Clinical and economic burden of respiratory syncytial virus in Spanish children: the BARI study.

Respiratory syncytial virus (RSV) infection is a major cause of morbidity in children. However, its disease burden remains poorly understood, particularly outside of the hospital setting. Our study aimed to estimate the burden of medically attended acute lower respiratory infection (ALRI) cases potentially related to RSV in Spanish children. Longitudinal data from September 2017 to June 2018 of 51,292 children aged < 5 years old from the National Healthcare System (NHS) of two Spanish regions were used. Three case definitions were considered: (a) RSV-specific; (b) RSV-specific and unspecified acute bronchiolitis (RSV-specific and Bronchiolitis), and; (c) RSV-specific and unspecified ALRI (RSV-specific and ALRI). A total of 3460 medically attended ALRI cases potentially due to RSV were identified, of which 257 (7.4%), 164 (4.7%), and 3039 (87.8%) coded with RSV-specific, unspecific bronchiolitis, and unspecific ALRI codes, respectively. Medically attended RSV-specific and ALRI cases per 1000 children was 134.4 in the first year of life, 119.4 in the second, and 35.3 between 2 and 5 years old. Most cases were observed in otherwise healthy children (93.1%). Mean direct healthcare cost per medically attended RSV-specific and ALRI case was €1753 in the first year of life, €896 in the second, and €683 between 2 and 5 years old. Hospitalization was the main driver of these costs, accounting for 55.6%, 38.0% and 33.4%, in each respective age group. In RSV-specific cases, mean direct healthcare cost per medically attended case was higher, mostly due to hospitalization: €3362 in the first year of life (72.9% from hospitalizations), €3252 in the second (72.1%), and €3514 between 2 and 5 years old (74.2%). These findings suggest that hospitalization data alone will underestimate the RSV infections requiring medical care, as will relying only on RSV-specific codes. RSV testing and codification must be improved and preventive solutions adopted, to protect all infants, particularly during the first year of life.

Incidence and clinical presentation of acute otitis media in children aged <6 years in European medical practices.

We conducted an epidemiological, observational cohort study to determine the incidence and complications of acute otitis media (AOM) in children aged <6 years. Data on physician-diagnosed AOM were collected from retrospective review of medical charts for the year preceding enrolment and then prospectively in the year following enrolment. The study included 5776 children in Germany, Italy, Spain, Sweden, and the UK. AOM incidence was 256/1000 person-years [95% confidence interval (CI) 243-270] in the prospective study period. Incidence was lowest in Italy (195, 95% CI 171-222) and highest in Spain (328, 95% CI 296-363). Complications were documented in <1% of episodes. Spontaneous tympanic membrane perforation was documented in 7% of episodes. Both retrospective and prospective study results were similar and show the high incidence during childhood in these five European countries. Differences by country may reflect true differences and differences in social structure and diagnostic procedures.

Spanish MYH7 founder mutation of Italian ancestry causing a large cluster of Laing myopathy patients.

Laing myopathy is a distal myopathy caused by mutations in the tail of the slow beta-myosin heavy chain gene MYH7. A large cluster of patients belonging to different families, with Laing myopathy due to p.K1729del mutation, was found in the Safor region, Spain. The same mutation was previously reported in an American family with Italian ancestry. The possibility that p.K1729del in MYH7 might be a founder mutation in the Safor patients and the chance of a common origin with the Italian-American family mutation was investigated by haplotype analyses, mutation data origin estimation and historical inquiry. Our results show that the p.K1729del in MYH7 harboured by patients from the Safor indeed is a founder mutation. A common ancestral origin of this mutation in the Spanish and Italian families is also suggested because they all share a core SNP haplotype at locus MYH7. Data estimation yields the origin of the mutation in the Safor at the beginning of the XVII century, when the Moorish were spelt and the region was resettled with Italian families.

[Vaccination schedule of the Spanish association of pediatrics: recommendations 2009]. / Calendario vacunal de la Asociación Española de Pediatría: Recomendaciones 2009.

Based on the available evidence, we, the Vaccine Advisory Committee (CAV) of the Spanish Association of Pediatrics (Asociación Española de Pediatría, AEP), provide information about and comments on vaccine-related innovation during 2008. Modifications to the Vaccine Schedule for 2009 are also discussed. The importance of the recommendation of administration of a varicella booster at start of school (3-4 years of age) is highlighted according to the technical specifications of one of the vaccines. The importance of making the heptavalent pneumococcal conjugate vaccine universally available is reiterated in accordance with the unquestionable results of scientific tests, WHO recommendations, the posture adopted by the majority of neighboring European countries, and the decision taken in 2006 by the autonomous community of Madrid (Spain). New scientific reasons are provided, corroborating the recommendation made by this committee in 2008, for the implementation by Spanish pediatricians of the vaccine against rotavirus and human papilloma virus. With regard to the latter, vaccination should be from 11 to 16 years of age, and then extended, in accordance with the technical specifications of the available vaccine preparations, to 26 years of age. As part of the recommendations, we insist that children in risk groups should be given flu vaccine and hepatitis A vaccine. The committee considers that these two vaccines must also be given, when pediatricians consider it appropriate, to children other than those in risk groups. This recommendation can be regarded as the first step towards a future recommendation of universal vaccination. Finally, this year we include an appendix with recommendations and vaccination strategies to be followed in children who have not previously received vaccines or who have not been completely immunized.

[Diagnostic challenges in epilepsy]. / Desafios diagnosticos en epilepsia.

INTRODUCTION: Epileptic seizures and epilepsy are part of daily clinical practice in neurology. Yet, the number of false positive diagnoses is surprisingly high. Almost one out of every five patients treated for epilepsy does not really have this diagnosis, which is a high percentage bearing in mind the social and medical consequences that being diagnosed with epilepsy entails. AIMS: To summarise the most important diagnostic challenges in epilepsy, to describe possible sources of diagnostic error and to offer advice on how to avoid them. DEVELOPMENT: Epilepsy is characterised by a tendency to suffer unprovoked epileptic seizures. The greatest obstacle when it comes to diagnosing a case of epilepsy is the fact that epileptic seizures are transient phenomena that occur relatively infrequently and the physician who must carry out the diagnosis will rarely see them. Moreover, there are other clinical events, such as syncopes or non-epileptic seizures, that may be similar to epileptic seizures in appearance and, consequently, can be mistaken for them. Finally, when interpreting the two most important complementary diagnostic techniques in epileptology, the electroencephalogram and magnetic resonance imaging of the brain, the most common errors must be taken into account in order to prevent mistaken diagnoses. CONCLUSIONS: The diagnosis of epilepsy is a challenge and must be based on a detailed and specific medical record. If there are any reasonable doubts, from the outset, about the diagnosis of epilepsy or if the patient does not respond well to the antiepileptic treatment, we recommend referring the patient to a specialised centre to establish a definitive diagnosis.

TITLE: Desafios diagnosticos en epilepsia.Introduccion. Las crisis epilepticas y la epilepsia son parte de la practica clinica diaria en neurologia. No obstante, el numero de diagnosticos falsos positivos es sorprendentemente alto. Casi uno de cada cinco pacientes tratado por epilepsia en realidad no tiene ese diagnostico, un porcentaje elevado teniendo en cuenta las consecuencias sociomedicas que conlleva el diagnostico de epilepsia. Objetivos. Resumir los desafios diagnosticos mas importantes en epilepsia, describir posibles fuentes de error en el diagnostico y proporcionar consejos sobre como evitarlos. Desarrollo. La epilepsia se caracteriza por una tendencia a sufrir crisis epilepticas no provocadas. El mayor obstaculo al diagnosticar una epilepsia radica en que las crisis epilepticas son fenomenos transitorios que ocurren relativamente con poca frecuencia y el medico que realiza el diagnostico raramente llega a verlas. Ademas, existen otros eventos clinicos, como por ejemplo sincopes o crisis no epilepticas, que pueden tener una apariencia similar a las crisis epilepticas y, en consecuencia, confundirse con ellas. Finalmente, al interpretar las dos tecnicas diagnosticas complementarias mas importantes en epileptologia, el electroencefalograma y la resonancia magnetica cerebral, deben tenerse en cuenta los errores mas comunes para prevenir diagnosticos erroneos. Conclusiones. El diagnostico de una epilepsia es un reto y debe basarse en una historia clinica detallada y especifica. Si desde el inicio existen dudas razonables sobre el diagnostico de epilepsia o si el paciente no responde bien al tratamiento antiepileptico, recomendamos derivar al paciente a un centro especializado que establezca un diagnostico definitivo.

[Why are pediatric empyemas on the increase in Spain?]. / Por qué hay más empiemas pediátricos en España?

There is a widespread perception among Spanish pediatricians that the incidence of empyema has significantly increased in the last few years, even though the objective information available is limited, and there is no specific active epidemiological surveillance system for this condition. In the present article, we review the situation of empyema in Spain, and discuss the main hypotheses put forward in the international literature to explain this increase, as well as the limitations of the sources available. Despite the scarcity of information, we draw the following conclusions: 1) the incidence of pediatric empyema is increasing in Spain, both generally and when caused by pneumococcus in particular; 2) the reason for this increase remains unknown, and to date no firm link has been established between this phenomenon and the heptavalent conjugate pneumococcal vaccine; and 3) this situation justifies the establishment of prospective systems for the surveillance and control of empyema and, once again, highlights the importance of developing active surveillance systems for pneumococcal disease.

[Criteria for including vaccines in the immunization schedule of the Spanish Association of Pediatrics]. / Criterios de inclusión de vacunas en el calendario de la Asociación Española de Pediatría.

The Vaccine Advisory Committee of the Spanish Association of Pediatrics analyzes and discusses the criteria followed when preparing their yearly Recommended Immunization Schedule for children and adolescents. The relative importance of each criterion in the final recommendation is assessed. Following a review of the current state of affairs of childhood immunization in Spain and of the crucial role played by pediatricians, some reflections are presented on the problems derived from the vaccines recommended by this Committee but not covered by the national health system. Suggestions are made for individual pediatricians who may need to establish specific priorities in the recommendation of these vaccines.

[Immunization schedule of the Spanish Association of Pediatrics: recommendations 2008]. / Calendario vacunal de la Asociación Española de Pediatría: recomendaciones 2008.

The Vaccine Advisory Committee of the Spanish Association of Pediatrics provides information on the new developments in vaccines that have taken place in 2007, based on the available evidence, and discusses these developments. Certain modifications to the Immunization Schedule for 2008 are recommended. A second varicella vaccine booster dose, administered together with the booster dose of the measles-mumps-rubella (MMR) vaccine when children start school (3-4 years), is recommended to avoid vaccine failures against the varicella-zoster virus. Based on current scientific evidence, the importance of universal heptavalent conjugate pneumococcal vaccination, as carried out in most similar European countries and in the autonomous community of Madrid in Spain, is stressed. Human papilloma virus vaccine is included in the Immunization Schedule for girls from 11 years old, and initially, at least up to the age of 16 years. Vaccination against rotavirus in children starting at 6 weeks and completing the series before 6 months is recommended. Other recommendations included in this year's Immunization Schedule are vaccination against influenza and hepatitis A virus in risk groups and at the pediatrician's discretion, as a first step toward the future recommendation of universal immunization.

[Vaccination schedule of the Spanish Association of Pediatrics: recommendations 2007]. / Calendario de vacunación de la Asociación Española de Pediatría: recomendaciones 2007.

The Vaccine Advisory Committee of the Spanish Association of Pediatrics provides information on the new developments in vaccines that have taken place in 2006 and recommends certain modifications to the Immunization Schedule for 2007. To ensure early protection, the measles-mumps-rubella (MMR) vaccine booster dose should be administered when children start school (3-4 years). Based on existing scientific evidence, the importance of universal heptavalent conjugate pneumococcal vaccination, as occurs in most similar European countries and in the autonomous community of Madrid in Spain, is confirmed. The safety and efficacy of rotavirus and human papilloma virus vaccines, as well as their use in our environment, is discussed and the role of pediatricians in their implementation is stressed. The recommended immunization schedule for children and adolescents starting vaccination late is also discussed.

[Human papillomavirus vaccines: a new challenge for pediatricians]. / Vacuna frente al virus del papiloma humano: un nuevo reto para el pediatra.

Human papillomavirus (HPV) infections are the most common sexually transmitted infections in the world. This infection is a necessary cause of cervical cancer, has been related to other forms of anogenital, airway and digestive cancers, and also causes anogenital warts. The recent advances in HPV prophylactic vaccines and their imminent commercial availability will post a new challenge to pediatricians: the indication and administration of these vaccines for the prevention of HPV infection, and consequently, of cervical cancer and other HPV-related diseases. The present article reviews the essentials of HPV infection, its relationship with cervical cancer, the advances in prophylactic HPV vaccines, and the role of the pediatrician in this context.

[Recommendations of the Vaccine Advisory Committee of the Spanish Association of Pediatrics: influenza vaccination campaign 2006-2007]. / Recomendaciones del Comité Asesor de Vacunas de la Asociación Española de Pediatría: vacunación antigripal campaña 2006-2007.

The recommendations of the Spanish Association of Pediatrics on influenza vaccination in the pediatric age group for the 2006-2007 season are presented. Influenza has special characteristics in children due to the high morbidity it carries. Moreover, children constitute the most frequent source of transmission. The risk factors supporting influenza vaccination in children and the need for immunization in persons living with high-risk children are discussed. The advisability of extending vaccination in health workers, and specifically to pediatricians and medical personnel in contact with sick children is stressed. The composition of the vaccine for the 2006-2007 seasons, the schedules and dosages in children depending on age, and the contraindications to vaccination are specified. Finally, the premises required to recommend universal vaccination in young children in Spain as a strategy to reduce morbidity due to this epidemic in children and adults are discussed.

[The role of the rotavirus vaccine in childhood vaccination schedules]. / El papel de la vacuna frente a rotavirus en los calendarios de vacunación infantil.

Rotavirus is the leading cause of diarrhea in infants. In developed countries, this infection leads to considerable morbidity with a high number of hospitalizations and medical interventions in the winter season, giving rise to substantial medical and social costs. In developing countries, rotavirus is a major cause of mortality in infants due to dehydration, with an estimated 600.000 deaths or more per year worldwide. A vaccine that is easy administrated, safe and with high efficacy would be the ideal means to reduce the burden of this disease and its high economic and social cost and to decrease the number of deaths in low-income countries. Recently, the results of two well-designed clinical trials with a large number of subjects have been reported. Both studies, which used different vaccines, reported high efficacy in the prevention of severe gastroenteritis and hospitalizations caused by rotavirus. When these vaccines become available in Europe, a reduction in hospitalizations, medical consultations, and days of work lost can be expected.

[Epidemiology of community-acquired pneumonia in children aged less than 5 years old in the Autonomous Community of Valencia (Spain)]. / Epidemiología de la neumonía adquirida en la comunidad en menores de 5 años en la Comunidad Valenciana.

OBJECTIVE: To assess the incidence of community acquired pneumonia in the Autonomous Community of Valencia in Spain, and describe its treatment and complications. METHODS: A retrospective cohort comprising 654 children born in 1995 and 1996 in Valencia and followed-up during the first 5 years of life by nine pediatricians was studied. The number of cases of pneumonia, treatment, complications and interventions was recorded. RESULTS: Ninety-nine episodes of community-acquired pneumonia in 80 children were recorded (1.24 cases/child). Fifty-one cases (51.1 %) occurred before the child's third birthday and 38 (38.4 %) occurred between the third and the fourth. Of the 99 cases, 51 were diagnosed in primary care and 46 in the emergency room. There was a mean of 2.44 visits per process in primary care (range 1-6). All the children were treated with antibiotics. The most frequently used were amoxicillin-clavulanate (43.3 %) and cefuroxime (26.3 %). Fourteen patients required a change of antibiotic. Twenty-three percent of the children were hospitalized. CONCLUSION: The incidence of community-acquired pneumonia in Valencia was 30.3 cases/1000 children aged less than 5 years/ year (95 % CI: 18.7-46.8), and the incidence of hospitalization was 7.03 cases/1000 children aged less than 5 years/year.

[Epidemiology and burden of acute otitis media in Valencia (Spain)]. / Epidemiología e impacto de la otitis media aguda en la Comunidad Valenciana.

OBJECTIVE: To assess the burden (incidence, treatment and complications) of acute otitis media (AOM) and otitis media with effusion (OME) in children younger than 5 years of age from Valencia, Spain. SUBJECT AND METHODS: We performed a retrospective cohort study of 1,399 children followed-up for the first 5 years of life. Seventeen pediatricians reviewed the medical records of their patients born in 1995 and 1996 and followed-up from birth until the age of 5 years. For each child, the number of otitis episodes, treatment, complications, and surgical interventions was obtained. RESULTS: There were 2,961 episodes of AOM in the first 5 years of life (2.23 cases/child). Four hundred seventy-six cases (16.1 %) occurred before 1 year of age and 1,346 between the first and second year of life (45.5 %). By the third year of life, 59.8 % had had at least one episode. In most children (80.9 %), diagnosis was made in primary care and required a median of 1.81 visits/episode for follow-up. A total of 94.5 % were treated with antibiotics (amoxicillin-clavulanate 38.8 %, cefuroxime 14.3 %, clarithromycin 8.2 % and amoxicillin 5.9 %) and 8.5 % required a change of antibiotic therapy. Two hundred seventeen children (15.2 %) had at least one episode of OME. Twenty-six patients (1.8 %, 95 % CI: 1.2-2.7 %) required insertion of ventilation tubes. Twenty-four patients (1.7 %) had secondary hypoacusis. There was one case of meningitis and two cases of chronic otorrhea. No cases of mastoiditis were recorded. CONCLUSIONS: The incidence of AOM in Valencia is 40,014 episodes/100,000 children younger than 5 years/year (95 % CI: 39,700-40,300). It represents a significant burden due to the large number of visits, antibiotic use, associated surgical procedures and need for auditory rehabilitation.

MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy.

OBJECTIVE: To describe a wide range of clinical and pathologic myopathic profiles associated with the p.K1729del mutation in the MYH7 gene, known to cause Laing distal myopathy. METHODS: A study conducted in the Safor region (Spain), setting of a large cluster of patients. Clinical, neurophysiologic, muscle imaging, and muscle biopsy studies and MYH7 gene sequencing were investigated in 32 patients from 4 kindreds. Data from 36 deceased or nonexamined patients were collected from hospital records or relatives. RESULTS: Onset ranged from congenital to the 6th decade. All patients presented weakness of great toe/ankle dorsiflexors and many had associated neck flexor, finger extensor, and mild facial weakness. In most cases, involvement of proximal and axial muscles was observed either clinically or by muscle imaging, sometimes giving rise to scapuloperoneal and limb-girdle syndromes. Disabling myalgias, skeletal deformities, and dilated cardiomyopathy in one patient were associated features. Life expectancy was not reduced but the spectrum of disability ranged from asymptomatic to wheelchair confined. Electromyographic neurogenic features were frequently recorded. Muscle fiber type disproportion, core/minicore lesions, and mitochondrial abnormalities were the most relevant pathologic alterations. All patients carried the p.K1729del mutation in MYH7. CONCLUSIONS: The p.K1729del mutation in the MYH7 gene expresses notable clinical variability and electromyographic and pathologic features that can lead to the misdiagnosis of neurogenic atrophies, congenital myopathies, or mitochondrial myopathies. Mutations in genes encoding other sarcomeric and reticulo-sarcoplasmic proteins involved in calcium regulation share pathologic characteristics with our patients, suggesting a possible pathogenetic connection.

[Neuroimaging study with morphometric analysis of hereditary and idiopathic ataxia]. / Estudio de neuroimagen con análisis morfométrico de lasataxias hereditarias e idiopáticas.

BACKGROUND: Hereditary and idiopathic ataxias are neurodegenerative disorders affecting diverse neuronal systems, particularly the cerebellum and its tracts. They are currently classified according to clinical and genetic criteria. Neuroimaging is a useful tool to help diagnosis but studies using quantitative methodology are scarce. OBJECTIVE: To apply digital morphometry to cerebral MRI and define objective patterns for clinical evaluation and follow up. PATIENTS AND METHODS: The study was carried out on 48 patients of whom 17 were Friedreich ataxia (FA), 6 non-Friedreich early onset spinocerebellar ataxia (EOCA), 9 autosomal dominant cerebellar ataxia type 1 (ADCA 1), 7 ADCA 3 and 9 idiopathic late onset cerebellar ataxia (ILOCA); 35 controls were grouped on early (< 30 years-old) and late age. Morphometric measures were done on previously selected MRI planes by image analyser digital software. RESULTS: Six out of 21 measurements and 3 ratios were significantly discriminant. By categories, the structures mainly involved were as follows: atrophy of cervical spinal cord (p = 0.001), cerebellum (p = 0.038) and protuberance (p = 0.002) in FA; atrophy of spinal cord (p = 0.009), cerebellum (p = 0.035) and widening of IV ventricle (p = 0.044) in EOCA; shrinkage of protuberance (p = 0.009), middle cerebellar peduncles (p = 0.004) and spinal cord atrophy (p = 0.001) in ADCA 1; cerebellar atrophy (p = 0.041) in ADCA 3; and cerebellar atrophy (p = 0.041) and shortening of middle cerebellar peduncles (p = 0.038) in ILOCA. CONCLUSIONS: This quantitative morphometric study confirms the existence of different pattern of cerebral involvement that is closely related with the distints clinical forms of hereditary and idiopathic ataxias. Only a few measurements can be used to obtain a morphometric profile for diagnostic and follow up purposes.

[Nonsystemic vasculitic neuropathy]. / Neuropatía vasculítica no sistémica.

BACKGROUND: Nonsystemic vasculitic neuropathy (NSVN) is an infrequent type of vasculitic neuropathy that evolves without manifestations of vasculitis in other organs and in the absence of serological abnormalities. There are non clarified conjectures about the pathogenesis, outcome and treatment approach. PATIENTS AND METHOD: A retrospective study of a series of six patients diagnosed of NSVN during a period of 12 years. Clinical, electrophysiological and pathological features, as well as the response to therapy and outcome are analysed. RESULTS: Four cases presented with a pattern of multiple mononeuropathy, evolving towards a symmetrical sensory and motor polyneuropathy in two of them. One patient presented with an acute sensory neuropathy and another had a subacute asymmetric sensory and motor neuropathy. No signs of accompanying systemic vasculitis were observed during the follow-up (mean 35 months) and the only outstanding serological abnormality was the presence of antibodies against hepatitis B virus in four of them. The nerve conduction studies showed typical features of axonal degeneration. The diagnostic was obtained due to the presence of a necrotizing vasculitis in the sural nerve biopsy in all cases. The mean time from symptom onset to diagnosis was 11 months. All patients were treated with immunosuppressive therapy presenting a favourable response, except the case of the sensory neuropathy that remained stable. CONCLUSIONS: NSVN is a benign type of vasculitic neuropathy with a variable clinical pattern of presentation and favourable response to immunosuppression. This neuropathy requires a high index of suspicion for diagnosis, so nerve biopsy must be carried out in all neuropathy of unknown etiology. Careful follow-up of patients is necessary, so that life-threatening systemic vasculitis neuropathy can be diagnosed early.

[Creutzfeldt-Jakob disease with unilateral onset: clinical profile and neuroimaging]. / Enfermedad de Creutzfeldt-Jakob de inicio unilateral: clínica y neuroimagen.

The usual clinical profile of Creutzfeldt-Jakob disease (CJD) is that of subacute dementia and intractable myoclonus. Occasionally, some cases present peculiar clinical features. We report on a case of CJD with an unilateral onset showing remarkable neuroimaging features. The patient, aged 72 years, began to suffer from sudden anomia, initially restricted to persons; but in a few weeks it evolved into a global aphasia, right hemiparesis, severe gait disorder, and finally akinetic mutism and intractable myoclonus. He died 11 weeks after onset. Early in the course, an analysis of 14-3-3 protein in CSF was positive. In advanced disease, the EEG showed the typical periodic activity of CJD. FLAIR MRI study showed a mesencephalic and focal cortical hyperintensity. Autopsy was performed and confirmed the diagnosis of CJD with an extensive presence of generalised spongiosis in cerebral grey matter. This case illustrates the usefulness of the life recent paraclinical methods to diagnose CJD in life. New MRI techniques seems to be particularly relevant, as they are not limited to exclude other conditions but can also offer data with validity to a positive diagnosis, like grey matter hyperintensity, that in this case was present also in the midbrain.