Effectiveness of a Meningococcal Group B Vaccine (4CMenB) in Children.

BACKGROUND: In September 2015, the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain. METHODS: We conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression. RESULTS: We compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated. CONCLUSIONS: Complete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.

Development of a prediction model for fatal and non-fatal coronary heart disease and cardiovascular disease in patients with newly diagnosed type 2 diabetes mellitus: the Basque Country Prospective Complications and Mortality Study risk engine (BASCORE).

AIMS/HYPOTHESIS: The aim of this study was to construct a model for predicting CHD and cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes in a southern European region. External validation of two other cardiovascular risk models and internal validation of our model were assessed. METHODS: We studied 65,651 people attending a primary care setting in the Basque Country Health Service. A 10-year prospective population-based cohort study was performed with 777 patients newly diagnosed with type 2 diabetes older than 24 years in a Sentinel Practice Network. Cardiovascular risk factors, CVD events and mortality were registered. Coefficients for the significant predictors of CHD and CVD were estimated using Cox models. We assessed the discrimination and calibration of the UK Prospective Diabetes Study risk engine (UKPDS-RE), the Framingham Risk Score-Regicor Study (FRS-RS) and the cardiovascular risk model we developed. RESULTS: The incidence rate per 1,000 patients/year was calculated for microvascular and cardiovascular complications, and death. Age, the ratio of non-HDL- to HDL-cholesterol, HbA1c, systolic blood pressure and smoking were significant predictors of cardiovascular events. A risk model was developed using these predictors. The UKPDS-RE and FRS-RS showed inadequate discrimination (Uno's C statistics 0.62 and 0.58, respectively) and calibration (24% overestimation and 51% underestimation, respectively) for predicting CHD risk. The internal discrimination and calibration of the developed model were acceptable for predicting fatal/non-fatal 2- and 5-, but not 10-year CHD and CVD risk. CONCLUSIONS/INTERPRETATION: This study is the first southern European validated population-derived model for predicting 5-year fatal/non-fatal CHD and CVD risk in patients with newly diagnosed type 2 diabetes.

Using surveillance data to estimate pandemic vaccine effectiveness against laboratory confirmed influenza A(H1N1)2009 infection: two case-control studies, Spain, season 2009-2010.

BACKGROUND: Physicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study. METHODS: We conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100. RESULTS: We included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected. CONCLUSION: Point estimates of the pandemic influenza vaccine effectiveness suggested a protective effect of the pandemic vaccine against laboratory-confirmed influenza A(H1N1)2009 in the season 2009-2010. Both studies were limited by the low vaccine coverage and the late start of the vaccination campaign. Routine influenza surveillance provides reliable estimates and could be used for influenza vaccine effectiveness studies in future seasons taken into account the surveillance system limitations.

A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report.

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. CASE PRESENTATION: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. CONCLUSIONS: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.

[Gender differences in early reperfusion treatment after myocardial infarction]. / Diferencias de género en el tratamiento de revascularización precoz del infarto agudo de miocardio.

BACKGROUND AND OBJECTIVE: Clinical variability in myocardial infarction (MI) regarding age, comorbidities and atypical symptoms could determine gender differences in inhospital care. This study analyzes the magnitude and determinants of differences between men and women in early reperfusion therapy in people hospitalized after MI. PATIENTS AND METHOD: 2,836 patients who arrived to hospital with MI were studied (IBERICA-Basque Country study). The relative risk (RR) of receiving early reperfusion for men versus women, adjusted by age, clinical characteristics, risk factors, and pre-hospital delay was estimated. The effect decomposition methodology and the log binomial regression were applied. RESULTS: 29% of patients were women with a median age of 77 years. The RR of revascularization in men compared to women was different according to age. When factors such as hypertension diabetes, Killip III-IV at admission and atypical symptoms were taken into account, statistically significant differences between sexes were not detected at 45 years old (RR=0.91; 95% CI=0.77-1.07). However, for 64 years old and over, the RR of reperfusion was 1.24 (95% CI=1.05-1.47). Both the differences by sex and the sex-age interaction were no longer statistically significant after adjusting by pre-hospital delay. CONCLUSIONS: The delay to receive medical care in elderly women is responsible of gender differences in early reperfusion. It is necessary to analyze the reasons for treatment-seeking delay.

[Analysis with the propensity score of the association between likelihood of treatment and event of interest in observational studies. An example with myocardial reperfusion]. / Análisis de la asociación entre un tratamiento y un acontecimiento de interés en estudios observacionales utilizando la probabilidad de recibir el tratamiento (Propensity Score). Un ejemplo con la reperfusión miocárdica.

INTRODUCTION AND OBJECTIVES: Analysis of the effect of treatment in observational studies is complex due to differences between treated and nontreated patients. Calculating the probability of receiving treatment conditioned on relevant covariates (propensity score [PS]) has been proposed as a method to control for these differences. We report an application of PS to assess the association between reperfusion treatment and 28-day case fatality in patients with acute myocardial infarction (AMI). METHOD: We describe the procedure used to calculate PS for receiving reperfusion treatment, and different strategies to analyze the association between PS and case fatality with regression modeling and matching. Data were from a population-based registry of 6307 patients with AMI in Spain during 1997-98. RESULTS: The PS for reperfusion was calculated in 5622 patients. In the multivariate analysis, reperfusion was associated with lower case fatality (OR = 0.59; 95% confidence interval [95% CI]: 0.46-0.77). When PS was included as a covariate, this association became non- significant (OR = 0.76; 95% CI: 0.57-1.01). In the subgroup of matched patients with a similar PS (n = 3138), treatment was not associated with case fatality (OR = 0.95; 95% CI: 0.72-1.26). When the influence of cases with missing data on PS was controlled for, reperfusion treatment was associated with lower fatality (OR = 0.66; 95% CI: 0.55-0.80). CONCLUSIONS: Calculating propensity score is a method that controls for differences between treated and nontreated patients. This score has limitations when matching is incomplete and when data are missing. Results of the present example suggest that reperfusion treatment reduces AMI case fatality.

[Hospital resources and myocardial infarction case fatality. The IBERICA study]. / Recursos hospitalarios y letalidad por infarto de miocardio. Estudio IBERICA.

INTRODUCTION AND OBJECTIVES: To determine the proportion of patients with myocardial infarction (MI) not admitted to a coronary care unit (CCU), the variables associated with admission into a CCU, and whether admission to a CCU, and the availability of coronary angiography in the same hospital, were associated with 28-day case fatality. PATIENTS AND METHOD: Population-based registry of MI in patients 25 to 74 years of age, admitted during 1996-1998. Demographic and clinical characteristics were recorded, as well as management, clinical course and survival after 28 days. Hospitals were classified according to the availability of a CCU and catheterization laboratory (advanced hospital), CCU only (intermediate hospital) or neither (basic hospital). Admission to the CCU was also recorded. RESULTS: In all, 9046 cases of MI were recorded; in 11.3% the patient was not admitted to a CCU. Age, smoking (OR=1.33; 95% CI, 1.08-1.64), non-Q MI (OR=0.62; 95% CI, 0.49-0.78) or undetermined location of MI (OR=0.34; 95% CI, 0.23-0.50), Killip 4 score on admission (OR=0.63; 95% CI, 0.40-1.00) and delay in arrival at the hospital >6 h were associated with CCU admission. Patients admitted to a CCU showed a lower case fatality in the first 24 h (4.2% vs 23.5%), which was independent of comorbidity, severity and treatment. The 24-hour survivors admitted to a basic hospital had higher case fatality (17.3% vs 7.8%) than other groups, which was related to differences in treatment. CONCLUSIONS: CCU admission is associated with a lower case fatality in the first 24 h. Admission to a basic hospital is associated with a higher 28-day case fatality even in patients who survive 24 h.

Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt-Jakob disease: a case report.

INTRODUCTION: The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported. CASE PRESENTATION: A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77.Neuropathological findings showed: spongiform change in the patient's cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous. CONCLUSION: Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt-Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies.

Vigilancia en salud pública: una necesidad inaplazable / Public health surveillance: a pressing need

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Escalas de cálculo del riesgo cardiovascular para pacientes con diabetes. ¿Qué son y de qué nos sirven? / Cardiovascular risk scores in patients with diabetes. What are they and what are they worth?

La enfermedad cardiovascular (ECV) representa la primera causa de mortalidad en las personas con diabetes mellitus, entre las cuales, el riesgo de mortalidad cardiovascular es 2-4 veces mayor que el de la población general. Las guías de práctica clínica recomiendan calcular el riesgo de ECV en la diabetes; sin embargo, se han desarrollado pocos modelos para estimar este riesgo en las personas con diabetes. Los primeros modelos de predicción de ECV en la diabetes mellitus tipo 2, que incluyeron junto a las variables de riesgo clásicas la HbA1c y los años de evolución, no son contemporáneos y no funcionan en poblaciones diferentes a las que participaron en su desarrollo. La creación de modelos de riesgo propios actuales y validados en diferentes poblaciones permitiría realizar intervenciones preventivas más agresivas y tempranas, y centradas en el paciente, con la finalidad de frenar la epidemia de ECV que padecen las personas con diabetes

Cardiovascular disease (CVD) remains the first cause of death in patients with diabetes mellitus. Cardiovascular mortality is between 2 and 4 times as high as the risk of matched controls in the general population. Although practice guidelines recommend calculating CVD risk in diabetes, few models for estimating cardiovascular risk have been developed specifically for diabetic patients. The first ones, taking into account HbA1c and diabetes duration plus classical risk factors, is not contemporary and perform sub-optimally in different populations with diabetes. Constructing updated population-derived and externally validated cardiovascular risk models will yield more aggressive patient-centered preventive interventions to curb the ongoing epidemic of CVD in patients with diabetes

Familial prion diseases in the Basque Country (Spain).

In 1995, a surveillance system for prion diseases was set up in the Basque Country, an autonomous region in northern Spain (2.1 million inhabitants). In the period from January 1993 to December 2003, we diagnosed 21 patients with familial prion diseases prospectively and another 4 patients retrospectively. They represent 35% of all the cases referred to the epidemiological registry. Two main possible explanations for this unusual high incidence of familial prion diseases are proposed: first, comprehensive case ascertainment by public health neurologists; second, a probable cluster of the D178N mutation within families of Basque origin related to a still unconfirmed common ancestor. Further genetic and genealogical studies should resolve this issue.

Diferencias de género en el tratamiento de revascularización precoz del infarto agudo de miocardio / Gender differences in early reperfusion treatment after myocardial infarction

Fundamento y objetivo: Diferencias en la presentación clínica del infarto agudo de miocardio (IAM), como la edad, la comorbilidad y la frecuencia de síntomas atípicos, podrían condicionar un proceso de cuidados hospitalarios distinto según el sexo. Este estudio analiza la magnitud y los determinantes de las diferencias entre sexos en la revascularización precoz en personas ingresadas por IAM. Pacientes y método: Se estudió a 2.836 pacientes con IAM que accedieron a cuidados hospitalarios (IBERICA-País Vasco). Se estimó el riesgo relativo (RR) de revascularización precoz en los varones respecto a las mujeres teniendo en cuenta la edad, la presentación clínica, los antecedentes y la demora extrahospitalaria. Se aplicó la metodología de descomposición de efectos y el análisis de regresión log-binomial. Resultados: El 29% de los pacientes eran mujeres y su edad mediana, de 77 años. El RR de revascularización de los varones respecto a las mujeres fue distinto según la edad. Tras ajustar por hipertensión arterial, diabetes, Killip III-IV al ingreso y síntomas atípicos, no se apreciaban diferencias significativas a los 45 años (RR = 0,91; intervalo de confianza [IC] del 95%, 0,77-1,07), mientras que para los mayores de 64 años, el RR de revascularización fue de 1,24 (IC del 95%, 1,05-1,47). Al ajustar por la demora extrahospitalaria, las diferencias por sexo y la interacción del sexo con la edad no eran significativas. Conclusiones: El retraso en el acceso a la atención sanitaria de las mujeres mayores es causa de las diferencias por sexo en la revascularización precoz. Es necesario analizar las razones de esta demora

Background and objective: Clinical variability in myocardial infarction (MI) regarding age, comorbidities and atypical symptoms could determine gender differences in inhospital care. This study analyzes the magnitude and determinants of differences between men and women in early reperfusion therapy in people hospitalized after MI. Patients and method: 2,836 patients who arrived to hospital with MI were studied (IBERICA-Basque Country study). The relative risk (RR) of receiving early reperfusion for men versus women, adjusted by age, clinical characteristics, risk factors, and pre-hospital delay was estimated. The effect decomposition methodology and the log binomial regression were applied. Results: 29% of patients were women with a median age of 77 years. The RR of revascularization in men compared to women was different according to age. When factors such as hypertension diabetes, Killip III-IV at admission and atypical symptoms were taken into account, statistically significant differences between sexes were not detected at 45 years old (RR = 0.91; 95% CI = 0.77-1.07). However, for 64 years old and over, the RR of reperfusion was 1.24 (95% CI = 1.05-1.47). Both the differences by sex and the sex-age interaction were no longer statistically significant after adjusting by pre-hospital delay. Conclusions: The delay to receive medical care in elderly women is responsible of gender differences in early reperfusion. It is necessary to analyze the reasons for treatment-seeking delay

Análisis de la asociación entre un tratamiento y un acontecimiento de interés en estudios observacionales utilizando la probabilidad de recibir el tratamiento (Propensity Score). Un ejemplo con la reperfusión miocárdica / Analysis with the propensity score of the association between likelihood of treatment and event of interest in observational studies. An example with myocardial reperfusion

Introducción y objetivos. Determinar el efecto de un tratamiento en estudios observacionales es problemático por las diferencias existentes entre tratados y no tratados. Un método propuesto para controlar estas diferenciases calcular la probabilidad condicionada por covariables de recibir el tratamiento, Propensity Score (PS).Presentamos una aplicación de este método analizándola asociación entre reperfusión y letalidad a 28 días en pacientes con infarto agudo de miocardio (IAM).Método. Se presenta cómo calcular la PS de recibir reperfusión y las diferentes estrategias para analizar posteriormente su asociación con la letalidad mediante modelos de regresión y apareamiento. Utilizamos datos de un registro poblacional de IAM realizado en España entre1997 y 1998 que incluyó 6.307 IAM. Resultados. Se calculó la PS de reperfusión en 5.622pacientes. En el análisis multivariado la reperfusión se asoció con menor letalidad (odds ratio [OR] = 0,59; intervalo de confianza [IC] del 95%, 0,46-0,77); al ajustara demás por la PS de reperfusión esta asociación no fue significativa (OR = 0,76; IC del 95%, 0,57-1,01). En el subgrupo de pacientes apareados, tratados y no tratados con PS de reperfusión similar (n = 3.138), este tratamiento no se asoció con letalidad (OR = 0,95; IC del95%, 0,72-1,26). Controlando el impacto de los casos con datos insuficientes en la PS de reperfusión, ésta se asoció con menor letalidad (OR = 0,66; IC del 95%,0,55-0,80).Conclusiones. El cálculo de la PS es un método para controlar las diferencias entre los grupos tratado y no tratado. Tiene limitaciones cuando el apareamiento es incompleto o hay datos insuficientes en la PS calculada. Los resultados del ejemplo presentado indican que la reperfusión reduce la letalidad del IAM

Introduction and objectives. Analysis of the effect of treatment in observational studies is complex due to differences between treated and non-treated patients. Calculating the probability of receiving treatment conditioned on relevant covariates (propensity score [PS]) has been proposed as a method to control for these differences. Were port an application of PS to assess the association between reperfusion treatment and 28-day case fatality in patients with acute myocardial infarction (AMI).Method. We describe the procedure used to calculate PS for receiving reperfusion treatment, and different strategies to analyze the association between PS and case fatality with regression modeling and matching. Data were from a population-based registry of 6307 patients with AMI in Spain during 1997-98.Results. The PS for reperfusion was calculated in 5622patients. In the multivariate analysis, reperfusion was associated with lower case fatality (OR = 0.59; 95% confidence interval [95% CI]: 0.46-0.77). When PS was included as a covariate, this association became non-significant (OR = 0.76; 95% CI: 0.57-1.01). In the subgroup of matched patients with a similar PS (n = 3138),treatment was not associated with case fatality (OR =0.95; 95% CI: 0.72-1.26). When the influence of cases with missing data on PS was controlled for, reperfusion treatment was associated with lower fatality (OR = 0.66;95% CI: 0.55-0.80).Conclusions. Calculating propensity score is a method that controls for differences between treated and non-treated patients. This score has limitations when matching is incomplete and when data are missing. Results of the present example suggest that reperfusion treatment reduces AMI case fatality