VIPERA: Viral Intra-Patient Evolution Reporting and Analysis.

Viral mutations within patients nurture the adaptive potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during chronic infections, which are a potential source of variants of concern. However, there is no integrated framework for the evolutionary analysis of intra-patient SARS-CoV-2 serial samples. Herein, we describe Viral Intra-Patient Evolution Reporting and Analysis (VIPERA), a new software that integrates the evaluation of the intra-patient ancestry of SARS-CoV-2 sequences with the analysis of evolutionary trajectories of serial sequences from the same viral infection. We have validated it using positive and negative control datasets and have successfully applied it to a new case, which revealed population dynamics and evidence of adaptive evolution. VIPERA is available under a free software license at https://github.com/PathoGenOmics-Lab/VIPERA.

Tracking the Emergence and Dissemination of a blaNDM-23 Gene in a Multidrug Resistance Plasmid of Klebsiella pneumoniae.

Since the discovery of blaNDM-1, NDM ß-lactamases have become one of the most widespread carbapenemases worldwide. To date, 43 different NDM variants have been reported but some, such as blaNDM-23, have not been characterized in detail yet. Here, we describe the emergence of a novel blaNDM-23 allele from a blaNDM-1 ancestor and the multidrug resistance plasmid that has disseminated it through a Klebsiella pneumoniae ST437 clone in several Spanish hospitals. Between 2016 and 2019, 1,972 isolates were collected in an epidemiological survey for extended-spectrum-ß-lactamase (ESBL)-producing Klebsiella pneumoniae in the Comunitat Valenciana (Spain). Three carbapenem-resistant strains failed to be detected by carbapenemase-producing Enterobacteriaceae (CPE) screening tests. These isolates carried a blaNDM-23 gene. To characterize this gene, its emergence, and its dissemination, we performed antimicrobial susceptibility tests, hybrid sequencing with Illumina and Nanopore technologies, and phylogenetic analyses. The MICs of the blaNDM-23 allele were identical to those of the blaNDM-1 allele. The blaNDM-23 allele was found in 14 isolates on a 97-kb nonmobilizable, multidrug-resistant plasmid carrying 19 resistance genes for 9 different antimicrobial families. In this plasmid, the blaNDM-23 gene is in the variable region of a complex class 1 integron with a singular genetic environment. The small genetic distance between blaNDM-23-producing isolates reflects a 5-year-long clonal dispersion involving several hospitals and interregional spread. We have characterized the genomic and epidemiological contexts in the emergence and community spread of a new blaNDM-23 allele in a multidrug resistance (MDR) plasmid of Klebsiella pneumoniae. IMPORTANCE At a time when antimicrobial resistance has become one of the biggest concerns worldwide, the emergence of novel alleles and extremely drug-resistant plasmids is a threat to public health worldwide, especially when they produce carbapenem resistance in one of the most problematic pathogens, such as Klebsiella pneumoniae. We used genomic epidemiology to describe the emergence of a novel NDM-23 allele and identify it in a MDR plasmid that has disseminated through a K. pneumoniae ST437 clone in several hospitals in Spain. Using bioinformatic and phylogenetic analyses, we have traced the evolutionary and epidemiological route of the new allele, the hosting plasmid, and the strain that carried both of them from Pakistan to Spain. A better understanding of the NDM-producing K. pneumoniae populations and plasmids has made evident the spread of this clone through the region, enhancing the importance of genomic surveillance in the control of antimicrobial resistance.

Coste de la incapacidad temporal debida a enfermedades musculoesqueléticas en España / Cost of temporary work disability due to musculoskeletal diseases in Spain

Objetivo: Estimar el coste anual de la incapacidad temporal (IT) ocasionada por las enfermedades musculoesqueléticas (EME) en España y su variabilidad entre comunidades autónomas (CC. AA.) y entidades pagadoras. Método: Estudio descriptivo de costes por IT debida a EME en las CC. AA. en el 2007. Se utilizaron datos agregados del Instituto Nacional de Seguridad Social (INSS) y extrapolaciones a las entidades que realizan el pago de la IT (INSS, mutuas y empresas). Resultados: Las EME fueron la primera causa de IT en España en 2007, produciendo 908.781 episodios de IT (18% del total), 39.342.857 días de baja (23%) y 1.702 millones de euros de coste (23%). La incidencia anual de procesos de IT por EME por cada 1.000 personas ocupadas fue de 45. El coste por proceso de IT fue de 1.873 oscilando entre un mínimo de 1.391 D (La Rioja) y un máximo de 2.429 D (País Vasco). Conclusión: Las EME producen anualmente en España más de 39 millones de días de baja por IT, con un coste superior a 1.700 millones de euros. El coste de la IT tiene una amplia variabilidad entre CC. AA (AU)

Objective: To estimate the annual cost of temporary work disability (TWD) caused by musculoskeletal diseases (MSDs) in Spain and its variations between regions (autonomous communities: ACs) and paying institutions. Method: Descriptive study of the costs of MSD-related TWD in ACs in 2007. The Spanish National Institute of Social Security (NISS) provided aggregate data. Extrapolations to the rest of the TWD payers (mutual societies and employers) were used. Results: MSDs were the leading cause of TWD in Spain in 2007, causing 908,781 episodes of TWD (18% of the total), 39,342,857 lost working days (23%), and a cost of 1,702 million euros (23%). The annual incidence of TWD episodes per 1,000 employed was 45. The cost per TWD process was 1,873 D, ranging from 1,391 D (La Rioja) to 2,429 D (Basque Country). Conclusion: MSDs produce annually in Spain over 39 million days lost by TWD with a cost of over 1,700 million euros. Regions observed wide variations of the TWD cost (AU)

Cost of temporary work disability due to musculoskeletal diseases in Spain.

OBJECTIVE: To estimate the annual cost of temporary work disability (TWD) caused by musculoskeletal diseases (MSDs) in Spain and its variations between regions (autonomous communities: ACs) and paying institutions. METHOD: Descriptive study of the costs of MSD-related TWD in ACs in 2007. The Spanish National Institute of Social Security (NISS) provided aggregate data. Extrapolations to the rest of the TWD payers (mutual societies and employers) were used. RESULTS: MSDs were the leading cause of TWD in Spain in 2007, causing 908,781 episodes of TWD (18% of the total), 39,342,857 lost working days (23%), and a cost of 1,702 million euros (23%). The annual incidence of TWD episodes per 1,000 employed was 45. The cost per TWD process was 1,873 €, ranging from 1,391 € (La Rioja) to 2,429 € (Basque Country). CONCLUSION: MSDs produce annually in Spain over 39 million days lost by TWD with a cost of over 1,700 million euros. Regions observed wide variations of the TWD cost.

Percepciones, actitudes y vivencias de los familiares de pacientes con enfermedades músculo-esqueléticas: una aproximación cualitativa / Perceptions, attitudes and experiences of family caregivers of patients with musculoskeletal diseases: a qualitative approach

Objetivo. Conocer las percepciones, las actitudes y las vivencias de los familiares que cuidan a los pacientes con enfermedades músculo-esqueléticas (EME). Métodos. Estudio cualitativo, descriptivo y exploratorio. Se realizaron 2 grupos de discusión con cuidadores seleccionados mediante las variables: sexo, edad del cuidador (de 31 a 45 años/de 46 a 65 años), diagnóstico (artritis reumatoide/espondilitis anquilosante) y situación laboral del paciente (amas de casa/pacientes con al menos 3 episodios de baja laboral/pacientes que abandonaron su trabajo/pacientes con incapacidad declarada). Se hizo un análisis de contenido basado en la Grounded Theory para detectar las categorías emergentes. Resultados. Las dimensiones emergentes fueron: alteraciones en la vida cotidiana, necesidad de apoyo del cuidador, repercusiones físicas y psicológicas sobre el cuidador, características del paciente y descripción de los cuidados. Entre las vivencias destaca que el diagnóstico de una EME altera la vida del paciente y los familiares, repercute en la esfera laboral, económica, social, psicológica y física llegando a necesitar ayuda para las actividades básicas de la vida diaria. Las EME diagnosticadas a edades tempranas o muy incapacitantes, exigen dedicación y esfuerzo en los cuidados que aumentan con el tiempo. Esto produce una gran sobrecarga emocional en el familiar, modulada por el apoyo recibido para cuidar. Conclusión. Las principales consecuencias detectadas para los cuidadores son pérdida de poder adquisitivo, problemas laborales, aislamiento social y su sobrecarga emocional. Se precisa desarrollar programas de apoyo domiciliario eficaces, con trámites oficiales ágiles para poder clasificar rápidamente el grado de discapacidad y así poder tramitar ayudas oficiales (AU)

Objective: To determine the perceptions, attitudes and experiences among family caregivers of patients with musculoskeletal diseases (MSD). Methods: Descriptive, exploratory, qualitative study. Two discussion groups were organized with family caregivers of MSD patients, representing the caregiver profile: gender (men/women) and age (31-45 years/46-65 years); and patient profiles: MSD type (rheumatoid arthritis/ankylosing spondylitis), work status (yes or no for the variables housewife, at least 3 episodes of sick leave, patients who abandoned their work, and patients with permanent work disability). A content analysis based on the Grounded Theory was done to detect and explore emerging categories. Results: The emerging dimensions were: alterations in daily life activities, need for caregiver support, physical and psychological impact on the caregiver, characteristics of the patient, and several aspects of care. Relevant experiences mentioned were: the diagnosis of a MSD changes the patient and their family members’ life affecting work, financial, social, psychological and physical spheres, making it necessary help for basic activities of daily living. Early age at onset or severe MSDs require dedication and effort on the part of caregivers which increases with time. This leads to a great emotional overload on the caregivers, which may be modulated by the support they receive when providing care. Conclusion: The primary consequences for caregivers are loss of purchasing power, work problems, social isolation and emotional stress. Programs for effective at-home support need to be developed with streamlined administrative processes to quickly classify the level of disability and provide official assistance (AU)

Conocimiento de la población española de las enfermedades músculo-esqueléticas / Knowledge on musculoskeletal diseases by the Spanish population

Objetivo: Explorar el conocimiento sobre enfermedades músculo-esqueléticas (EME) en la población española. Métodos: Estudio transversal, dirigido a la población general española mediante encuesta telefónica a 1.009 sujetos mayores de 18 años estratificados por tamaño del hábitat, edad, género y zona geográfica. Con un cuestionario estructurado, se recogió información de los sujetos, su conocimiento general de las EME (CG), su conocimiento específico de EME concretas (CE) y su conocimiento del impacto social (CIS). Se elaboraron indicadores sintéticos (escala 0-1) de nivel de conocimiento para analizar, mediante análisis univariante y multivariante, las variables asociadas al nivel de conocimiento. Resultados: El nivel de CIS es medio-alto (media: 0,62 ± 0,16) y recoge el reconocimiento mayoritario de las EME como incapacitantes, que afectan a la capacidad laboral y provocan un alto coste personal y social. El nivel de CG es intermedio (media: 0,50 ± 0,17), un 60% conoce algo sobre las EME, aunque el 54% califica su información como mala/muy mala. El nivel de CE es bajo (media: 0,18 ± 0,10), existiendo EME muy poco conocidas (lupus y espondilitis). Ser hombre, jubilado o presentar una EME, se asocia con más conocimiento sobre las EME. Conclusión: La población espa˜nola tiene un nivel medio de conocimiento de la frecuencia y medida en que las EME afectan el desempeño de las actividades de quienes las presentan. Las identifican suficientemente, conociendo a grandes rasgos su sintomatología, aunque saben poco de ellas. El nivel de conocimiento varía según los factores sociodemográficos y la experiencia directa e indirecta de presentación de EME(AU)

Objective: To explore knowledge on musculoskeletal-diseases (MSDs) by the Spanish population. Methods: This was a cross-sectional study of the general population (> 18 years) using a telephone survey of 1,009 subjects stratified by habitat size, age, sex, and geographic area. A structured questionnaire was used to collect information on the subjects, their general knowledge of MSDs (GK), their specific knowledge of particular MSDs (SK), and their knowledge of their social impact (KSI). Synthetic indicators of the level of knowledge were used to analyze, using univariate and multivariate models, variables associated to the level of knowledge. Results: The KSI level ranges from medium-high (mean: 0.62 ± 0.16 out of 1), suggesting that most subjects recognize MSDs as disabling conditions which affect the ability to work and have a high personal and social cost. The GK level is intermediate (mean: 0.50 ± 0.17); 60% of subjects know something about MSDs, but 54% state that their information is poor/very poor. The SK level is low (mean: 0.18 ± 0.10), and there are some MSDs that are little known (lupus, spondylitis). Being male or retired or having a MSD is associated to a greater knowledge of MSDs. Conclusion: The Spanish population has a medium level of knowledge of the frequency and extent to which MSDs affect performance of activities by those who suffer them. They identify them adequately and have a GK of their symptoms, but have little information about them. The level of knowledge varies depending on social and demographic factors and on whether or not the subject has direct or indirect experience of what a MSD means(AU)

Knowledge on musculoskeletal diseases by the Spanish population.

OBJECTIVE: To explore knowledge on musculoskeletal-diseases (MSDs) by the Spanish population. METHODS: This was a cross-sectional study of the general population (> 18 years) using a telephone survey of 1,009 subjects stratified by habitat size, age, sex, and geographic area. A structured questionnaire was used to collect information on the subjects, their general knowledge of MSDs (GK), their specific knowledge of particular MSDs (SK), and their knowledge of their social impact (KSI). Synthetic indicators of the level of knowledge were used to analyze, using univariate and multivariate models, variables associated to the level of knowledge. RESULTS: The KSI level ranges from medium-high (mean: 0.62 ± 0.16 out of 1), suggesting that most subjects recognize MSDs as disabling conditions which affect the ability to work and have a high personal and social cost. The GK level is intermediate (mean: 0.50 ± 0.17); 60% of subjects know something about MSDs, but 54% state that their information is poor/very poor. The SK level is low (mean: 0.18 ± 0.10), and there are some MSDs that are little known (lupus, spondylitis). Being male or retired or having a MSD is associated to a greater knowledge of MSDs. CONCLUSION: The Spanish population has a medium level of knowledge of the frequency and extent to which MSDs affect performance of activities by those who suffer them. They identify them adequately and have a GK of their symptoms, but have little information about them. The level of knowledge varies depending on social and demographic factors and on whether or not the subject has direct or indirect experience of what a MSD means.

Perceptions, attitudes and experiences of family caregivers of patients with musculoskeletal diseases: a qualitative approach.

OBJECTIVE: To determine the perceptions, attitudes and experiences among family caregivers of patients with musculoskeletal diseases (MSD). METHODS: Descriptive, exploratory, qualitative study. Two discussion groups were organized with family caregivers of MSD patients, representing the caregiver profile: gender (men/women) and age (31-45 years/46-65 years); and patient profiles: MSD type (rheumatoid arthritis/ankylosing spondylitis), work status (yes or no for the variables housewife, at least 3 episodes of sick leave, patients who abandoned their work, and patients with permanent work disability). A content analysis based on the Grounded Theory was done to detect and explore emerging categories. RESULTS: The emerging dimensions were: alterations in daily life activities, need for caregiver support, physical and psychological impact on the caregiver, characteristics of the patient, and several aspects of care. Relevant experiences mentioned were: the diagnosis of a MSD changes the patient and their family members' life affecting work, financial, social, psychological and physical spheres, making it necessary help for basic activities of daily living. Early age at onset or severe MSDs require dedication and effort on the part of caregivers which increases with time. This leads to a great emotional overload on the caregivers, which may be modulated by the support they receive when providing care. CONCLUSION: The primary consequences for caregivers are loss of purchasing power, work problems, social isolation and emotional stress. Programs for effective at-home support need to be developed with streamlined administrative processes to quickly classify the level of disability and provide official assistance.