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People with mosaicism for trisomy 21 have been shown to exhibit the many of same phenotypic traits present in people with non-mosaic Down syndrome, but with varying symptom severity. However, the behavioral phenotype of people with mosaic Down syndrome (mDS) has not been well characterized. This study aimed to examine the prevalence of self-report and caregiver-report symptoms of depression and anxiety among a sample of 62 participants with mDS aged 12 - 46, and assess their association with the percentage of trisomy 21 in blood and/or buccal mucosa cells. The results showed that 53% of the participants reported clinically significant depression symptoms and 76% reported clinically significant anxiety symptoms. No clear associations were observed between the percentage of trisomic cells and total anxiety or depression, but a significant positive association between the proband-reported specific fears subscale and the percentage of trisomic cells in buccal specimens was detected (r = .43, p = .007). This study highlights the high occurrence of depression and anxiety symptoms in individuals with mDS and the need for routine assessment to optimize their care. It also demonstrates the ability of people with mDS to complete these evaluations, thereby supporting their inclusion in research studies/clinical trials.
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Loss of previously acquired developmental skills in children with Down syndrome (DS) is not a well characterized phenomenon. We identified 20 confirmed cases of childhood-onset skill loss for descriptive analysis. Eligible participants were recruited from a specialty clinic for persons with DS at a large medical center. Age and gender-matched participants also with DS but without skill loss were used as a comparison group. Case and control participants were between 3 and 14 years (mean 7.6 yr) at the time of evaluation. Loss of previously acquired communication, social-communication, and play skills was experienced by all cases, as well as new-onset or intensification of pre-existing maladaptive behaviors. The Aberrant Behavior Checklist (ABC)-community was helpful in distinguishing group differences in maladaptive behavior among cases and controls. All cases met DSMIV criteria for autism. Developmental skill loss associated with autism is an extreme example of within-group phenotypic variability and needs to be the focus of further research.
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Trastorno del Espectro Autista , Trastorno Autístico , Síndrome de Down , Niño , Humanos , Síndrome de Down/complicacionesRESUMEN
Individuals with Down syndrome (DS) or Autism Spectrum Disorder (ASD), and especially those with both DS and co-occurring ASD (DS + ASD) commonly display behavioral and psychiatric symptoms that can impact quality of life and places increased burden on caregivers. While the mainstay of treatment in DS and ASD is focused on educational and behavioral therapies, pharmacological treatments can be used to reduce symptom burden. There is a paucity of evidence and limited clinical trials in DS and DS + ASD. Some scientific evidence is available, primarily in open label studies and case series that can guide treatment choices. Additionally, clinical decisions are often extrapolated from evidence and experience from those with ASD, or intellectual disability in those without DS. This article reviews current research in pharmacological treatment in DS, ASD, and DS + ASD, reviews co-occurring neurodevelopmental and mental health diagnoses in individuals with DS + ASD across the lifespan, and describes practical approaches to psychopharmacological management.
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Trastorno del Espectro Autista , Síndrome de Down , Discapacidad Intelectual , Humanos , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/diagnóstico , Síndrome de Down/complicaciones , Síndrome de Down/tratamiento farmacológico , Síndrome de Down/diagnóstico , Calidad de VidaRESUMEN
Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9-12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, P = 0.001), abnormal MRI (χ2 = 7.78, P = 0.005), and abnormal LP (χ2 = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.
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Síndrome de Down , Humanos , Síndrome de Down/terapia , Inmunoglobulinas Intravenosas , Estudios Prospectivos , Inmunoterapia , RecurrenciaRESUMEN
Studies regarding cardiometabolic risk (CMR) for individuals with Down syndrome (DS) conflict. Our previous research in youth with DS, aged 10-20 years, found increased prevalence of dyslipidemia and prediabetes compared to matched peers without DS. Herein, we compare CMR in young adults with DS, aged 18-35 years, to a similar population-based sample from the 2001-2018 National Health and Nutrition Examination Survey (NHANES). The group with DS had higher NonHDL-C (mean DS 131.9 mg/dL; NHANES 126.1 p < 0.001), lower HDL-C (DS 47.5 mg/dL; NHANES 52.2 p < 0.001), higher LDL-C (DS 109.3 mg/dL; NHANES 105.4 p < 0.001), higher triglycerides (DS 102.9 mg/dL; NHANES 86.9 p < 0.001), but lower fasting glucose (DS 85.8 mg/dL; NHANES 95.2 p < 0.0001), lower HOMA-IR (DS 2.17; NHANES 2.24 p = 0.0006), lower systolic (DS 109.7 mmHg; NHANES 114.6 p < 0.0001) and lower diastolic (DS 60.9 mmHg; NHANES 67.8 p < 0.0001) blood pressures. There was relationship of higher HDL-C, triglycerides, glucose, systolic, and diastolic blood pressure with increasing BMI in the NHANES cohort which was dampened in the group with DS. These results indicate that more information is needed to guide clinicians in screening for CMR in individuals with DS.
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Enfermedades Cardiovasculares , Síndrome de Down , Adolescente , Humanos , Adulto Joven , Encuestas Nutricionales , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Triglicéridos , Glucemia , Factores de RiesgoRESUMEN
Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean off therapy after 9-12 months of treatment. Baseline, on therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, p = 0.001), abnormal MRI (χ2 = 7.78, p = 0.005), and abnormal LP (χ2 = 5.45, p = 0.02), and a personal history of autoimmunity (OR: 6.11, p < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.
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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.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Síndrome de Down , Cardiopatías Congénitas , Embarazo , Femenino , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Síndrome de Down/terapia , Consenso , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/epidemiologíaRESUMEN
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.
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The recent National Institute of Health (NIH) INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) initiative has bolstered capacity for the current increase in clinical trials involving individuals with Down syndrome (DS). This new NIH funding mechanism offers new opportunities to expand and develop novel approaches in engaging and effectively enrolling a broader representation of clinical trials participants addressing current medical issues faced by individuals with DS. To address this opportunity, the NIH assembled leading clinicians, scientists, and representatives of advocacy groups to review existing methods and to identify those areas where new approaches are needed to engage and prepare DS populations for participation in clinical trial research. This paper summarizes the results of the Clinical Trial Readiness Working Group that was part of the INCLUDE Project Workshop: Planning a Virtual Down Syndrome Cohort Across the Lifespan Workshop held virtually September 23 and 24, 2019.
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Síndrome de Down , Estudios de Cohortes , Síndrome de Down/complicaciones , Síndrome de Down/terapia , HumanosRESUMEN
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.
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BACKGROUND: There is a high degree of inter- and intra-individual variability observed within the phenotype of Down syndrome. The Down Syndrome Cognition Project was formed to capture this variability by developing a large nationwide database of cognitive, behavioral, health, and genetic information on individuals with Down syndrome, ages 6-25 years. The current study used the Down Syndrome Cognition Project database to characterize cognitive and behavioral variability among individuals with Down syndrome. METHODS: Latent profile analysis was used to identify classes across a sample of 314 participants based on their cognition (IQ and executive functioning), adaptive and maladaptive behavior, and autism spectrum disorder symptomatology. A multivariate multinomial regression model simultaneously examined demographic correlates of class. RESULTS: Results supported a 3-class model. Each class demonstrated a unique profile across the subdomains of cognition and behavior. The "normative" class was the largest (n = 153, 48%) and displayed a relatively consistent profile of cognition and adaptive behavior, with low rates of maladaptive behavior and autism symptomatology. The "cognitive" class (n = 109, 35%) displayed low cognitive scores and adaptive behavior and more autism symptomatology, but with low rates of maladaptive behavior. The "behavioral" class, the smallest group (n = 52, 17%), demonstrated higher rates of maladaptive behavior and autism symptomatology, but with cognition levels similar to the "normative" class; their adaptive behavior scores fell in between the other two classes. Household income and sex were the only demographic variables to differ among classes. CONCLUSIONS: These findings highlight the importance of subtyping the cognitive and behavioral phenotype among individuals with Down syndrome to identify more homogeneous classes for future intervention and etiologic studies. Results also demonstrate the feasibility of using latent profile analysis to distinguish subtypes in this population. Limitations and future directions are discussed.
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Síndrome de Down , Adaptación Psicológica , Adolescente , Adulto , Trastorno del Espectro Autista , Niño , Cognición , Función Ejecutiva , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
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.
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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.
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Síndrome de Down/epidemiología , Neumonía/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Adulto , COVID-19/epidemiología , Síndrome de Down/complicaciones , Síndrome de Down/mortalidad , Síndrome de Down/terapia , Humanos , Pandemias , Neumonía/complicaciones , Neumonía/mortalidad , Neumonía/terapia , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/patología , Factores de Riesgo , SARS-CoV-2/fisiología , Índice de Severidad de la EnfermedadRESUMEN
Atrioventricular septal defects (AVSD) are a severe congenital heart defect present in individuals with Down syndrome (DS) at a > 2000-fold increased prevalence compared to the general population. This study aimed to identify risk-associated genes and pathways and to examine a potential polygenic contribution to AVSD in DS. We analyzed a total cohort of 702 individuals with DS with or without AVSD, with genomic data from whole exome sequencing, whole genome sequencing, and/or array-based imputation. We utilized sequence kernel association testing and polygenic risk score (PRS) methods to examine rare and common variants. Our findings suggest that the Notch pathway, particularly NOTCH4, as well as genes involved in the ciliome including CEP290 may play a role in AVSD in DS. These pathways have also been implicated in DS-associated AVSD in prior studies. A polygenic component for AVSD in DS has not been examined previously. Using weights based on the largest genome-wide association study of congenital heart defects available (2594 cases and 5159 controls; all general population samples), we found PRS to be associated with AVSD with odds ratios ranging from 1.2 to 1.3 per standard deviation increase in PRS and corresponding liability r2 values of approximately 1%, suggesting at least a small polygenic contribution to DS-associated AVSD. Future studies with larger sample sizes will improve identification and quantification of genetic contributions to AVSD in DS.
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Antígenos de Neoplasias , Proteínas de Ciclo Celular , Proteínas del Citoesqueleto , Síndrome de Down/genética , Estudio de Asociación del Genoma Completo , Defectos de los Tabiques Cardíacos/genética , Receptor Notch4 , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Riesgo , Secuenciación Completa del GenomaRESUMEN
Importance: Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients. Objective: To develop an evidence-based clinical practice guideline for adults with Down syndrome. Evidence Review: The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence. Findings: From 11â¯295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome. Conclusions and Relevance: These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.
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Síndrome de Down/terapia , Adulto , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/epidemiología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Comorbilidad , Complicaciones de la Diabetes/epidemiología , Síndrome de Down/complicaciones , Medicina Basada en la Evidencia , Humanos , Tamizaje Masivo , Obesidad/complicacionesRESUMEN
OBJECTIVE: To estimate receipt of recommended gynecologic care, including cancer screening and menstrual care, among women with Down syndrome in the United States. METHODS: We conducted a retrospective cohort study of women participating in DS-Connect, the National Institute of Health's registry of women with Down syndrome. Using 2013-2019 survey data, we estimated the proportion of women receiving recommended age-appropriate well-woman care (Pap tests, mammogram, breast examination, pelvic examination) and compared receipt of gynecologic care to receipt of other preventive health care. We also estimated proportion receiving care for menstrual regulation. RESULTS: Of 70 participants with Down syndrome, 23% (95% CI 13-33) of women received all recommended gynecologic components of a well-woman examination. Forty-four percent (95% CI 32-56) of women aged 18 years and older reported ever having a gynecologic examination, and 26% (95% CI 15-37) reported ever having a Pap test. Of women aged 40 years or older, 50% (95% CI 22-78) had had a mammogram. Fifty-two percent (95% CI 41-65) had tried medication for menstrual regulation, and 89% (95% CI 81-96) received all recommended components of nongynecologic routine health care. CONCLUSION: Women with Down syndrome received gynecologic care, including cancer screening, at lower-than-recommended rates and at substantially lower rates than other forms of health care. Efforts to improve gynecologic care in this vulnerable population are needed.
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Síndrome de Down , Enfermedades de los Genitales Femeninos/prevención & control , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Servicios de Salud para Personas con Discapacidad/estadística & datos numéricos , Servicios Preventivos de Salud/estadística & datos numéricos , Servicios de Salud Reproductiva/estadística & datos numéricos , Adulto , Anciano , Estudios de Cohortes , Síndrome de Down/complicaciones , Femenino , Enfermedades de los Genitales Femeninos/complicaciones , Humanos , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co-occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk-factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision-making and management of these medically complex individuals. The creation of evidence-based clinical guidance for this population will not be possible until these gaps are addressed.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Síndrome de Down/tratamiento farmacológico , Enfermedades Hematológicas/tratamiento farmacológico , Adulto , Toma de Decisiones Clínicas , Atención a la Salud/tendencias , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Síndrome de Down/patología , Femenino , Guías como Asunto , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/epidemiología , Enfermedades Hematológicas/patología , Humanos , Masculino , Tamizaje Masivo , Factores de RiesgoRESUMEN
Translational research means different things to different people. In the biomedical research community, translational research is the process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs such as new therapies. Translational research then is a "bench to bedside" bridge specifically designed to improve health outcomes ( Wetmore & Garner, 2010 ). In this sense, animal models or cell culture systems may be used to learn about basic underlying genetic and physiologic systems that are exceedingly difficult to study in human subjects ( Reeves et al., 2019 ). This has been a major theme in Down syndrome (DS) research since the mid-1980s when mouse models that approximate the condition of trisomy 21 (Ts21) first became available ( Das & Reeves 2011 ). Translational research has recently taken on a more expansive meaning, as the process of turning observations from the laboratory, the clinic, and the community can all lead to new therapeutic approaches to improve population health outcomes ( Rubio et al., 2010 ). This model has received increased attention in the last decade as it is clear that improving developmental outcomes for people with DS requires a community effort on the part of all stakeholders ( Capone, 2010 ).
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Síndrome de Down , Participación de los Interesados , Investigación Biomédica Traslacional , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Síndrome de Down/terapia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Investigación Biomédica Traslacional/historia , Investigación Biomédica Traslacional/tendenciasRESUMEN
PURPOSE: An entity of regression in Down syndrome (DS) exists that affects adolescents and young adults and differs from autism spectrum disorder and Alzheimer disease. METHODS: Since 2017, an international consortium of DS clinics assembled a database of patients with unexplained regression and age- and sex-matched controls. Standardized data on clinical symptoms and tiered medical evaluations were collected. Elements of the proposed definition of unexplained regression in DS were analyzed by paired comparisons between regression cases and matched controls. RESULTS: We identified 35 patients with DS and unexplained regression, with a mean age at regression of 17.5 years. Diagnostic features differed substantially between regression cases and matched controls (p < 0.001 for all but externalizing behaviors). Patients with regression had four times as many mental health concerns (p < 0.001), six times as many stressors (p < 0.001), and seven times as many depressive symptoms (p < 0.001). Tiered medical evaluation most often identified abnormalities in vitamin D 25-OH levels, polysomnograms, thyroid peroxidase antibodies, and celiac screens. Analysis of the subset of patients with nondiagnostic medical evaluations reinforced the proposed definition. CONCLUSIONS: Our case-control evidence supports a proposed definition of unexplained regression in Down syndrome. Establishing this clinical definition supports future research and investigation of an underlying mechanism.