Browsing by Author "Potter, Beth K"

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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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    Evaluation of the quality of clinical data collection for a pan-Canadian cohort of children affected by inherited metabolic diseases: lessons learned from the Canadian Inherited Metabolic Diseases Research Network
    (2020-04-10) Tingley, Kylie; Lamoureux, Monica; Pugliese, Michael; Geraghty, Michael T; Kronick, Jonathan B; Potter, Beth K; Coyle, Doug; Wilson, Kumanan; Kowalski, Michael; Austin, Valerie; Brunel-Guitton, Catherine; Buhas, Daniela; Chan, Alicia K J; Dyack, Sarah; Feigenbaum, Annette; Giezen, Alette; Goobie, Sharan; Greenberg, Cheryl R; Ghai, Shailly J; Inbar-Feigenberg, Michal; Karp, Natalya; Kozenko, Mariya; Langley, Erica; Lines, Matthew; Little, Julian; MacKenzie, Jennifer; Maranda, Bruno; Mercimek-Andrews, Saadet; Mohan, Connie; Mhanni, Aizeddin; Mitchell, Grant; Mitchell, John J; Nagy, Laura; Napier, Melanie; Pender, Amy; Potter, Murray; Prasad, Chitra; Ratko, Suzanne; Salvarinova, Ramona; Schulze, Andreas; Siriwardena, Komudi; Sondheimer, Neal; Sparkes, Rebecca; Stockler-Ipsiroglu, Sylvia; Trakadis, Yannis; Turner, Lesley; Van Karnebeek, Clara; Vallance, Hilary; Vandersteen, Anthony; Walia, Jagdeep; Wilson, Ashley; Wilson, Brenda J; Yu, Andrea C; Yuskiv, Nataliya; Chakraborty, Pranesh
    Abstract Background The Canadian Inherited Metabolic Diseases Research Network (CIMDRN) is a pan-Canadian practice-based research network of 14 Hereditary Metabolic Disease Treatment Centres and over 50 investigators. CIMDRN aims to develop evidence to improve health outcomes for children with inherited metabolic diseases (IMD). We describe the development of our clinical data collection platform, discuss our data quality management plan, and present the findings to date from our data quality assessment, highlighting key lessons that can serve as a resource for future clinical research initiatives relating to rare diseases. Methods At participating centres, children born from 2006 to 2015 who were diagnosed with one of 31 targeted IMD were eligible to participate in CIMDRN’s clinical research stream. For all participants, we collected a minimum data set that includes information about demographics and diagnosis. For children with five prioritized IMD, we collected longitudinal data including interventions, clinical outcomes, and indicators of disease management. The data quality management plan included: design of user-friendly and intuitive clinical data collection forms; validation measures at point of data entry, designed to minimize data entry errors; regular communications with each CIMDRN site; and routine review of aggregate data. Results As of June 2019, CIMDRN has enrolled 798 participants of whom 764 (96%) have complete minimum data set information. Results from our data quality assessment revealed that potential data quality issues were related to interpretation of definitions of some variables, participants who transferred care across institutions, and the organization of information within the patient charts (e.g., neuropsychological test results). Little information was missing regarding disease ascertainment and diagnosis (e.g., ascertainment method – 0% missing). Discussion Using several data quality management strategies, we have established a comprehensive clinical database that provides information about care and outcomes for Canadian children affected by IMD. We describe quality issues and lessons for consideration in future clinical research initiatives for rare diseases, including accurately accommodating different clinic workflows and balancing comprehensiveness of data collection with available resources. Integrating data collection within clinical care, leveraging electronic medical records, and implementing core outcome sets will be essential for achieving sustainability.
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    Health services use among children diagnosed with medium-chain acyl-CoA dehydrogenase deficiency through newborn screening: a cohort study in Ontario, Canada
    (2019-03-22) Karaceper, Maria D; Khangura, Sara D; Wilson, Kumanan; Coyle, Doug; Brownell, Marni; Davies, Christine; Dodds, Linda; Feigenbaum, Annette; Fell, Deshayne B; Grosse, Scott D; Guttmann, Astrid; Hawken, Steven; Hayeems, Robin Z; Kronick, Jonathan B; Laberge, Anne-Marie; Little, Julian; Mhanni, Aizeddin; Mitchell, John J; Nakhla, Meranda; Potter, Murray; Prasad, Chitra; Rockman-Greenberg, Cheryl; Sparkes, Rebecca; Stockler, Sylvia; Ueda, Keiko; Vallance, Hilary; Wilson, Brenda J; Chakraborty, Pranesh; Potter, Beth K
    Abstract Background We describe early health services utilization for children diagnosed with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency through newborn screening in Ontario, Canada, relative to a screen negative comparison cohort. Methods Eligible children were identified via newborn screening between April 1, 2006 and March 31, 2010. Age-stratified rates of physician encounters, emergency department (ED) visits and inpatient hospitalizations to March 31, 2012 were compared using incidence rate ratios (IRR) and incidence rate differences (IRD). We used negative binomial regression to adjust IRRs for sex, gestational age, birth weight, socioeconomic status and rural/urban residence. Results Throughout the first few years of life, children with MCAD deficiency (n = 40) experienced statistically significantly higher rates of physician encounters, ED visits, and hospital stays compared with the screen negative cohort. The highest rates of ED visits and hospitalizations in the MCAD deficiency cohort occurred from 6 months to 2 years of age (ED use: 2.1–2.5 visits per child per year; hospitalization: 0.5–0.6 visits per child per year), after which rates gradually declined. Conclusions This study confirms that young children with MCAD deficiency use health services more frequently than the general population throughout the first few years of life. Rates of service use in this population gradually diminish after 24 months of age.
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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)