Adapting prescribing criteria for amyloid-targeted antibodies for adults with Down syndrome.

Prior authorization criteria for Federal Drug Administration (FDA) approved immunotherapeutics, among the class of anti-amyloid monoclonal antibodies (mAbs), established by state drug formulary committees, are tailored for adults with late-onset Alzheimer's disease. This overlooks adults with Down syndrome (DS), who often experience dementia at a younger age and with different diagnostic assessment outcomes. This exclusion may deny DS adults access to potential disease-modifying treatments. To address this issue, an international expert panel convened to establish adaptations of prescribing criteria suitable for DS patients and parameters for access to Centers for Medicare & Medicaid Services (CMS) registries. The panel proposed mitigating disparities by modifying CMS and payer criteria to account for younger onset age, using alternative language and assessment instruments validated for cognitive decline in the DS population. The panel also recommended enhancing prescribing clinicians' diagnostic capabilities for DS and initiated awareness-raising activities within healthcare organizations. These efforts facilitated discussions with federal officials, aimed at achieving equity in access to anti-amyloid immunotherapeutics, with implications for national authorities worldwide evaluating these and other new disease-modifying therapeutics for Alzheimer's disease.

Retrospective review of the code status of individuals with Down syndrome during the COVID-19 era.

Code status is a label in the medical record indicating a patient's wishes for end-of-life (EOL) care in the event of a cardiopulmonary arrest. People with intellectual disabilities had a higher risk of both diagnosis and mortality from coronavirus infections (COVID-19) than the general population. Clinicians and disability advocates raised concerns that bias, diagnostic overshadowing, and ableism could impact the allocation of code status and treatment options, for patients with intellectual disabilities, including Down syndrome (DS). To study this, retrospective claims data from the Vizient® Clinical Data Base (used with permission of Vizient, all rights reserved.) of inpatient encounters with pneumonia (PNA) and/or COVID-19 at 825 hospitals from January 2019 to June 2022 were included. Claims data was analyzed for risk of mortality and risk of "Do Not Resuscitate" (DNR) status upon admission, considering patient age, admission source, Elixhauser comorbidities (excluding behavioral health), and DS. Logistic regression models with backward selection were created. In total, 1,739,549 inpatient encounters with diagnoses of COVID-19, PNA, or both were included. After controlling for other risk factors, a person with a diagnosis of DS and a diagnosis of COVID-19 PNA had 6.321 odds ratio of having a DNR status ordered at admission to the hospital compared with those with COVID-19 PNA without DS. The diagnosis of DS had the strongest association with DNR status after controlling for other risk factors. Open and honest discussions among healthcare professionals to foster equitable approaches to EOL care and code status are needed.

Cardiovascular Complications of Down Syndrome: Scoping Review and Expert Consensus.

Cardiovascular disease is a leading cause of morbidity and mortality in individuals with Down syndrome. Congenital heart disease is the most common cardiovascular condition in this group, present in up to 50% of people with Down syndrome and contributing to poor outcomes. Additional factors contributing to cardiovascular outcomes include pulmonary hypertension; coexistent pulmonary, endocrine, and metabolic diseases; and risk factors for atherosclerotic disease. Moreover, disparities in the cardiovascular care of people with Down syndrome compared with the general population, which vary across different geographies and health care systems, further contribute to cardiovascular mortality; this issue is often overlooked by the wider medical community. This review focuses on the diagnosis, prevalence, and management of cardiovascular disease encountered in people with Down syndrome and summarizes available evidence in 10 key areas relating to Down syndrome and cardiac disease, from prenatal diagnosis to disparities in care in areas of differing resource availability. All specialists and nonspecialist clinicians providing care for people with Down syndrome should be aware of best clinical practice in all aspects of care of this distinct population.

Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus.

Objective: To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome. Background: There are no consensus criteria for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area. Methods: The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome. Results: During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on "other" studies) as were diagnostic criteria (96% agreement). Conclusions: The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.

Considering Dignity of Risk in the Care of People with Intellectual Disabilities: A Clinical Perspective.

The dignity of risk implies respect for individuals' right to make their own decisions, to participate in a broad range of desired activities, even if those activities have risk, and to expose themselves to potential consequences or learning opportunities. Historically, a more paternalistic approach, done as a benevolent assurance of safety, has been taken with individuals with intellectual disabilities. While optimizing safety, this approach can limit opportunity and, more importantly, limit the dignity of the individual. However, the concern for safety and the sense of responsibility to keep individuals with intellectual disabilities from harm is solidly entrenched and is not without some merit. "Supported decision-making" can offer an alternative to guardianship for some individuals, providing structured processes to enhance full participation. Strategies to involve individuals with intellectual disabilities in their own decision-making and to optimize the safety of those decisions include expanding the discussion of the concept of dignity of risk with family members and care providers of individuals with intellectual disabilities before they turn 18 years old; providing social-skills training and other educational opportunities that promote the likelihood of success in activities and decision-making; and maintaining guardrails when needed to prevent serious harms.

Differences in clinical presentation, severity, and treatment of COVID-19 among individuals with Down syndrome from India and high-income countries: Data from the Trisomy 21 Research Society survey.

Background: People with Down syndrome (DS) are one of the highest risk groups for mortality associated with COVID-19, but outcomes may differ across countries due to different co-morbidity profiles, exposures, and societal practices, which could have implications for disease management. This study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and several high-income countries (HICs). Methods: We used data from an international survey to examine the differences in disease manifestation and management for COVID-19 patients with DS from India vs HIC. De-identified survey data collected from April 2020 to August 2021 were analysed. Results: COVID-19 patients with DS from India were on average nine years younger than those from HICs. Comorbidities associated with a higher risk for severe COVID-19 were more frequent among the patients from India than from HICs. Hospitalizations were more frequent among patients from India as were COVID-19-related medical complications. Treatment strategies differed between India and HICs, with more frequent use of antibiotics in India. The average severity score of 3.31 was recorded for Indian DS in contrast to 2.3 for European and 2.04 for US cases. Conclusions: Presentation and outcomes of COVID-19 among individuals with DS were more severe for patients from India than for those from HIC. Global efforts should especially target vaccination campaigns and other risk-reducing interventions for individuals with DS from low-income countries.

COVID-19 Vaccination of Individuals with Down Syndrome-Data from the Trisomy 21 Research Society Survey on Safety, Efficacy, and Factors Associated with the Decision to Be Vaccinated.

Individuals with Down syndrome (DS) are among the groups with the highest risk for severe COVID-19. Better understanding of the efficacy and risks of COVID-19 vaccines for individuals with DS may help improve uptake of vaccination. The T21RS COVID-19 Initiative launched an international survey to obtain information on safety and efficacy of COVID-19 vaccines for individuals with DS. De-identified survey data collected between March and December 2021 were analyzed. Of 2172 individuals with DS, 1973 (91%) had received at least one vaccine dose (57% BNT162b2), 107 (5%) were unvaccinated by choice, and 92 (4%) were unvaccinated for other reasons. Most participants had either no side effects (54%) or mild ones such as pain at the injection site (29%), fatigue (12%), and fever (7%). Severe side effects occurred in <0.5% of participants. About 1% of the vaccinated individuals with DS contracted COVID-19 after vaccination, and all recovered. Individuals with DS who were unvaccinated by choice were more likely to be younger, previously recovered from COVID-19, and also unvaccinated against other recommended vaccines. COVID-19 vaccines have been shown to be safe for individuals with DS and effective in terms of resulting in minimal breakthrough infections and milder disease outcomes among fully vaccinated individuals with DS.

Ableism at the Bedside: People with Intellectual Disabilities and COVID-19.

People with intellectual and developmental disabilities have a higher risk of mortality from COVID-19 than the general population. Providers may assume that this is due to the burden of comorbidities for this population; however, the disparity in mortality persists even when controlling for comorbidities. We review the current policies and practices that may be contributing to this higher level of mortality. We contend that pervasive ableism among medical providers leads to a variation in the medical care options that are provided to people with intellectual disabilities and their families. Due to this bias, poor outcomes for people with intellectual disabilities may become a self-fulfilling prophecy. We make recommendations to address the modifiable factors that are contributing to the higher level of mortality for people with intellectual disabilities who are infected with COVID-19, provide strategies to combat ableism within the medical field, and discuss the unique role of the primary care physician as an advocate.

Prevalence of Mental Health Conditions Among 6078 Individuals With Down Syndrome in the United States.

Findings from a recent study of the largest documented cohort of individuals with Down syndrome (DS) in the United States described prevalence of common disease conditions and strongly suggested significant disparity in mental health conditions among these individuals as compared with age- and sex-matched individuals without DS. The retrospective, descriptive study reported herein is a follow-up to document prevalence of 58 mental health conditions across 28 years of data from 6078 individuals with DS and 30,326 age- and sex-matched controls. Patient data were abstracted from electronic medical records within a large integrated health system. In general, individuals with DS had higher prevalence of mood disorders (including depression); anxiety disorders (including obsessive-compulsive disorder); schizophrenia; psychosis (including hallucinations); pseudobulbar affect; personality disorder; dementia (including Alzheimer's disease); mental disorder due to physiologic causes; conduct disorder; tic disorder; and impulse control disorder. Conversely, the DS cohort experienced lower prevalence of bipolar I disorder; generalized anxiety, panic, phobic, and posttraumatic stress disorders; substance use disorders (including alcohol, opioid, cannabis, cocaine, and nicotine disorders); and attention-deficit/hyperactivity disorder. Prevalence of many mental health conditions in the setting of DS vastly differs from comparable individuals without DS. These findings delineate a heretofore unclear jumping-off point for ongoing research.

Prevalence of Infectious Diseases Among 6078 Individuals With Down Syndrome in the United States.

A recent disease prevalence study of the largest documented Down syndrome (DS) cohort in the United States strongly suggested significant disparity in general infectious disease conditions among individuals with DS versus those without DS. In this follow-up retrospective analysis, we explored these differences in greater detail by calculating prevalence of 52 infectious diseases, across 28 years of data among 6078 individuals with DS and 30,326 age- and sex-matched controls, abstracted from electronic medical records within a large Midwestern health system. We found that the DS cohort had higher prevalence of pneumonias (including aspiration, viral, bacterial, pneumococcal, and unspecified/atypical); otitis externa; and the skin infections impetigo, abscess, and cellulitis. To the contrary, the DS cohort had lower prevalence of many respiratory infections other than pneumonia (including influenza, strep pharyngitis, upper respiratory infection, sinusitis, tonsillitis, laryngitis, bronchitis, scarlet fever, and otitis media); sexually transmitted infections (including bacterial vaginosis, chlamydia, genital herpes, HIV/AIDS, human papillomavirus, pelvic inflammatory disease, and trichomoniasis); mononucleosis; shingles; unspecified hepatitis; intestinal infections; and enteritis. These findings highlight that individuals with DS could be more or less prone to different infectious diseases than their non-DS matched counterparts. Additional research to understand why these differences exist and how they might affect the clinical approach to patients with DS is warranted.

Prevalence of Endocrine Disorders Among 6078 Individuals With Down Syndrome in the United States.

Findings from a recent study describing prevalence of common disease conditions in the largest documented cohort of individuals with Down syndrome (DS) in the United States strongly suggested significant disparity in endocrine disorders among these individuals when compared with age- and sex-matched individuals without DS. This retrospective, descriptive study is a follow-up report documenting prevalence of 21 endocrine disorder conditions, across 28 years of data, from 6078 individuals with DS and 30,326 age- and sex-matched controls, abstracted from electronic medical records within a large integrated health system. Overall, individuals with DS experienced higher prevalence of adrenal insufficiency and Addison's disease; thyroid disorders, including hypothyroidism, hyperthyroidism, Hashimoto's disease, and Graves' disease; prolactinoma/hyperprolactinemia; diabetes insipidus; type I diabetes mellitus; and gout. Conversely, those with DS had lower prevalence of polycystic ovary syndrome and type II diabetes mellitus. Many prevalences of endocrine conditions seen in individuals with DS significantly differ relative to their non-DS matched counterparts. These varied findings warrant further exploration into how screening for and treatment of endocrine conditions may need to be approached differently for individuals with DS.

COVID-19 in Children with Down Syndrome: Data from the Trisomy 21 Research Society Survey.

Adults with Down Syndrome (DS) are at higher risk for severe outcomes of coronavirus disease 2019 (COVID-19) than the general population, but evidence is required to understand the risks for children with DS, which is necessary to inform COVID-19 shielding advice and vaccination priorities. We aimed to determine the epidemiological and clinical characteristics of COVID-19 in children with DS. Using data from an international survey obtained from a range of countries and control data from the United States, we compared the prevalence of symptoms and medical complications and risk factors for severe outcomes between DS and non-DS paediatric populations with COVID-19. Hospitalised COVID-19 patients <18 years with DS had a higher incidence of respiratory symptoms, fever, and several medical complications from COVID-19 than control patients without DS <18 years. Older age, obesity, and epilepsy were significant risk factors for hospitalisation among paediatric COVID-19 patients with DS, and age and thyroid disorder were significant risk factors for acute respiratory distress syndrome. Mortality rates were low in all paediatric COVID-19 patients (with and without DS), contrasting with previous findings in adults with DS (who exhibit higher mortality than those without DS). Children with DS are at increased risk for more severe presentations of COVID-19. Efforts should be made to ensure the comprehensive and early detection of COVID-19 in this population and to identify children with DS who present comorbidities that pose a risk for a severe course of COVID-19. Our results emphasize the importance of vaccinating children with DS as soon as they become eligible.

Opportunities, barriers, and recommendations in down syndrome research.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

Prevalence of Common Disease Conditions in a Large Cohort of Individuals With Down Syndrome in the United States.

PURPOSE: Given the current life expectancy and number of individuals living with Down syndrome (DS), it is important to learn common occurrences of disease conditions across the developmental lifespan. This study analyzed data from a large cohort of individuals with DS in an effort to better understand these disease conditions, inform future screening practices, tailor medical care guidelines, and improve utilization of health care resources. METHODS: This retrospective, descriptive study incorporated up to 28 years of data, compiled from 6078 individuals with DS and 30,326 controls matched on age and sex. Data were abstracted from electronic medical records within a large Midwestern health system. RESULTS: In general, individuals with DS experienced higher prevalence of testicular cancer, leukemias, moyamoya disease, mental health conditions, bronchitis and pneumonia, gastrointestinal conditions, thyroid disorder, neurological conditions, atlantoaxial subluxation, osteoporosis, dysphagia, diseases of the eyes/adnexa and of the ears/mastoid process, and sleep apnea, relative to matched controls. Individuals with DS experienced lower prevalence of solid tumors, heart disease conditions, sexually transmitted diseases, HIV, influenza, sinusitis, urinary tract infections, and diabetes. Similar rates of prevalence were seen for lymphomas, skin melanomas, stroke, acute myocardial infarction, hepatitis, cellulitis, and osteoarthritis. CONCLUSIONS: While it is challenging to draw a widespread conclusion about comorbidities in individuals with Down syndrome, it is safe to conclude that care for individuals with DS should not automatically mirror screening, prevention, or treatment guidelines for the general U.S. population. Rather, care for those with DS should reflect the unique needs and common comorbidities of this population.

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study.

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid ß peptides (Aß1-40, Aß1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

Medical vulnerability of individuals with Down syndrome to severe COVID-19-data from the Trisomy 21 Research Society and the UK ISARIC4C survey.

BACKGROUND: Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. METHODS: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. FINDINGS: The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent (p < 0.01), whereas altered consciousness/confusion were more frequent (p < 0.01). Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. INTERPRETATION: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40. FUNDING: Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices.

Development of a symptom menu to facilitate Goal Attainment Scaling in adults with Down syndrome-associated Alzheimer's disease: a qualitative study to identify meaningful symptoms.

BACKGROUND: As life expectancy of people with Down syndrome (DS) increases, so does the risk of Alzheimer's disease (AD). Identifying symptoms and tracking disease progression is especially challenging whenever levels of function vary before the onset of dementia. Goal Attainment Scaling (GAS), an individualized patient-reported outcome, can aid in monitoring disease progression and treatment effectiveness in adults with DS. Here, with clinical input, a validated dementia symptom menu was revised to facilitate GAS in adults living with Down Syndrome-associated Alzheimer's disease (DS-AD). METHODS: Four clinicians with expertise in DS-AD and ten caregivers of adults living with DS-AD participated in semi-structured interviews to review the menu. Each participant reviewed 9-15 goal areas to assess their clarity and comprehensiveness. Responses were systematically and independently coded by two researchers as 'clear', 'modify', 'remove' or 'new'. Caregivers were encouraged to suggest additional items and recommend changes to clarify items. RESULTS: Median caregiver age was 65 years (range 54-77). Most were female (9/10) with ≥15 years of education (10/10). Adults with DS-AD had a median age of 58 years (range 52-61) and either a formal diagnosis (6/10) or clinical suspicion (4/10) of dementia. The initial symptom menu consisted of 67 symptoms each with 2-12 descriptors (589 total). The clinicians' adaptation yielded 58 symptoms each with 4-17 descriptors (580 total). Of these 580 descriptors, caregivers identified 37 (6%) as unclear; these were reworded, and one goal area (4 descriptors) was removed. A further 47 descriptors and one goal area were added to include caregiver-identified concepts. The final menu contained 58 goal areas, each with 7-17 descriptors (623 total). CONCLUSIONS: A comprehensive symptom menu for adults living with DS-AD was developed to facilitate GAS. Incorporating expert clinician opinion and input from caregivers of adults with DS-AD identified meaningful items that incorporate patient/caregiver perspectives.

Pneumonia and respiratory infections in Down syndrome: A scoping review of the literature.

Pneumonia and respiratory infections impact infants and children with Down syndrome; pneumonia is a leading cause of mortality in adults with Down syndrome. We aimed to review the literature to evaluate gaps and address key questions. A series of key questions were formulated a priori to inform the search strategy and review process; addressed prevalence, severity, etiology, risk factors, preventive methods, screening, and financial costs, potential benefits or harms of screening. Using the National Library of Medicine database, PubMed, detailed literature searches on pneumonia and respiratory infections in Down syndrome were performed. Previously identified review articles were also assessed. The quality of available evidence was then evaluated and knowledge gaps were identified. Forty-two relevant original articles were identified which addressed at least one key question. Study details including research design, internal validity, external validity, and relevant results are presented. Pneumonia and respiratory infections are more prevalent and more severe in individuals with Down syndrome compared to healthy controls through literature review, yet there are gaps in the literature regarding the etiology of pneumonia, the infectious organism, risk factors for infection, and to guide options for prevention and screening. There is urgent need for additional research studies in Down syndrome, especially in the time of the current COVID-19 pandemic.

A randomized controlled trial of an online health tool about Down syndrome.

PURPOSE: We sought to determine if a novel online health tool, called Down Syndrome Clinic to You (DSC2U), could improve adherence to national Down syndrome (DS) guidelines. We also sought to determine if primary care providers (PCPs) and caregivers are satisfied with this personalized online health tool. METHODS: In a national, randomized controlled trial of 230 caregivers who had children or dependents with DS without access to a DS specialist, 117 were randomized to receive DSC2U and 113 to receive usual care. The primary outcome was adherence to five health evaluations indicated by national guidelines for DS. DSC2U is completed electronically, in all mobile settings, by caregivers at home. The outputs-personalized checklists-are used during annual wellness visits with the patient's PCP. RESULTS: A total of 213 participants completed a 7-month follow-up evaluation. In the intention-to-treat analysis, the intervention group had a 1.6-fold increase in the number of indicated evaluations that were recommended by the primary care provider or completed compared with controls. Both caregivers and PCPs reported high levels of satisfaction with DSC2U. CONCLUSIONS: DSC2U improved adherence to the national DS health-care guidelines with a novel modality that was highly valued by both caregivers and PCPs.