An Early Evaluation of Remote Site Visits for ACGME Program Applications.

Background: Prior to the COVID-19 pandemic, accreditation site visit interviews occurred in-person. In response to the pandemic, the Accreditation Council for Graduate Medical Education (ACGME) developed a remote site visit protocol. Objective: To perform an early assessment of the remote accreditation site visits for programs applying for initial ACGME accreditation. Methods: A cohort of residency and fellowship programs that had remote site visits was evaluated from June to August 2020. Surveys were sent to program personnel, ACGME accreditation field representatives, and executive directors following the site visits. Comparison of accreditation decisions (Initial Accreditation or Accreditation Withheld) was completed for matched residency or fellowship programs having in-person site visits in 2019. Results: Surveys were sent to all program personnel from the 58 residency and fellowship programs that had remote site visits for new program applications, as well as the accreditation field representatives who performed the remote visits. The survey response rate was 58% (352 of 607). Ninety-one percent of all respondents were extremely or very confident that remote site visits provided a thorough assessment of proposed residency or fellowship programs. Fifty-four programs having remote site visits were matched by specialty to programs having had in-person program application site visits in 2019. Forty-six programs that had remote site visits received Initial Accreditation, and 52 programs that had in-person site visits in 2019 received Initial Accreditation (P=.093, 95% CI 0.91-22.38). Conclusions: Most program personnel and accreditation field representatives were confident that remote site visits conducted for program applications provided fair and thorough assessments of the program.

Families' healthcare experiences for children with inherited metabolic diseases: protocol for a mixed methods cohort study.

INTRODUCTION: Children with inherited metabolic diseases (IMDs) often have complex and intensive healthcare needs and their families face challenges in receiving high-quality, family centred health services. Improvement in care requires complex interventions involving multiple components and stakeholders, customised to specific care contexts. This study aims to comprehensively understand the healthcare experiences of children with IMDs and their families across Canada. METHODS AND ANALYSIS: A two-stage explanatory sequential mixed methods design will be used. Stage 1: quantitative data on healthcare networks and encounter experiences will be collected from 100 parent/guardians through a care map, 2 baseline questionnaires and 17 weekly diaries over 5-7 months. Care networks will be analysed using social network analysis. Relationships between demographic or clinical variables and ratings of healthcare experiences across a range of family centred care dimensions will be analysed using generalised linear regression. Other quantitative data related to family experiences and healthcare experiences will be summarised descriptively. Ongoing analysis of quantitative data and purposive, maximum variation sampling will inform sample selection for stage 2: a subset of stage 1 participants will participate in one-on-one videoconference interviews to elaborate on the quantitative data regarding care networks and healthcare experiences. Interview data will be analysed thematically. Qualitative and quantitative data will be merged during analysis to arrive at an enhanced understanding of care experiences. Quantitative and qualitative data will be combined and presented narratively using a weaving approach (jointly on a theme-by-theme basis) and visually in a side-by-side joint display. ETHICS AND DISSEMINATION: The study protocol and procedures were approved by the Children's Hospital of Eastern Ontario's Research Ethics Board, the University of Ottawa Research Ethics Board and the research ethics boards of each participating study centre. Findings will be published in peer-reviewed journals and presented at scientific conferences.

Family Experiences with Care for Children with Inherited Metabolic Diseases in Canada: A Cross-Sectional Survey.

BACKGROUND AND OBJECTIVE: Children with inherited metabolic diseases often require complex and highly specialized care. Patient and family-centered care can improve health outcomes that are important to families. This study aimed to examine experiences of family caregivers (parents/guardians) of children diagnosed with inherited metabolic diseases with healthcare to inform strategies to improve those experiences. METHODS: A cross-sectional mailed survey was conducted of family caregivers recruited from an ongoing cohort study. Participants rated their healthcare experiences during their child's visits to five types of healthcare settings common for inherited metabolic diseases: the metabolic clinic, the emergency department, hospital inpatient units, the blood laboratory, and the pharmacy. Participants provided narrative descriptions of any memorable negative or positive experiences. RESULTS: There were 248 respondents (response rate 49%). Caregivers were generally very or somewhat satisfied with the care provided at each care setting. Appropriate treatment, provider knowledge, provider communication, and care coordination were deemed essential aspects of satisfaction with care by the majority of participants across many settings. Memorable negative experiences were reported by 8-22% of participants, varying by setting. Among participants who reported memorable negative experiences, contributing factors included providers' demeanor, lack of communication, lack of involvement of the family, and disregard of an emergency protocol letter provided by the family. CONCLUSIONS: While caregivers' satisfaction with care for children with inherited metabolic diseases was high, we identified gaps in family-centered care and factors contributing to negative experiences that are important to consider in the future development of strategies to improve pediatric care for inherited metabolic diseases.

Core Outcome Sets for Medium-Chain Acyl-CoA Dehydrogenase Deficiency and Phenylketonuria.

BACKGROUND: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enhance the capacity to compare and synthesize findings across studies. METHODS: Parents and/or caregivers, health professionals, and health policy advisors completed a Delphi survey and participated in a consensus workshop to select core outcomes from candidate lists of outcomes for MCAD deficiency and PKU. Delphi participants rated the importance of outcomes on a nine-point scale (1-3: not important, 4-6: important but not critical, 7-9: critical). Candidate outcomes were progressively narrowed down over 3 survey rounds. At the workshop, participants evaluated the remaining candidate outcomes using an adapted nominal technique, open discussion, and voting. After the workshop, we finalized the COSs and recommended measurement instruments for each outcome. RESULTS: There were 85, 61, and 53 participants across 3 Delphi rounds, respectively. The candidate core outcome lists were narrowed down to 20 outcomes per disease to be discussed at the consensus workshop. Voting by 18 workshop participants led to COSs composed of 8 and 9 outcomes for MCAD deficiency and PKU, respectively, with measurement recommendations. CONCLUSIONS: These are the first known pediatric COSs for MCAD deficiency and PKU. Adoption in future studies will help to ensure best use of limited research resources to ultimately improve care for children with these rare diseases.

Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review.

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.

Personal goal-setting among women living with breast cancer: protocol for a scoping review.

BACKGROUND: Breast cancer and its treatment can have many physical and psychological effects on affected women. Women's personal goals may provide insight into their priorities and motivations in the context of breast cancer. Incorporating personal goal-setting into support and care interventions may have an effect on psychological well-being. This protocol describes our scoping review methods, the aim of which is to examine and map the existing evidence on personal goal-setting among women with a breast cancer diagnosis. METHODS: Our scoping review will search for published, full-length articles, where personal goal-setting is a major component of the study, and the study population is females with breast cancer. MEDLINE, PsycInfo, CINAHL, EMBASE, the Cochrane Library, and AMED databases will be searched. Two independent reviewers will conduct all screening and extract data. Descriptive information about the studies, participants, any interventions, measurement tools, outcomes, and results will be reported. DISCUSSION: The results from this review will chart the literature, contributing to optimizing the incorporation of personal goal-setting approaches into effective interventions for the care and support of women with breast cancer.

Improvement in Context: Exploring Aims, Improvement Priorities, and Environmental Considerations in a National Sample of Programs Using "Small Data".

BACKGROUND: In 2013, the Accreditation Council for Graduate Medical Education (ACGME) transitioned into a new accreditation system to reduce burden, focus on outcomes, and promote innovation and improvement. One component is a self-study that includes aims, an environmental assessment, and setting improvement priorities. The ACGME initiated voluntary site visits following the self-study. OBJECTIVE: We explored common themes in program aims and assessment of their environment. METHODS: Using grounded theory, inductive and deductive qualitative methods, and truth grounding, we analyzed data from voluntary site visits of 396 core and subspecialty programs between June 2015 and September 2017, with a focus on common themes. RESULTS: We report common themes for aims and the dimensions of the environmental assessment. Themes for strengths include a collegial, supportive learning environment; responsive leaders; and experiences that prepare residents for unsupervised practice. Improvement priorities encompass low learner engagement and "content mismatch" in didactic education, balancing education and service at a time of growing clinical volumes, and improving the utility of assessment systems. Common opportunities encompass collaborations that improve education, involving alumni and harnessing technology to enrich education, while threats include an unsustainable effort for many program leaders, clinical pressures on faculty, and loss of external sites important for education. Linked dimensions of the environmental assessment suggest benefit in a growing focus on learners, and approaches to ensure a humanistic learning environment that allows for growth, self-determination, and inclusion. CONCLUSIONS: The findings highlight actionable themes for the environmental assessment. We discuss implications for programs, institutions, and the ACGME.

Label-free DNA sequencing using Millikan detection.

A label-free method for DNA sequencing based on the principle of the Millikan oil drop experiment was developed. This sequencing-by-synthesis approach sensed increases in bead charge as nucleotides were added by a polymerase to DNA templates attached to beads. The balance between an electrical force, which was dependent on the number of nucleotide charges on a bead, and opposing hydrodynamic drag and restoring tether forces resulted in a bead velocity that was a function of the number of nucleotides attached to the bead. The velocity of beads tethered via a polymer to a microfluidic channel and subjected to an oscillating electric field was measured using dark-field microscopy and used to determine how many nucleotides were incorporated during each sequencing-by-synthesis cycle. Increases in bead velocity of approximately 1% were reliably detected during DNA polymerization, allowing for sequencing of short DNA templates. The method could lead to a low-cost, high-throughput sequencing platform that could enable routine sequencing in medical applications.

Single-molecule enzymology based on the principle of the Millikan oil drop experiment.

The ability to monitor the progress of single-molecule enzyme reactions is often limited by the need to use fluorogenic substrates. A method based on the principle of the Millikan oil drop experiment was developed to monitor the change in charge of substrates bound to a nanoparticle and offers a means of detecting single-enzyme reactions without fluorescence detection. As a proof of principle of the ability to monitor reactions that result in a change in substrate charge, polymerization on a single DNA template was detected. A custom oligonucleotide was synthesized that allowed for the attachment of single DNA templates to gold nanoparticles with a single polymer tether. The nanoparticles were then tethered to the surface of a microfluidic channel where the positions of the nanoparticles, subjected to an oscillating electric field, were monitored using dark field microscopy. With short averaging times, the signal-to-noise level was low enough to discriminate changes in charge of less than 1.2%. Polymerization of a long DNA template demonstrated the ability to use the system to monitor single-molecule enzymatic activity. Finally, nanoparticle surfaces were modified with thiolated moieties to reduce and/or shield the number of unproductive charges and allow for improved sensitivity.

Nucleic acid amplification of individual molecules in a microfluidic device.

A microfluidic device was developed that enabled rapid polymerase chain reaction (PCR) analysis of individual DNA molecules. The device combined a means for accessing samples serially from a microtiter plate, channels for assembling eight parallel PCR reactions, and integrated resistive heaters for rapid thermocycling (>5 degrees C/s heating, >7 degrees C/s cooling) of samples as they flowed continuously through PCR channels. Amplification was monitored by fluorescence detection of Taqman probes. The long, narrow channels (10 microm x 180 microm x 40 mm) allowed sufficient separation between neighboring DNA templates to enable amplification of discreet DNA molecules. The functionality of the device was demonstrated by reproducibly amplifying a 2D6.6 CYP450 template and distinguishing between wild-type and mutant sequences using Taqman probes. A comparison of the rate of individual amplification events to the expected Poisson distribution confirmed that the device could reliably analyze individual DNA molecules. This work establishes the feasibility of rapid, single-molecule interrogation of nucleic acids.

DNA separations.

The use of two types of commercialized microfluidic chips for separation of double-stranded DNA (dsDNA), suitable for personal scale and high throughput use, is described. Compared with conventional approaches such as slab-gel and capillary electrophoresis (CE), these devices offer the advantages of faster separation times, better data reproducibility, greater ease of use, labor savings in quantitative analysis, and ease in data archiving and data sharing owing to the digital data format. With some simple precautions taken in keeping bubbles and particulates out of the microchannels, Lab-on-a-Chip devices have been adopted by many researchers in molecular biology and genomics laboratories to increase their productivity.

Protein separations.

This chapter describes the use of two types of commercialized microfluidic chips for protein separation, suitable for personal scale and high-throughput use. Compared with conventional approaches, such as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and capillary electrophoresis (CE), these devices offer the advantages of faster separation times, better data reproducibility, greater ease of use, labor savings in quantitative analysis, and ease in data archiving and data sharing owing to the digital data format. With some simple precautions taken to keep bubbles and particulates out of the microchannels, Lab-on-a-Chip devices have been adopted by many researchers in protein processing, protein engineering, and proteomics research laboratories to increase their productivity.

Determination of efficiency of attachment of biotinylated antibodies to avidin-linked, aqueous-based microcapsules by flow cytometry.

We used flow cytometry to determine the percentage of aqueous-based microcapsules bearing antibodies specific for various antigen-presenting cells (APCs) within a given population of putative APC-specific microcapsules. Flow cytometry offers a high-throughput, rapid and simple method to analyze antibody binding to noncellular, nonspherical material.