30 results on '"Szadkowski, Leah"'
Search Results
2. COVID-19 vaccine antibody responses in community-dwelling adults to 48 weeks post primary vaccine series
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Walmsley, Sharon L., Szadkowski, Leah, Wouters, Bradly, Clarke, Rosemarie, Colwill, Karen, Rochon, Paula, Brudno, Michael, Ravindran, Rizanni, Raboud, Janet, McGeer, Allison, Oza, Amit, Graham, Christopher, Silva, Amanda, Manase, Dorin, Maksymowsky, Peter, Parente, Laura, Dayam, Roaya Monica, Simpson, Jacqueline, Pasculescu, Adrian, and Gingras, Anne-Claude
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- 2023
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3. 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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- 2022
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4. 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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- 2021
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5. 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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6. 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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7. Pilot study assessing the Rotterdam Healthy Aging Score in a cohort of HIV-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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8. A tale of two countries: all‐cause mortality among people living with HIV and receiving combination antiretroviral therapy in the UK and Canada
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Patterson, S, Jose, S, Samji, H, Cescon, A, Ding, E, Zhu, J, Anderson, J, Burchell, AN, Cooper, C, Hill, T, Hull, M, Klein, MB, Loutfy, M, Martin, F, Machouf, N, Montaner, JSG, Nelson, M, Raboud, J, Rourke, SB, Tsoukas, C, Hogg, RS, Sabin, C, Kelly, Deborah, Sanche, Stephen, Wong, Alexander, Antoniou, Tony, Bayoumi, Ahmed, Nosyk, Bohdan, Cotterchio, Michelle, Goldsmith, Charlie, Guillemi, Silvia, Richard Harrigan, P., Harris, Marianne, Hosein, Sean, Johnston, Sharon, Liddy, Clare, Lima, Viviane, Moore, David, Palmer, Alexis, Phillips, Peter, Rachlis, Anita, Smieja, Marek, Trottier, Benoit, Wainberg, Mark, Walmsley, Sharon, Archibald, Chris, Clement, Ken, Doolittle‐Romas, Monique, Edmiston, Laurie, Huskins, Brian, Lawless, Jerry, Lee, Douglas, Masching, Renee, Tattle, Stephen, Zahirieh, Alireza, Allen, Claire, Calvez, Stryker, Colley, Guillaume, Chia, Jason, Corsi, Daniel, Gilbert, Louise, Gataric, Nada, Leslie, Alia, Light, Lucia, Mackie, David, Pexos, Costa, Shurgold, Susan, Szadkowski, Leah, Wong, John, Yip, Benita, Younger, Jaime, Ainsworth, Jonathan, Allan, Sris, Babiker, Abdel, Chadwick, David, Delpech, Valerie, Dunn, David, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hay, Phillip, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Pritchard, Jillian, Sachikonye, Memory, Schwenk, Achim, Tariq, Anjum, Walsh, John, Thornton, Alicia, Glabay, Adam, Perry, Nicky, Tilbury, Stuart, Youssef, Elaney, Churchill, Duncan, Everett, Rhiannon, Asboe, David, Mandalia, Sundhiya, Korat, Hardik, Taylor, Chris, Gleisner, Zachary, Ibrahim, Fowzia, Campbell, Lucy, Brima, Nataliya, Williams, Ian, Youle, Mike, Lampe, Fiona, Smith, Colette, Tsintas, Rob, Chaloner, Clinton, Hutchinson, Samantha, Huntington, Susie, Mackie, Nicky, Winston, Alan, Weber, Jonathan, Ramzan, Farhan, Carder, Mark, Lynch, Janet, Hand, James, de Souza, Carl, Munshi, Sajid, Miller, Sheila, Wood, Chris, Wilson, Alan, Morris, Sheila, Allan, Sue, Memon, Khurram, Lewszuk, Adam, Cope, Emma, Gibson, Jane, Main, Paul, Dhillon, Mandip, Russell‐Sharpe, Sarah, Harte, Andrew, Clay, Stephen, Spencer, Hazel, Jones, Ron, Cumming, Shirley, Atkinson, Claire, and Trevelion, Roy
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- 2017
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9. 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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- 2013
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10. Decentralized study of COVID Vaccine Antibody Response (STOPCoV): Results of a participant satisfaction survey.
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Ravindran, Rizani, Szadkowski, Leah, Lovblom, Leif Erik, Clarke, Rosemarie, Huang, Qian Wen, Manase, Dorin, Parente, Laura, and Walmsley, Sharon
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- 2023
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11. Quality of initial HIV care in Canada: extension of a composite programmatic assessment tool for HIV therapy
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Kesselring, S, Cescon, A, Colley, G, Osborne, C, Zhang, W, Raboud, JM, Hosein, SR, Burchell, AN, Cooper, C, Klein, MB, Loutfy, M, Machouf, N, Montaner, JSG, Rachlis, A, Tsoukas, C, Hogg, RS, Lima, VD, Hogg, Robert, Kelly, Deborah, Sanche, Stephen, Wong, Alexander, Antoniou, Tony, Bayoumi, Ahmed, Hull, Mark, Nosyk, Bohdan, Cotterchio, Michelle, Goldsmith, Charlie, Guillemi, Silvia, Harrigan, P. Richard, Harris, Marianne, Johnston, Sharon, Kendall, Claire, Liddy, Clare, Marsh, David, Moore, David, Palmer, Alexis, Patterson, Sophie, Phillips, Peter, Rachlis, Anita, Rourke, Sean B., Samji, Hasina, Smieja, Marek, Trottier, Benoit, Wainberg, Mark, Walmsley, Sharon, Archibald, Chris, Clement, Ken, Crouzat, Fred, DoolittleRomas, Monique, Edmiston, Laurie, Gardner, Sandra, Huskins, Brian, Lee, Douglas, Masching, Renee, Tattle, Stephen, Zahirieh, Alireza, Calvez, Stryker, Chia, Jason, Corsi, Daniel, Gilbert, Louise, Gataric, Nada, Light, Lucia, Mackie, David, Merritt, Katelyn, Pexos, Costas, Shurgold, Susan, Szadkowski, Leah, Galanakis, Chrissi, Sandler, Ina, Yip, Benita, Younger, Jaime, and Zhu, Julia
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- 2017
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12. 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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13. 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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14. Adult attachment, depression, and eating disorder symptoms: The mediating role of affect regulation strategies
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Tasca, Giorgio A., Szadkowski, Leah, Illing, Vanessa, Trinneer, Anne, Grenon, Renee, Demidenko, Natasha, Krysanski, Valerie, Balfour, Louise, and Bissada, Hany
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- 2009
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15. 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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16. 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/mm3; 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]
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- 2021
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17. 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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18. 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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19. 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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20. 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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21. 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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22. 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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23. 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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24. Novel imaging modalities for the comparison of bone microarchitecture among HIV+ patients with and without fractures: a pilot study.
- Author
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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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25. 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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26. Herpes Simplex Virus Type 2 Serostatus Is Not Associated with Inflammatory or Metabolic Markers in Antiretroviral Therapy-Treated HIV.
- Author
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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.
- Abstract
Systemic inflammation and immune activation may persist in HIV-infected persons on suppressive combination antiretroviral therapy (cART) and contribute to adverse health outcomes. We compared markers of immune activation, inflammation, and abnormal glucose and lipid metabolism in HIV-infected adults according to herpes simplex virus type 2 (HSV-2) serostatus in a 6-month observational cohort study in Toronto, Canada. HIV-infected adults on suppressive (viral load <50 copies/ml) cART were categorized as HSV-2 seropositive or seronegative using the HerpeSelect ELISA, and underwent study visits at baseline, 3 months, and 6 months. The primary outcome was the median percentage of activated (CD38
+ HLADR+ ) CD8 T cells. Secondary outcome measures included additional immune (activated CD4, regulatory T cells) and inflammatory (hsCRP, D-dimer, IL-1b, IL-6, MCP-1, TNF, sICAM-1, sVCAM-1, Ang1/Ang2 ratio) markers. Metabolic outcomes included the proportion with impaired fasting glucose/impaired glucose tolerance/diabetes, insulin sensitivity (calculated using the Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and fasting lipids. The impact of HSV-2 on each outcome was estimated using generalized estimating equation regression models. Of 84 participants, 38 (45%) were HSV-2 seropositive. HSV signs and symptoms were uncommon. Aside from D-dimer, which was more often detectable in HSV-2 seropositives (adjusted odds ratio=3.58, 95% CI=1.27, 10.07), HSV-2 serostatus was not associated with differences in any other immune, inflammatory cytokine, acute phase reactant, endothelial activation, or metabolic markers examined in univariable or multivariable models. During the study, CD8 and CD4 T cell activation declined by 0.16% and 0.08% per month, respectively, while regulatory T cells increased by 0.05% per month. HSV-2 serostatus was not consistently associated with immune activation, inflammatory, or lipid and glucose metabolic markers in this cohort of HIV-infected adults on suppressive cART. [ABSTRACT FROM AUTHOR]- Published
- 2015
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27. 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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28. 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.
- Abstract
Older HIV-positive patients may experience reduced benefit and increased toxicities from combination anti-retroviral therapies (cART) due to late diagnosis, weakened immune systems, and other age-related physiological changes. This study investigates the effect of age on time to virologic suppression and CD4 cell count response to cART. Data were collected from a tertiary care immunodeficiency clinic in Toronto. HIV-positive patients with cART initiation after 1/1/1998 were included. Log logistic accelerated failure time models were used to estimate the effect of age on time to virologic suppression. Mixed linear models were used to evaluate CD4 cell response to treatment. A total of 502 patients were studied; 445 were less than 50 years old and 57 were age 50 or over. Of these 73% were male. Thirty-one percent started treatment with boosted protease inhibitors and 43% with non-nucleoside reverse transcriptase inhibitors. In a log logistic model adjusting for gender, immigration status, AIDS-defining illness, years since HIV diagnosis, baseline CD4 count and viral load, cART type, calendar year of cART initiation, and hepatitis C diagnosis, older age was not associated with time to virologic suppression (n =418, time ratio = 0.94, p = 0.20). In a multivariable mixed linear regression model adjusting for the same covariates, age was not associated with CD4 cell count response (n = 418, ß = 0.34, p = 0.96). Time to virologic suppression and im-munologic response were not significantly different among older and younger patients. Further studies should investigate adherence, comorbidities, and regimen changes in addition to the current covariates. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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29. Evaluating associations between patient-to-nurse ratios and mortality, process of care events and vital sign documentation on paediatric wards: a secondary analysis of data from the EPOCH cluster-randomised trial.
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Gawronski O, Parshuram CS, Cecchetti C, Tiozzo E, Szadkowski L, Ciofi Degli Atti ML, Dryden-Palmer K, Dall'Oglio I, Raponi M, Joffe AR, and Tomlinson G
- Subjects
- Humans, Child, Female, Male, Child, Preschool, Infant, Adolescent, Canada epidemiology, Nursing Staff, Hospital, New Zealand, Bayes Theorem, Hospitals, Pediatric statistics & numerical data, Vital Signs, Hospital Mortality, Documentation statistics & numerical data, Documentation standards
- Abstract
Objective: To describe the associations between patient-to-nurse staffing ratios and rates of mortality, process of care events and vital sign documentation., Design: Secondary analysis of data from the evaluating processes of care and outcomes of children in hospital (EPOCH) cluster-randomised trial., Setting: 22 hospitals caring for children in Canada, Europe and New Zealand., Participants: Eligible hospitalised patients were aged>37 weeks and <18 years., Primary and Secondary Outcome Measures: The primary outcome was all-cause hospital mortality. Secondary outcomes included five events reflecting the process of care, collected for all EPOCH patients; the frequency of documentation for each of eight vital signs on a random sample of patients; four measures describing nursing perceptions of care., Results: A total of 217 714 patient admissions accounting for 849 798 patient days over the course of the study were analysed. The overall mortality rate was 1.65/1000 patient discharges. The median (IQR) number of patients cared for by an individual nurse was 3.0 (2.8-3.6). Univariate Bayesian models estimating the rate ratio (RR) for the patient-to-nurse ratio and the probability that the RR was less than one found that a higher patient-to-nurse ratio was associated with fewer clinical deterioration events (RR=0.88, 95% credible interval (CrI) 0.77-1.03; P (RR<1)=95%) and late intensive care unit admissions (RR=0.76, 95% CrI 0.53-1.06; P (RR<1)=95%). In adjusted models, a higher patient-to-nurse ratio was associated with lower hospital mortality (OR=0.77, 95% CrI=0.57-1.00; P (OR<1)=98%). Nurses from hospitals with a higher patient-to-nurse ratio had lower ratings for their ability to influence care and reduced documentation of most individual vital signs and of the complete set of vital signs., Conclusions: The data from this study challenge the assumption that lower patient-to-nurse ratios will improve the safety of paediatric care in contexts where ratios are low. The mechanism of these effects warrants further evaluation including factors, such as nursing skill mix, experience, education, work environment and physician staffing ratios., Trial Registration Number: EPOCH clinical trial registered on clinical trial.gov NCT01260831; post-results., Competing Interests: Competing interests: CSP is a named inventor of the Bedside Paediatric Early Warning System and has shares in a decision support company in part owned by SickKids that was established to commercialise the Bedside Paediatric Early Warning System. All other authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
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30. Tenofovir and emtricitabine resistance among antiretroviral-naive patients in the Canadian Observational Cohort Collaboration: implications for PrEP.
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Younger J, Raboud J, Szadkowski L, Harrigan R, Walmsley S, Bayoumi AM, Klein MB, Cooper C, Burchell AN, Loutfy M, Hull M, Wong A, Thomas R, Hogg R, Montaner J, Tsoukas C, and Antoniou T
- Subjects
- Adult, CD4 Lymphocyte Count, Canada epidemiology, Emtricitabine therapeutic use, Female, HIV Infections drug therapy, HIV Infections prevention & control, HIV-1 genetics, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Pre-Exposure Prophylaxis, Proportional Hazards Models, Public Health Surveillance, Retrospective Studies, Tenofovir therapeutic use, Viral Load, Drug Resistance, Viral, Emtricitabine pharmacology, HIV Infections epidemiology, HIV Infections virology, HIV-1 drug effects, Tenofovir pharmacology
- Abstract
Background: The real-world effectiveness of pre-exposure prophylaxis (PrEP) may be influenced by circulating HIV strains resistant to either tenofovir or emtricitabine. Yet, few studies have examined rates of resistance to these drugs in clinical settings., Methods: We conducted a retrospective cohort study of antiretroviral-naive participants in the Canadian Observational Cohort collaboration who initiated antiretroviral therapy between 2006 and 2014. In separate analyses, we determined the prevalence of pretherapy resistance and cumulative incidence of follow-up resistance to tenofovir and emtricitabine. We used multivariable proportional hazards models to examine associations between baseline variables and the development of resistance., Results: We studied 6,622 antiretroviral-naive participants initiating therapy, of whom 5,428 (82.0%) had a baseline resistance test. Baseline resistance to tenofovir and emtricitabine was observed in 83 (1.5%) and 21 (0.4%) patients, respectively. Among patients without baseline resistance, the cumulative incidence of resistance to tenofovir and emtricitabine 5 years following treatment initiation was 0.0070 (95% CI 0.0046, 0.0095) and 0.033 (95% CI 0.028, 0.038), respectively. Following multivariable analysis, a baseline viral load ≥100,000 copies/ml was associated with emergence of tenofovir (hazard ratio [HR] 2.88; 95% CI 1.35, 6.15) and emtricitabine (HR 2.27; 95% CI 1.64, 3.15) resistance. Initiating an integrase inhibitor-based regimen and CD4
+ T-cell count below 200 cells/mm3 were also associated with resistance to each drug., Conclusions: We observed a low prevalence of baseline resistance and a low incidence of emergence of resistance to tenofovir and emtricitabine among antiretroviral-naive patients in routine clinical care.- Published
- 2019
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