Unexpected complexity in the molecular diagnosis of spastic paraplegia 11.

BACKGROUND: Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the SPG11 gene (MIM *610844). METHODS: The proband is a 36-year-old female referred for genetic evaluation due to cognitive dysfunction, gait impairment, and corpus callosum atrophy (brain MRI was normal at 25-years-old). Diagnostic approaches included CGH array, next-generation sequencing, and whole transcriptome sequencing. RESULTS: CGH array revealed a 180 kb deletion located upstream of SPG11. Sequencing of SPG11 uncovered two rare single nucleotide variants: the novel variant c.3143C>T in exon 17 (in cis with the deletion), and the previously reported pathogenic variant c.6409C>T in exon 34 (in trans). Whole transcriptome sequencing revealed that the variant c.3143C>T caused exon 17 skipping. CONCLUSION: We report a novel sequence variant in the SPG11 gene resulting in exon 17 skipping, which, along with a nonsense variant, causes Spastic Paraplegia 11 in our proband. In addition, a deletion upstream of SPG11 was identified in the patient, whose implication in the phenotype remains uncertain. Nonetheless, the deletion apparently affects cis-regulatory elements of the gene, suggesting a potential new pathogenic mechanism underlying the disease in a subset of undiagnosed patients. Our findings further support the hypothesis that the origin of thin corpus callosum in patients with SPG11 is of progressive nature.

Patient Safety Incidents in Primary Care: Comparing APEAS-2007 (Spanish Patient Safety Adverse Events Study in Primary Care) with Data from a Health Area in Catalonia (Spain) in 2019.

The initial APEAS study, conducted in June 2007, examined adverse events (AEs) in Spanish Primary Healthcare (PHC). Since then, significant changes have occurred in healthcare systems. To evaluate these changes, a study was conducted in the Camp de Tarragona PHC region (CTPHC) in June 2019. This cross-sectional study aimed to identify AEs in 20 PHC centres in Camp de Tarragona. Data collection used an online questionnaire adapted from APEAS-2007, and a comparative statistical analysis between APEAS-2007 and CTPHC-2019 was performed. The results revealed an increase in nursing notifications and a decrease in notifications from family doctors. Furthermore, fewer AEs were reported overall, particularly in medication-related incidents and healthcare-associated infections, with an increase noted in no-harm incidents. However, AEs related to worsened clinical outcomes, communication issues, care management, and administrative errors increased. Concerning severity, there was a decrease in severe AEs, coupled with an increase in moderate AEs. Despite family doctors perceiving a reduction in medication-related incidents, the overall preventability of AEs remained unchanged. In conclusion, the reporting patterns, nature, and causal factors of AEs in Spanish PHC have evolved over time. While there has been a decrease in medication-related incidents and severe AEs, challenges persist in communication, care management, and clinical outcomes. Although professionals reported reduced severity, the perception of preventability remains an area that requires attention.

Precision and agreement of axial length in paediatric population measured with MYAH and AL-Scan biometers.

CLINICAL RELEVANCE: Measuring axial length is key in the field of myopia development and control. Hence, the precision and agreement of commercially available biometers is of vital interest to understand their variability and interchangeability in the paediatric population. BACKGROUND: Different biometers are available to measure axial length and monitor myopia progression in clinical practice. The purpose of this study was to assess the precision (repeatability and reproducibility) and agreement of the MYAH and AL-Scan biometers in a paediatric population. METHODS: Three consecutive measurements were performed using MYAH and AL-Scan biometers in each subject by the same operator to test for repeatability. To test for reproducibility, two measurements were performed for each subject by two different observers with a 5-min interval between measurements. To test the agreement, each subject was measured once with each instrument. RESULTS: A total of 187 subjects, with a mean age of 8.5 ± 0.3 years and mean spherical equivalent refractive error of +0.22 ± 0.77 D participated in the study. For the repeatability study, the within-subject standard deviation was 0.01 mm, and the repeatability limit was 0.04 mm for both instruments, with no statistically significant differences among repeated measures (p = 0.162 for MYAH and p = 0.774 for AL-Scan). For the reproducibility study, the within-subject standard deviation was 0.01 mm and the repeatability limit was 0.04 mm. There were statistically significant differences for the repeated measures for the AL-Scan (p = 0.002) but not for the MYAH (p = 0.643). Regarding the agreement between both instruments, the 95% limit of agreement ranged from -0.04 to 0.05 mm, and the differences were statistically significant (p = 0.021). CONCLUSIONS: The repeatability, reproducibility, and agreement of the MYAH and AL-Scan biometers seem optimal for following children with myopia.

Antibodies against the flotillin-1/2 complex in patients with multiple sclerosis.

Multiple sclerosis is a tissue-specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin-1/2 complex have been described in 1-2% of the patients in a recent study. Other candidate antigens as anoctamin-2 or neurofascin-155 have been previously described in multiple sclerosis patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against neurofascin-155, anoctamin-2 and flotillin-1/2 complex in multiple sclerosis. Serum (n = 252) and CSF (n = 50) samples from 282 multiple sclerosis patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti-flotillin-1/2, anti-anoctamin-2 and anti-neurofascin-155 antibodies were tested by cell-based assays using transfected cells. We identified six multiple sclerosis patients with antibodies against the flotillin-1/2 complex (2.1%) and one multiple sclerosis patient with antibodies against anoctamin-2 (0.35%). All multiple sclerosis patients were negative for anti-neurofascin-155 antibodies. Three of the anti-flotillin-1/2 positive patients showed anti-flotillin-1/2 positivity in other serum samples extracted at different moments of their disease. Immunoglobulin G subclasses of anti-flotillin-1/2 antibodies were predominantly one and three. We confirm that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis.

The role of specialist nurses in detecting spasticity and related symptoms in multiple sclerosis.

BACKGROUND: Spasticity is a frequent symptom of multiple sclerosis (MS), which may negatively influence daily living activities (ADL). OBJECTIVES: To (1) explore the feasibility to conduct a structured interview by specialist nurses about limitations in ADL; (2) determine the percentage of people with MS (PwMS) with limitations in ADL related to spasticity; (3) to assess the knowledge about spasticity and describe its clinical features. DESIGN: Observational, cross-sectional, multicentre study in 16 MS units of Catalonia (Spain). Participants were recruited from the outpatient facility and day-care hospital between July 2018 and June 2019 and met the following criteria: (1) age 18 or older, (2) diagnosis of MS according to McDonald criteria 2010 and (3) no clinical relapse in previous 30 days. METHODS: Specialist nurses conducted a structured interview divided in two parts: the assessment of (1) limitations in the ADL and (2) the presence of spasticity and associated symptoms. The usefulness of this intervention was requested. This study met the STROBE reporting guidelines checklist for observational studies. RESULTS: Three hundred sixty eight pwMS (244 women) with a mean age of 46 years and a median Expanded Disability Status Scale score of 2.5 (range, 0-8.5) were included. 262 (71%) pwMS had limitations in the ADL, and spasticity was reported as the most limiting symptom in 59 (23%). As a result of the interview, spasticity was observed in 199 (76%) participants; 47 (24%) of them were unaware that they had spasticity and 102 (51%) would not have reported it spontaneously. The level of the interview satisfaction was high (90%). CONCLUSIONS: Spasticity is a complex and limiting symptom in MS. The structured interview conducted by specialist nurses is feasible and has good acceptance. PATIENT CONTRIBUTION: Specialist nurses can be proactive in MS clinical assessment, which may help to detect symptoms with negative impact on quality of life.

[Patient safety incidents reported before and after the start of the COVID-19 pandemic in Primary Care in Tarragona]. / Incidentes de seguridad del paciente notificados antes y después del inicio de la pandemia de COVID-19 en atención primaria en Tarragona.

OBJECTIVE: To analyse and compare the epidemiology of patient safety incidents reported in Primary Health Care, before and after the start of the COVID-19 pandemic. DESIGN AND SETTING: Analytical descriptive study comparing reported incidents from March 1st 2019 to February 28th 2020, and from March 1st 2020 to February 28th 2021, notified through the TPSC Cloud™ platform accessible from the Intranet corporative in 25 Primary Health Care centres from Tarragona district, in Catalonia (Spain). MEASUREMENTS: Data obtained from voluntary notifications, through electronic, standardized and anonymized forms. VARIABLES: Centre, professional, incident type, risk matrix, causal factors and contributing factors, and avoidability. STATISTICAL ANALYSIS: Every notification was included in descriptive analysis, and another one specifically for adverse events, comparing both periods. RESULTS: 2231 incidents were reported. Comparing both periods, during the pandemic a reduction in the number of reported incidents was observed (only represented 20% of the total). However, the percentage of reported notifications from health care professionals and adverse events that required observation were increased. Causal factors related to attendance and diagnosis were incremented whereas the causal factors related to medication were decreased. In addition, an increase in contributing factors related to the professional was observed. Avoidability was high (>95%) in both periods. CONCLUSIONS: During the pandemic, fewer patient safety incidents have been reported, but proportionally more adverse events, most of which are preventable. The professional himself becomes the main contributing factor.

Analysis of Patient Safety Incidents in Primary Care Reported in an Electronic Registry Application.

OBJECTIVES: (1) To describe the epidemiology of patient safety (PS) incidents registered in an electronic notification system in primary care (PC) health centres; (2) to define a risk map; and (3) to identify the critical areas where intervention is needed. DESIGN: Descriptive analytical study of incidents reported from 1 January to 31 December 2018, on the TPSC Cloud™ platform (The Patient Safety Company) accessible from the corporate website (Intranet) of the regional public health service. SETTING: 24 Catalan Institute of Health PC health centres of the Tarragona region (Spain). PARTICIPANTS: Professionals from the PC health centres and a Patient Safety Functional Unit. MEASUREMENTS: Data obtained from records voluntarily submitted to an electronic, standardised and anonymised form. Data recorded: healthcare unit, notifier, type of incident, risk matrix, causal and contributing factors, preventability, level of resolution and improvement actions. RESULTS: A total of 1544 reports were reviewed and 1129 PS incidents were analysed: 25.0% of incidents did not reach the patient; 66.5% reached the patient without causing harm, and 8.5% caused adverse events. Nurses provided half of the reports (48.5%), while doctors reported more adverse events (70.8%; p < 0.01). Of the 96 adverse events, 46.9% only required observation, 34.4% caused temporary damage that required treatment, 13.5% required (or prolonged) hospitalization, and 5.2% caused severe permanent damage and/or a situation close to death. Notably, 99.2% were considered preventable. The main critical areas were: communication (27.8%), clinical-administrative management (25.1%), care delivery (23.5%) and medicines (18.4%); few incidents were related to diagnosis (3.6%). CONCLUSIONS: PS incident notification applications are adequate for reporting incidents and adverse events associated with healthcare. Approximately 75% and 10% of incidents reach the patient and cause some damage, respectively, and most cases are considered preventable. Adequate and strengthened risk management of critical areas is required to improve PS.

Effectiveness of New Tools to Define an Up-to-Date Patient Safety Risk Map: A Primary Care Study Protocol.

BACKGROUND: Reducing incidents related to health care interventions to improve patient safety is a health policy priority. To strengthen a culture of safety, reporting incidents is essential. This study aims to define a patient safety risk map using the description and analysis of incidents within a primary care region with a prior patient safety improvement strategy organisationally developed and promoted. METHODS: The study will be conducted in two phases: (1) a cross-sectional descriptive observational study to describe reported incidents; and (2) a quasi-experimental study to compare reported incidents. The study will take place in the Camp de Tarragona Primary Care Management (Catalan Institute of Health). In Phase 1, all reactive notifications collected within one year (2018) will be analysed; during Phase 2, all proactive notifications of the second and third weeks of June 2019 will be analysed. Adverse events will also be assessed. Phases 1 and 2 will use a digital platform and the proactive tool proSP to notify and analyse incidents related to patient safety. EXPECTED RESULTS: To obtain an up-to-date, primary care patient safety risk map to prioritise strategies that result in safer practices.

Assessment of Biological Contribution to Natural Recovery of Anthropized Freshwater Sediments From Argentina: Autochthonous Microbiome Structure and Functional Prediction.

Monitored natural recovery (MNR) is an in situ technique of conventional remediation for the treatment of contaminated sediments that relies on natural processes to reduce the bioavailability or toxicity of contaminants. Metabarcoding and bioinformatics approaches to infer functional prediction were applied in bottom sediments of a tributary drainage channel of Río de La Plata estuary, in order to assess the biological contribution to MNR. Hydrocarbon concentration in water samples and surface sediments was below the detection limit. Surface sediments were represented with high available phosphorous, alkaline pH, and the bacterial classes Anaerolineae, Planctomycetia, and Deltaproteobacteria. The functional prediction in surface sediments showed an increase of metabolic activity, carbon fixation, methanogenesis, and synergistic relationships between Archaeas, Syntrophobacterales, and Desulfobacterales. The prediction in non-surface sediments suggested the capacity to respond to different kinds of environmental stresses (oxidative, osmotic, heat, acid pH, and heavy metals), predicted mostly in Lactobacillales order, and the capacity of Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Actinomyces classes to degrade xenobiotic compounds. Canonical correspondence analysis (CCA) suggests that depth, phosphate content, redox potential, and pH were the variables that structured the bacterial community and not the hydrocarbons. The characterization of sediments by metabarcoding and functional prediction approaches, allowed to assess how the microbial activity would contribute to the recovery of the site.

Children's visual impairment and visual care related to socioeconomic status in Catalonia (Spain).

BACKGROUND: The objective of this study is to assess the prevalence of visual impairment and visual care practices and its association with socioeconomic conditions in the infant population in Catalonia. METHODS: The Catalan Institute of Statistics provided a random sample of 0 to 14-year-old non-institutionalized children whose parents were interviewed in a continuous health survey from 2011 to 2015 in Catalonia. A multistage stratified and random sampling procedure considering age, sex, county and town was followed. All results have been weighted according to the sample design and are presented as the proportion of the condition with its 95% confidence limits. Chi-square tests were performed to evaluate the association between categorical variables. To study the association of visual care with independent variables, a multiple logistic regression model was used. RESULTS: In 0 to 14-year-old children, a 12.9% (95% confidence interval [CI] [11.8-13.9]) prevalence of correctable visual impairment was observed. The prevalence of non-correctable visual impairment was 0.9% (95% CI [0.6-1.2]). Non-correctable visual impairment was more prevalent in families with lower education levels, manual professions or unemployed. Of children without visual impairment, 13,5% (95% CI:12.3-14.6) visited a visual care professional in the last 12 months while this proportion was 67.4% (95% CI [63.3-71.5]) among those with correctable visual impairment. When parents have a university degree or non-manual professions, a higher level of visual care was observed. In children with correctable visual impairment, visual reviews were more frequent when parents are employed in a non-manual profession. CONCLUSIONS: For the first time, indicators related to visual impairment in children in Catalonia have been recorded. There is an association between lower socioeconomic status and having non-correctable visual impairment, and conversely, having correctable visual impairment was significantly associated with employed parents. More visual care is associated with higher socioeconomic status.

[Nutritional education in school-age children through Programa Nutriplato®]. / Educación nutricional en niños en edad escolar a través del Programa Nutriplato®.

INTRODUCTION: Introduction: promoting healthy eating habits among childhood is one of the key aspects to improve medium and long-term health outcomes. Objectives: the main aims are to improve eating habits, promote the Mediterranean diet (MD) and prevent and/or reverse overweight and obesity in children from 3 to 12 years old. Methods: the program has a one-year follow-up and includes three to five visits with registered dietitians, one telephone control and one practical workshop. Anthropometric, body composition and eating habits data are collected, and nutritional education is carried out. A total sample of 1,000 children will be included. Results: until now, 622 participants have been included (51.6 % boys; median age 8.5 years). At the beginning, 32.2 % of participants were overweight or obese and 38.9 % had an adequate MD. Although no differences were found in the assessment of the Kidmed questionnaire regarding sex (p = 0.214) or body mass index (BMI) subgroups (p = 0.181), differences were found regarding age (p = 0.023) and BMI Z-score (p = 0.004), showing slightly lower values in those having and adequate MD. At the moment, 362 participants have made the six-month visit, of which 61.6 % presented an adequate MD, with statistically significant differences compared to the baseline visit (p < 0.0001). Conclusions: preliminary results show the need for nutritional education in children and suggest that Programa Nutriplato® can be effective in improving eating habits.

INTRODUCCIÓN: Introducción: promocionar hábitos de alimentación saludable durante la infancia es uno de los aspectos clave para fomentar un buen estado de salud a medio y largo plazo. Objetivos: los objetivos principales son mejorar los hábitos alimentarios, promocionar la dieta mediterránea (DM) y prevenir y/o revertir el sobrepeso y la obesidad en niños de 3 a 12 años. Métodos: el programa tiene un seguimiento de un año e incluye de tres a cinco visitas con dietistas-nutricionistas, un control telefónico y un taller práctico. Se recogen datos antropométricos, de composición corporal y de hábitos alimentarios, y se realiza educación nutricional. Se incluirán un total de 1.000 niños. Resultados: hasta el momento, se han incluido 622 participantes (51,6 % niños; mediana de edad de 8,5 años). Al inicio, el 32,2 % presentaba sobrepeso u obesidad y el 38,9 % seguía una DM óptima. No se encontraron diferencias en la valoración del cuestionario Kidmed en función del sexo (p = 0,214) ni del subgrupo de índice de masa corporal (IMC) (p = 0,181), pero sí en función de la edad (p = 0,023) y del Z-score del IMC (p = 0,004), mostrando valores ligeramente menores en aquellos que presentaban una DM óptima. Por ahora, 362 participantes han realizado la visita de los seis meses, de los cuales el 61,6 % presentó una DM óptima, con diferencias estadísticamente significativas en comparación con la inicial (p < 0,0001). Conclusiones: los resultados preliminares muestran la necesidad de realizar educación nutricional en los niños y sugieren que el Programa Nutriplato® puede ser efectivo en la mejora de hábitos alimentarios.

Impact of the COVID-19 Pandemic on an Emergency Traumatology Service: Experience at a Tertiary Trauma Centre in Spain.

INTRODUCTION: The severe disruptions caused by the SARS-CoV-2 coronavirus have necessitated a redistribution of resources to meet hospitals' current service needs during this pandemic. The aim of this study was to provide an overview of the impact of the pandemic, and its corresponding State of Emergency, on a tertiary traumatology emergency service. METHODS: An observational study was performed at a tertiary hospital within the Spanish National Health System. Four different periods were studied, including the first 20 days of Spain's current State of Emergency, from March 14 to April 02, 2020 (Period 4). This period was compared to the 20-day period prior to the State of Emergency (Period 3), and to matching periods in the two previous years (Periods 1 and 2). A total of 6,565 patient visits were analyzed: 1909 in Period 1 (29.1%), 2161 in Period 2 (32.9%), 1983 in Period 3 (30.2%), and 512 in Period 4 (7.8%). Variables collected included patient age and sex, insurance type, discharge destination and reason for hospital admission. RESULTS: The patients' mean age was 55.1 years old (Standard Deviation (SD): 22.1), and 51.8% were women (3495/6565). During the COVID-19 pandemic, there were significant reductions in total visits to the trauma emergency department, workplace accidents, traffic accidents and number of hospital admissions, particularly during Period 4. However, no statistically-significant differences were found in the number of osteoporotic hip fractures admitted between the four periods. The numbers of hospital admissions for osteoporotic hip fracture were 42 during Period 1, 41 during Period 2, 43 during Period 3 and 36 during Period 4. CONCLUSIONS: While most traumatological presentations decreased in frequency over the course of the outbreak, the number of osteoporotic hip fractures remained stable. Thus, contingency plans in times of crisis need to be carefully targeted, and to keep in mind certain public health issues that do not decrease, despite a State of Emergency, like osteoporotic hip fractures.

Traducción y validación de la versión española de la escala Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD) / Translation and validation of the Spanish version of the Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD)

Introducción: La escala Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD) fue creada para evaluar de forma breve el funcionamiento de las personas con trastorno de desarrollo intelectual y problemas de salud mental/trastornos de conducta. El objetivo del presente trabajo fue estudiar las evidencias sobre la validez de las puntuaciones obtenidas con la escala HoNOS-LD traducida al castellano. Material y método: La muestra estaba formada por 111 participantes que fueron evaluados con la HoNOS-LD traducida al castellano y otros cuestionarios relacionados. Para estudiar la fiabilidad entre examinadores y la fiabilidad test-retest, 33 participantes fueron evaluados por 2 examinadores y reevaluados al cabo de 7 días. Resultados: De acuerdo con criterios clínicos y conceptuales, y con el resultado del análisis paralelo, se seleccionó una solución factorial con único factor. La consistencia interna fue buena (coeficiente omega de 0,87). Las fiabilidades entre examinadores y test-retest fueron excelentes (coeficientes de correlación intraclase de 0,95 y 0,98, respectivamente). Las correlaciones entre secciones de la HoNOS-LD y los instrumentos relacionados fueron en el sentido esperado y altamente significativas (p<0,001), y la puntuación HoNOS-LD aumentaba con el nivel de apoyos necesario de los participantes, resultados que aportaron evidencia sobre la validez de asociación con otras variables externas. Conclusiones: La versión en castellano de la HoNOS-LD representa un instrumento breve, válido y fiable, que permitirá la evaluación rutinaria del funcionamiento con distintas finalidades, incluyendo el diagnóstico y la intervención

Introduction: The Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD) is a brief instrument that assesses functioning in people with intellectual development disorder and mental health problems/behaviour disorders. The aim of the present study was to examine the evidence on the validity of the scores based on the Spanish version of the HoNOS-LD. Material and methods: The study included 111 participants that were assessed by the Spanish version of the HoNOS-LD and other questionnaires that measured different variables related to the scale. Thirty-three participants were assessed by 2 examiners, and retested 7 days later, in order to study inter-examiner reliability and test-retest reliabilities. Results: Based on clinical and conceptual criteria, and on the results of the parallel analysis, a factorial solution with one factor was selected. Internal consistency was good (Omega coefficient of 0.87). Inter-examiner and test-retest reliabilities were excellent (intraclass correlation coefficients of 0.95 and 0.98, respectively). Correlations between sections of the HoNOS-LD and the related instruments showed the expected direction, and were highly significant (P<.001), and the HoNOS-LD score increased with the intensity of the support required by the participants. These results showed evidence of the validity of association with other external variables. Conclusions: The Spanish version of the HoNOS-LD is a brief, valid and reliable instrument, which will enable a routine assessment of functioning for different uses, including diagnosis and intervention

A longitudinal study of brain anatomy changes preceding dementia in Down syndrome.

Background: We longitudinally assessed Down syndrome individuals at the age of risk of developing dementia to measure changes in brain anatomy and their relationship to cognitive impairment progression. Methods: Forty-two Down syndrome individuals were initially included, of whom 27 (mean age 46.8 years) were evaluable on the basis of completing the 2-year follow-up and success in obtaining good quality MRI exams. Voxel-based morphometry was used to estimate regional brain volumes at baseline and follow-up on 3D anatomical images. Longitudinal volume changes for the group and their relationship with change in general cognitive status and specific cognitive domains were mapped. Results: As a group, significant volume reduction was identified in the substantia innominata region of the basal forebrain, hippocampus, lateral temporal cortex and left arcuate fasciculus. Volume reduction in the substantia innominata and hippocampus was more prominent in individuals whose clinical status changed from cognitively stable to mild cognitive impairment or dementia during the follow-up. Relevantly, longitudinal memory score change was specifically associated with volume change in the hippocampus, prospective memory with prefrontal lobe and verbal comprehension with language-related brain areas. Conclusions: Results are notably concordant with the well-established anatomical changes signaling the progression to dementia in Alzheimer's disease, despite the dense baseline pathology that developmentally accumulates in Down syndrome. This commonality supports the potential value of Down syndrome as a genetic model of Alzheimer's neurodegeneration and may serve to further support the view that Down syndrome patients are best candidates to benefit from treatment research in Alzheimer's disease.

•Longitudinal changes in brain anatomy were identified in Down syndrome individuals.•Basal forebrain and hippocampal volume reductions paralleled clinical progression.•The overall anatomical pattern identified resembled Alzheimer's neurodegeneration.

High Incidence of Copy Number Variants in Adults with Intellectual Disability and Co-morbid Psychiatric Disorders.

A genetic analysis of unexplained mild-moderate intellectual disability and co-morbid psychiatric or behavioural disorders is not systematically conducted in adults. A cohort of 100 adult patients affected by both phenotypes were analysed in order to identify the presence of copy number variants (CNVs) responsible for their condition identifying a yield of 12.8% of pathogenic CNVs (19% when including clinically recognizable microdeletion syndromes). Moreover, there is a detailed clinical description of an additional 11% of the patients harbouring possible pathogenic CNVs-including a 7q31 deletion (IMMP2L) in two unrelated patients and duplications in 3q29, 9p24.2p24.1 and 15q14q15.1-providing new evidence of its contribution to the phenotype. This study adds further proof of including chromosomal microarray analysis (CMA) as a mandatory test to improve the diagnosis in the adult patients in psychiatric services.

Neurodevelopmental risk copy number variants in adults with intellectual disabilities and comorbid psychiatric disorders.

BACKGROUND: Copy number variants (CNVs) are established risk factors for neurodevelopmental disorders. To date the study of CNVs in psychiatric illness has focused on single disorder populations. The role of CNVs in individuals with intellectual disabilities and psychiatric comorbidities are less well characterised.AimsTo determine the type and frequency of CNVs in adults with intellectual disabilities and comorbid psychiatric disorders. METHOD: A chromosomal microarray analysis of 599 adults recruited from intellectual disabilities psychiatry services at three European sites. RESULTS: The yield of pathogenic CNVs was high - 13%. Focusing on established neurodevelopmental disorder risk loci we find a significantly higher frequency in individuals with intellectual disabilities and comorbid psychiatric disorder (10%) compared with healthy controls (1.2%, P<0.0001), schizophrenia (3.1%, P<0.0001) and intellectual disability/autism spectrum disorder (6.5%, P < 0.00084) populations. CONCLUSIONS: In the largest sample of adults with intellectual disabilities and comorbid psychiatric disorders to date, we find a high rate of pathogenic CNVs. This has clinical implications for the use of genetic investigations in intellectual disability psychiatry.Declaration of interestNone.

Translation and validation of the Spanish version of the Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD). / Traducción y validación de la versión española de la escala Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD).

INTRODUCTION: The Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD) is a brief instrument that assesses functioning in people with intellectual development disorder and mental health problems/behaviour disorders. The aim of the present study was to examine the evidence on the validity of the scores based on the Spanish version of the HoNOS-LD. MATERIAL AND METHODS: The study included 111 participants that were assessed by the Spanish version of the HoNOS-LD and other questionnaires that measured different variables related to the scale. Thirty-three participants were assessed by 2 examiners, and retested 7 days later, in order to study inter-examiner reliability and test-retest reliabilities. RESULTS: Based on clinical and conceptual criteria, and on the results of the parallel analysis, a factorial solution with one factor was selected. Internal consistency was good (Omega coefficient of 0.87). Inter-examiner and test-retest reliabilities were excellent (intraclass correlation coefficients of 0.95 and 0.98, respectively). Correlations between sections of the HoNOS-LD and the related instruments showed the expected direction, and were highly significant (P<.001), and the HoNOS-LD score increased with the intensity of the support required by the participants. These results showed evidence of the validity of association with other external variables. CONCLUSIONS: The Spanish version of the HoNOS-LD is a brief, valid and reliable instrument, which will enable a routine assessment of functioning for different uses, including diagnosis and intervention.

Validation and Normalization of the Tower of London-Drexel University Test 2nd Edition in an Adult Population with Intellectual Disability.

Despite how important it is to assess executive functioning in persons with Intellectual Disability (ID), instruments adapted and validated for this population are scarce. This study's primary goal was to find evidence for the validity of the ID version of the Tower of London (TOLDXtm) test in persons with mild (IDMi) and moderate (IDMo) levels of ID with Down Syndrome (DS). A multicenter study was carried out. Subjects (n = 63, ≥ 39 years old) had DS with mild (n = 39) or moderate ID (n = 24) with no minor neurocognitive disorder or Alzheimer's disease. Assessment protocol: TOLDXtm for ID, Kaufman Brief Intelligence Test Second Edition (K-BIT II), Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS), Weigl's Color-Form Sorting Test (WCFST), Barcelona Test for Intellectual Disability (BT-ID), and the Behavior Rating Inventory of Executive Function (BRIEF-P). The internal consistency (IDMi and IDMo), factor structure of the different subscales, and relationship between TOLDXtm subscales and other cognitive measures (BT-ID, WCFST, and BRIEF-P) were analyzed. A normative data table with ID population quartiles is provided. TOLDXtm for ID showed a robust one factor structure and coherentassociations with other, related neuropsychological instruments. Significant differences between IDMi and IDMo on movement-related variables like Correct (Corr; p = .002) and Moves (Mov; p = .042) were observed, along with good internal consistency values, Corr (α = .75), Mov (α = .52). Regarding internal consistency, no between-groups differences were observed (all p-value > 0.05). The TOLDXtm for ID is thus an instrument, supported by good validity evidence, to evaluate problem-solving and planning in ID. It distinguishes between individuals with mild and moderate ID, and is highly associated with other measures of executive functioning.

Anomalous White Matter Structure and the Effect of Age in Down Syndrome Patients.

BACKGROUND: Neural tissue alterations in Down syndrome are fully expressed at relatively late developmental stages. In addition, there is an early presence of neurodegenerative changes in the late life stages. OBJECTIVE: The aims of this study were both to characterize white matter abnormalities in the brain of adult Down syndrome patients using diffusion tensor imaging (DTI) and to investigate whether degenerative alterations in white matter structure are detectable before dementia is clinically evident. METHODS: Forty-five adult non-demented Down syndrome patients showing a wide age range (18-52 years) and a matched 45-subject control group were assessed. DTI fractional anisotropy (FA) brain maps were generated and selected cognitive tests were administered. RESULTS: Compared with healthy controls, non-demented Down syndrome patients showed lower DTI FA in white matter involving the major pathways, but with more severe alterations in the frontal-subcortical circuits. White matter FA decreased with age at a similar rate in both DS and control groups. CONCLUSIONS: Our results contribute to characterizing the expression of white matter structural alterations in adult Down syndrome. However, an accelerated aging effect was not demonstrated, which may suggest that the FA measurements used are not sufficiently sensitive or, alternatively, age-related white matter neurodegeneration is not obvious prior to overt clinical dementia.

Validation and normalization of the tower of London-Drexel University Test 2nd edition in an adult population with intellectual disability

Despite how important it is to assess executive functioning in persons with Intellectual Disability (ID), instruments adapted and validated for this population are scarce. This study’s primary goal was to find evidence for the validity of the ID version of the Tower of London (TOLDXtm) test in persons with mild (IDMi) and moderate (IDMo) levels of ID with Down Syndrome (DS). A multicenter study was carried out. Subjects (n = 63, ≥ 39 years old) had DS with mild (n = 39) or moderate ID (n = 24) with no minor neurocognitive disorder or Alzheimer’s disease. Assessment protocol: TOLDXtm for ID, Kaufman Brief Intelligence Test Second Edition (K-BIT II), Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX-DS), Weigl’s Color-Form Sorting Test (WCFST), Barcelona Test for Intellectual Disability (BT-ID), and the Behavior Rating Inventory of Executive Function (BRIEF-P). The internal consistency (IDMi and IDMo), factor structure of the different subscales, and relationship between TOLDXtm subscales and other cognitive measures (BT-ID, WCFST, and BRIEF-P) were analyzed. A normative data table with ID population quartiles is provided. TOLDXtm for ID showed a robust one factor structure and coherentassociations with other, related neuropsychological instruments. Significant differences between IDMi and IDMo on movement-related variables like Correct (Corr; p = .002) and Moves (Mov; p = .042) were observed, along with good internal consistency values, Corr (α = .75), Mov (α = .52). Regarding internal consistency, no between-groups differences were observed (all p-value > 0.05). The TOLDXtm for ID is thus an instrument, supported by good validity evidence, to evaluate problemsolving and planning in ID. It distinguishes between individuals with mild and moderate ID, and is highly associated with other measures of executive functioning (AU)

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