RUNA - Repositorio de Saúde
Not a member yet
11570 research outputs found
Sort by
Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study
Get PDFRituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4-7 cycles, and/or every 2 months maintenance monotherapy for FL for 6-12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade >/=3 in 38.6% and were serious in 30.0%. AARs occurred in 48.6%, mostly (84.9%) at the injection site, with only 2.1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69.6%. After a median follow-up of 33.5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life
SEOM clinical guideline on hereditary colorectal cancer (2019)
Get PDFIn the last 2 decades, clinical genetics on hereditary colorectal syndromes has shifted from just a molecular characterization of the different syndromes to the estimation of the individual risk of cancer and appropriate risk reduction strategies. In the last years, new specific therapies for some subgroups of patients have emerged as very effective alternatives. At the same time, germline multigene panel testing by next-generation sequencing (NGS) technology has become the new gold standard for molecular genetics
Identification, clinical manifestation and structural mechanisms of mutations in AMPK associated cardiac glycogen storage disease
Get PDFBACKGROUND: Although 21 causative mutations have been associated with PRKAG2 syndrome, our understanding of the syndrome remains incomplete. The aim of this project is to further investigate its unique genetic background, clinical manifestations, and underlying structural changes. METHODS: We recruited 885 hypertrophic cardiomyopathy (HCM) probands and their families internationally. Targeted next-generation sequencing of sudden cardiac death (SCD) genes was performed. The role of the identified variants was assessed using histological techniques and computational modeling. FINDINGS: Twelve PRKAG2 syndrome kindreds harboring 5 distinct variants were identified. The clinical penetrance of 25 carriers was 100.0%. Twenty-two family members died of SCD or heart failure (HF). All probands developed bradycardia (HRmin, 36.3+/-9.8bpm) and cardiac conduction defects, and 33% had evidence of atrial fibrillation/paroxysmal supraventricular tachycardia (PSVT) and 67% had ventricular preexcitation, respectively. Some carriers presented with apical hypertrophy, hypertension, hyperlipidemia, and renal insufficiency. Histological study revealed reduced AMPK activity and major cardiac channels in the heart tissue with K485E mutation. Computational modelling suggests that K485E disrupts the salt bridge connecting the beta and gamma subunits of AMPK, R302Q/P decreases the binding affinity for ATP, T400N and H401D alter the orientation of H383 and R531 residues, thus altering nucleotide binding, and N488I and L341S lead to structural instability in the Bateman domain, which disrupts the intramolecular regulation. INTERPRETATION: Including 4 families with 3 new mutations, we describe a cohort of 12 kindreds with PRKAG2 syndrome with novel pathogenic mechanisms by computational modelling. Severe clinical cardiac phenotypes may be developed, including HF, requiring close follow-up
Evaluación de los resultados de una intervención asistida por animales en un hospital de día pediátrico: percepciones de niños y padres
No full textThere is a growing interest in the use of animal-assisted intervention (AAI) as a non-pharmacological strategy to improve child welfare in hospitals. However, the efficacy of implementation of programmes based on activities with dogs in a paediatric day hospital is not known. An intra-subject quasi-experimental longitudinal design was used for the purpose of assessing the feasibility of such an intervention, as well as exploring the perceptions of its outcomes by children and parents/guardians. A total of 55 children in outpatient care at a paediatric day hospital participated in an AAI session. The application of this intervention was feasible. Self-assessment by the paediatric patients revealed a statistically significant improvement in their emotional state after the session, which was large in size. Parents confirmed this improvement in their child, perceiving significant changes in their mood, which were large in size. This study suggests that AAI is an effective approach when it comes to promoting the emotional welfare of children during their stay in hospital care environments. Participating in recreational occupations with dogs could contribute in a relevant and efficient way to the development of significant and gratifying experiences and to a more positive perception of healthcare centres on the part of children
Impact of footwear and foot deformities in patients with Parkinson’s disease: A case-series study
Get PDFBackground: Parkinson's disease (PD) is a common and complex neurological problem. Gait abnormalities are frequent in PD patients, and this increases the risk of falls. However, little is known about foot deformities and footwear in this vulnerable population. Here we investigate whether patients with PD use an appropriate shoe size and know if they have foot deformities or alterations. Methodology: A study of a series of observational descriptive cases in a convenience sample (n = 53 patients) diagnosed with Parkinson's disease. One trained investigator evaluated foot and ankle health. The footwear and foot measurements were obtained using a Brannock device. Results: The podiatric examination and footwear examination detected a high presence of podiatric pathologies and inappropriate footwear. This has a negative impact on the quality of life of these patients. Conclusions: This research detected an elevated number of people with foot deformities or alterations. Moreover, a high proportion of participants with PD wear inadequate footwear (in length, width, or both)
Influencia de la comunicación técnica en la coordinación de la atención geriátrica durante la crisis del COVID-19 en la provincia de Lugo. Estudio prospectivo
No full textIntroducción: La pandemia producida por el coronavirus SARS-CoV-2 supone un gran reto sanitario con efectos económicos y sociales patentes. La salud de la población mundial peligra y las formas habituales de afrontar situaciones epidémicas son puestas en cuestión, lo que hace necesario un esfuerzo de coordinación en la atención a las personas mayores. Objetivo: Conocer la influencia que la comunicación técnica producida durante la crisis sanitaria generada a raíz del COVID-19 podrá ejercer sobre la coordinación de la atención geriátrica en la provincia de Lugo. Metodología: Estudio prospectivo Delphi empleando un cuestionario de doble circulación a cumplimentar por expertos en Geriatría y Gerontología de la provincia de Lugo constituidos en dos paneles. Resultados: N = 26 (20 mujeres, 6 hombres). Rango de edad: 25 – 63 años. Las respuestas medias de ambos paneles se han aproximado y los rangos se han estrechado en la segunda circulación de la encuesta. Conclusión: Una estrategia de comunicación bidireccional entre los profesionales de la Geriatría y la Gerontología, basada en documentación técnica y científica, facilitará la coordinación entre niveles asistenciales y mejorará las expectativas de salud de las personas mayores en situaciones de crisis aunque también en la cronicidad
A Comparison of Forensic Age Prediction Models Using Data From Four DNA Methylation Technologies
Get PDFIndividual age estimation can be applied to criminal, legal, and anthropological investigations. DNA methylation has been established as the biomarker of choice for age prediction, since it was observed that specific CpG positions in the genome show systematic changes during an individual's lifetime, with progressive increases or decreases in methylation levels. Subsequently, several forensic age prediction models have been reported, providing average age prediction error ranges of +/-3-4 years, using a broad spectrum of technologies and underlying statistical analyses. DNA methylation assessment is not categorical but quantitative. Therefore, the detection platform used plays a pivotal role, since quantitative and semi-quantitative technologies could potentially result in differences in detected DNA methylation levels. In the present study, we analyzed as a shared sample pool, 84 blood-based DNA controls ranging from 18 to 99 years old using four different technologies: EpiTYPER((R)), pyrosequencing, MiSeq, and SNaPshot(TM). The DNA methylation levels detected for CpG sites from ELOVL2, FHL2, and MIR29B2 with each system were compared. A restricted three CpG-site age prediction model was rebuilt for each system, as well as for a combination of technologies, based on previous training datasets, and age predictions were calculated accordingly for all the samples detected with the previous technologies. While the DNA methylation patterns and subsequent age predictions from EpiTYPER((R)), pyrosequencing, and MiSeq systems are largely comparable for the CpG sites studied, SNaPshot(TM) gives bigger differences reflected in higher predictive errors. However, these differences can be reduced by applying a z-score data transformation
Germline Genetic Findings Which May Impact Therapeutic Decisions in Families with a Presumed Predisposition for Hereditary Breast and Ovarian Cancer
Get PDFIn this study, we aim to gain insight in the germline mutation spectrum of ATM, BARD1, BRIP1, ERCC4, PALB2, RAD51C and RAD51D in breast and ovarian cancer families from Spain. We have selected 180 index cases in whom a germline mutation in BRCA1 and BRCA2 was previously ruled out. The importance of disease-causing variants in these genes lies in the fact that they may have possible therapeutic implications according to clinical guidelines. All variants were assessed by combined annotation dependent depletion (CADD) for scoring their deleteriousness. In addition, we used the cancer genome interpreter to explore the implications of some variants in drug response. Finally, we compiled and evaluated the family history to assess whether carrying a pathogenic mutation was associated with age at diagnosis, tumour diversity of the pedigree and total number of cancer cases in the family. Eight unequivocal pathogenic mutations were found and another fourteen were prioritized as possible causal variants. Some of these molecular results could contribute to cancer diagnosis, treatment selection and prevention. We found a statistically significant association between tumour diversity in the family and carrying a variant with a high score predicting pathogenicity (p = 0.0003)
Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy. A Cohort Study
No full textBackground: The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations.
Objective: To describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART.
Design: Cohort study.
Setting: HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020.
Participants: 77 590 HIV-positive persons receiving ART.
Measurements: Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction-confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models.
Results: Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risks for COVID-19 diagnosis and hospitalization were greater in men and persons older than 70 years. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died.
Limitation: Residual confounding by comorbid conditions cannot be completely excluded.
Conclusion: HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV.Instituto de Salud Carlos III (ISCIII)National Institutes of Healt
Antiretrovirals and Risk of COVID-19 Diagnosis and Hospitalization in HIV-Positive Persons
Get PDFThe risk of COVID-19 diagnosis and hospitalization among HIV-positive individuals is lower in those receiving treatment with TDF/FTC than in those receiving other ART regimes. This association does not seem to be explained by confounding due to unmeasured clinical characteristics. Our finding is compatible with accumulating evidence on a potential effect of TDF/FTC against SARS-CoV-2 infection