Medical care of adults with Down Syndrome a clinical guideline

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. To develop an evidence-based clinical practice guideline for adults with Down syndrome. 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. From 11 295 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. 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.

Contribution of Clostridium difficile infection to the development of lower gastrointestinal adverse events during autologous stem cell transplantation.

BACKGROUND: Lower gastrointestinal (GI) adverse events (LGAE) are common afflictions of patients undergoing stem cell transplantation (SCT). Unfortunately, the pathophysiology remains poorly characterized. Emerging data suggest a prominent role of intestinal microbiota; however, contributions of pathogenic gut microbiota such as Clostridium difficile are not well defined. We performed a genome-wide association study (GWAS) to investigate clinical and genetic factors associated with development of LGAE. METHODS: A total of 972 patients undergoing autologous SCT were graded for LGAE based on Common Terminology Criteria for Adverse Events (v 4.0). Germline DNA material was obtained from leukapharesis products and genotyped using Illumina(®) Whole Genome Genotyping Infinium chemistry and HumanOmni1-Quad Bead chips containing over 1.1 million single nucleotide polymorphisms (SNPs) (Illumina, San Diego, California, USA). Statistical models incorporating clinical factors, genetic factors, and a combination of clinical plus genetic factors were utilized to compare patients who developed severe LGAE (grade 2 or above) and others. RESULTS: Among 972 patients, 459 (47.2%) developed severe LGAE. Baseline hemoglobin and hematocrit, estimated glomerular filtration rate, ß2-microglobulin, protocol type, and C. difficile infection (CDI) were associated with severe LGAE on univariate analysis, Genomic comparisons between groups did not reveal any SNPs associated with severe LGAE and neither did incorporation of genetic factors into the clinical model. In addition, 11 candidate SNPs associated with upper GI mucositis were evaluated, alongside clinical factors in a multivariate model. Only CDI was found to be associated with severe LGAE in all models. CONCLUSION: CDI is a prominent factor in the development of LGAE in patients undergoing autologous SCT.

Low bone turnover and low bone density in a cohort of adults with Down syndrome.

UNLABELLED: Increased incidence of osteoporosis in Down syndrome has been reported, but etiology is not established. We report low bone turnover markers and bone mineral density (BMD) in a cohort of people with Down syndrome without consistent clinical risk factors. Our results should guide future studies and treatments for this common problem. INTRODUCTION: To better understand the etiology for osteoporosis in Down syndrome (DS), we measured bone density by dual-energy X-ray absorptiometry (DXA) and circulating biochemical markers of bone formation and resorption in a cohort of 30 community-dwelling DS adults. METHODS: Seventeen males and 13 females followed in the University of Arkansas Down Syndrome Clinic were evaluated by DXA to estimate BMD and underwent phlebotomy to measure serum procollagen type-1 intact N-terminal propeptide (P1NP) to evaluate bone formation, and serum C-terminal peptide of type-I collagen (CTx) to evaluate bone resorption. RESULTS: Seven of 13 DS females and 12 of 17 DS males had low bone mass at one of measured sites (z≤-2.0). When data were grouped by age, males had apparent osteopenia earlier than females. The mean P1NP in the normal group was 19.2±5.2 ng/ml vs. 2.2±0.9 ng/ml in the DS group (P=0.002). Serum CTx levels in the normal group were 0.4±0.1 ng/ml vs. 0.3±0.1 ng/ml (P=0.369). CONCLUSIONS: Low BMD in adults with DS is correlated with a significant decrease in bone formation markers, compared to controls without DS, and is independent of gender. These data suggest that diminished osteoblastic bone formation and inadequate accrual of bone mass, with no significant differences in bone resorption, are responsible for the low bone mass in DS. These observations question the use of antiresorptive therapy in this population and focus attention on increasing bone mass by other interventions.