous variables and chi-square or Fisher's exact test for categorical variables. The effect of admission sources on binary outcomes was estimated using univariable conditional logistic regression models with stratification by matched set of anaesthesia and non-anaesthesia admission sources. Results Most admissions were <1 year of age and for respiratory reasons. Admissions post-anaesthesia were shorter, occurred later in the day, and were more likely to be mechanically ventilated. Admissions post-anaesthesia were less likely to have had a previous ICU admission (4.8% compared to 11%, P=0.032) or PIM 'high-risk diagnosis' (9.5% versus 17.2%, P=0.035) but there was no difference in the number of subsequent ICU admissions. There was no difference in the PIM severity of illness score and no mortality difference between the groups. Conclusions Young children and respiratory indications dominated unplanned ICU admissions post-anaesthesia, which was more likely later in the day and with mechanical ventilation. [ABSTRACT FROM AUTHOR]
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- 2022
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4. What are we missing? The quality of intraoperative handover before and after introduction of a checklist.
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Lane, Sophia, Gross, Marketa, Arzola, Cristian, Malavade, Archana, Szadkowski, Leah, Huszti, Ella, and Friedman, Zeev
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Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2022
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5. Death and Dying in Hospitalized Pediatric Patients: A Prospective Multicenter, Multinational Study.
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Nicoll, Jessica, Dryden-Palmer, Karen, Frndova, Helena, Gottesman, Ronald, Gray, Martin, Hunt, Elizabeth A., Hutchison, James S., Joffe, Ari R., Lacroix, Jacques, Middaugh, Kristen, Nadkarni, Vinay, Szadkowski, Leah, Tomlinson, George A., Wensley, David, Parshuram, Chris S., and Farrell, Catherine
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INTENSIVE care units ,RESEARCH ,TERMINAL care ,PEDIATRICS ,MEDICAL cooperation ,POPULATION geography ,HOSPITAL care of teenagers ,MEDICAL protocols ,HOSPITAL mortality ,DESCRIPTIVE statistics ,DEATH ,HOSPITAL care of children ,LONGITUDINAL method ,SECONDARY analysis - Abstract
Background: For hospitalized children admitted outside of a critical care unit, the location, mode of death, "do-not-resuscitate" order (DNR) use, and involvement of palliative care teams have not been described across high-income countries. Objective: To describe location of death, patient and terminal care plan characteristics of pediatric inpatient deaths inside and outside the pediatric intensive care unit (PICU). Design: Secondary analysis of inpatient deaths in the Evaluating Processes of Care and Outcomes of Children in Hospital (EPOCH) randomized controlled trial. Setting/Subjects: Twenty-one centers from Canada, Belgium, the United Kingdom, Ireland, Italy, the Netherlands, and New Zealand. Measurement: Descriptive statistics were used to compare patient and terminal care plan characteristics. A multivariable generalized estimating equation examined if palliative care consult during hospital admission was associated with location of death. Results: A total of 365 of 144,539 patients enrolled in EPOCH died; 219 (60%) died in PICU and 143 (40%) died on another inpatient unit. Compared with other inpatient wards, patients who died in PICU were less likely to be expected to die, have a DNR or palliative care consult. Hospital palliative care consultation was more common in older children and independently associated with a lower adjusted odds (95% confidence interval) of dying in PICU [0.59 (0.52–0.68)]. Conclusion: Most pediatric inpatient deaths occur in PICU where patients were less likely to have a DNR or palliative care consult. Palliative care consultation could be better integrated into end-of-life care for younger children and those dying in PICU. [ABSTRACT FROM AUTHOR]
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- 2022
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6. A pragmatic randomized trial of a primary care antimicrobial stewardship intervention in Ontario, Canada.
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McIsaac, Warren, Kukan, Sahana, Huszti, Ella, Szadkowski, Leah, O'Neill, Braden, Virani, Sophia, Ivers, Noah, Lall, Rosemarie, Toor, Navsheer, Shah, Mruna, Alvi, Ruby, Bhatt, Aashka, Nakamachi, Yoshiko, and Morris, Andrew M.
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ANTIBIOTICS ,ANTIMICROBIAL stewardship ,EVALUATION of medical care ,RESPIRATORY diseases ,CONFIDENCE intervals ,URINARY tract infections ,ANTI-infective agents ,PRIMARY health care ,RANDOMIZED controlled trials ,COMPARATIVE studies ,DRUGS ,DESCRIPTIVE statistics ,ODDS ratio - Abstract
Background: More than 90% of antibiotics are prescribed in primary care, but 50% may be unnecessary. Reducing unnecessary antibiotic overuse is needed to limit antimicrobial resistance. We conducted a pragmatic trial of a primary care provider-focused antimicrobial stewardship intervention to reduce antibiotic prescriptions in primary care. Methods: Primary care practitioners from six primary care clinics in Toronto, Ontario were assigned to intervention or control groups to evaluate the effectiveness of a multi-faceted intervention for reducing antibiotic prescriptions to adults with respiratory and urinary tract infections. The intervention included provider education, clinical decision aids, and audit and feedback of antibiotic prescribing. The primary outcome was total antibiotic prescriptions for these infections. Secondary outcomes were delayed prescriptions, prescriptions longer than 7 days, recommended antibiotic use, and outcomes for individual infections. Generalized estimating equations were used to estimate treatment effects, adjusting for clustering by clinic and baseline differences. Results: There were 1682 encounters involving 54 primary care providers from January until May 31, 2019. In intervention clinics, the odds of any antibiotic prescription was reduced 22% (adjusted Odds Ratio (OR) = 0.78; 95% Confidence Interval (CI) = 0.64.0.96). The odds that a delay in filling a prescription was recommended was increased (adjusted OR=2.29; 95% CI=1.37, 3.83), while prescription durations greater than 7 days were reduced (adjusted OR=0.24; 95% CI=0.13, 0.43). Recommended antibiotic use was similar in control (85.4%) and intervention clinics (91.8%, p=0.37). Conclusions: A community-based, primary care provider-focused antimicrobial stewardship intervention was associated with a reduced likelihood of antibiotic prescriptions for respiratory and urinary infections, an increase in delayed prescriptions, and reduced prescription durations. Trial registration: clinicaltrials.gov (NCT03517215). [ABSTRACT FROM AUTHOR]
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- 2021
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7. Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression.
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Rousseau, Rodney K., Szadkowski, Leah, Kovacs, Colin M., Saikali, Michael F., Nadeem, Rabea, Malazogu, Fat, Huibner, Sanja, Cummins, Carolyn L., Kaul, Rupert, and Walmsley, Sharon L.
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T cells ,HIV infections ,HIV ,BLOOD cells ,BIOMARKERS ,CALRETININ - Abstract
Objective: Serious non-AIDS disease events (SNAE) are experienced disproportionately by immunologic non-responders (INRs), HIV-infected individuals who do not restore CD4 T cells in blood despite effective viral suppression. We aimed to characterize the inflammatory biomarker profile of the INR phenotype. Methods: Blinded cross-sectional cohort study comparing markers of immune activation and gut homing between INR and non-INR individuals. HIV-positive participants had HIV RNA suppression on antiretroviral therapy and were categorized as either INR (N = 36) or Clinical Responders ("CR"; CD4>350/mm
3 ; N = 47). 18 HIV-negative comparator individuals were included. Cellular markers were assessed by flow cytometry, with soluble markers assessed by ELISA and LC/MS-MS. Multivariable linear regression models estimated the association between INR phenotype and markers, adjusting for age, sex, duration of ART, and recent infection/vaccination. Results: INR participants demonstrated a reduced CD4/CD8 ratio (p<0.001), 35% more CD8 activation (p = 0.02), 36% greater α4β7+ CD4 T cells (p<0.01), 54% more HLA-DR+ CD4 T cells (p<0.001), and 20% higher plasma VCAM (p<0.01) compared to CRs. The INR phenotype was not associated with levels of Kyn/Trp, CRP, TNF, IFNγ, IL-8, IL-6, sCD14, D-Dimer, I-FABP, MCP-1, ICAM or CD8%HLA-DR+. Conclusions: Peripheral CD4 non-recovery during long-term treated HIV infection is characterized by elevated CD8 activation and CD4 gut homing. Gut-focused interventions may be warranted in the INR context, and CD8 activation may serve as a surrogate endpoint for clinical interventions. [ABSTRACT FROM AUTHOR]- Published
- 2021
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8. Intimate partner and client‐perpetrated violence are associated with reduced HIV pre‐exposure prophylaxis (PrEP) uptake, depression and generalized anxiety in a cross‐sectional study of female sex workers from Nairobi, Kenya.
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Leis, Maria, McDermott, Miranda, Koziarz, Alex, Szadkowski, Leah, Kariri, Antony, Beattie, Tara S, Kaul, Rupert, and Kimani, Joshua
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INTIMATE partner violence ,PRE-exposure prophylaxis ,VIOLENCE against women ,SEX workers ,ANXIETY ,DATING violence - Abstract
Introduction: UNAIDS has identified female sex workers (FSW) as a key HIV at‐risk population. FSW disproportionately experience gender‐based violence, which compounds their risk of HIV acquisition and may contribute to adverse mental health outcomes. Pre‐exposure prophylaxis (PrEP) is a powerful but underused HIV prevention tool for these women. This study explored the associations between intimate partner violence (IPV) and client‐perpetrated violence against FSW, mental health outcomes and PrEP use. Methods: An anonymous questionnaire was administered to a convenience sample of 220 Nairobi FSW attending dedicated clinics from June to July 2019, where PrEP was available free of charge. A modified version of the WHO Violence Against Women Instrument assessed IPV and client‐perpetrated violence, and the Patient Health Questionnaire‐9 (PHQ‐9) and Generalized Anxiety Disorder‐7 (GAD‐7) assessed depressive and anxiety symptoms respectively. Multivariable logistic regressions evaluated predictors of depression, generalized anxiety and PrEP use. Results: Of the total 220 women (median [IQR] age 32 [27‐39]), 56.8% (125/220) reported depression (PHQ‐9 ≥ 10) and 39.1% (86/220) reported anxiety (GAD‐7 ≥ 10). Only 41.4% (91/220) reported optimal use of PrEP (taken correctly six to seven days/week) despite the cohort pursuing sex work for a median of 7 (4 to 12) years. Most women reported experiencing any violence in the past 12 months (90%, 198/220). Any recent IPV was frequent (78.7%, 129/164), particularly emotional IPV (66.5%, 109/164), as was any client‐perpetrated violence in the past 12 months (80.9%, 178/220). Regression analyses found that violence was independently associated with depression (adjusted OR [aOR] 9.39, 95% CI 2.90 to 30.42, p = 0.0002) and generalized anxiety (aOR 3.47, 95% CI 1.10 to 10.88, p = 0.03), with the strongest associations between emotional IPV and both depression and anxiety. Recent client‐perpetrated emotional violence (aOR 0.23, 95% CI 0.07 to 0.71, p = 0.01) was associated with decreased PrEP use, whereas client‐perpetrated physical violence was associated with increased PrEP use (aOR 3.01, 95% CI 1.16 to 7.81, p = 0.02). Conclusions: There was a high prevalence of recent violence by different perpetrators as well as depression and anxiety among FSW from Nairobi. PrEP use was relatively infrequent, and recent client‐perpetrated emotional violence was associated with PrEP non‐use. Interventions to reduce gender‐based violence may independently enhance HIV prevention and reduce the mental health burden in this community. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Intimate partner and client‐perpetrated violence are associated with reduced HIV pre‐exposure prophylaxis (PrEP) uptake, depression and generalized anxiety in a cross‐sectional study of female sex workers from Nairobi, Kenya.
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Leis, Maria, McDermott, Miranda, Koziarz, Alex, Szadkowski, Leah, Kariri, Antony, Beattie, Tara S, Kaul, Rupert, and Kimani, Joshua
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INTIMATE partner violence ,PRE-exposure prophylaxis ,VIOLENCE against women ,SEX workers ,ANXIETY ,DATING violence - Abstract
Introduction: UNAIDS has identified female sex workers (FSW) as a key HIV at‐risk population. FSW disproportionately experience gender‐based violence, which compounds their risk of HIV acquisition and may contribute to adverse mental health outcomes. Pre‐exposure prophylaxis (PrEP) is a powerful but underused HIV prevention tool for these women. This study explored the associations between intimate partner violence (IPV) and client‐perpetrated violence against FSW, mental health outcomes and PrEP use. Methods: An anonymous questionnaire was administered to a convenience sample of 220 Nairobi FSW attending dedicated clinics from June to July 2019, where PrEP was available free of charge. A modified version of the WHO Violence Against Women Instrument assessed IPV and client‐perpetrated violence, and the Patient Health Questionnaire‐9 (PHQ‐9) and Generalized Anxiety Disorder‐7 (GAD‐7) assessed depressive and anxiety symptoms respectively. Multivariable logistic regressions evaluated predictors of depression, generalized anxiety and PrEP use. Results: Of the total 220 women (median [IQR] age 32 [27‐39]), 56.8% (125/220) reported depression (PHQ‐9 ≥ 10) and 39.1% (86/220) reported anxiety (GAD‐7 ≥ 10). Only 41.4% (91/220) reported optimal use of PrEP (taken correctly six to seven days/week) despite the cohort pursuing sex work for a median of 7 (4 to 12) years. Most women reported experiencing any violence in the past 12 months (90%, 198/220). Any recent IPV was frequent (78.7%, 129/164), particularly emotional IPV (66.5%, 109/164), as was any client‐perpetrated violence in the past 12 months (80.9%, 178/220). Regression analyses found that violence was independently associated with depression (adjusted OR [aOR] 9.39, 95% CI 2.90 to 30.42, p = 0.0002) and generalized anxiety (aOR 3.47, 95% CI 1.10 to 10.88, p = 0.03), with the strongest associations between emotional IPV and both depression and anxiety. Recent client‐perpetrated emotional violence (aOR 0.23, 95% CI 0.07 to 0.71, p = 0.01) was associated with decreased PrEP use, whereas client‐perpetrated physical violence was associated with increased PrEP use (aOR 3.01, 95% CI 1.16 to 7.81, p = 0.02). Conclusions: There was a high prevalence of recent violence by different perpetrators as well as depression and anxiety among FSW from Nairobi. PrEP use was relatively infrequent, and recent client‐perpetrated emotional violence was associated with PrEP non‐use. Interventions to reduce gender‐based violence may independently enhance HIV prevention and reduce the mental health burden in this community. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Increased CD4 : CD8 ratio normalization with implementation of current ART management guidelines.
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Zhabokritsky, Alice, Szadkowski, Leah, Cooper, Curtis, Loutfy, Mona, Wong, Alexander, McClean, Alison, Hogg, Robert S, Walmsley, Sharon L, Collaboration, the Canadian Observational Cohort (CANOC), and Canadian Observational Cohort (CANOC) Collaboration
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ANTI-HIV agents ,HIV infections ,RESEARCH ,RESEARCH methodology ,RETROSPECTIVE studies ,MEDICAL cooperation ,EVALUATION research ,HIGHLY active antiretroviral therapy ,COMPARATIVE studies ,CD4 lymphocyte count ,RESEARCH funding ,T cells - Abstract
Objectives: To determine the time to CD4 : CD8 ratio normalization among Canadian adults living with HIV in the modern ART era. To identify characteristics associated with ratio normalization.Patients and Methods: Retrospective analysis of the Canadian Observational Cohort (CANOC), an interprovincial cohort of ART-naive adults living with HIV, recruited from 11 treatment centres across Canada. We studied participants initiating ART between 1 January 2011 and 31 December 2016 with baseline CD4 : CD8 ratio <1.0 and ≥2 follow-up measurements. Normalization was defined as two consecutive CD4 : CD8 ratios ≥1.0. Kaplan-Meier estimates and log-rank tests described time to normalization. Univariable and multivariable proportional hazards (PH) models identified factors associated with ratio normalization.Results: Among 3218 participants, 909 (28%) normalized during a median 2.6 years of follow-up. Participants with higher baseline CD4+ T-cell count were more likely to achieve normalization; the probability of normalization by 5 years was 0.68 (95% CI 0.62-0.74) for those with baseline CD4+ T-cell count >500 cells/mm3 compared with 0.16 (95% CI 0.11-0.21) for those with ≤200 cells/mm3 (P < 0.0001). In a multivariable PH model, baseline CD4+ T-cell count was associated with a higher likelihood of achieving ratio normalization (adjusted HR = 1.5, 95% CI 1.5-1.6 per 100 cells/mm3, P < 0.0001). After adjusting for baseline characteristics, time-dependent ART class was not associated with ratio normalization.Conclusions: Early ART initiation, at higher baseline CD4+ T-cell counts, has the greatest impact on CD4 : CD8 ratio normalization. Our study supports current treatment guidelines recommending immediate ART start, with no difference in ratio normalization observed based on ART class used. [ABSTRACT FROM AUTHOR]- Published
- 2021
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11. Deciphering the serological response to syphilis treatment in men living with HIV.
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Ren, Melody, Szadkowski, Leah, and Walmsley, Sharon L.
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- 2020
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12. Pilot study assessing the rotterdam healthy aging score in a cohort of human immunodeficiency virus positive adults in Toronto, Canada.
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Walmsley, Sharon L., Ren, Melody, Simon, Ceylon, Clarke, Rosemarie, and Szadkowski, Leah
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- 2020
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13. Inflammatory biomarker levels over 48 weeks with dual vs triple lopinavir/ritonavir-based therapy: Substudy of a randomized trial.
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Tan, Darrell H. S., Rolon, Maria Jose, Figueroa, Maria Ines, Sued, Omar, Gun, Ana, Kaul, Rupert, Raboud, Janet M., Szadkowski, Leah, Hull, Mark W., Walmsley, Sharon L., Cahn, Pedro, and null, null
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RITONAVIR ,NUCLEOSIDE reverse transcriptase inhibitors ,GENERALIZED estimating equations ,CD4 lymphocyte count - Abstract
Background: Inflammation has been associated with increased morbidity and mortality in HIV-positive patients. We compared inflammatory biomarkers with dual therapy using lopinavir/ritonavir plus lamivudine (LPV/r+3TC) versus triple therapy using LPV/r plus two nucleoside reverse transcriptase inhibitors (LPV/r+2NRTIs) in treatment-naïve HIV-positive adults. Methods: This was a substudy among Argentinian participants in the randomized trial GARDEL. We measured hsCRP, IL-6, MCP-1, TNF, D-dimer and sCD14 from plasma collected at baseline, week 24 and week 48. Generalized estimating equations with an identity/logit link were used to model the average impact of dual versus triple therapy on each biomarker over time, controlling for baseline levels. Additional models estimated the average effect of virologic suppression on biomarker levels over time, adjusting for age, sex, and baseline CD4 count. Results: Of 191 trial participants enrolled in Argentina, 172 had baseline and follow-up measurements and were included. Median (IQR) age was 35.5 (28.5, 45) years and CD4 cell count was 310 (219, 414) cells/mm
3 . Dual therapy was not associated with significantly different biomarker levels over 48 weeks relative to triple therapy. Virologic suppression was associated with statistically significant decreases in MCP-1, TNF and D-dimer levels and an unexpected increase in sCD14 levels. No change was observed in hsCRP or the proportion of participants with undetectable IL-6 levels. Conclusions: In addition to having virologic non-inferiority, LPV/r+3TC dual therapy is generally associated with similar inflammatory biomarker levels over 48 weeks compared to LPV/r+2NRTIs triple therapy in treatment-naïve adults. Further study of dual treatment regimens is warranted. [ABSTRACT FROM AUTHOR]- Published
- 2019
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14. Effect of valaciclovir on CD4 count decline in untreated HIV: an international randomized controlled trial.
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Tan, Darrell H S, Raboud, Janet M, Szadkowski, Leah, Grinsztejn, Beatriz, Madruga, José Valdez, Figueroa, Maria Ines, Cahn, Pedro, Barton, Simon E, Clarke, Amanda, Fox, Julie, Zubyk, Wendy, Walmsley, Sharon L, Group, the VALIDATE Study, and VALIDATE Study Group
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VALACYCLOVIR ,HIV infections ,RANDOMIZED controlled trials ,DISEASE progression ,VIRAL load ,HERPES simplex virus - Abstract
Objectives: To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults.Methods: In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400-900 cells/mm3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Secondary analyses compared the rate of CD4 percentage decline, HIV VL, herpes simplex virus (HSV) recurrences and drug-related adverse events. The trial closed after release of the START trial results in August 2015.Results: We enrolled 198 participants in Canada, Brazil, Argentina and the UK. Median (IQR) age was 35 (30-43) years. Baseline CD4 count was 592 (491-694) cells/mm3 and VL was 4.04 (3.5-4.5) log10 copies/mL. Over 276 person-years of follow-up, CD4 counts declined by 49 cells/mm3/year in the valaciclovir arm versus 58 cells/mm3/year in the placebo arm (P = 0.65). No differences were seen in the rate of change in CD4 percentage (-1.2%/year versus -1.7%/year, P = 0.34). VL was 0.27 log10 copies/mL lower in valaciclovir participants overall (P<0.001). Placebo participants had more HSV recurrences (62 versus 21/100 person-years, P < 0.0001) but similar rates of grade ≥2 drug-related adverse events.Conclusions: Unlike prior trials using aciclovir, we found that valaciclovir did not slow CD4 count decline in cART-untreated adults, although power was limited due to premature study discontinuation. Valaciclovir modestly lowered HIV VL. [ABSTRACT FROM AUTHOR]- Published
- 2019
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15. Effect of valaciclovir on CD4 count decline in untreated HIV: an international randomized controlled trial.
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Tan, Darrell H S, Raboud, Janet M, Szadkowski, Leah, Grinsztejn, Beatriz, Madruga, José Valdez, Figueroa, Maria Ines, Cahn, Pedro, Barton, Simon E, Clarke, Amanda, Fox, Julie, Zubyk, Wendy, Walmsley, Sharon L, and Group, the VALIDATE Study
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ACYCLOVIR ,HIV-positive persons ,VIRAL load ,VALACYCLOVIR ,PLACEBOS - Abstract
Objectives To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults. Methods In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400–900 cells/mm
3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Secondary analyses compared the rate of CD4 percentage decline, HIV VL, herpes simplex virus (HSV) recurrences and drug-related adverse events. The trial closed after release of the START trial results in August 2015. Results We enrolled 198 participants in Canada, Brazil, Argentina and the UK. Median (IQR) age was 35 (30–43) years. Baseline CD4 count was 592 (491–694) cells/mm3 and VL was 4.04 (3.5–4.5) log10 copies/mL. Over 276 person-years of follow-up, CD4 counts declined by 49 cells/mm3 /year in the valaciclovir arm versus 58 cells/mm3 /year in the placebo arm (P = 0.65). No differences were seen in the rate of change in CD4 percentage (−1.2%/year versus −1.7%/year, P = 0.34). VL was 0.27 log10 copies/mL lower in valaciclovir participants overall (P <0.001). Placebo participants had more HSV recurrences (62 versus 21/100 person-years, P < 0.0001) but similar rates of grade ≥2 drug-related adverse events. Conclusions Unlike prior trials using aciclovir, we found that valaciclovir did not slow CD4 count decline in cART-untreated adults, although power was limited due to premature study discontinuation. Valaciclovir modestly lowered HIV VL. [ABSTRACT FROM AUTHOR]- Published
- 2019
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16. Acceptability and tolerability of and adherence to HIV preexposure prophylaxis among Toronto gay and bisexual men: a pilot study.
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Tan, Darrell H.S., Schnubb, Alexandre, Lawless, James, Szadkowski, Leah, Grennan, Troy, Wilton, James, Fowler, Shawn, Hart, Trevor A., Maxwell, John, and Raboud, Janet M.
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Background: Preexposure prophylaxis is efficacious at preventing HIV infection, but concerns persist about adherence and sexually transmitted infections (STIs). We assessed preexposure prophylaxis acceptability, adherence and clinical outcomes in a pilot demonstration project. Methods: HIV-uninfected adult gay and bisexual men who scored 10 or higher on a validated HIV risk score (HIV Incidence Risk Index for MSM) and reported condomless receptive anal sex were sequentially enrolled into a 1-year open-label single-arm pilot study of daily oral therapy with tenofovir disoproxil fumarate/emtricitabine in Toronto. The primary outcome was acceptability of preexposure prophylaxis. Secondary outcomes were preexposure prophylaxis adherence (4-d recall, pill count and dried blood spot analysis), HIV seroconversion, STIs and adverse events. Results: Of the 86 men screened, 52 were enrolled. Participants were mostly young (median age 33 yr [interquartile range (IQR) 28–37 yr) white (38 [73%]) gay (49 [94%]) men. Preexposure prophylaxis acceptability was high: all participants reported their experience as "good" or "very good." The median adherence rate was high, at 100% (IQR 95%–100%) by self-report and 96.9% (IQR 93.4%–98.4%) by pill count. Dried blood spot analysis suggested that doses were taken 4–7 days/week at 88.7% (173/195) of month 3–12 visits. No cases of HIV seroconversion occurred, but 25 participants (48%) experienced at least 1 bacterial STI, with incidence rates per 100 person-years of 32.8, 32.8, 8.2 and 8.2 for chlamydia, gonorrhea, syphilis and lymphogranuloma venereum, respectively. No adverse events led to discontinuation of prophylaxis, but the estimated glomerular filtration rate declined by 0.22 mL/min per month. Interpretation: Preexposure prophylaxis was associated with high adherence and acceptability and no HIV infections in this study. Frequent STIs and clinically unapparent toxic renal effects reinforce the need for ongoing vigilance. Trial registration: ClinicalTrials. gov, no. NCT02149888 [ABSTRACT FROM AUTHOR]
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- 2018
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17. High retention in HIV care at a tertiary care centre in Toronto, Canada.
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Szadkowski, Leah, Walmsley, Sharon, Burchell, Ann N., Collins, Evan, Rourke, Sean B., and Raboud, Janet
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AGE distribution ,MENTAL depression ,DRUGS of abuse ,PSYCHOLOGY of HIV-positive persons ,MULTIVARIATE analysis ,PATIENT compliance ,QUESTIONNAIRES ,RACE ,SAMPLE size (Statistics) ,VIRAL load ,INTRAVENOUS drug abusers ,PATIENT dropouts ,DISEASE duration ,DATA analysis software ,DESCRIPTIVE statistics ,CD4 lymphocyte count ,TERTIARY care - Abstract
Poor retention in HIV care is associated with poor clinical outcomes and mortality. Previous studies of predictors of poor retention have been conducted with a wide variety of populations, using different measures of retention, and occasionally have conflicting results. We studied demographic and psychosocial factors associated with inter-visit interval length in a setting of universal health care and modern cART. Patients attending ≥2 appointments with an HIV specialist at the Toronto General Hospital Immunodeficiency Clinic from 2004 to 2013 were studied. A sub-analysis included psychosocial measures from annual questionnaires for Ontario HIV Treatment Network Cohort Study (OCS) participants. Median inter-visit interval and constancy (percentage of 4-month intervals with ≥1 visit) were calculated by patient. Multivariable generalized estimating equation models identified factors associated with inter-visit interval length and intervals ≥12 months. 1591 patients were included. 615 patients completed an OCS questionnaire and were more likely to be older white MSM from Canada with a viral load (VL) <50 copies/ml. The median (IQR) of patients’ median inter-visit intervals was 3.15 (2.78, 3.84) months and median (IQR) constancy was 90% (71%, 100%). Two percent of inter-visit intervals were ≥12 months and 25% of patients had ≥1 interval ≥12 months. Longer inter-visit intervals were associated with younger age, white race, earlier calendar year, longer duration of HIV, VL < 50 copies/mL and higher CD4 counts. Patients who were younger, white, had injection drug use as a risk factor, had a longer duration of HIV, and had VL ≥50 copies/mL were more likely to have an inter-visit interval ≥12 months. In the OCS sub-analysis including psychosocial variables, lower levels of depression were associated with longer inter-visit intervals. Retention at this tertiary care centre was high. Efforts to maximize attendance should focus on younger patients and those with substance abuse issues. [ABSTRACT FROM PUBLISHER]
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- 2018
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18. Comparison of atazanavir/ritonavir and darunavir/ritonavir based antiretroviral therapy for antiretroviral naïve patients.
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Antoniou, Tony, Szadkowski, Leah, Walmsley, Sharon, Cooper, Curtis, Burchel, Ann N., Bayoumi, Ahmed M., Montaner, Julio S. G., Loutfy, Mona, Klein, Marina B., Machouf, Nima, Tsoukas, Christos, Wong, Alexander, Hogg, Robert S., Raboud, Janet, Burchell, Ann N, and Canadian Observational Cohort (CANOC) collaboration
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ATAZANAVIR ,HIV-positive persons ,RITONAVIR ,HIV protease inhibitors ,VIROLOGY ,COMBINATION drug therapy ,COMPARATIVE studies ,HIV ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,RESEARCH funding ,EVALUATION research ,RETROSPECTIVE studies ,ANTI-HIV agents ,THERAPEUTICS - Abstract
Background: Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical practice are lacking.Methods: We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort (CANOC) collaboration initiating atazanavir/ritonavir- or darunavir/ritonavir-based treatment. We used separate Fine and Gray competing risk regression models to compare times to regimen failure (composite of virologic failure or discontinuation for any reason). Additional endpoints included virologic failure, discontinuation due to virologic failure, discontinuation for other reasons, and virologic suppression.Results: We studied 222 patients treated with darunavir/ritonavir and 1791 patients treated with atazanavir/ritonavir. Following multivariable adjustment, there was no difference between darunavir/ritonavir and atazanavir-ritonavir in the risk of regimen failure (adjusted hazard ratio 0.76, 95% CI 0.56 to 1.03) Darunavir/ritonavir-treated patients were at lower risk of virologic failure relative to atazanavir/ritonavir treated patients (aHR 0.50, 95% CI 0.28 to 0.91), findings driven largely by high rates of virologic failure among atazanavir/ritonavir-treated patients in the province of British Columbia. Of 108 discontinuations due to virologic failure, all occurred in patients starting atazanavir/ritonavir. There was no difference between regimens in time to discontinuation for reasons other than virologic failure (aHR 0.93; 95% CI 0.65 to 1.33) or virologic suppression (aHR 0.99, 95% CI 0.82 to 1.21).Conclusions: The risk of regimen failure was similar between patients treated with darunavir/ritonavir and atazanavir/ritonavir. Although darunavir/ritonavir was associated with a lower risk of virologic failure relative to atazanavir/ritonavir, this difference varied substantially by Canadian province and likely reflects regional variation in prescribing practices and patient characteristics. [ABSTRACT FROM AUTHOR]- Published
- 2017
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19. Novel imaging modalities for the comparison of bone microarchitecture among HIV+ patients with and without fractures: a pilot study.
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Tan, Darrell H. S., Raboud, Janet, Szadkowski, Leah, Szabo, Eva, Hu, Hanxian, Wong, Queenie, Cheung, Angela M., and Walmsley, Sharon L.
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DIAGNOSIS of HIV infections ,RISK factors of fractures ,BONE density ,COMPUTED tomography ,BONE remodeling - Abstract
Background:HIV-infected adults have increased fracture risk. Objectives:To generate pilot data comparing bone density, structure, and strength between HIV-infected adults with and without a prior fracture. Methods:Adults with and without a prior fracture after their HIV diagnosis were matched 1:1 based on age, sex, race, and smoking history. Participants underwent dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), hip structural analyses (HSA), vertebral fracture assessment (VFA), high-resolution peripheral quantitative tomography (HR-pQCT) and measurement of bone turnover markers. Results were compared between cases and controls, with differences expressed as percentages of control group values. Results:23 pairs were included. On DXA, cases had lower areal bone mineral density (aBMD) at the total hip (median difference in T-score −0.25,p = 0.04), but not the lumbar spine (median difference in T-score 0.10,p = 0.68). Cases had greater abnormalities in HSA and most HR-pQCT and HSA measures, by up to 15%. VFA revealed two subclinical fractures among cases but none among controls. TBS, CTX, and P1NP levels were similar between groups, with differences of 1.9% (p = 0.90), 9.7% (p = 0.55), and 10.0% (p = 0.24), respectively. For each parameter, we report the median and interquartile range for the absolute and relative difference between cases and controls, the correlation between cases and controls, and our recruitment rates, to inform the design of future studies. Conclusions:These pilot data suggest potential differences in bone structure, estimated bone strength, and asymptomatic vertebral fractures among HIV-infected adults with and without fracture, warranting further study as markers of fracture risk in HIV. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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20. Effect of Intercurrent Infections and Vaccinations on Immune and Inflammatory Biomarkers Among Human Immunodeficiency Virus-Infected Adults on Suppressive Antiretroviral Therapy.
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Tan, Darrell H. S., Szadkowski, Leah, Raboud, Janet, Tae Joon Yi, Shannon, Brett, Kaul, Rupert, Liles, W. Conrad, and Walmsley, Sharon
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HIV infections ,BIOMARKERS - Abstract
We used generalized estimating equations to quantify the impact of recent vaccination or intercurrent infections on immune and inflammatory biomarkers among 144 human immunodeficiency virus (HIV)-infected adults with HIV RNA < 50 copies/mL on antiretroviral therapy. These events were associated with a 2.244 μg/mL increase in high sensitivity C-reactive protein and should be routinely assessed in future studies. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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21. Herpes Simplex Virus Type 2 Serostatus Is Not Associated with Inflammatory or Metabolic Markers in Antiretroviral Therapy-Treated HIV.
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Tan, Darrell H.S., Raboud, Janet M., Szadkowski, Leah, Yi, Tae Joon, Shannon, Brett, Kaul, Rupert, Liles, W. Conrad, and Walmsley, Sharon L.
- Published
- 2015
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22. A Randomized Controlled Pilot Trial of Valacyclovir for Attenuating Inflammation and Immune Activation in HIV/Herpes Simplex Virus 2–Coinfected Adults on Suppressive Antiretroviral Therapy.
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Yi, Tae Joon, Walmsley, Sharon, Szadkowski, Leah, Raboud, Janet, Rajwans, Nimerta, Shannon, Brett, Kumar, Sachin, Kain, Kevin C., Kaul, Rupert, and Tan, Darrell H. S.
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ANTIVIRAL agents ,INFLAMMATION ,HIV infections ,HERPES simplex ,RANDOMIZED controlled trials ,MEDICAL statistics - Abstract
Herpes simplex virus type 2 (HSV-2) coinfection in HIV-infected individuals may contribute to increased systemic inflammation and immune activation that persist despite suppressive antiretroviral therapy. Valacyclovir did not decrease systemic immune activation in HIV-1/HSV-2–coinfected adults on suppressive antiretroviral therapy.Background. Human immunodeficiency virus (HIV) is associated with increased systemic inflammation and immune activation that persist despite suppressive antiretroviral therapy (ART). Herpes simplex virus type 2 (HSV-2) is a common coinfection that may contribute to this inflammation.Methods. Sixty HIV type 1 (HIV-1)/HSV-2–coinfected adults on suppressive ART were randomized 1:1:1 to 12 weeks of placebo, low-dose valacyclovir (500 mg twice daily), or high-dose valacyclovir (1 g twice daily) in this 18-week trial. Co–primary outcome measures were the percentage of activated (CD38+HLA-DR+) CD8 T cells in blood, and highly sensitive C-reactive protein, interleukin 6, and soluble intercellular adhesion molecule 1 in plasma. Secondary outcomes included additional immune, inflammatory cytokine, and endothelial activation markers. The impact of valacyclovir (both groups combined) on each outcome was estimated using treatment × time interaction terms in generalized estimating equation regression models.Results. Participants were mostly white (75%) men who have sex with men (80%). Median age was 51 (interquartile range [IQR], 47–56) years, median duration of HIV infection was 15 (IQR, 8–21) years, median CD4 count at enrollment was 520 (IQR, 392–719) cells/µL, and median nadir CD4 count was 142 (IQR, 42–240) cells/µL. Valacyclovir was not associated with significant changes in any primary or secondary immunological outcomes in bivariate or multivariable models. Medication adherence was 97% by self-report, 96% by pill count, and 84% by urine monitoring. Eight patients had adverse events deemed possibly related to the study drug (5 placebo, 1 low-dose, 2 high-dose), and 6 patients reported at least 1 HSV outbreak (3 placebo, 3 low-dose, 0 high-dose).Conclusions. Valacyclovir did not decrease systemic immune activation or inflammatory biomarkers in HIV-1/HSV-2–coinfected adults on suppressive ART.Clinical Trials Registration. NCT01176409. [ABSTRACT FROM PUBLISHER]
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- 2013
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23. Association of Age With Polypharmacy and Risk of Drug Interactions With Antiretroviral Medications in HIV-Positive Patients.
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Tseng, Alice, Szadkowski, Leah, Walmsley, Sharon, Salit, Irving, and Raboud, Janet
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- 2013
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24. Short Communication Effects of Age on Virologie Suppression and CD4 Cell Response in HIV-Positive Patients Initiating Combination Antiretroviral Therapy.
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Szadkowski, Leah, Tseng, Alice, Walmsley, Sharon L., Salit, Irving, and Raboud, Janet M.
- Published
- 2012
- Full Text
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