The Expanding Phenotypical Spectrum of WARS2 -Related Disorder : Four Novel Cases with a Common Recurrent Variant

Biallelic variants in the mitochondrial form of the tryptophanyl-tRNA synthetases (WARS2) can cause a neurodevelopmental disorder with movement disorders including early-onset tremor-parkinsonism syndrome. Here, we describe four new patients, who all presented at a young age with a tremor-parkinsonism syndrome and responded well to levodopa. All patients carry the same recurrent, hypomorphic missense variant (NM_015836.4: c.37T>G; p.Trp13Gly) either together with a previously described truncating variant (NM_015836.4: c.797Cdel; p.Pro266ArgfsTer10), a novel truncating variant (NM_015836.4: c.346C>T; p.Gln116Ter), a novel canonical splice site variant (NM_015836.4: c.349-1G>A), or a novel missense variant (NM_015836.4: c.475A>C, p.Thr159Pro). We investigated the mitochondrial function in patients and found increased levels of mitochondrially encoded cytochrome C Oxidase II as part of the mitochondrial respiratory chain as well as decreased mitochondrial integrity and branching. Finally, we conducted a literature review and here summarize the broad phenotypical spectrum of reported WARS2 -related disorders. In conclusion, WARS2 -related disorders are diagnostically challenging diseases due to the broad phenotypic spectrum and the disease relevance of a relatively common missense change that is often filtered out in a diagnostic setting since it occurs in ~0.5% of the general European population

Nomophobia in university students during COVID-19 outbreak: a cross-sectional study

Introduction: Currently, access to the Internet through smartphones has led to their functions going beyond purely communicative ones, allowing the management of massive, instantaneous, and easily accessible information. This research analyzed the differences in smartphone use and the prevalence of nomophobia, mainly according to gender and university degree of Health Sciences students at the University of Zaragoza during the COVID-19 confinement in Spain. Methods: A descriptive cross-sectional study was carried out on a sample of 318 first and second-grade students, who completed an online questionnaire sent to their institutional email, which included sociodemographic questions, other questions about smartphone use, and the Nomophobia Questionnaire (NMP-Q) scale. Results: Compared to men (n = 58), women (n = 260) were more likely to use their smartphones more intensively daily, as were occupational therapy students compared to the other degree programs studied. The prevalence of nomophobia was moderate, being around the risk of suffering from it. No significant differences in scores for nomophobia among students were found according to gender, university degree, or population nucleus for the nomophobia scores of the students. Discussion: The present study extends the existing literature on nomophobia by providing results of interest in terms of gender and the exceptional healthcare context of COVID-19. The results suggest that despite intense daily smartphone use young people did not reach severe nomophobia figures. This fact underlines the need for appropriate and healthy technology education. Understanding the characteristics of the populations that use the smartphone the most may help to analyze nomophobia rates and the massive use of the device

Nomophobia in university students during COVID-19 outbreak: a cross-sectional study

IntroductionCurrently, access to the Internet through smartphones has led to their functions going beyond purely communicative ones, allowing the management of massive, instantaneous, and easily accessible information. This research analyzed the differences in smartphone use and the prevalence of nomophobia, mainly according to gender and university degree of Health Sciences students at the University of Zaragoza during the COVID-19 confinement in Spain.MethodsA descriptive cross-sectional study was carried out on a sample of 318 first and second-grade students, who completed an online questionnaire sent to their institutional email, which included sociodemographic questions, other questions about smartphone use, and the Nomophobia Questionnaire (NMP-Q) scale.ResultsCompared to men (n = 58), women (n = 260) were more likely to use their smartphones more intensively daily, as were occupational therapy students compared to the other degree programs studied. The prevalence of nomophobia was moderate, being around the risk of suffering from it. No significant differences in scores for nomophobia among students were found according to gender, university degree, or population nucleus for the nomophobia scores of the students.DiscussionThe present study extends the existing literature on nomophobia by providing results of interest in terms of gender and the exceptional healthcare context of COVID-19. The results suggest that despite intense daily smartphone use young people did not reach severe nomophobia figures. This fact underlines the need for appropriate and healthy technology education. Understanding the characteristics of the populations that use the smartphone the most may help to analyze nomophobia rates and the massive use of the device

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Trabajo a turnos como factor de riesgo psicosocial en el personal sanitario: consecuencias para la salud

Una gran parte de los profesionales sanitarios realizan trabajo a turnos y nocturno. La realización de trabajo a turnos podría afectar negativamente a su salud. El objetivo de este estudio es describir las consecuencias para la salud del trabajo a turnos en el personal sanitario, en relación con las enfermedades más frecuentes, la salud mental, el bienestar emocional y social y proponiendo medidas preventivas generales. Se ha realizado una revisión sistemática en bases de datos electrónicas (PubMed, ProQuest Central, Academic Search Premier y Web of Science), período 2016-2021. Los estudios seleccionados han sido analizados a texto completo extrayendo la información más relevante. Tras aplicar los descriptores en las bases de datos se han encontrado 1259 estudios, de los cuales 12 se han seleccionado tras aplicar los criterios de inclusión y exclusión. Los estudios seleccionados son de di seño observacional, específicamente estudios descriptivos transversales. Los hallazgos muestran que los principales problemas de salud de los profesionales sanitarios con trabajo a turnos son los trastornos del sueño, el agotamiento, los trastornos de la alimentación y los trastornos del estado de ánimo (depresión y ansiedad). Además, el trabajo a turnos dificulta la conciliación de la vida laboral y familiar, lo que puede agravar este riesgo ante la falta de apoyo social. Los resultados indican la necesidad de realizar evaluaciones periódicas de la salud de profesionales sanitarios con trabajo a turnos, así como reducir el horario de los turnos y ampliar la rotación lo máximo posible para reducir este riesgo y los trastornos asociados

Quality of Life after Radical Prostatectomy: A Longitudinal Study

Background: Men with prostate cancer who undergo radical prostatectomy experience a decrease in quality of life, often related to sexual disfunction and urinary incontinence. Knowing and measuring the impact of radical prostatectomy on the individual’s social, emotional, and family quality of life could help to plan and develop an appropriate, patient-centred therapeutic approach. Aim: In this study, we aimed to evaluate changes in quality of life of patients with prostate cancer before and after radical prostatectomy. Methods: A longitudinal, observational study of 114 participants was conducted using the method of test–retest. Quality of life before and after radical prostatectomy was measured through the following self-administered questionnaires: (1) The EORTC QLQ-C30 in its Spanish version was used to assess the generic quality of life the participants; (2) the EORTC QLQ-PR25 in its Spanish version was used to assess the specific, health-related quality of life of prostate cancer patients. Results: A total of 114 men took part in this study. The results from the QLQ-C30 questionnaire indicated an improvement in the dimensions of emotional role and cognitive function, as well as in the symptoms of fatigue, pain, nausea and vomiting, insomnia, and loss of appetite, after surgery. Patients scored lower in the dimensions of role functioning, social function, and economic impact after radical prostatectomy. According to the results from the QLQ-PR25 questionnaire, 61.40% of the participants experienced sexual impotence and 26.31% suffered urinary incontinence after surgery. There were significant differences in some postsurgical outcomes between patients who had neurovascular bundles preserved and those who had not. Conclusions: In-depth knowledge of, and measurement of changes in, quality of life after radical prostatectomy should allow for comprehensive, multidisciplinary, patient-centred care planning. Psychosocial assessment, both before and after surgery, is crucial in patients with prostate cancer. This study was prospectively registered with the CEIC-A on 2012-06-27, with registration number C.P.-C.I. PI12/008

Validation of clinical exome sequencing in the diagnostic procedure of patients with intellectual disability in clinical practice

Abstract Intellectual disability (ID) has a prevalence of 1–3% and aproximately 30–50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a high diagnostic potential. The aim of this work was to evaluate the diagnostic yield of clinical exome sequencing in 188 ID patients and the economic impact of its introduction in clinical practice. An analysis of diagnostic yield according to the different clinical variables was performed in order to establish an efficient diagnostic protocol for ID patients. Diagnostic yield of clinical exome sequencing was significant (34%) supporting its utility in diagnosis of ID patients. Wide genetic heterogeneity and predominance of autosomal dominant de novo variants in ID patients were observed. Time to diagnosis was shortened and diagnostic study costs decreased by 62% after implementation of clinical exome sequencing. No association was found between any of the variables analyzed and a higher diagnostic yield; added to the fact that many of the diagnoses weren’t clinically detectable, the reduction of time to diagnosis and the economic savings with respect to classical diagnostic studies, strengthen the clinical and economical convenience of early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice