Risk factors associated with COVID-19 infection and mortality in nursing homes.

OBJECTIVE: The aim of this paper was to analyse the association of demographic, clinical and pharmacological risk factors with the presence of SARS-COV-2 virus infection, as well as to know the variables related to mortality from COVID-19 in nursing home (NH) residents. DESIGN: Retrospective case-control study. The study variables of those residents who acquired the infection (case) were compared with those of the residents who did not acquire it (control). A subgroup analysis was carried out to study those variables related to mortality. SITE: Nursing homes in the region of Guipúzcoa (Spain). PARTICIPANTS AND INTERVENTIONS: 4 NHs with outbreaks of SARS-CoV-2 between March and December 2020 participated in the study. The infectivity and, secondary, mortality was studied, as well as demographic, clinical and pharmacological variables associated with them. Data were collected from the computerised clinical records. MAIN MEASUREMENTS: Infection and mortality rate. Risk factors associated with infection and mortality. RESULTS: 436 residents were studied (median age 87 years (IQR 11)), 173 acquired SARS-CoV-2 (39.7%). People with dementia and Global Deterioration Scale ≥6 were less likely to be infected by SARS-CoV-2 virus [OR=0.65 (95% CI 0.43-0.97; p<.05)]. Overall case fatality rate was 10.3% (a mortality of 26% among those who acquired the infection). COVID-19 mortality was significantly associated with a Global Deterioration Scale ≥6 (OR=4.9 (95% CI 1.5-16.1)), COPD diagnosis (OR=7.8 (95% CI 1.9-31.3)) and antipsychotic use (OR=3.1 (95% CI 1.0-9.0)). CONCLUSIONS: Advanced dementia has been associated with less risk of SARS-CoV-2 infection but higher risk of COVID-19 mortality. COPD and chronic use of antipsychotics have also been associated with mortality. These results highlight the importance of determining the stage of diseases such as dementia as well as maintaining some caution in the use of some drugs such as antipsychotics.

Inter-individual differences in CpG methylation at D4Z4 correlate with clinical variability in FSHD1 and FSHD2.

Facioscapulohumeral muscular dystrophy (FSHD: MIM#158900) is a common myopathy with marked but largely unexplained clinical inter- and intra-familial variability. It is caused by contractions of the D4Z4 repeat array on chromosome 4 to 1-10 units (FSHD1), or by mutations in the D4Z4-binding chromatin modifier SMCHD1 (FSHD2). Both situations lead to a partial opening of the D4Z4 chromatin structure and transcription of D4Z4-encoded polyadenylated DUX4 mRNA in muscle. We measured D4Z4 CpG methylation in control, FSHD1 and FSHD2 individuals and found a significant correlation with the D4Z4 repeat array size. After correction for repeat array size, we show that the variability in clinical severity in FSHD1 and FSHD2 individuals is dependent on individual differences in susceptibility to D4Z4 hypomethylation. In FSHD1, for individuals with D4Z4 repeat arrays of 1-6 units, the clinical severity mainly depends on the size of the D4Z4 repeat. However, in individuals with arrays of 7-10 units, the clinical severity also depends on other factors that regulate D4Z4 methylation because affected individuals, but not non-penetrant mutation carriers, have a greater reduction of D4Z4 CpG methylation than can be expected based on the size of the pathogenic D4Z4 repeat array. In FSHD2, this epigenetic susceptibility depends on the nature of the SMCHD1 mutation in combination with D4Z4 repeat array size with dominant negative mutations being more deleterious than haploinsufficiency mutations. Our study thus identifies an epigenetic basis for the striking variability in onset and disease progression that is considered a clinical hallmark of FSHD.

Patients with a phenotype consistent with facioscapulohumeral muscular dystrophy display genetic and epigenetic heterogeneity.

OBJECTIVE: To identify the genetic and epigenetic defects in patients presenting with a facioscapulohumeral (FSHD) clinical phenotype without D4Z4 contractions on chromosome 4q35 tested by linear gel electrophoresis and Southern blot analysis. DESIGN AND PATIENTS: The authors studied 16 patients displaying an FSHD-like phenotype, with normal cardiovascular and respiratory function, a myopathic pattern on electromyography, and a muscle biopsy being normal or displaying only mild and aspecific dystrophic changes. They sequenced the genes calpain 3 (CAPN3), valosin containing protein (VCP) and four-and-a-half LIM domains protein 1 (FHL1), and they analysed the D4Z4 repeat arrays by extensive genotyping and DNA methylation analysis. RESULTS: The authors identified one patient carrying a complex rearrangement in the FSHD locus that masked the D4Z4 contraction associated with FSHD1 in standard genetic testing, one patient with somatic mosaicism for the D4Z4 4q35 contraction, six patients that were diagnosed as having FSHD2, four patients with CAPN3 mutations and two patients with a VCP mutation, No mutations were detected in FHL1, and in two patients, the authors could not identify the genetic defect. CONCLUSIONS: In patients presenting with an FSHD-like clinical phenotype with a negative molecular testing for FSHD, consider (1) detailed genetic testing including D4Z4 contraction of permissive hybrid D4Z4 repeat arrays, p13E-11 probe deletions, and D4Z4 hypomethylation in the absence of repeat contraction as observed in FSHD2; (2) mutations in CAPN3 even in the absence of protein deficiency on western blot analysis; and (3) VCP mutations even in the absence of cognitive impairment, Paget disease and typical inclusion in muscle biopsy.

Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert / Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease

Antecedentes y objetivos: La enfermedad de Steinert o distrofia miotónica tipo 1 (DM1), (OMIM 160900) es la miopatía más prevalente en el adulto. Es una enfermedad multisistémica con alteración de prácticamente todos los órganos y tejidos y una variabilidad fenotípica muy amplia, lo que implica que deba ser atendida por diferentes especialistas que dominen las alteraciones más importantes. En los últimos años se ha avanzado de manera exponencial en el conocimiento de la enfermedad y en su manejo. El objetivo de la guía es establecer recomendaciones para el diagnóstico, el pronóstico, el seguimiento y el tratamiento de las diferentes alteraciones de la DM1. Material y métodos: Esta guía de consenso se ha realizado de manera multidisciplinar. Se ha contado con neurólogos, neumólogos, cardiólogos, endocrinólogos, neuropediatras y genetistas que han realizado una revisión sistemática de la literatura. Recomendaciones: Se recomienda realizar un diagnóstico genético con cuantificación precisa de tripletes CTG. Los pacientes con DM1 deben seguir control cardiológico y neumológico de por vida. Antes de cualquier cirugía con anestesia general debe realizarse una evaluación respiratoria. Debe monitorizarse la presencia de síntomas de disfagia periódicamente. Debe ofrecerse consejo genético a los pacientes con DM1 y a sus familiares. Conclusión: La DM1 es una enfermedad multisistémica que requiere un seguimiento en unidades especializadas multidisciplinares

Background and objectives: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. Material and methods: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. Recommendations: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. Conclusion: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up