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1.
BMC Pediatr ; 24(1): 300, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702643

ABSTRACT

BACKGROUND: Complex social determinants of health may not be easily recognized by health care providers and pose a unique challenge in the vulnerable pediatric population where patients may not be able to advocate for themselves. The goal of this study was to examine the acceptability and feasibility of health care providers using an integrated brief pediatric screening tool in primary care and hospital settings. METHODS: The framework of the Child and Adolescent Needs and Strengths (CANS) and Pediatric Intermed tools was used to inform the selection of items for the 9-item Child and Adolescent Needs and Strengths-Pediatric Complexity Indicator (CANS-PCI). The tool consisted of three domains: biological, psychological, and social. Semi-structured interviews were conducted with health care providers in pediatric medical facilities in Ottawa, Canada. A low inference and iterative thematic synthesis approach was used to analyze the qualitative interview data specific to acceptability and feasibility. RESULTS: Thirteen health care providers participated in interviews. Six overarching themes were identified: acceptability, logistics, feasibility, pros/cons, risk, and privacy. Overall, participants agreed that a routine, trained provider-led pediatric tool for the screening of social determinants of health is important (n = 10, 76.9%), acceptable (n = 11; 84.6%), and feasible (n = 7, 53.8%). INTERPRETATION: Though the importance of social determinants of health are widely recognized, there are limited systematic methods of assessing, describing, and communicating amongst health care providers about the biomedical and psychosocial complexities of pediatric patients. Based on this study's findings, implementation of a brief provider-led screening tool into pediatric care practices may contribute to this gap.


Subject(s)
Feasibility Studies , Mass Screening , Social Determinants of Health , Humans , Child , Mass Screening/methods , Female , Male , Adolescent , Primary Health Care , Attitude of Health Personnel , Qualitative Research , Interviews as Topic , Pediatrics
2.
J Healthc Leadersh ; 15: 11-18, 2023.
Article in English | MEDLINE | ID: mdl-36691566

ABSTRACT

Purpose: The Division Chief at an academic health sciences centre has many leadership roles and responsibilities. There are no data on leadership training needs for Division Chiefs, and so we sought to design and implement a needs assessment for pediatric Division Chiefs at CHEO, a pediatric academic health sciences centre in Eastern Ontario, Canada. Methods: A needs assessment survey was developed with the aim to document demographics, preparedness for the role of Division Chief and desired leadership training for the role. This survey was piloted, revised and then distributed to all the Division Chiefs at our institution. The results of each question were collated, and simple descriptive statistics were calculated. Results: The survey was completed by 22 of 31 Division Chiefs. The majority of respondents were from the Department of Pediatrics (63.6%), followed by Surgery (20%), Psychiatry (3.3%) and Laboratory Medicine (3.3%). Their mean length of time as Division Chief was 5.5 years. Seventy-seven percent had concurrent leadership roles in addition to the role of Division Chief. None felt they were very well prepared for the role, five felt they were somewhat well prepared, nine were neutral, five were somewhat unprepared and three were very unprepared for the role. Half of the respondents received mentoring, either formal or informal, for their role and all but one felt that formal mentoring would have been useful. In terms of desired training, the Division Chiefs felt they had the most knowledge and skills in patient safety. All wanted training in developing divisional budgets, and many desired training in supporting the academic mission of the Division. Conclusion: Overall, this needs assessment identified an unmet need for leadership training and development among Division Chiefs. The findings are being used to optimize onboarding of Division Chiefs and an ongoing leadership development program targeted at this group.

3.
HIV Med ; 24(2): 130-138, 2023 02.
Article in English | MEDLINE | ID: mdl-35699235

ABSTRACT

BACKGROUND: While treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies. METHODS: The Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as 'preferred/alternative' as per HHS HIV perinatal guidelines, or 'other than preferred/alternative'. RESULTS: We identified 3673 pregnancies from 2720 women. The proportion of women that conceived while on ARV treatment increased from 29% in 2003 to 90% in 2020. Other than preferred/alternative ARV treatments were received in 1112 (30%) of pregnancies and this was significantly associated with having initiated ARV treatment before conception. CONCLUSION: In Canada during the study period, a high number of women were prescribed an other than preferred/alternative ARV treatment during pregnancy. Further optimization of ARV treatment in women of childbearing age living with HIV is warranted.


Subject(s)
HIV Infections , Pregnancy Complications, Infectious , Pregnancy , Adult , Infant , Female , Humans , HIV Infections/drug therapy , HIV Infections/epidemiology , Canada/epidemiology , Anti-Retroviral Agents/therapeutic use , Mothers , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/epidemiology
4.
Viruses ; 14(12)2022 11 23.
Article in English | MEDLINE | ID: mdl-36560606

ABSTRACT

Perinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-sectional study of CLWH, enrolled in the Early Pediatric Initiation Canadian Child Cure Cohort Study (EPIC4). Plasma levels of CHI3L1, pro-inflammatory cytokines, and markers of microbial translocation were measured by enzyme-linked immunosorbent assays. Longitudinal clinical characteristics (viral load, neutrophil count, CD4+ and CD8+ T-lymphocyte counts, and antiretroviral (ARV) regimen) were abstracted from patient medical records. One-hundred-and-five (105) CLWH (median age 13 years, 62% female) were included in the study. Seventy-seven (81%) had viral suppression on combination antiviral therapy (cART). The median CHI3L1 level was 25 µg/L (IQR 19-39). CHI3L1 was directly correlated with neutrophil count (ρ = 0.22, p = 0.023) and inversely correlated with CD4/CD8 lymphocyte ratio (ρ = -0.35, p = 0.00040). Children with detectable viral load had higher levels of CHI3L1 (40 µg/L (interquartile range, IQR 33-44) versus 24 µg/L (IQR 19-35), p = 0.0047). CHI3L1 levels were also correlated with markers of microbial translocation soluble CD14 (ρ = 0.26, p = 0.010) and lipopolysaccharide-binding protein (ρ = 0.23, p = 0.023). We did not detect differences in CHI3L1 between different cART regimens. High levels of neutrophil activation marker CHI3L1 are associated with poor virologic control, immune dysregulation, and microbial translocation in CLWH on cART.


Subject(s)
Chitinase-3-Like Protein 1 , HIV Infections , Adolescent , Child , Female , Humans , Male , Antiretroviral Therapy, Highly Active , Canada , CD4 Lymphocyte Count , Cohort Studies , Cross-Sectional Studies , HIV Infections/diagnosis , HIV Infections/immunology , Viral Load
5.
Vaccine ; 38(15): 3073-3078, 2020 03 30.
Article in English | MEDLINE | ID: mdl-32147300

ABSTRACT

HPV vaccination schedules have changed as evidence has supported reduced dosing and extended intervals. Women living with HIV (WLWH) represent an important population with no data on alternative dosing. Girls and WLWH received quadrivalent HPV (qHPV) vaccine in a pan-Canadian study of immunogenicity and efficacy. Serology was performed at months 0/2/7/12/18/24. Medical and sexual history was collected throughout. Linear regression was used to determine if spacing of doses was associated with peak antibody titer. Multivariable analyses demonstrated significant relationships between peak antibody titer and time to blood draw post last vaccine dose, naivety to the relevant HPV type, and HIV viral load for all qHPV types. There was a significant relationship between peak HPV16/18 antibody titer and age. Taking age, time to serology, CD4 cell count, CD4 nadir, HIV viral load, and HPV naivety into account, spacing of the three qHPV vaccine doses did not significantly impact peak antibody titers.


Subject(s)
Antibodies, Viral/blood , HIV Infections , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage , Papillomavirus Infections , Canada , Female , Human papillomavirus 16 , Human papillomavirus 18 , Humans , Papillomavirus Infections/prevention & control , Vaccines, Combined/administration & dosage , Viral Load
6.
J Acquir Immune Defic Syndr ; 83(3): 230-234, 2020 03 01.
Article in English | MEDLINE | ID: mdl-31917750

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) vaccines have promising safety and immunogenicity data in women living with HIV (WLWH). However, it is critical to understand the residual burden of oncogenic HPV within WLWH to inform postvaccination cervical screening needs. We assessed rates of persistent infection with nonquadrivalent HPV (qHPV) oncogenic types in a cohort of qHPV-vaccinated WLWH. SETTING: Multicentre, longitudinal cohort across Canada. METHODS: WLWH were scheduled to receive 3 doses of qHPV vaccine. Participants provided health data and HPV DNA samples. Persistent cases of HPV were defined as new HPV in samples from ≥2 consecutive visits or as HPV present in the last sample. HPV31/33/35/39/45/51/52/56/58/59/68/82 were considered to have oncogenic potential. Median follow-up time was 4 years after initial vaccine dose. RESULTS: A total of 284 participants were eligible for this analysis with 1205 person-years (PY) of follow-up (≥1 dose of vaccine, ≥1 HPV DNA result after vaccination). The highest incidence of persistent infection was with HPV51 (1.38/100 PY), followed by HPV52 (1.18/100 PY), and HPV39 (1.06/100 PY). The incidence of persistent infection with pooled HPV types added in the nonavalent vaccine (HPV31/33/45/52/58) was lower than the incidence of persistent oncogenic HPV types not contained within available vaccines (HPV35/39/51/56/59/68) (2.4/100 PY versus 3.6/100 PY, respectively). CONCLUSIONS: qHPV-vaccinated WLWH continue to face a burden of persistent oncogenic HPV infection. Although the nonavalent vaccine could alleviate some of this burden, 2 of the top 3 persistent oncogenic HPVs in this cohort are not contained within any available vaccine. This highlights the need for ongoing cervical screening in HPV-vaccinated WLWH.


Subject(s)
Alphapapillomavirus/genetics , Alphapapillomavirus/isolation & purification , HIV Infections/complications , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/immunology , Papillomavirus Infections/complications , Adult , Canada , Female , Genotype , HIV Infections/epidemiology , Humans , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology
7.
Clin Infect Dis ; 70(5): 859-866, 2020 02 14.
Article in English | MEDLINE | ID: mdl-30919879

ABSTRACT

BACKGROUND: The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus-1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years. METHODS: HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO). RESULTS: Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P < .001, P = .036, and P < .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P < .001, respectively) and inversely with the proportion of life spent on effective cART (P < .001, P = .01, and P < .001, respectively) and proportion of life spent with SVS (P < .001, P = .079, and P < .001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P = .037) or later (rho = 0.87; P < .001). S/COs correlated with HIV-1 DNA (P = .003), but less so with inducible cell-free HIV-1 RNA (P = .09). CONCLUSIONS: The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection.


Subject(s)
HIV Infections , HIV-1 , Canada , Child , Cohort Studies , HIV Infections/drug therapy , HIV-1/genetics , Humans , Leukocytes, Mononuclear , Prospective Studies , RNA , Viral Load
8.
J Acquir Immune Defic Syndr ; 80(5): 590-595, 2019 04 15.
Article in English | MEDLINE | ID: mdl-30865052

ABSTRACT

BACKGROUND: Systemic inflammation, platelet dysfunction, and endothelial activation persist in people living with HIV despite sustained virologic suppression (SVS) with combined antiretroviral therapy (cART) and may lead to complications such as atherosclerosis and cardiovascular disease. Angiopoietin-1 (Ang-1) is a key regulator of angiogenesis and endothelial activation and has been studied as an objective biomarker in disease states such as atherosclerosis, sepsis, and severe malaria. SETTING: Eight pediatric HIV care centers across Canada. METHODS: Cross-sectional study of 61 children living with vertically acquired HIV on cART with undetectable RNA viral load. Plasma levels of Ang-1 were measured by ELISA and analyzed in relation to clinical characteristics abstracted from medical records. RESULTS: Ang-1 levels were directly correlated with clinical indices of virologic control: cumulative proportion of life on effective cART (ρ = +0.35, P = 0.0078) and cumulative proportion of life with SVS (ρ = +0.36, P = 0.0049). Furthermore, higher Ang-1 levels were associated with younger age at SVS (ρ = -0.56, P < 0.0001). These associations remained statistically significant in multivariable linear regression models adjusting for potential confounders (P < 0.05 for all associations). CONCLUSIONS: Early effective cART and SVS were associated with higher Ang-1 levels in children living with vertically acquired HIV-1.


Subject(s)
Angiopoietin-1/blood , Anti-HIV Agents/therapeutic use , HIV Infections/blood , HIV-1/drug effects , Adolescent , Child , Cross-Sectional Studies , Female , HIV Infections/drug therapy , Humans , Infectious Disease Transmission, Vertical , Male , Treatment Outcome , Viral Load/drug effects
9.
CMAJ Open ; 6(2): E202-E210, 2018 May 10.
Article in English | MEDLINE | ID: mdl-29759976

ABSTRACT

BACKGROUND: Vertical HIV transmission has declined in Canada, but missed opportunities for prevention continue to occur. We sought to determine the adequacy, and changes over time in adequacy, of uptake of maternal and neonatal antiretroviral therapy for the prevention of vertical HIV transmission, and to determine the vertical transmission rate over time and according to adequacy of antenatal antiretroviral therapy during the combination antiretroviral therapy era in Canada. METHODS: The Canadian Perinatal HIV Surveillance Program collects data annually through retrospective chart review concerning HIV-infected women and their infants. We determined receipt of adequate antiretroviral treatment (antenatal combination antiretroviral treatment for ≥ 4 wk, intrapartum intravenous zidovudine treatment and 4-6 wk of infant oral zidovudine treatment) and predictors of inadequate antenatal combination antiretroviral therapy (none or < 4 wk) in Canada in 1997-2016. RESULTS: We identified 3785 mother-infant pairs. Uptake of 4 weeks or more of antenatal combination antiretroviral therapy increased over time across all provinces/territories and regardless of maternal race/ethnicity or risk category (p < 0.001). During 2011-2016, 92 women (6.5%) received no or less than 4 weeks of antenatal combination antiretroviral therapy, 146 women (10.7%) received no intrapartum zidovudine treatment, and 43 infants (3.1%) received less than 4 weeks of zidovudine treatment. In multivariate analysis restricted to 2011-2016, higher uptake of adequate antenatal combination antiretroviral therapy was seen among black women than among Indigenous (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.23-7.26) or white (OR 1.87, 95% CI 0.99-1.27) women and in British Columbia/Yukon Territory than in Alberta (OR 3.31, 95% CI 1.06-10.32), Ontario (OR 3.16, 95% CI 1.08-9.26) or Quebec (OR 3.44, 95% CI 1.09-10.84). Among the 14 vertical HIV transmission events during 2011-2016 (vertical transmission rate 1.0%), maternal HIV infection was diagnosed before the onset of labour in 5 cases, and only 2 women received adequate antenatal combination antiretroviral therapy. INTERPRETATION: Efforts to improve timely access to care, HIV screening and treatment for all women, combined with enhanced resources targeting populations at increased risk for HIV infection, will be needed if vertical HIV transmission is to be eliminated in Canada.

10.
Viruses ; 10(2)2018 02 11.
Article in English | MEDLINE | ID: mdl-29439467

ABSTRACT

Long-term outcomes of perinatal exposure to maternal antiretroviral therapy in HIV-exposed uninfected (HEU) children are unknown. However, both HIV antiretroviral therapy and autism spectrum disorder (ASD) have been associated with mitochondrial alterations. Leukocyte mitochondrial DNA (mtDNA) content can serve as a marker for mitochondrial dysfunction. In this cross-sectional, nested case-control study, HEU children with ASD were matched approximately 1:3 on age, sex, and ethnicity to HEU children without ASD, HIV-unexposed uninfected (HUU) controls, and HUU children with ASD. Leukocyte mtDNA content was measured using quantitative PCR. Among 299 HEU in this study, 14 (4.7%) were diagnosed with ASD, which is higher than the general population prevalence estimates. HEU children without ASD and HUU children with ASD had higher mtDNA content than HUU controls. HEU children with ASD had significantly higher mtDNA content than all other study groups. Our results suggest a clear association between elevated leukocyte mtDNA content and both HEU and ASD status. This may implicate mitochondrial dysfunction as a contributor to the high ASD prevalence observed in our cohort.


Subject(s)
Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/etiology , DNA, Mitochondrial , Environmental Exposure , HIV Infections , Adolescent , Age Factors , Antiretroviral Therapy, Highly Active/adverse effects , Autism Spectrum Disorder/blood , Case-Control Studies , Child , Child, Preschool , DNA, Mitochondrial/blood , DNA, Mitochondrial/genetics , Female , HIV Infections/complications , HIV Infections/drug therapy , Humans , Male
11.
PLoS One ; 13(1): e0190247, 2018.
Article in English | MEDLINE | ID: mdl-29320539

ABSTRACT

BACKGROUND: Champlain BASE™ (Building Access to Specialists through eConsultation) is a web-based asynchronous electronic communication service that allows primary-care- practitioners (PCPs) to submit "elective" clinical questions to a specialist. For adults, PCPs have reported improved access and timeliness to specialist advice, averted face-to-face specialist referrals in up to 40% of cases and high provider satisfaction. OBJECTIVE: To determine whether the expansion of eConsult to a pediatric setting would result in similar measures of improved healthcare system process and high provider acceptance reported in adults. DESIGN: Prospective observational cohort study. SETTING: Single Canadian tertiary-care academic pediatric hospital (June 2014-16) servicing 1.2 million people. PARTICIPANTS: 1. PCPs already using eConsult. 2.Volunteer pediatric specialists provided services in addition to their regular workload. 3.Pediatric patients (< 18 years-old) referred for none-acute care conditions. MAIN OUTCOMES AND MEASURES: Specialty service utilization and access, impact on PCP course-of-action and referral-patterns and survey-based provider satisfaction data were collected. RESULTS: 1064 eConsult requests from 367 PCPs were answered by 23 pediatric specialists representing 14 specialty-services. The top three specialties represented were: General Pediatrics 393 cases (36.9%), Orthopedics 162 (15.2%) and Psychiatry 123 (11.6%). Median specialist response time was 0.9 days (range <1 hour-27 days), most consults (63.2%) required <10minutes to complete and 21/21(100%) specialist survey-respondents reported minimal workload burden. For 515/1064(48.4%) referrals, PCPs received advice for a new or additional course of action; 391/1064(36.7%) referrals resulted in an averted face-to-face specialist visit. In 9 specialties with complete data, the median wait-time was significantly less (p<0.001) for an eConsult (1 day, 95%CI:0.9-1.2) compared with a face-to-face referral (132 days; 95%CI:127-136). The majority (>93.3%) of PCPs rated eConsult as very good/excellent value for both patients and themselves. All specialist survey-respondents indicated eConsult should be a continued service. CONCLUSIONS AND RELEVANCE: Similar to adults, eConsult improves PCP access and timeliness to elective pediatric specialist advice and influences their care decisions, while reporting high end-user satisfaction. Further study is warranted to assess impact on resource utilization and clinical outcomes.


Subject(s)
Pediatrics , Referral and Consultation , Remote Consultation , Tertiary Care Centers/organization & administration , Canada , Caregivers , Cost Savings , Humans , Parents , Patient Satisfaction , Prospective Studies , Tertiary Care Centers/economics
12.
Pediatr Infect Dis J ; 37(6): 595-597, 2018 06.
Article in English | MEDLINE | ID: mdl-29278613

ABSTRACT

We evaluated quadrivalent human papillomavirus vaccine seroresponses among 35 girls living with HIV (9-13 years of ages) and compared with data on girls without HIV, as part of a subgroup analysis. The quadrivalent human papillomavirus vaccine was safe and well tolerated. However, antibody response was significantly lower in girls living with HIV relative to girls without HIV. HIV virologic suppression predicted better antibody response.


Subject(s)
HIV Infections/virology , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/immunology , Immunogenicity, Vaccine , Papillomavirus Infections/prevention & control , Adolescent , Antibodies, Viral/blood , CD4 Lymphocyte Count , Canada , Child , Female , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/adverse effects , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/therapeutic use , Humans , Longitudinal Studies , Prospective Studies
13.
Antivir Ther ; 22(6): 545-549, 2017.
Article in English | MEDLINE | ID: mdl-28198351

ABSTRACT

We report a case of therapeutic drug monitoring guided raltegravir use for the prevention of vertical HIV transmission in a premature neonate born to a woman living with perinatally acquired HIV and documented resistance to multiple HIV drugs. Maternal viral load was above 1,000 copies/ml at delivery. This case demonstrates delayed raltegravir elimination in a neonate born at 33 weeks gestational age and a need for less frequent raltegravir dosing than is used in older infants and children.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/prevention & control , HIV Infections/transmission , Infant, Premature , Infectious Disease Transmission, Vertical/prevention & control , Raltegravir Potassium/administration & dosage , Adult , Anti-HIV Agents/pharmacokinetics , Antiretroviral Therapy, Highly Active , Drug Monitoring , Drug Resistance, Viral , Female , HIV Infections/diagnosis , HIV Infections/virology , Humans , Infant, Newborn , Post-Exposure Prophylaxis , Pregnancy , Pregnancy Complications, Infectious , Raltegravir Potassium/pharmacokinetics , Treatment Outcome , Viral Load
14.
J Acquir Immune Defic Syndr ; 74(5): 493-498, 2017 Apr 15.
Article in English | MEDLINE | ID: mdl-28114187

ABSTRACT

BACKGROUND: Nevirapine (NVP)-based combination antiretroviral therapy is routinely prescribed to infants deemed at high risk of vertical HIV infection in our centers. We evaluated NVP pharmacokinetics and safety of this regimen. METHODS: Neonates were recruited prospectively between September 2012 and April 2015 or enrolled retrospectively if treated similarly before prospective study initiation. NVP was dosed at 150 mg/m daily for 14 days, then twice daily for 14 days. NVP levels were drawn at weeks 1, 2, and 4 [target trough (NVP-T): 3-8 mg/L]. RESULTS: Thirty-three neonates were included (23 prospectively). Median gestational age (GA) and birth weight were 38 weeks (32-41 weeks) and 2.9 kg (1.5-4.2 kg), respectively. Median NVP-Ts were 8.2 mg/L (1.6-25.1 mg/L), 3.5 mg/L (1.6-6.8 mg/L), and 4.3 mg/L (0.1-19.9 mg/L) at weeks 1, 2, and 4, respectively. The proportions with therapeutic NVP-T were 42%, 61%, and 73% at these same timepoints. Median apparent oral clearance (CL/F) increased from 0.05 L·kg·h (0.01-0.50 L·kg·h) at week 2 to 0.18 L·kg·h (0.01-0.78 L·kg·h) at week 4. Increased drug exposure [area under the curve (AUCτ)] correlated with younger GA (r = 0.459, P = 0.032) and lower birth weight (r = 0.542, P = 0.009). The most common adverse events potentially attributable to combination antiretroviral therapy were transient asymptomatic hyperlactatemia (26%), anemia (24.7%), and neutropenia (22.1%). CONCLUSIONS: Treatment dose NVP was generally well-tolerated and associated with normalization of trough levels over time in most cases without dose adjustment. Lower empiric dosing is recommended for infants <34 weeks of GA. Routine therapeutic drug monitoring may not be required for infants ≥34 weeks of GA.


Subject(s)
Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacokinetics , Antiretroviral Therapy, Highly Active/methods , HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Nevirapine/adverse effects , Nevirapine/pharmacokinetics , Adult , Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active/adverse effects , Chemoprevention/adverse effects , Chemoprevention/methods , Female , Humans , Infant, Newborn , Male , Nevirapine/administration & dosage , Prospective Studies , Retrospective Studies , Young Adult
15.
Vaccine ; 34(40): 4799-806, 2016 09 14.
Article in English | MEDLINE | ID: mdl-27544584

ABSTRACT

OBJECTIVE: To evaluate the immunogenicity and safety of the quadrivalent HPV (qHPV) vaccine in HIV-positive women over 24months. DESIGN: Between November 2008 and December 2012, 372 women aged 15 and older were enrolled from 14 Canadian HIV outpatient clinics in an open label cohort study. The qHPV vaccine (0.5mL) was administered intramuscularly at months 0, 2 and 6. The primary study endpoint was seroconversion to any of the HPV types targeted by the qHPV vaccine. Antibody levels were measured at 0, 2, 7, 12, 18, and 24months. Adverse events were recorded throughout. RESULTS: Of 372 participants enrolled, 310 (83%) received at least one dose of the qHPV vaccine and 277 (74%) received all three doses. Ninety-five percent (293/308) were seronegative for at least one vaccine type at baseline. The median age was 38years (IQR 32-45, range 15-66), 36% were white, 44% black and 13% were of Indigenous origin. Seventy-two percent of participants had a suppressed HIV viral load (VL<40c/ml) at baseline, with a median CD4 count of 510cells/mm(3) (376-695). Month 7 HPV type-specific seroconversion rates were 99.0%, 98.7%, 98.1% and 93.6% for HPV types 6, 11, 16 and 18 respectively in the per-protocol population. Participants with suppressed HIV VL at first vaccine had a 1.74-3.05fold higher peak antibody response compared to those without (p from 0.006 to <0.0001). CONCLUSIONS: This study is the first to examine the qHPV vaccine in HIV-positive women out to 24months and the first to include HIV-positive women through to age 66. The qHPV vaccine was well tolerated, and highly immunogenic. As women with suppressed viral load had higher antibody responses, planning HPV vaccination to occur when persons are virologically suppressed would be optimal for maximizing immune response. Findings provide strong evidence that older HIV-positive women can still benefit from HPV vaccination. CLINICAL TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN33674451.


Subject(s)
Antibodies, Viral/blood , HIV Infections/immunology , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/therapeutic use , Papillomavirus Infections/prevention & control , Viral Load , Adolescent , Adult , Antibody Formation , CD4 Lymphocyte Count , Canada , Female , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage , Humans , Longitudinal Studies , Middle Aged , Prospective Studies , Seroconversion , Young Adult
16.
Can J Infect Dis Med Microbiol ; 2016: 1546365, 2016.
Article in English | MEDLINE | ID: mdl-27528877

ABSTRACT

Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990-2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990-2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03-1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12-6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04-1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30-40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness.

17.
Leadersh Health Serv (Bradf Engl) ; 29(3): 220-30, 2016 07 04.
Article in English | MEDLINE | ID: mdl-27397745

ABSTRACT

Purpose Physicians are often ill-equipped for the leadership activities their work demands. In part, this is due to a gap in traditional medical education. An emergent international network is developing a globally relevant leadership curriculum for postgraduate medical education. The purpose of this article is to share key learnings from this process to date. Design/methodology/approach The Toronto International Summit on Leadership Education for Physicians (TISLEP) was hosted by the Royal College of Physicians and Surgeons of Canada, and the University of Toronto's Faculty of Medicine and Institute of Health Policy, Management and Evaluation. Of 64 attendees from eight countries, 34 joined working groups to develop leadership competencies. The CanMEDS Competency Framework, stage of learner development and venue of learning formed the scaffold for the work. Emotional intelligence was selected as the topic to test the feasibility of fruitful international collaboration; results were presented at TISLEP 2015. Findings Dedicated international stakeholders engaged actively and constructively through defined working groups to develop a globally relevant, competency-based curriculum for physician leadership education. Eleven principles are recommended for consideration in physician leadership curriculum development. Defining common language and taxonomy is essential for a harmonized product. The importance of establishing an international network to support implementation, evaluation, sustainability and dissemination of the work was underscored. Originality/value International stakeholders are collaborating successfully on a graduated, competency-based leadership curriculum for postgraduate medical learners. The final product will be available for adaptation to local needs. An international physician leadership education network is being developed to support and expand the work underway.


Subject(s)
Curriculum , Leadership , Physicians , Canada , Education, Medical , Humans , Internationality
18.
Leadersh Health Serv (Bradf Engl) ; 29(3): 231-9, 2016 07 04.
Article in English | MEDLINE | ID: mdl-27397746

ABSTRACT

Purpose This paper aims to highlight the importance of leadership development for all physicians within a competency-based medical education (CBME) framework. It describes the importance of timely international collaboration as a key strategy in promoting physician leadership development. Design/methodology/approach The paper explores published and Grey literature around physician leadership development and proposes that international collaboration will meet the expanding call for development of leadership competencies in postgraduate medical learners. Two grounding frameworks were used: complexity science supports adding physician leadership training to the current momentum of CBME adoption, and relational cultural theory supports the engagement of diverse stakeholders in multiple jurisdictions around the world to ensure inclusivity in leadership education development. Findings An international collaborative identified key insights regarding the need to frame physician leadership education within a competency-based model. Practical implications International collaboration can be a vehicle for developing a globally relevant, generalizable physician leadership curriculum. This model can be expanded to encourage innovation, scholarship and program evaluation. Originality/value A competency-based leadership development curriculum is being designed by an international collaborative. The curriculum is based on established leadership and education frameworks. The international collaboration model provides opportunities for ongoing sharing, networking and diversification.


Subject(s)
Competency-Based Education , Leadership , Physicians , Curriculum , Program Evaluation
19.
J Int AIDS Soc ; 19(1): 20520, 2016.
Article in English | MEDLINE | ID: mdl-26880241

ABSTRACT

INTRODUCTION: The optimal management of infants born to HIV-positive mothers who are untreated or have detectable viral load prior to delivery remains controversial. Despite the increasing use of combination antiretroviral therapy (cART) for post-exposure prophylaxis (PEP) of neonates at high risk of HIV infection, there is little safety and pharmacokinetic data to support this approach. The objective of this study was to evaluate the safety and tolerability of cART for PEP in HIV-exposed neonates. METHODS: Retrospective study on 148 cART and 145 Zidovudine (ZDV) monotherapy-exposed infants identified from four Canadian centres where cART for PEP has routinely been prescribed in high-risk situations. Physician-reported adverse events and clinical outcomes were extracted by chart review. Haematological and growth parameters at birth, one and six months of age were compared between cART and ZDV-exposed infants using multivariate mixed effects modelling. RESULTS: Non-specific signs and symptoms were reported in 10.2% of cART recipients versus none of the ZDV recipients. Treatment was discontinued prematurely in 9.5% of cART recipients versus 2.1% of ZDV recipients (p=0.01). In the multivariate model, cART recipients had lower mean haemoglobin (decrease of 2.07 g/L) over the 6-month period compared with ZDV recipients (p=0.04), but no effect was seen on absolute neutrophil count. cART recipients had lower weight and smaller head circumference at birth and one month of age compared with ZDV-exposed infants; these differences were no longer significant at six months of age. CONCLUSIONS: cART administered at treatment doses for PEP in neonates was generally well tolerated, though a higher incidence of non-specific signs and symptoms and early treatment discontinuation occurred among cART recipients.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Adult , Anti-HIV Agents/adverse effects , Canada , Drug Therapy, Combination , Female , Humans , Infant, Newborn , Male , Pregnancy , Retrospective Studies
20.
Paediatr Child Health ; 20(7): 403-13, 2015 Oct.
Article in English, French | MEDLINE | ID: mdl-26527164

ABSTRACT

Housing affects the health of children and youth. One-third of households in Canada live in substandard conditions or in housing need. The present statement reviews the literature documenting the impacts of housing on personal health and the health care system. Types of housing need are defined, including unsuitable or crowded housing, unaffordable housing and inadequate housing, or housing in need of major repairs. The health effects of each type of housing need, as well as of unsafe neighbourhoods, infestations and other environmental exposures are outlined. Paediatricians and other physicians caring for children need to understand the housing status of patients to fully determine their health issues and ability to access and engage in health care. Recommendations and sample tools to assess and address housing need at the patient, family, community and policy levels are described. Canada is the only G8 country without a national housing strategy. Recommendations also include advocating for enhanced action at all levels of government and for housing-supportive policies, including a national housing strategy.


Le logement a une incidence sur la santé des enfants et des adolescents. Le tiers des ménages canadiens habite dans des conditions déplorables ou éprouve des besoins en matière de logement. Le présent document contient une analyse bibliographique des répercussions du logement sur la santé personnelle et le système de santé. Les types de besoins en matière de logement sont définis, y compris les logements de taille inadéquate ou surpeuplés, les logements inabordables ou en mauvais état et ceux qui ont besoin de réparations majeures. Les effets de chaque type de besoins en matière de logement sur la santé, de même que les quartiers mal famés, les infestations et les autres expositions environnementales, sont présentés. Les pédiatres et les autres médecins qui s'occupent d'enfants doivent connaître les conditions de logement de leurs patients pour cerner leurs problèmes de santé ainsi que leur capacité d'obtenir des soins et de s'y conformer. Sont présentés des recommandations et des modèles d'outils pour évaluer les besoins en matière de logement et de politiques de la santé pour le patient, la famille et la collectivité, ainsi que pour y répondre. Le Canada est le seul pays du G8 à ne pas être doté d'une stratégie nationale en matière de logement. Les recommandations incluent également la nécessité de préconiser des mesures plus énergiques à tous les ordres de gouvernement et d'adopter des politiques en appui au logement, y compris une stratégie nationale en matière de logement.

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