Adults with Down syndrome: a comprehensive approach to manage complexity.

BACKGROUND: Down syndrome (DS) is characterised by premature ageing that affects selected organ systems, and persons with this condition can present patterns of co-morbidities and deficits often observed in the older population without DS. However, information on the characteristics of adult persons with DS is limited. The objective of the study is to describe characteristics of adults with DS collected with a standardised, comprehensive assessment instrument. METHODS: Cross-sectional study. Four hundred thirty adults with DS (age range 18/75 years) from three countries (Italy, n = 95; USA, n = 175; and Canada, n = 160). A standardised assessment instrument (interRAI intellectual disability) was used to assess sample characteristics. RESULTS: Mean age ranged from 35.2 (standard deviation 12.0) years in the US sample to 48.8 (standard deviation 9.0) years in the Canadian sample. Most participants in the Italian and US sample were living in private homes, while more than half of those in the Canadian sample were institutionalised. Prevalences of geriatric conditions, including cognitive deficits, disability in the common activities of daily living, symptoms of withdrawal or anhedonia, aggressive behaviour, communication problems, falls and hearing problems were high in the study sample. Gastrointestinal symptoms, skin and dental problems and obesity were also frequently observed. CONCLUSIONS: Adults with DS present with a high level of complexity, which may suggest the need for an approach based on a comprehensive assessment and management that can provide adequate care. Further research is needed to understand better the effectiveness of such an approach in the DS population.

The Relationship between Anaemia and Frailty: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: There is increasing evidence that frailty may play a role in chronic diseases, but the associations with specific chronic disorders are still unclear. OBJECTIVES: To conduct a systematic review and meta-analysis assessing the association of anaemia and frailty in observational studies. METHODS: The review was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/2002-10/09/2017. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I2 statistic. Publication bias was assessed with Egger's and Begg's tests. RESULTS: Nineteen studies were included; two longitudinal, seventeen cross-sectional. All studies except three reported an association between anaemia and frailty. The pooled prevalence of prefrailty in individuals with anaemia was 49% (95% CI=38-59%; I2=89.96%) and 24% (95% CI=17-31%; I2= 94.78%) for frailty. Persons with anaemia had more than a twofold odds of frailty (pooled OR=2.24 95% CI=1.53-3.30; I2=91.8%). Only two studies longitudinally examined the association between anaemia and frailty, producing conflicting results. CONCLUSIONS: Frailty and prefrailty are common in anaemic persons. Older persons with anaemia have more than a two-fold increased odds of frailty. These results may have clinical implications, as they identify the need to assess frailty in anaemic people and investigate any potential negative effects associated with the co-occurrence of both conditions. Longitudinal research that examines temporal changes in anaemia and effect of treatment are needed to further clarify the relationship between anaemia and frailty.

Bone mineral density in adults with Down syndrome.

This study analyzed data of bone mineral density (BMD) from a large cohort of adults with Down syndrome (DS). BMD was found to decrease with age more rapidly in these subjects than in the general population, exposing adults with DS to an increased risk of osteoporosis and bone fracture. INTRODUCTION: Down syndrome (DS) in adulthood presents with a high prevalence of osteoporosis. However, in DS, bone mineral density (BMD) can be underestimated due to short stature. Furthermore, the rate of age-related decline in BMD and its association with gender in DS has been rarely evaluated or compared with the general population. The present study is aimed at assessing the variation of BMD with age and gender in a sample of adults with DS and to compare these data with those of the general population, after adjusting for anthropometric differences. METHODS: Adults with DS, aged 18 or older, were assessed dual-energy-X-ray-absorptiometry (DXA) at the femoral neck and at the lumbar spine. They were compared with the general population enrolled in the National Health and Nutrition Examination Survey (NHANES) 2009-2010 dataset. Bone mineral apparent density (BMAD) was calculated for each individual. RESULTS: DXA was evaluated in 234 subjects with DS (mean age 36.93 ± 11.83 years, ranging from 20 to 69 years; 50.4% females). In the lumbar spine both mean BMD (DS 0.880 ± 0.141 vs. NHANES 1.062 ± 0.167, p < 0.001) and BMAD (DS 0.138 ± 0.020 vs. NHANES 0.152 ± 0.020, p < 0.001) were significantly lower in the DS sample than in the NAHNES cohort. The same trend was observed at the femoral neck in both BMD (DS 0.658 ± 0.128 vs. NHANES 0.835 ± 0.137, p < 0.001) and BMAD (DS 0.151 ± 0.030 vs. NHANES 0.159 ± 0.028, p<0.001). Age was associated with lower femoral neck BMAD in both samples; importantly, this association was significantly stronger in the DS sample. In the lumbar spine region, no significant association between BMAD and age could be observed in both samples. CONCLUSIONS: Adults with DS have lower bone mineral density compared to the general population and they experience a steeper decline with age. Early screening programs are needed in DS population.

Thyroid Function and its Implications in Oxidative Stress Influencing the Pathogenesis of Osteoporosis in Adults with Down Syndrome: A Cohort Study.

People with Down syndrome (DS) show lower bone mass density (BMD) and a higher prevalence of hypothyroidism compared to general population. Furthermore, DS is a well-known high oxidative stress (OS) condition because genes involved in OS map on chromosome 21. Thyroid function too is involved in OS. Since both thyroid function and OS lead to lower BMD and osteoporotic fractures, we have explored correlations among BMD, thyroid hormones, and parameters of OS in DS adults. A total of 105 DS patients (48 males; 21-71 years; mean BMI 28.88±7.12 kg/m(2)) were enrolled in a cohort study, 48 of them undergoing thyroid replacement therapy. We evaluated thyroid function, BMD, and total antioxidant capacity (TAC) in blood plasma. TAC was assayed by H2O2-metmyoglobin system, as source of radicals, and by the chromogenous ABTS, with a latency time (LAG) in the appearance of its cation ABTS+proportional to antioxidant concentration. BMD was evaluated with DEXA, using WHO criteria to classify osteoporosis. Low BMD was found in 83.78% of patients. TSH and LAG did not correlate with BMD. Nevertheless, LAG significantly correlates to Z-scores estimated at the lumbar spine (r(2)=0.558; p=0.03) in hypothyroid patients. Our data show that low TAC could be more associated with reduced BMD rather than TSH itself in DS patients and that the OS could have a role in the pathogenesis of osteoporosis regarding the hypothyroid subgroup.

AAV-mediated photoreceptor transduction of the pig cone-enriched retina.

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated RPE transduction appears efficient, independently of the serotype used and species treated, AAV-mediated photoreceptor gene transfer has not been systematically investigated thus so far in large animal models, which also may allow identifying relevant species-specific differences in AAV-mediated retinal transduction. In the present study, we used the porcine retina, which has a high cone/rod ratio. This feature allows to properly evaluate both cone and rod photoreceptors transduction and compare the transduction characteristics of AAV2/5 and 2/8, the two most efficient AAV vector serotypes for photoreceptor targeting. Here we show that AAV2/5 and 2/8 transduces both RPE and photoreceptors. AAV2/8 infects and transduces photoreceptor more efficiently than AAV2/5, similarly to what we have observed in the murine retina. The use of the photoreceptor-specific rhodopsin promoter restricts transgene expression to porcine rods and cones, and results in photoreceptor transduction levels similar to those obtained with the ubiquitous promoters tested. Finally, immunological, toxicological and biodistribution studies support the safety of AAV subretinal administration to the large porcine retina. The data presented here on AAV-mediated transduction of the cone-enriched porcine retina may affect the development of gene-based therapies for rare and common severe photoreceptor diseases.

Sequential combined treatment with intravitreal bevacizumab and photodynamic therapy for retinal angiomatous proliferation.

PURPOSE: To study visual and anatomical outcomes of sequenced combined therapy using intravitreal bevacizumab followed by photodynamic therapy (PDT) in eyes with retinal angiomatous proliferation (RAP). Safety and rate of intravitreal injections were also evaluated. METHODS: We conducted a prospective non-comparative pilot study of consecutive patients newly diagnosed with RAP. PDT guided by indocyanine green (ICG) angiography was applied 8+/-2 days after the intravitreal bevacizumab (1.25 mg) injection. At baseline and every month after the injection, best-corrected visual acuity (BCVA) measurement, complete eye examination including dynamic fluorescein and ICG angiography, and optical coherence tomography (OCT) were performed. RESULTS: In all, 21 eyes of 18 patients with RAP were enrolled. The mean age was 77 (range 65-86) years. Mean visual acuity at baseline was 0.63+/-0.25 logMAR. After treatment BCVA showed no statistically significant differences between each visit (P=0.10, ANOVA). At 9 months, the BCVA improved by three or more lines in three eyes (14%), remained stable in twelve eyes (57%), and worsened in six eyes (29%). Foveal thickness decreased significantly between baseline and all the follow-up visits (P<0.01, ANOVA). A total of 36 intravitreal injections were given during the study with a mean of 1.7 injections per eye (range 1-3 injections per eye). No ocular or systemic adverse events were reported. CONCLUSION: A possible synergistic effect may arise from the combination of intravitreal bevacizumab with PDT for the treatment of RAP. These findings also suggest a possible benefit of combo therapy in the rate of intravitreal re-injections.