Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the participant's underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders and in 5 out of 28 ($18%) children with hearing loss. We discovered actionable findings in four participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal-recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in two children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.
Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders, and in 5 out of 28 (~18%) children with hearing loss. We discovered actionable findings in 4 participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in 2 children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.
BackgroundUsing next-generation sequencing (NGS) in newborn screening (NBS) could expand the number of genetic conditions detected pre-symptomatically, simultaneously challenging current precedents, raising ethical concerns, and extending the role of parental decision-making in NBS. The NC NEXUS (Newborn Exome Sequencing for Universal Screening) study seeks to assess the technical possibilities and limitations of NGS-NBS, devise and evaluate a framework to convey various types of genetic information, and develop best practices for incorporating NGS-NBS into clinical care. The study is enrolling both a healthy cohort and a cohort diagnosed with known disorders identified through recent routine NBS. It uses a novel age-based metric to categorize a priori the large amount of data generated by NGS-NBS and interactive online decision aids to guide parental decision-making. Primary outcomes include: (1) assessment of NGS-NBS sensitivity, (2) decision regret, and (3) parental decision-making about NGS-NBS, and, for parents randomized to have the option of requesting them, additional findings (diagnosed and healthy cohorts). Secondary outcomes assess parents’ reactions to the study and to decision-making.Methods/designParticipants are parents and children in a well-child cohort recruited from a prenatal clinic and a diagnosed cohort recruited from pediatric clinics that treat children with disorders diagnosed through traditional NBS (goal of 200 children in each cohort). In phase 1, all parent participants use an online decision aid to decide whether to accept NGS-NBS for their child and provide consent for NGS-NBS. In phase 2, parents who consent to NGS-NBS are randomized to a decision arm or control arm (2:1 allocation) and learn their child’s NGS-NBS results, which include conditions from standard (non-NGS) NBS plus other highly actionable childhood-onset conditions. Parents in the decision arm use a second decision aid to make decisions about additional results from their child’s sequencing. In phase 3, decision arm participants learn additional results they have requested. Online questionnaires are administered at up to five time points.DiscussionNC NEXUS will use a rigorous interdisciplinary approach designed to collect rich data to inform policy, practice, and future research.Trial registrationclinicaltrials.gov, NCT02826694. Registered on 11 July, 2016.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2686-4) contains supplementary material, which is available to authorized users.
Background Pediatric diabetes clinics around the world rapidly adapted care in response to COVID‐19. We explored provider perceptions of care delivery adaptations and challenges for providers and patients across nine international pediatric diabetes clinics. Methods Providers in a quality improvement collaborative completed a questionnaire about clinic adaptations, including roles, care delivery methods, and provider and patient concerns and challenges. We employed a rapid analysis to identify main themes. Results Providers described adaptations within multiple domains of care delivery, including provider roles and workload, clinical encounter and team meeting format, care delivery platforms, self‐management technology education, and patient‐provider data sharing. Providers reported concerns about potential negative impacts on patients from COVID‐19 and the clinical adaptations it required, including fears related to telemedicine efficacy, blood glucose and insulin pump/pen data sharing, and delayed care‐seeking. Particular concern was expressed about already vulnerable patients. Simultaneously, providers reported 'silver linings' of adaptations that they perceived as having potential to inform care and self‐management recommendations going forward, including time‐saving clinic processes, telemedicine, lifestyle changes compelled by COVID‐19, and improvements to family and clinic staff literacy around data sharing. Conclusions Providers across diverse clinical settings reported care delivery adaptations in response to COVID‐19—particularly telemedicine processes—created challenges and opportunities to improve care quality and patient health. To develop quality care during COVID‐19, providers emphasized the importance of generating evidence about which in‐person or telemedicine processes were most beneficial for specific care scenarios, and incorporating the unique care needs of the most vulnerable patients.
Running Title: Boston DeclarationWord Count: 689 (not including the table) 2 Nearly three out of every four deaths globally in 2017 were caused by non-communicable diseases (NCDs). 1 Many countries have made progress reducing NCD risk factors such as tobacco use, hyperlipidemia, and hypertension, but no countries have successfully reversed the increasing trends in diabetes prevalence and mortality from diabetes is increasing. 1 This represents a massive global health failure considering the fact that type 2 diabetes is largely preventable with lifestyle modification and that cost-effective treatments exist for both type 2 and type 1 diabetes. 2 Specific concern is needed for type 1 diabetes, which without insulin, it is fatal.In parallel, forced migration has reached a record high with 68.5 million people displaced from their homes around the world, 85% being hosted in low or middle-income countries such as, Uganda, Lebanon, and Pakistan, and 65% occurring in protracted refugee situations. 3 In addition, there are over 100 million conflict-affected non-displaced people and 175 million people who are affected by natural disasters annually. 4 These individuals are particularly vulnerable in crises due to disrupted health services and unpredictable-and often unhealthy-food supplies, which may exacerbate their condition and lead to complications.To date, diabetes and other NCDs have largely been underserved in humanitarian settings. 5,6,7 The true scope of the problem has not been established and it is not known which interventions are efficacious, feasible, and cost-effective in these contexts. With respect to type 1 diabetes, arguably the most immediately life-threatening NCD, the supply and cost of insulin, blood glucose monitoring and diagnostic tools are barriers for both humanitarian responders and their host countries, as well as patient adherence, life expectancy, quality of life, follow-up and provider training in diabetes care.In order to begin to address these major gaps, on 4-5 April 2019, Harvard University convened a meeting of humanitarian and other actors in global health to discuss the immediate needs and barriers to tackling diabetes in humanitarian crises, and to adopt a unified, action-oriented agenda to address this pressing global health issue (http://globalendocrinology.bwh.harvard.edu/symposium). Whilst it was recognised that there are substantial gaps in care for diabetes in all low-resource settings, 8 not just humanitarian crises, and that many other NCDs (e.g., cardiovascular disease, chronic obstructive pulmonary disease and asthma) are also prevalent globally and inadequately addressed in humanitarian settings, 9 we chose to prioritize efforts on diabetes in humanitarian crises, for the following reasons:First, because people with type 1 diabetes who cannot access insulin and continuity of care in a crisis are at acute risk of death. The principles of the Humanitarian Charter and United Nations Universal Declaration of Human Rights include the right to life with dignity. 10 The human rig...
Objective: To determine whether glycemia early in the course of type 1 diabetes changed between 2002 and 2016 across discrete youth cohorts. Research Design and Methods: Data from 3,956 youth in the SEARCH for Diabetes in Youth study were used to test whether glycemia worsened between 2002 and 2016 among successive cohorts of youth with type 1 diabetes examined within 30 months of diagnosis. We used linear regression for hemoglobin A1c (HbA1c) and logistic regression for poor glycemic control (HbA1c>9%) stratified by diabetes duration (<6 months, 6-12 months, and 12-30 months) at the time of measurement. Models included survey weights and were adjusted for potential demographic confounders. Results: Fully adjusted models revealed that mean HbA1c and frequency of poor glycemic control remained stable over time across successive youth cohorts with type 1 diabetes. Overall mean unadjusted HbA1c was 7.9% ± 1.5 (63 mmol/mol ± 16.4) in 2002 and 7.8% ± 2.4 (62 mmol/mol ± 26.2) in 2016, p=0.6 for trend. Estimates from weighted linear regression models found no overall change in HbA1c with index year, but a small linear reduction in HbA1c with each index year in the <6 months diabetes duration stratum, which was no longer statistically significant after adjusting for age, sex, race/ethnicity, and clinical site. No time trends were found for either of the other two duration strata (6-12 and 12-30 months). Although interaction effects with race/ethnicity and gender were not detected, the proportion of youth with poor glycemic control was higher among non-white (mean 28.9%, range 24.9-33.7%) than among white youth (mean 12.5%, range 8.8-17.8%) across all years. Conclusions: HbA1c levels remained stable but higher than recommended across discrete cohorts of SEARCH youth with type 1 diabetes duration ≤ 30 months, particularly among non-white youth. Future studies should elucidate predictors of elevated glycemia among youth early in the course of type 1 diabetes. Disclosure D. Igudesman: None. F. Malik: None. E. J. Mayer-davis: None. B. A. Reboussin: None. K. J. Souris: None. C. Pihoker: None. L. M. Dolan: None. S. Saydah: None. D. Dabelea: None. N. Clouet-foraison: None. S. M. Marcovina: None. Funding National Institute for Health Research (1UC4DK108173-01); Centers for Disease Control and Prevention (RFPDP15-002); Kaiser Permanente Southern California (U18DP006133, U48/CCU919219, U01DP000246, U18DP002714); University of Colorado Denver (U18DP006139, U48/CCU819241-3, U01DP000247, U18DP000247-06A1); Cincinnati Children’s Hospital Medical Center (U18DP006134, U48/CCU519239, U01DP000248, 1U18DP002709); University of North Carolina at Chapel Hill (U18DP006138, U48/CCU419249, U01DP000254, U18DP002708); Seattle Children’s Hospital (U18DP006136, U58/CCU019235-4, U01DP000244, U18DP002710-01); Wake Forest University School of Medicine (U18DP006131, U48/CCU919219, U01DP000250, 200-2010-35171); South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina (UL1TR001450); Seattle Children’s Hospital and the University of Washington (UL1TR00423); University of Colorado Pediatric Clinical and Translational Research Center (UL1TR000154); Barbara Davis Center for Diabetes at the University of Colorado Denver (P30-DK-57516); University of Cincinnati (UL1TR001425); Ohio Department of Health
Background The impact of weight management in persons with type 1 diabetes (T1D) from childhood into adulthood has not been well described. The purpose of the study was to explore qualitative themes presented by young adults with T1D with respect to the dual management of weight and T1D. Methods We analyzed focus group data from 17 young adults with T1D (65% female, age 21.7 ± 2.1 years, HbA1c 8.1% ± 1.5) via inductive qualitative analysis methods. Major themes were compared to themes presented by youth with T1D ages 13‐16 years in previously published study in order to categorize thematic progression from early adolescence through adulthood. Results Themes from young adults with T1D, when compared to those from youth were categorized as: (a) persistent and unchanged themes, (b) evolving themes, and (c) newly reported themes. Hypoglycemia and a sense of futility around exercise was an unchanged theme. Importance of insulin usage and a healthy relationship with T1D evolved to gather greater conviction. Newly reported themes are unique to integration of adulthood into T1D, such as family planning and managing T1D with work obligations. Young adults also reported negative experiences with providers in their younger years and desire for more supportive provider relationships. Conclusions Issues identified by youth regarding the dual management of T1D and weight rarely resolve, but rather, persist or evolve to integrate other aspects of young adulthood. Individualized and age‐appropriate clinical support and practice guidelines are warranted to facilitate the dual management of weight and T1D in persons with T1D.
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