Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study.

BACKGROUND: In high-resource settings the survival of immunocompromised (IC) children has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools and outcome of IC children with TB in Europe. METHODS: Multicentre, matched case-control study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), capturing TB cases <18 years diagnosed 2000-2020. RESULTS: 417 TB cases were included, comprising 139 children with IC (HIV, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions) and 278 non-IC children as controls. Non-respiratory TB was more frequent among cases than controls (32.4% vs. 21.2%; p = 0.013). IC patients had an increased likelihood of presenting with severe disease (57.6% vs. 38.5%; p < 0.001; OR [95% CI]: 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs. 6.0%; p < 0.001) and QuantiFERON-TB Gold assay (30.0% vs. 7.3%; p < 0.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs. 49.3%; p = 0.083). Although the mortality in IC children was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs. 6.1%; p = 0.004). CONCLUSIONS: IC children with TB disease in Europe have increased rates of non-respiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in IC patients, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

A Bayesian Model to Predict COVID-19 Severity in Children.

BACKGROUND: We aimed to identify risk factors causing critical disease in hospitalized children with COVID-19 and to build a predictive model to anticipate the probability of need for critical care. METHODS: We conducted a multicenter, prospective study of children with SARS-CoV-2 infection in 52 Spanish hospitals. The primary outcome was the need for critical care. We used a multivariable Bayesian model to estimate the probability of needing critical care. RESULTS: The study enrolled 350 children from March 12, 2020, to July 1, 2020: 292 (83.4%) and 214 (73.7%) were considered to have relevant COVID-19, of whom 24.2% required critical care. Four major clinical syndromes of decreasing severity were identified: multi-inflammatory syndrome (MIS-C) (17.3%), bronchopulmonary (51.4%), gastrointestinal (11.6%), and mild syndrome (19.6%). Main risk factors were high C-reactive protein and creatinine concentration, lymphopenia, low platelets, anemia, tachycardia, age, neutrophilia, leukocytosis, and low oxygen saturation. These risk factors increased the risk of critical disease depending on the syndrome: the more severe the syndrome, the more risk the factors conferred. Based on our findings, we developed an online risk prediction tool (https://rserver.h12o.es/pediatria/EPICOAPP/, username: user, password: 0000). CONCLUSIONS: Risk factors for severe COVID-19 include inflammation, cytopenia, age, comorbidities, and organ dysfunction. The more severe the syndrome, the more the risk factor increases the risk of critical illness. Risk of severe disease can be predicted with a Bayesian model.

Prevalence of thrombotic complications in children with SARS-CoV-2.

Knowledge of thrombosis in children with SARS-CoV-2 is scarce. In this multicentre national cohort of children with SARS-CoV-2 involving 49 hospitals, 4 patients out of 537 infected children developed a thrombotic complication (prevalence of 0.7% (95% CI: 0.2% to 1.9%) out of the global cohort and 1.1% (95% CI: 0.3% to 2.8%) out of the hospitalised patients). We describe their characteristics and review other published paediatric cases. Three out of the four patients were adolescent girls, and only two cases had significant thrombotic risk factors. In this paediatric cohort, D-dimer value was not specific enough to predict thrombotic complications. Adolescence and previous thrombotic risk factors may be considered when initiating anticoagulant prophylaxis on children with SARS-CoV-2 disease (COVID-19).

SARS-COV-2 infection in pregnant women and newborns in a Spanish cohort (GESNEO-COVID) during the first wave.

BACKGROUND: Knowledge about SARS-CoV-2 infection in pregnancy and newborns is scarce. The objective of this study is to analyse clinical and epidemiological characteristics of a cohort of women infected with SARS-CoV-2 during pregnancy and their newborns exposed to SARS-CoV-2 during gestation. METHODS: Multicentric observational study of Spanish hospitals from the GESNEO-COVD cohort, participants in RECLIP (Spanish Network of Paediatric Clinical Assays). Women with confirmed SARS-CoV-2 infection by PCR and/or serology during pregnancy, diagnosed and delivering during the period 15/03/2020-31/07/2020 were included. Epidemiological, clinical, and analytical data was collected. RESULTS: A total of 105 pregnant women with a median of 34.1 years old (IQR: 28.8-37.1) and 107 newborns were included. Globally, almost 65% of pregnant women had some COVID-19 symptoms and more than 43% were treated for SARS-COV-2. Overall, 30.8% of pregnant women had pneumonia and 5 (4.8%) women were admitted to the intensive care unit needing invasive mechanical ventilation. There was a rate of 36.2% of caesarean sections, which was associated with pneumonia during pregnancy (OR: 4.203, CI 95%: 1.473-11.995) and lower gestational age at delivery (OR: 0.724, CI 95%: 0.578-0.906). The prevalence of preterm birth was 20.6% and prematurity was associated with pneumonia during gestation (OR: 6.970, CI95%: 2.340-22.750) and having a positive SARS-CoV-2 PCR at delivery (OR: 6.520, CI95%: 1.840-31.790). All nasopharyngeal PCR in newborns were negative at birth and one positivized at 15 days of life. Two newborns died, one due to causes related to prematurity and another of unexpected sudden death during early skin-to-skin contact after delivery. CONCLUSIONS: Although vertical transmission has not been reported in this cohort, the prognosis of newborns could be worsened by SARS-CoV-2 infection during pregnancy as COVID-19 pneumonia increased the risk of caesarean section deliveries and preterm births.

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.

Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain.

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.

Effects of fatigue induced by repetitive movements and isometric tasks on reaction time.

PURPOSE: The understanding of fatigue of the human motor system is important in the fields of ergonomics, sport, rehabilitation and neurology. In order to understand the interactions between fatigue and reaction time, we evaluated the effects of two different fatiguing tasks on reaction time. METHODS: 83 healthy subjects were included in a case-control study with three arms where single and double choice reaction time tasks were performed before and after 2 min fatiguing task (an isometric task, a finger tapping task and at rest). RESULTS: After an isometric task, the right-fatigued hand was slower in the choice component of a double choice reaction time task (calculated as the individual difference between single and double choice reaction times); also, the subjects that felt more fatigued had slower choice reaction time respect to the baseline assessment. Moreover, in relationship to the performance decay after two minutes, finger tapping task produces more intense fatigability perception. CONCLUSIONS: We confirmed that two minutes of isometric or repetitive tasks are enough to produce fatigue. The fatigue perception is more intense for finger tapping tasks in relation to the performance decay. We therefore confirmed that the two fatiguing tasks produced two different kind of fatigue demonstrating that with a very simple protocol it is possible to test subjects or patients to quantify different form of fatigue.

Exercise Interventions for Improving Flexibility in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background and objectives: People with multiple sclerosis (MS) often experience limitations in joint range of motion, which is linked to spasticity and continued inactivity. Low flexibility levels in this population have been linked to postural problems and muscular pain. Therefore, the purpose of this study was to conduct a systematic review and a meta-analysis aimed at identifying the characteristics and methodological quality of investigations studying the effects of exercise interventions on the flexibility levels of people with MS. Materials and Methods: Three electronic databases (MEDLINE/PubMed, SPORTDiscus and Scopus) were systematically searched up to May 2019 for intervention studies focused on the effects of exercise on the flexibility levels of people with MS. A meta-analysis, including randomized controlled trials (RCT), which reported information regarding the effects of exercise on flexibility, was also conducted. The methodological quality of included studies was assessed using the Physiotherapy Evidence Database, and the Quality Assessment Tool for Before-After Studies, with no control group. The quality of the information reported, regarding the programs conducted, was assessed by means of the Consensus on Exercise Reporting Template (CERT) scale. Results: Seven studies, four RCTs and three uncontrolled investigations were finally selected. The methodological quality of the RCTs was considered "poor" in one study, and "good" and "excellent" in two studies and one investigation, respectively. The three uncontrolled studies showed a methodological quality between "fair" and "poor". Following the CERT scale, four studies were graded as "high" and three as "low". Findings from the meta-analysis indicated no significant effects on hamstring flexibility, or the range of motion in the hips, knees or ankles. Conclusions: There is preliminary evidence from individual studies which indicates that people with MS can improve their lower limb flexibility following participation in physical exercise programs, but the meta-analysis did not confirm these findings.

Fatigue in Multiple Sclerosis: General and Perceived Fatigue Does Not Depend on Corticospinal Tract Dysfunction.

Background: Multiple sclerosis (MS) is an autoimmune disorder of the CNS in which inflammation, demyelination, and axonal damage of the central nervous system coexist. Fatigue is one of the most disabling symptoms in MS and little is known about the neurophysiological mechanisms involved. Methods: To give more mechanistic insight of fatigue in MS, we studied a cohort of 17 MS patients and a group of 16 age-matched healthy controls. Baseline Fatigue Severity Scales and Fatigue Rating were obtained from both groups to check the level of fatigue and to perform statistical correlations with fatigue-induced neurophysiologic changes. To induce fatigue we used a handgrip task. During the fatiguing task, we evaluated fatigue state (using a dynamometer) and after the task we evaluated the Borg Rating of Perceived Exertion Scale. Transcranial magnetic stimulation and peripheral electric stimulation were used to assess corticospinal tract and peripheral system functions before and after the task. Results: Clinically significant fatigue and central motor conduction time were greater in patients than in controls, while motor cortex excitability was decreased and maximal handgrip strength reduced in patients. Interestingly, fatigue state was positively correlated to perceived fatigue in controls but not in patients. Furthermore, in the presence of similar fatigue state over time, controls showed a significant fatigue-related reduction in motor evoked potential (a putative marker of central fatigue) whereas this effect was not seen in patients. Conclusions: in MS patients the pathogenesis of fatigue seems not driven by the mechanisms directly related to corticospinal function (that characterize fatigue in controls) but seems probably due to other "central abnormalities" upstream to primary motor cortex.

Las tareas de contracción muscular isométricas o de movimientos repetitivos para evaluar los efectos de la fatiga / Una revisión sistemática The isometric muscle contraction tasks or repetitive movements to evaluate the effects of fatigue. A systematic review

La fatiga es definida como un fenómeno relacionado con el tiempo de disminución de la capacidad máxima de generación de fuerza, expresándose, como un deterioro en la contracción máxima voluntaria (CMV). La aparición de la fatiga en el músculo esquelético durante un esfuerzo ha sido de interés para los fisiólogos, especialmente porque la fatiga es un factor limitante, tanto en el rendimiento deportivo como en la realización de cualquier tarea. El objetivo del artículo es analizar la literatura y proporcionar una revisión sistemática sobre la fatiga inducida por tareas de contracción muscular, provocadas por contracciones isométricas o mediante tapping de dedos. Para ello se realizó una investigación basada en la metodología PRISMA (Artículos de informes preferidos para revisiones sistemáticas y metanálisis). Llevando a cabo una búsqueda de artículos en las bases de datos PubMed, Medline, Science Direct y Google Scholar, entre los meses de junio y noviembre de 2017 con fecha posterior al año 2000. De los 315 estudios identificados inicialmente, sólo 12 cumplieron con los criterios de selección establecidos. La variabilidad metodológica de los distintos estudios permite observar como a través de las tareas de tapping (movimientos repetitivos de dedos), o mediante tareas de contracción isométrica se pueden determinar los distintos parámetros de la fatiga que se evalúan en cada estudio, siendo un instrumento muy utilizado para abordar dicho tema. La fatiga muscular se ha estudiado predominantemente cuando es inducida por tareas isométricas, habiendo un mayor número de investigaciones que utilizan este tipo de metodología, ya que, aunque el tapping de dedos sea un procedimiento fiable para evaluar los mecanismos neurofisiológicos subyacentes de la fatiga, apenas se ha explorado

Fatigue has been defined as a phenomenon related to the time of decrease of the maximum capacity of generation of force, expressing itself, generally, as a deterioration in the maximum voluntary contraction (CMV). The appearance of fatigue in skeletal muscle during an effort has long been of interest to physiologists, especially because fatigue is a limiting factor in athletic performance or in the performance of any task. The aim of the article is to analyze the literature and provide a systematic review on fatigue induced by muscle contraction tasks, caused by isometric contractions or by finger tapping. To this end, an investigation was carried out based on the PRISMA methodology (Articles of preferred reports for systematic reviews and meta-analyzes). Conducting a search of articles in the PubMed, Medline, Science Direct and Google Scholar databases, between the months of June and November of 2017 after the year 2000. Of the 315 studies initially identified, only 12 complied with the established selection criteria. The methodological variability of the different studies allows to observe how through the tapping tasks (repetitive movements of fingers), or through isometric contraction tasks, it is possible to determine the different parameters of fatigue that are evaluated in each study, being a very used to address that topic. Muscle fatigue has been predominantly studied when induced by isometric tasks, with a greater number of investigations using this type of methodology, since, although finger tapping is a reliable procedure to evaluate the underlying neurophysiological mechanisms of fatigue, It has been explored