OBJECTIVE
To identify and define clinically meaningful type 1 diabetes outcomes beyond hemoglobin A1c (HbA1c) based upon a review of the evidence, consensus from clinical experts, and input from ...researchers, people with type 1 diabetes, and industry. Priority outcomes include hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). While priority outcomes for type 1 and type 2 diabetes may overlap, type 1 diabetes was the focus of this work.
RESEARCH AND METHODS
A Steering Committee—comprising representatives from the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange—was the decision-making body for the Type 1 Diabetes Outcomes Program. Their work was informed by input from researchers, industry, and people with diabetes through Advisory Committees representing each stakeholder group. Stakeholder surveys were used to identify priority outcomes. The outcomes prioritized in the surveys were hypoglycemia, hyperglycemia, time in range, DKA, and PROs. To develop consensus on the definitions of these outcomes, the Steering Committee relied on published evidence, their clinical expertise, and feedback from the Advisory Committees.
RESULTS
The Steering Committee developed definitions for hypoglycemia, hyperglycemia, time in range, and DKA in type 1 diabetes. The definitions reflect their assessment of the outcome’s short- and long-term clinical impact on people with type 1 diabetes. Knowledge gaps to be addressed by future research were identified. The Steering Committee discussed PROs and concluded that further type 1 diabetes–specific development is needed.
CONCLUSIONS
The Steering Committee recommends use of the defined clinically meaningful outcomes beyond HbA1c in the research, development, and evaluation of type 1 diabetes therapies.
Abstract In this article we review the existing fertility preservation options for women diagnosed with Turner syndrome and provide practical guidelines for the practitioner. Turner syndrome is the ...most common sex chromosome abnormality in women, occurring in approximately 1 in 2500 live births. Women with Turner syndrome are at extremely high risk for primary ovarian insufficiency and infertility. Although approximately 70%-80% have no spontaneous pubertal development and 90% experience primary amenorrhea, the remainder might possess a small residual of ovarian follicles at birth or early childhood. The present challenge is to identify these women as early in life as is possible, to allow them to benefit from a variety of existing fertility preservation options. To maximize the benefits of fertility preservation, all women with Turner syndrome should be evaluated by an expert as soon as possible in childhood because the vast majority will have their ovarian reserve depleted before adulthood. Cryopreservation of mature oocytes and embryos is a proven fertility preservation approach, and cryopreservation of ovarian tissue is a promising technique with a growing number of live births, but remains investigational. Oocyte cryopreservation has been performed in children with Turner syndrome as young as 13 years of age and ovarian tissue cryopreservation in affected prepubertal children. However, current efficacy of these approaches is unknown in this cohort. For those who have already lost their ovarian reserve, oocyte or embryo donation and adoption are strategies that allow fulfillment of the desire for parenting. For those with Turner syndrome-related cardiac contraindications to pregnancy, use of gestational surrogacy allows the possibility of biological parenting using their own oocytes. Alternatively, gestational surrogacy can serve to carry pregnancy resulting from the use of donor oocytes or embryos, if needed.
The Connecticut Newborn Screening (NBS) Network, in partnership with the Connecticut Department of Public Health, strategically utilized the
electronic health record (EHR) system to establish ...registries for tracking long-term follow-up (LTFU) of NBS patients. After launching the LTFU registry in 2019, the Network obtained funding from the Health Resources and Services Administration to address the slow adoption by specialty care teams. An LTFU model was implemented in the three highest-volume specialty care teams at Connecticut Children's, involving an early childhood cohort diagnosed with an NBS-identified disorder since the formation of the Network in March 2019. This cohort grew from 87 to 115 over the two-year project. Methods included optimizing registries, capturing external data from Health Information Exchanges, incorporating evidence-based guidelines, and conducting qualitative and quantitative evaluations. The early childhood cohort demonstrated significant and sustainable improvements in the percentage of visits up-to-date (%UTD) compared to the non-intervention legacy cohort of patients diagnosed with an NBS disorder before the formation of the Network. Positive trends in the early childhood cohort, including %UTD for visits and condition-specific performance metrics, were observed. The qualitative evaluation highlighted the achievability of practice behavior changes for specialty care teams through responsive support from the nurse analyst. The Network's model serves as a use case for applying and achieving the adoption of population health tools within an EHR system to track care delivery and quickly fill identified care gaps, with the aim of improving long-term health for NBS patients.
To highlight the importance of an improved, seamless, and effective transition from pediatric to adult care, especially for medically complex conditions such as Turner syndrome (TS).
The morbidities ...in adult patients with TS are reviewed, including features of the metabolic syndrome, congenital and acquired cardiovascular conditions, osteopenia and osteoporosis, autoimmune thyroid disease, and obesity, and psychobehavioral issues are addressed, in terms of promoting the development of independent self-care and autonomy in adolescent patients.
An essential component of high-quality health care, transition for adolescents with TS needs to be reengineered as a staged process initiated during early-stage adolescence (about age 12 years), when exogenous estrogen therapy is begun in coordination with the final phase of growth hormone therapy. At this time, the focus of care shifts from the parent to the adolescent and from maximizing final adult height to inducing puberty with gradually increasing doses of estrogen. During this transition, the development of healthful and independent healthcare behaviors should be promoted to prepare patients with TS for the adult responsibility of self-care. During the final phase of transition, an adult care plan should be formulated in collaboration with the adolescent with TS and her providers of adult care to improve the likelihood that she will continue to be carefully monitored in a way that optimizes her adult health and longevity.
The transitional period from pediatrics to adulthood is the ideal time for patients with TS to be made aware of their health history and health needs and of the evolving impact of TS into adulthood.
Despite only limited reports of a greater number of fractures during childhood or adulthood, osteoporosis historically has been described as a feature in Turner syndrome, because of the frequent ...observation of radiographic osteopenia and the coarse trabecular pattern of the carpal bones on radiographs. The pathogenesis of the skeletal demineralization remains unclear, but the data support the concept of an intrinsic bone defect that is then exacerbated by a number of hormonal factors, including the growth-regulating hormones, the gonadal steroids, and possibly the calcium-regulating hormones. The advent of more refined methods, such as single- and dual-photon absorptiometry and dual energy x-ray absorptiometry, has led to improved insights into bone mineral density (BMD) status in Turner syndrome (TS). A major limitation of these projection methods is that they report areal and not true volumetric BMD, resulting in an underestimation of the true BMD in smaller subjects. In assessing BMD in TS, various methods have been used to eliminate the confounding effect of bone size. Some consistent patterns do emerge in persons with TS who are not treated with long-term growth hormone (GH) or estrogen therapy. A significant deficit in cortical bone commonly appears in childhood and usually is associated with a low bone-turnover state. Significant osteopenia at predominantly trabecular sites develops during mid- to late adolescence and persists into adulthood, when it is associated with increased bone turnover. Preliminary BMD data on patients after long-term GH therapy show an absence of osteopenia. With respect to the impact of long-term estrogen therapy, the BMD deficit in adults with TS who have been treated adequately with estrogen, but who have not been treated with GH, is less than it is in those who have been insufficiently treated or not treated at all with estrogen. The available data indicate that long-term GH treatment during the prepubertal and early to midpubertal years optimizes BMD and improves the prognosis for adequate peak bone mass being achieved after a puberty that, most often, has been induced with exogenous estrogen. Long-term treatment with estrogen and progestin that is initiated during mid- to late adolescence and is continued throughout adulthood appears necessary for a normal peak bone mass to be achieved and the BMD to be preserved well beyond the time of peak bone mass. Additional measures to prevent osteoporosis must be used, such as ensuring adequate calcium intake and ample weight-bearing activities, focusing on preventing injuries and avoiding overtreatment with thyroid hormones. Long-term surveillance with measurement of BMD and of bone turnover in a large TS population into their later adult years is necessary before it can be concluded that the osteopenia observed in TS is a nonprogressive asymptomatic bone defect of no clinical consequences.
The optimal pubertal hormone replacement therapy in females and males is unclear.
To review hormone replacement options for hypogonadal teenagers and to determine the relevant attitudes and practices ...of pediatric endocrinologists in the United States.
A workshop on pubertal hormone replacement options was held during the Lawson Wilkins Pediatric Endocrine Society meeting in 2004. A questionnaire was distributed to investigate the audience's attitudes and practices in inducing puberty.
The majority of respondents used conjugated estrogens to treat hypogonadal girls with the primary aim of treatment being attainment of maximal adult height. The majority of respondents used depot testosterone to treat hypogonadal boys with the primary aim of treatment being pubertal development and virilization.
The use of physiological sex hormone replacement to optimize the induction of puberty in hypogonadal adolescents was recommended. The workshop revealed striking differences between US and European pediatric endocrinologists regarding their practices and attitudes regarding the induction of puberty in hypogonadal females. Detailed studies are necessary to develop more uniform guidelines.
Access to pediatric specialty care is a challenge, particularly for medically underserved populations.
One evolving method that has shown promise in helping ameliorate this disparity is electronic ...consultations (e-consults).
This retrospective cohort study compared two groups: patients referred to pediatric cardiology, endocrinology, or pulmonology from a Federally-Qualified Health Center 10 months before the implementation of an evidence-based care pathway and those referred in the 10 months after implementation. The care pathway included evidence-based referral guidelines for common pediatric diagnoses and an e-consult process. Data included patient demographics, dates of referral requests, appointment dates, e-consult response dates and times, diagnosis codes, and consultants' recommendations.
Twenty-three percent of all referrals made postimplementation were submitted for an e-consult, with 53% preventing an unnecessary face-to-face visit. The most common reason for an e-consult was heart murmur/chest pain for cardiology, short stature for endocrinology, and asthma for pulmonology.
Providers used e-consults for nearly one-quarter of all consultations postimplementation, resulting in 17% of consultations not needing a face-to-face visit. The use of e-consults combined with evidence-based referral guidelines provided a useful tool to help front line pediatric primary care providers manage complex problems and identify those not needing to see a specialist in person.
Evidence-based care pathways combined with e-consults can help improve access to pediatric specialty care by reducing demand for in-person visits and allowing more care to be delivered in primary care.
In the randomized "Toddler Turner" study, girls who received growth hormone (GH) starting at ages 9 months to 4 years (early-treated ET group) had marked catch-up growth and were 1.6 ± 0.6 SD taller ...than untreated (early-untreated EUT) control girls after 2 years. However, whether the early catch-up growth would result in greater near-adult height (NAH) was unknown. Therefore, this extension study examined the long-term effects of toddler-age GH treatment on height, pubertal development, and safety parameters.
Toddler Turner study participants were invited to enroll in a 10-year observational extension study for annual assessments of growth, pubertal status, and safety during long-term GH treatment to NAH for both ET and EUT groups.
The ET group was taller than the EUT group at all time points from preschool to maturity and was significantly taller at the onset of puberty (p = 0.016), however, the difference was not significant at NAH. For the full cohort (ET + EUT combined, n = 50) mean (± SD) NAH was 151.2 ± 7.1 cm at age 15.0 ± 1.3 years. NAH standard deviation score (SDS) was within the normal range (>-2.0) for 76% of ET and 60% of EUT subjects (68% overall) and correlated strongly with height SDS at GH start (r = 0.78; p < 0.01), which in turn had a modest inverse correlation with age at GH start (i.e., height SDS declined with increasing age in untreated girls r = -0.30; p = 0.016). No new safety concerns arose.
Although the ET group was taller throughout, height SDS at NAH was not significantly different between groups due to catch-down growth of ET girls during lapses in GH treatment after the Toddler study and similar long-term GH exposure overall. Early initiation of GH by age 6 years, followed by uninterrupted treatment during childhood, can prevent ongoing growth failure and enable attainment of height within the normal range during childhood, adolescence, and adulthood.
Abstract Background In pediatric medicine, inadequate access to subspecialty care is widespread. Referral Guidelines are structured tools that describe criteria for subspecialty referral and may ...decrease medically unnecessary referrals and thereby improve access. Problem Variation in referral rates and suboptimal communication around pediatric subspecialty referrals leads to inappropriate and ineffective use of scarce clinical resources. Goals Connecticut Children׳s Medical Center prioritized the development of collaborative care tools at the interface between primary and subspecialty care, including Referral Guidelines. Strategy A comprehensive set of Referral Guidelines was developed and consisted of background information on a given condition, strategies for initial evaluation and management, instructions for how and when to refer, and what the patient and family could expect at the visit with the subspecialist. A key component of the initiative was the integral role of the PCP during development. Results Twenty-eight Referral Guidelines have been developed among 15 subspecialty areas. A novel process for active dissemination of Referral Guidelines was piloted in one medical subspecialty area and led to a reduction in overall referrals and an increase in the proportion of referrals meeting the necessary criteria.
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