Browsing by Author "Hutton, Brian"

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    Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes
    (2017-05-05) Veroniki, Areti A; Cogo, Elise; Rios, Patricia; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D’Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C
    Abstract Background Pregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis. Methods MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes). Results After screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23–7.07), valproate (OR, 2.93; 95% CrI, 2.36–3.69), topiramate (OR, 1.90; 95% CrI, 1.17–2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35–2.47), phenytoin (OR, 1.67; 95% CrI, 1.30–2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10–1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72–1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43–1.16) were not. Conclusion The newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control. Systematic Review Registration PROSPERO CRD42014008925
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    Effectiveness of stop smoking interventions among adults: protocol for an overview of systematic reviews and an updated systematic review
    (2019-01-19) Hersi, Mona; Traversy, Gregory; Thombs, Brett D; Beck, Andrew; Skidmore, Becky; Groulx, Stéphane; Lang, Eddy; Reynolds, Donna L; Wilson, Brenda; Bernstein, Steven L; Selby, Peter; Johnson-Obaseki, Stephanie; Manuel, Douglas; Pakhale, Smita; Presseau, Justin; Courage, Susan; Hutton, Brian; Shea, Beverley J; Welch, Vivian; Morrow, Matt; Little, Julian; Stevens, Adrienne
    Abstract Background Tobacco smoking is the leading cause of cancer, preventable death, and disability. Smoking cessation can increase life expectancy by nearly a decade if achieved in the third or fourth decades of life. Various stop smoking interventions are available including pharmacotherapies, electronic cigarettes, behavioural support, and alternative therapies. This protocol outlines an evidence review which will evaluate the benefits and harms of stop smoking interventions in adults. Methods The evidence review will consist of two stages. First, an overview of systematic reviews evaluating the benefits and harms of various stop smoking interventions delivered in or referred from the primary care setting will be conducted. The second stage will involve updating a systematic review on electronic cigarettes identified in the overview; randomized controlled trials will be considered for outcomes relating to benefits while randomized controlled trials, non-randomized controlled trials, and comparative observational studies will be considered for evaluating harms. Search strategies will be developed and peer-reviewed by medical information specialists. The search strategy for the updated review on e-cigarettes will be developed using that of the candidate systematic review. The MEDLINE®, PsycINFO, Embase, and the Cochrane Library electronic databases will be searched as of 2008 for the overview of reviews and from the last search date of the selected review for the updated review. Organizational websites and trial registries will be searched for unpublished or ongoing reviews/studies. Two reviewers will independently screen the title and abstracts of citations using the liberal accelerated method. Full-text screening will be performed independently by two reviewers. Extracted data will be verified by a second reviewer. Disagreements regarding full-text screening and data extraction will be resolved by consensus or third-party adjudication. The methodological quality of systematic reviews, risk of bias of randomized and non-randomized trials, and methodological quality of cohort studies will be evaluated using AMSTAR 2, the Cochrane risk of bias tool, and a modified version of the Scottish Intercollegiate Guidelines Network critical appraisal tool, respectively. The GRADE framework will be used to assess the quality of the evidence for outcomes. Discussion The evidence review will evaluate the benefits and harms of various stop smoking interventions for adults. Findings will be used to inform a national tobacco cessation guideline by the Canadian Task Force on Preventive Health Care. Systematic review registration PROSPERO (CRD42018099691, CRD42018099692)
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    Enhancing the uptake of systematic reviews of effects: what is the best format for health care managers and policy-makers? A mixed-methods study
    (2018-06-22) Marquez, Christine; Johnson, Alekhya M; Jassemi, Sabrina; Park, Jamie; Moore, Julia E; Blaine, Caroline; Bourdon, Gertrude; Chignell, Mark; Ellen, Moriah E; Fortin, Jacques; Graham, Ian D; Hayes, Anne; Hamid, Jemila; Hemmelgarn, Brenda; Hillmer, Michael; Holmes, Bev; Holroyd-Leduc, Jayna; Hubert, Linda; Hutton, Brian; Kastner, Monika; Lavis, John N; Michell, Karen; Moher, David; Ouimet, Mathieu; Perrier, Laure; Proctor, Andrea; Noseworthy, Thomas; Schuckel, Victoria; Stayberg, Sharlene; Tonelli, Marcello; Tricco, Andrea C; Straus, Sharon E
    Abstract Background Systematic reviews are infrequently used by health care managers (HCMs) and policy-makers (PMs) in decision-making. HCMs and PMs co-developed and tested novel systematic review of effects formats to increase their use. Methods A three-phased approach was used to evaluate the determinants to uptake of systematic reviews of effects and the usability of an innovative and a traditional systematic review of effects format. In phase 1, survey and interviews were conducted with HCMs and PMs in four Canadian provinces to determine perceptions of a traditional systematic review format. In phase 2, systematic review format prototypes were created by HCMs and PMs via Conceptboard©. In phase 3, prototypes underwent usability testing by HCMs and PMs. Results Two hundred two participants (80 HCMs, 122 PMs) completed the phase 1 survey. Respondents reported that inadequate format (Mdn = 4; IQR = 4; range = 1–7) and content (Mdn = 4; IQR = 3; range = 1–7) influenced their use of systematic reviews. Most respondents (76%; n = 136/180) reported they would be more likely to use systematic reviews if the format was modified. Findings from 11 interviews (5 HCMs, 6 PMs) revealed that participants preferred systematic reviews of effects that were easy to access and read and provided more information on intervention effectiveness and less information on review methodology. The mean System Usability Scale (SUS) score was 55.7 (standard deviation [SD] 17.2) for the traditional format; a SUS score < 68 is below average usability. In phase 2, 14 HCMs and 20 PMs co-created prototypes, one for HCMs and one for PMs. HCMs preferred a traditional information order (i.e., methods, study flow diagram, forest plots) whereas PMs preferred an alternative order (i.e., background and key messages on one page; methods and limitations on another). In phase 3, the prototypes underwent usability testing with 5 HCMs and 7 PMs, 11 out of 12 participants co-created the prototypes (mean SUS score 86 [SD 9.3]). Conclusions HCMs and PMs co-created prototypes for systematic review of effects formats based on their needs. The prototypes will be compared to a traditional format in a randomized trial.
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    Establishing core outcome sets for phenylketonuria (PKU) and medium-chain Acyl-CoA dehydrogenase (MCAD) deficiency in children: study protocol for systematic reviews and Delphi surveys
    (2017-12-19) Potter, Beth K; Hutton, Brian; Clifford, Tammy J; Pallone, Nicole; Smith, Maureen; Stockler, Sylvia; Chakraborty, Pranesh; Barbeau, Pauline; Garritty, Chantelle M; Pugliese, Michael; Rahman, Alvi; Skidmore, Becky; Tessier, Laure; Tingley, Kylie; Coyle, Doug; Greenberg, Cheryl R; Korngut, Lawrence; MacKenzie, Alex; Mitchell, John J; Nicholls, Stuart; Offringa, Martin; Schulze, Andreas; Taljaard, Monica
    Abstract Background Inherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life. There are important evidence gaps related to the comparative effectiveness of therapies for IMD, which are in part due to challenges in conducting randomized controlled trials (RCTs) for rare diseases. Registry-based RCTs present a unique opportunity to address these challenges provided the registries implement standardized collection of outcomes that are important to patients and their caregivers and to clinical providers and healthcare systems. Currently there is no core outcome set (COS) for studies evaluating interventions for paediatric IMD. This protocol outlines a study that will establish COS for each of two relatively common IMD in children, phenylketonuria (PKU) and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. Methods This two-part study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative. Part 1 includes a rapid review and development of an evidence map to identify a comprehensive listing of outcomes reported in past studies of PKU and MCAD deficiency. The review follows established methods for knowledge synthesis, including a comprehensive search strategy, two stages of screening citations against inclusion/exclusion criteria by two reviewers working independently, and extraction of important data elements from eligible studies, including details of the outcomes collected and outcome measurement instruments. The review findings will inform part 2 of our study, a set of Delphi surveys to establish consensus on the highest priority outcomes for each condition. Healthcare providers, families of children with PKU or MCAD deficiency, and health system decision-makers will be invited to participate in two to three rounds of Delphi surveys. The design of the surveys will involve parents of children with IMD who are part of a family advisory forum. Discussion This protocol is a crucial step in developing the capacity to launch RCTs with meaningful outcomes that address comparative effectiveness questions in the field of paediatric IMD. Such trials will contribute high-quality evidence to inform decision-making by patients and their family members, clinicians, and policy-makers.
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    Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review
    (2020-01-14) Pugliese, Michael; Tingley, Kylie; Chow, Andrea; Pallone, Nicole; Smith, Maureen; Rahman, Alvi; Chakraborty, Pranesh; Geraghty, Michael T; Irwin, Julie; Tessier, Laure; Nicholls, Stuart G; Offringa, Martin; Butcher, Nancy J; Iverson, Ryan; Clifford, Tammy J; Stockler, Sylvia; Hutton, Brian; Paik, Karen; Tao, Jessica; Skidmore, Becky; Coyle, Doug; Duddy, Kathleen; Dyack, Sarah; Greenberg, Cheryl R; Ghai, Shailly J; Karp, Natalya; Korngut, Lawrence; Kronick, Jonathan; MacKenzie, Alex; MacKenzie, Jennifer; Maranda, Bruno; Mitchell, John J; Potter, Murray; Prasad, Chitra; Schulze, Andreas; Sparkes, Rebecca; Taljaard, Monica; Trakadis, Yannis; Walia, Jagdeep; Potter, Beth K
    Abstract Background Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. Methods We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. Results For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. Conclusions Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies.
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    Screening for depression in children and adolescents: a protocol for a systematic review update
    (2021-01-12) Beck, Andrew; LeBlanc, John C; Morissette, Kate; Hamel, Candyce; Skidmore, Becky; Colquhoun, Heather; Lang, Eddy; Moore, Ainsley; Riva, John J; Thombs, Brett D; Patten, Scott; Bragg, Heather; Colman, Ian; Goldfield, Gary S; Nicholls, Stuart G; Pajer, Kathleen; Potter, Beth K; Meeder, Robert; Vasa, Priya; Hutton, Brian; Shea, Beverley J; Graham, Eva; Little, Julian; Moher, David; Stevens, Adrienne
    Abstract Background Major depressive disorder is common, debilitating, and affects feelings, thoughts, mood, and behaviors. Childhood and adolescence are critical periods for the development of depression and adolescence is marked by an increased incidence of mental health disorders. This protocol outlines the planned scope and methods for a systematic review update that will evaluate the benefits and harms of screening for depression in children and adolescents. Methods This review will update a previously published systematic review by Roseman and colleagues. Eligible studies are randomized controlled trials (RCTs) assessing formal screening in primary care to identify children or adolescents not already self-reporting symptoms of, diagnosed with, or treated for depression. If no or only a single RCT is available, we will consider controlled studies without random assignment. Studies of participants with characteristics associated with an elevated risk of depression will be analyzed separately. Outcomes of interest are symptoms of depression, classification of major depressive disorder based on a validated diagnostic interview, suicidality, health-related quality of life, social function, impact on lifestyle behavior (e.g., substance use, school performance, lost time at work, or school), false-positive results, overdiagnosis, overtreatment, labeling, and other harms such as those arising from treatment. We will search MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, and grey literature sources. Two reviewers will independently screen the titles and abstracts using the liberal accelerated method. Full-text screening will be performed independently by two reviewers using pre-specified eligibility criteria. Data extraction and risk of bias assessments will be performed independently by two reviewers. Pre-planned analyses, including subgroup and sensitivity analyses, are detailed within this protocol. Two independent reviewers will assess and finalize through consensus the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and prepare GRADE evidence profiles and summary of findings tables for each outcome of interest. Discussion The systematic review will provide a current state of the evidence of benefits and harms of depression screening in children and adolescents. These findings will be used by the Canadian Task Force on Preventive Health Care to inform the development of recommendations on depression screening. Systematic review registration PROSPERO CRD42020150373
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    Screening for depression in women during pregnancy or the first year postpartum and in the general adult population: a protocol for two systematic reviews to update a guideline of the Canadian Task Force on Preventive Health Care
    (2019-01-19) Hamel, Candyce; Lang, Eddy; Morissette, Kate; Beck, Andrew; Stevens, Adrienne; Skidmore, Becky; Colquhoun, Heather; LeBlanc, John; Moore, Ainsley; Riva, John J; Thombs, Brett D; Colman, Ian; Grigoriadis, Sophie; Nicholls, Stuart G; Potter, Beth K; Ritchie, Kerri; Robert, Julie; Vasa, Priya; Lauria-Horner, Bianca; Patten, Scott; Vigod, Simone N; Hutton, Brian; Shea, Beverley J; Shanmugasegaram, Shamila; Little, Julian; Moher, David
    Abstract Background In 2018, the World Health Organization reported that depression is the most common cause of disability worldwide, with over 300 million people currently living with depression. Depression affects an individual’s physical health and well-being, impacts psychosocial functioning, and has specific negative short- and long-term effects on maternal health, child health, developmental trajectories, and family health. The aim of these reviews is to identify evidence on the benefits and harms of screening for depression in the general adult population and in pregnant and postpartum women. Methods Search strategies were developed and tested through an iterative process by an experienced medical information specialist in consultation with the review team. We will search MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library, and a randomized controlled trial filter will be used. The general adult review will be an update of a systematic review previously used by the Canadian Task Force on Preventive Health Care for their 2013 guideline recommendation. The search strategy will be updated and will start from the last search date of the previous review (May 2012). The pregnant and postpartum review will be a de novo review with no date restriction. For both reviews, we will search for unpublished documents following the CADTH Grey Matters checklist and relevant websites. Titles and abstracts will be screened using the liberal accelerated method. Two reviewers will independently screen full-text articles for relevance using pre-specified eligibility criteria and assess the risk of bias of included studies using the Cochrane Risk of Bias tool. Outcomes of interest for the general adult population review include symptoms of depression or diagnosis of major depressive disorder, health-related quality of life, day-to-day functionality, lost time at work/school, impact on lifestyle behaviour, suicidality, false-positive result, labelling/stigma, overdiagnosis or overtreatment, and harms of treatment. Outcomes of interest for the pregnant and postpartum review include mental health outcomes (e.g. diagnosis of major depressive disorder), parenting outcomes (e.g. mother-child interactions), and infant outcomes (e.g. infant health and development). Discussion These two systematic reviews will offer informative evaluations of depression screening. The findings will be used by the Task Force to help develop guideline recommendations on depression screening in the general adult population and in pregnant and postpartum women in Canada. Systematic review registration PROSPERO (CRD42018099690)