Browsing by Author "Ahmed, Sofia B."
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Item Open Access A comparison of prediction equations for the estimation of glomerular filtration rate in transgender individuals(2023-06) Turino Miranda, Keila; Ahmed, Sofia B.; Dumanski, Sandra M.; Ahmed, Sofia B.; Dumanski, Sandra M.; Saad, NathalieThe transgender population (gender identity differs from sex assigned at birth) is estimated to be comprised of 25 million people worldwide. An accurate assessment of kidney function in this population is imperative to ensure appropriate and timely health care delivery to meet the needs of this growing yet medically underserved population. However, whether the variable “sex assigned at birth” or a binary “gender identity” is most appropriate to use in calculation of kidney function with currently used glomerular filtration rate (GFR) estimation equations is unknown, with important implications for care of the transgender, gender-diverse, and non-binary individuals. Furthermore, the use of gender-affirming hormone therapy for the acquisition of secondary sex characteristics to align these individuals with their affirmed gender is increasingly common with associated changes in serum creatinine, a biomarker commonly used to estimate kidney function. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in transgender, gender-diverse and non-binary individuals on gender-affirming hormone therapy makes it difficult to accurately assess the effects of gender-affirming hormone therapy on kidney function. Creatinine increases with the use of gender-affirming testosterone in transmasculine individuals and decreases in association with use of gender-affirming estrogen therapy in transfeminine individuals. Whether these alternations in serum creatinine reflect changes in kidney function or simply changes in muscle mass is unknown. Therefore, the work described in this thesis aims to compare existing GFR prediction equations with the gold standard, directly measured GFR, in transgender, gender-diverse, and non-binary individuals on a stable regimen of gender-affirming hormone therapy. This project addresses methods for optimal estimation of kidney function in the transgender, gender-diverse, and non-binary population on gender-affirming hormone therapy, which may guide clinical decision-making including nephrology consultation, medication dosing, risk of acute kidney injury with diagnostic imaging with intravenous contrast, referral for kidney transplantation, and timing of dialysis initiation.Item Open Access Heat Shock Protein 25 Vaccination Attenuates Atherogenesis after Ovariectomy via Down-Regulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Upregulation of Low Density Lipoprotein Receptor(2019-01-25) Maarouf, Nadia; O'Brien, Edward R.; Ahmed, Sofia B.; Braun, Janice E. A.Women are relatively spared from the development of atherosclerotic coronary artery disease (ASCAD) until after menopause when the frequency of ASCAD accelerates and surpasses that of men. From early observational studies, it was believed that ovarian production of estrogen delayed the onset of ASCAD in pre-menopausal women. However, surprisingly, randomized clinical trials of exogenous estrogen replacement administered to post-menopausal women failed to recapitulate this protection from ASCAD. This suggests that the mechanism for ASCAD protection in women remains poorly understood. In addition to natural menopause and the cessation of endogenous estrogen production, many women may undergo surgically-induced menopause which potentially places them at early increased risk for ASCAD. Approximately 15 years ago, the O’Brien laboratory discovered that heat shock protein 27 (HSP27) can attenuate atherogenesis by reducing cholesterol levels in the blood and artery wall. Furthermore, ovariectomy abolished atheroprotection in HSP27 over-expressing mice but could be restored with therapeutic supplementation of exogenous estrogen receptor modulators. More recently the O’Brien laboratory has discovered that natural antibodies to HSP27 appear to potentiate the beneficial biological effects of HSP27 on the vessel wall as well as on cholesterol metabolism and have developed a vaccination approach as an atheroprotective therapeutic. Based on these prior observations, I hypothesized that vaccination with HSP25 (the murine orthologue of the human HSP27) following ovariectomy would prevent atherogenesis in a mouse model by favorably regulating cholesterol metabolism. To address my hypothesis, two in vivo experiments were pursued in atherosclerosis-prone ApoE-/- mice subjected to ovariectomy (OVX) or sham surgery, fed a high fat diet and randomized to receive active treatment with rHSP25 vaccination, estradiol (E2) or control: i) An 8-week experiment with a supra-physiological dose of estrogen. ii) A 5-week experiment involving a physiological dose of estrogen. In addition, I pursued in vitro experiments looking specifically at the mechanism(s) by which rHSP25/27 may reduce atherogenesis. In the first in vivo experiment, using a previously-validated but supra-physiological dose of replacement estrogen, atherogenesis was attenuated by 21% and 72% in OVX mice either vaccinated with rHSP25 or receiving E2 replacement, respectively. Treatment with E2, but not rHSP25 vaccination, reduced total cholesterol levels. In the second in vivo experiment, using a physiological dose of estrogen, atherogenesis was attenuated by 19% and 33% in OVX mice receiving either rHSP25 vaccine or E2 and total cholesterol levels fell by 20% and 37%, respectively. However, expression of proprotein convertase subtilisin/kexin 9 (PCSK9), a negative regulator of cholesterol metabolism, increased in E2-treated mice by 2.5-fold but was reduced by 62% when combined with rHSP25 vaccination. PCSK9 levels in mice vaccinated with rHSP25 alone were similar to those of sham and control-treated OVX mice. Hepatic LDLR transcript levels increased with rHSP25 vaccination, ~4-fold in rHSP25-treated sham-operated mice and ~3.2-fold in rHSP25-treated OVX mice, but low-density lipoprotein receptor (LDLR) mRNA levels were unchanged with E2 therapy or control treatment. In vitro, E2 increased PCSK9 promoter activity in a dose-dependent manner that, again, could be reduced by 41.2% by treating simultaneously with rHSP27. Both E2 and rHSP27 treatments increased LDLR promoter activity by 7.7- and 6.4-fold, respectively. Taken together, these studies demonstrate, in a murine model of surgical menopause, that rHSP25 vaccination can attenuate atherogenesis and, unlike E2 therapy, does not increase PCSK9 or cause off-target effects on estrogen-responsive tissues (i.e. the uterus and fallopian tubes). The upregulation of LDLR by rHSP25/27 is a unique observation that offers an excellent opportunity for the development of novel therapeutics. This thesis presents novel findings that elucidate key acquired mechanisms by which rHSP25, and its human orthologue rHSP27, prevent atherogenesis in ApoE-/- mice. The major finding is that rHSP25 vaccination is effective in reducing atherosclerotic plaque development following ovariectomy and the loss of endogenous estrogens. The protective actions of HSP25 on the vasculature are multifaceted and the mechanisms include: 1) lowering of total plasma cholesterol, 2) reduction of circulating VLDL-c and LDL-c, 3) reduction of plasma PCSK9, and 4) up-regulation of hepatic LDLR gene expression in vivo. In vitro mechanistic studies using the human hepatocyte cell line HepG2 confirmed that rHSP27 treatment downregulates PCSK9 promoter activity and upregulates LDLR promoter activity. These studies produced five main findings: 1) rHSP25 vaccination mediates athero-protection following OVX in ApoE-/- mice without adverse effects (Figure 4.2, Figure 4.8, Figure 4.13, Figure 4.17), 2) the combination therapy of rHSP25 vaccination plus physiological dose E2 yields synergistic atherogenesis prevention effects (Figure 4.13), 3) E2 upregulates PCSK9 promoter activity in vitro in a dose-dependent manner (Figure 4.22), 4) rHSP27/pAb complex treatment abolishes PCSK9 promoter activity in human hepatocytes (Figure 4.23), and 5) the rHSP27/pAb complex upregulates LDLR expression both in vivo and in vitro (Figure 4.24) (as evidenced by increased LDLR promoter activity). Taken together, these findings provide a novel and exciting evidence that the therapeutic actions of rHSP25/rHSP27 are independent of estrogen and that athero-protection appears to be mediated though the PCSK9/LDLR/cholesterol pathway. These observations support the working hypothesis of this thesis and support the possibility that rHSP27 is a novel therapeutic intervention for the prevention of post-menopausal ASCAD.Item Open Access Interventions on gender equity in the workplace: a scoping review(2024-04-05) Tricco, Andrea C.; Parker, Amanda; Khan, Paul A.; Nincic, Vera; Robson, Reid; MacDonald, Heather; Warren, Rachel; Cleary, Olga; Zibrowski, Elaine; Baxter, Nancy; Burns, Karen E. A.; Coyle, Doug; Ndjaboue, Ruth; Clark, Jocalyn P.; Langlois, Etienne V.; Ahmed, Sofia B.; Witteman, Holly O.; Graham, Ian D.; El-Adhami, Wafa; Skidmore, Becky; Légaré, France; Curran, Janet; Hawker, Gillian; Watt, Jennifer; Bourgeault, Ivy L.; Leigh, Jeanna P.; Lawford, Karen; Aiken, Alice; McCabe, Christopher; Shepperd, Sasha; Pattani, Reena; Leon, Natalie; Lundine, Jamie; Adisso, Évèhouénou L.; Ono, Santa; Rabeneck, Linda; Straus, Sharon E.Abstract Background Various studies have demonstrated gender disparities in workplace settings and the need for further intervention. This study identifies and examines evidence from randomized controlled trials (RCTs) on interventions examining gender equity in workplace or volunteer settings. An additional aim was to determine whether interventions considered intersection of gender and other variables, including PROGRESS-Plus equity variables (e.g., race/ethnicity). Methods Scoping review conducted using the JBI guide. Literature was searched in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, ERIC, Index to Legal Periodicals and Books, PAIS Index, Policy Index File, and the Canadian Business & Current Affairs Database from inception to May 9, 2022, with an updated search on October 17, 2022. Results were reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to scoping reviews (PRISMA-ScR), Sex and Gender Equity in Research (SAGER) guidance, Strengthening the Integration of Intersectionality Theory in Health Inequality Analysis (SIITHIA) checklist, and Guidance for Reporting Involvement of Patients and the Public (GRIPP) version 2 checklist. All employment or volunteer sectors settings were included. Included interventions were designed to promote workplace gender equity that targeted: (a) individuals, (b) organizations, or (c) systems. Any comparator was eligible. Outcomes measures included any gender equity related outcome, whether it was measuring intervention effectiveness (as defined by included studies) or implementation. Data analyses were descriptive in nature. As recommended in the JBI guide to scoping reviews, only high-level content analysis was conducted to categorize the interventions, which were reported using a previously published framework. Results We screened 8855 citations, 803 grey literature sources, and 663 full-text articles, resulting in 24 unique RCTs and one companion report that met inclusion criteria. Most studies (91.7%) failed to report how they established sex or gender. Twenty-three of 24 (95.8%) studies reported at least one PROGRESS-Plus variable: typically sex or gender or occupation. Two RCTs (8.3%) identified a non-binary gender identity. None of the RCTs reported on relationships between gender and other characteristics (e.g., disability, age, etc.). We identified 24 gender equity promoting interventions in the workplace that were evaluated and categorized into one or more of the following themes: (i) quantifying gender impacts; (ii) behavioural or systemic changes; (iii) career flexibility; (iv) increased visibility, recognition, and representation; (v) creating opportunities for development, mentorship, and sponsorship; and (vi) financial support. Of these interventions, 20/24 (83.3%) had positive conclusion statements for their primary outcomes (e.g., improved academic productivity, increased self-esteem) across heterogeneous outcomes. Conclusions There is a paucity of literature on interventions to promote workplace gender equity. While some interventions elicited positive conclusions across a variety of outcomes, standardized outcome measures considering specific contexts and cultures are required. Few PROGRESS-Plus items were reported. Non-binary gender identities and issues related to intersectionality were not adequately considered. Future research should provide consistent and contemporary definitions of gender and sex. Trial registration Open Science Framework https://osf.io/x8yae .Item Open Access Pneumatic compression devices during hemodialysis(2012-08-28) Tai, Davina Julia; Ahmed, Sofia B.; MacRae, Jennifer M.Hemodynamic stability during hemodialysis requires maintenance of central blood volume (CBV), which pneumatic compression devices (PCDs) may help preserve. We performed a randomized crossover trial to determine the effect of PCDs on CBV during hemodialysis. Fifty-one patients were randomized to begin the first of two hemodialysis sessions with or without PCDs. The median change in CBV for PCDs vs control was -0.08 vs -0.05L (p=0.62). There was no difference in change in cardiac output (-0.63 vs -0.49L/min, p=0.78) or systemic vascular resistance (+1.30 vs +1.55mmHg/L/min, p=0.67) for PCDs vs control. There was a greater reduction in total body water (-2.6 vs -2.3L, p=0.05) and intracellular fluid volume (-1.3 vs -1.1L, p=0.03), with no difference in extracellular fluid volume (-1.3 vs -1.2L, p=0.09) for PCDs vs control. Compared with standard of care, PCDs have no effect on intradialytic hemodynamic parameters, including CBV, although they may allow greater capacity for fluid removal.Item Open Access Restricted visitation policies in acute care settings during the COVID-19 pandemic: a scoping review(2021-09-25) Moss, Stephana J.; Krewulak, Karla D.; Stelfox, Henry T.; Ahmed, Sofia B.; Anglin, Melanie C.; Bagshaw, Sean M.; Burns, Karen E. A.; Cook, Deborah J.; Doig, Christopher J.; Fox-Robichaud, Alison; Fowler, Robert; Hernández, Laura; Kho, Michelle E.; Kredentser, Maia; Makuk, Kira; Murthy, Srinivas; Niven, Daniel J.; Olafson, Kendiss; Parhar, Ken K. S.; Patten, Scott B.; Rewa, Oleksa G.; Rochwerg, Bram; Sept, Bonnie; Soo, Andrea; Spence, Krista; Spence, Sean; Straus, Sharon; West, Andrew; Parsons Leigh, Jeanna; Fiest, Kirsten M.Abstract Background Restricted visitation policies in acute care settings because of the COVID-19 pandemic have negative consequences. The objective of this scoping review is to identify impacts of restricted visitation policies in acute care settings, and describe perspectives and mitigation approaches among patients, families, and healthcare professionals. Methods We searched Medline, Embase, PsycINFO, Healthstar, CINAHL, Cochrane Central Register of Controlled Trials on January 01/2021, unrestricted, for published primary research records reporting any study design. We included secondary (e.g., reviews) and non-research records (e.g., commentaries), and performed manual searches in web-based resources. We excluded records that did not report primary data. Two reviewers independently abstracted data in duplicate. Results Of 7810 citations, we included 155 records. Sixty-six records (43%) were primary research; 29 (44%) case reports or case series, and 26 (39%) cohort studies; 21 (14%) were literature reviews and 8 (5%) were expert recommendations; 54 (35%) were commentary, editorial, or opinion pieces. Restricted visitation policies impacted coping and daily function (n = 31, 20%) and mental health outcomes (n = 29, 19%) of patients, families, and healthcare professionals. Participants described a need for coping and support (n = 107, 69%), connection and communication (n = 107, 69%), and awareness of state of well-being (n = 101, 65%). Eighty-seven approaches to mitigate impact of restricted visitation were identified, targeting families (n = 61, 70%), patients (n = 51, 59%), and healthcare professionals (n = 40, 46%). Conclusions Patients, families, and healthcare professionals were impacted by restricted visitation polices in acute care settings during COVID-19. The consequences of this approach on patients and families are understudied and warrant evaluation of approaches to mitigate their impact. Future pandemic policy development should include the perspectives of patients, families, and healthcare professionals. Trial registration: The review was registered on PROSPERO (CRD42020221662) and a protocol peer-reviewed prior to data extraction.Item Open Access Social factors associated with self-reported changes in mental health symptoms among youth in the COVID-19 pandemic: a cross-sectional survey(2024-02-28) Moss, Stephana J.; Stelfox, Maia; McArthur, Eric; Sriskandarajah, Cynthia; Ahmed, Sofia B.; Birnie, Kathryn; Halperin, Donna M.; Halperin, Scott A.; Harley, Micaela; Hu, Jia; Kamstra, Josh N.; Leppan, Laura; Nickel, Angie; Racine, Nicole; Russell, Kristine; Smith, Stacie; Solis, May; Tutelman, Perri R.; Stelfox, Henry T.; Fiest, Kirsten M.; Parsons Leigh, JeannaAbstract Background Children and youth experienced marked impacts on day-to-day life in the COVID-19 pandemic that were associated with poorer familial and friend relationships, and greater mental health challenges. Few studies provide self-report data on mental health symptoms from children and youth themselves. We sought to examine the associations between social factors and child and youth self-reported symptoms of worsened mood, anxiety, and irritability during the COVID-19 pandemic. Methods A nationally representative cross-sectional survey was administered online to collect self-report data across 10 Canadian provinces among children (11–14 years) and youth (15–18 years), April–May 2022. Age-appropriate questions were based on The Partnership for Maternal, Newborn & Child Health and the World Health Organization of the United Nations H6 + Technical Working Group on Adolescent Health and Well-Being consensus framework and the Coronavirus Health and Impact Survey. Associations between a priori defined social factors (e.g., relationship quality) and respondent self-reported mental health were evaluated using ordinal logistic regression models adjusted for age, sex, and geographic location. Results We analyzed data from 483 (51.7%) children (11–14 years; 227, 47.0% girls) and 450 (48.3%) youth (15–18 years; 204, 45.3% girls). The parents of most children and youth had resided in Canada for over 20 years (678, 72.7%). Over one-quarter of children and youth self-identified as Black, Indigenous, or a Person of Color (134, 27.7%; 134, 29.8%, respectively). Over one-third of children and youth self-reported symptoms of worsened mood (149, 30.9%; 125, 27.8%, respectively), anxiety (181, 37.5%; 167, 37.1%, respectively), or irritability (160, 33.1%; 160, 35.6%, respectively) during, compared to pre-pandemic. In descending order of odds ratios (OR), for children and youth, worsened familial relationships (during compared to pre-pandemic) was associated with the self-reported symptoms of worsened mood (child: OR 4.22, 95%CI 2.51–6.88; youth: OR 6.65 95%CI 3.98–11.23), anxiety (child: OR 4.24, 95%CI2.69–6.75; youth: OR 5.28, 95%CI 3.17–8.86), and irritability (child: OR 2.83, 95%CI 1.76–4.56; youth: OR 6.46, 95%CI 3.88–10.90). Conclusions Self-reported data from a nationally representative sample of children and youth suggest strong associations between social factors and mental health during the COVID-19 pandemic. Interventions targeting child and youth familial relationships may positively impact child and youth mental health.Item Embargo The Impact and Treatment of Postural Orthostatic Tachycardia Syndrome(2024-04-24) Bourne, Kate; Raj, Satish Ramnarayan; Sheldon, Robert Stanley; Exner, Derek V.; Ahmed, Sofia B.; Mak, SusannaBackground: Postural orthostatic tachycardia syndrome (POTS) is a debilitating cardiovascular autonomic nervous system disorder. Patients with POTS experience a high symptom burden and significant reductions in quality of life, but the full impacts of POTS were previously not fully understood. There are no approved medications for treating POTS, and evidence for off-label medication use and non-pharmacological treatments is of poor quality. Aims: The two aims of this program of research were to (1) investigate the multi-factorial impacts of POTS, and (2) evaluate compression garments as a potential non-pharmacological treatment. Methods: Aim 1 consisted of two studies: A large survey used to evaluate the economic and employment impacts of POTS, the role of sex differences in POTS, and the impact of pregnancy on POTS symptoms, and a survey of patients at a specialist autonomic centre to evaluate long-term outcomes of POTS. Aim 2 consisted of three studies: an in lab clinical trial of a proof-of-concept compression garment, an at home clinical trial using “real-world” compression garments, and a qualitative interview project evaluating the patient experience with compression garments. Results: Aim 1: Patients with POTS experience significant employment and economic impacts. Female patients with POTS experienced longer diagnostic delays and were more likely to be told their POTS was all in their head compared to male patients. Most patients who had been pregnant experienced a worsening of POTS symptoms during pregnancy. Over the long term, most patients with POTS continue to experience POTS symptoms. Aim 2: Body compression of the abdomen and legs reduces heart rate and improves symptoms by increasing stroke volume. Patients reported benefits from compression garments, as well as limitations; it is important for clinicians to be aware of this. Conclusions: Patients with POTS experience significant impacts including economic and employment loss, female patients with POTS experience a longer diagnostic delay than male patients, and most patients experience worse POTS symptoms during pregnancy. Compression garments are a cost-effective treatment that should be recommended for patients with POTS. Easy to implement treatments like compression garments may help to reduce symptom burden and negative impacts of POTS.Item Open Access Well-being approaches targeted to improve child and youth health post-COVID-19 pandemic: a scoping review(2024-06-21) Moss, Stephana J.; Sriskandarajah, Cynthia; Brundin-Mather, Rebecca; Cherak, Michal S.; Mizen, Sara J.; Stelfox, Maia; Halperin, Donna; Halperin, Scott; Ahmed, Sofia B.; Lorenzetti, Diane L.; Smith, Stacie; Harley, Micaela; Tutelman, Perri R.; Birnie, Kathryn A.; Anglin, Melanie C.; Stelfox, Henry T.; Fiest, Kirsten M.; Racine, Nicole; Parsons Leigh, JeannaAbstract Background Our previous work synthesized published studies on well-being interventions during COVID-19. As we move into a post-COVID-19 pandemic period there is a need to comprehensively review published strategies, approaches, and interventions to improve child and youth well-being beyond deleterious impacts experienced during COVID-19. Methods Seven databases were searched from inception to January 2023. Studies were included if they: (1) presented original data on an approach (i.e., approach applied) or (2) provided recommendations to inform development of a future approach (i.e., approach suggested), (3) targeted to mitigate negative impacts of COVID-19 on child and youth (≤18 year) well-being, and (4) published on or after December 2019. Results 39 studies (n = 4/39, 10.3% randomized controlled trials) from 2021 to 2023 were included. Twenty-two studies applied an approach (n = 22/39, 56.4%) whereas seventeen studies (n = 17/39, 43.6%) suggested an approach; youth aged 13–18 year (n = 27/39, 69.2%) were most frequently studied. Approach applied records most frequently adopted an experimental design (n = 11/22, 50.0%), whereas approach suggested records most frequently adopted a cross-sectional design (n = 13/22, 59.1%). The most frequently reported outcomes related to good health and optimum nutrition (n = 28/39, 71.8%), followed by connectedness (n = 22/39, 56.4%), learning, competence, education, skills, and employability (n = 18/39, 46.1%), and agency and resilience (n = 16/39, 41.0%). Conclusions The rapid onset and unpredictability of COVID-19 precluded meaningful engagement of children and youth in strategy development despite widespread recognition that early engagement can enhance usefulness and acceptability of interventions. Published or recommended strategies were most frequently targeted to improve connectedness, belonging, and socialization among children and youth.