Angel Vila-Corcoles

Institut Català de la Salut, Cerdanyola del Vallès, Catalonia, Spain

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Publications (46)198.31 Total impact

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    ABSTRACT: Background: This study investigated the burden (incidence, mortality and serotype distribution) of pneumococcal pneumonia among older adults in the region of Tarragona (Spain). Methods: Population-based cohort study involving 27,204 individuals ≥60 years in Tarragonès county (Southern Catalonia), who were prospectively followed between 01/12/2008 and 30/11/2011. Bacteremic and nonbacteremic (positive sputum culture and/or urinary antigen test) pneumococcal pneumonias were recruited. Results: A total of 125 pneumococcal pneumonias (16 bacteremic and 109 nonbacteremic) was observed. Incidence rates (per 1000 person-years) were 0.21 (95% confidence interval [CI]: 0.13-0.35) for bacteremic cases and 1.45 (95% CI: 1.20-1.75) for nonbacteremic cases. Case-fatality rate was 10.4% (12.5% in bacteremic and 10.1% in nonbacteremic cases). Five serotypes (types 3, 6C, 19A, 22F and 35B) were the most common serotypes, accounting for 64.3% of overall isolated serotypes. 73.1% of cases were due to the strains included in the 23-valent vaccine whereas 53.6% were due to the strains included in the 13-valent vaccine. Conclusion: The burden of pneumococcal pneumonia remains considerable (especially among oldest people and nursing-home residents) despite a publicly funded anti-pneumococcal vaccination program operative for several years.
    No preview · Article · Dec 2015 · Medicina Clínica

  • No preview · Article · Dec 2015 · Revista Española de Salud Pública
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    ABSTRACT: Objective: The objective of this study was to investigate incidence and mortality from ischemic stroke in older adults with specific underlying chronic conditions, evaluating the influence of these conditions in developing stroke. Materials & methods: Population-based cohort study involving 27,204 individuals ≥60 years old in Southern Catalonia, Spain. All cases of hospitalization from ischemic stroke (confirmed by neuro-imaging) were collected from 01/12/2008 until 30/11/2011. Incidence rates and 30-day mortality were estimated according to age, sex, chronic illnesses, and underlying conditions. Multivariable Cox regression analysis was used to calculate Hazards Ratio (HR) and estimate the association between baseline conditions and risk of developing stroke. Results: Mean incidence rate reached 453 cases per 100,000 person-years. Maximum rates appeared among individuals with history of prior stroke (2926 per 100,000), atrial fibrillation (1815 per 100,000), coronary artery disease (1104 per 100,000), nursing-home residence (1014 per 100,000), and advanced age ≥80 years (1006 per 100,000). Thirty-day mortality was 13% overall, reaching 21% among patients over 80 years. Age [HR: 1.06; 95% confidence interval (CI): 1.04-1.07], history of prior stroke (HR: 5.08; 95% CI: 3.96-6.51), history of coronary artery disease (HR: 1.65; 95% CI: 1.21-2.25), atrial fibrillation (HR: 2.96; 95% CI: 2.30-3.81), diabetes mellitus (HR: 1.55; 95% CI: 1.23-1.95), and smoking (HR: 1.64; 95% CI: 1.15-2.34) emerged independently associated with an increased risk of ischemic stroke. Conclusion: Incidence and mortality from ischemic stroke remains considerable. Apart from age and history of atherosclerosis (prior stroke or coronary artery disease), atrial fibrillation, diabetes, and smoking were the underlying conditions most strongly associated with an increased risk.
    No preview · Article · Nov 2015 · Acta Neurologica Scandinavica
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    ABSTRACT: Objective: This study investigated incidence and serotype distribution of Streptococcus pneumoniae causing acute otitis media (AOM) in Catalonian children, evaluating vaccination effectiveness in the current era of extended valency pneumococcal conjugate vaccines (PCVs). Methods: Population-based surveillance study that included all AOM cases with isolation of pneumococcus (from otic fluids/otorrea) identified among children ≤14 years in the region of Tarragona (Southern Catalonia, Spain) from 01/01/2007 to 31/12/2013. Prevalence of infections caused by serotypes covered by the different PCVs formulations were calculated for the periods before and after 30/06/2010 (date of PCV7/PCV13 replacement). The indirect cohort method was used to estimate PCV7/13 effectiveness against vaccine-type infections. Results: A total of 78 children with a pneumococcal AOM were identified across study period, which meant an incidence rate of 23 cases per 100,000 population-year. Thirty-six cases (46.2%) occurred within the late PCV7 era and 42 cases (53.8%) during the early PCV13 era. Overall, the most common serotypes were type 19A (21.7%), type 3 (13.3%) and type 15B (6.7%). Prevalence of cases caused by serotypes included in PCV7 did not substantially change between the first and the second study period (from 10.3% to 12.9%), whereas prevalence of cases caused by PCV13 serotypes showed a decreasing trend between both periods (from 65.5% to 48.4%). The aggregate PCV7/13 effectiveness against vaccine-type infections was 72% (95% confidence interval: -26 to 94). Conclusion: Pneumococcal conjugate vaccination appears an acceptable preventive option to prevent pneumococcal AOM in infants. However, its serotype coverage and clinical effectiveness are not optimal.
    No preview · Article · Sep 2015 · International journal of pediatric otorhinolaryngology
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    ABSTRACT: To investigate hospitalizations from pneumococcal pneumonia in older adults with specific underlying chronic conditions, evaluating the influence of these conditions in developing pneumonia. Population-based cohort study involving 27,204 individuals ≥60 years old in Southern Catalonia, Spain. All cases of hospitalization from pneumococcal pneumonia (bacteremic and nonbacteremic) were collected since 01/12/2008 until 30/11/2011. Cox regression was used to calculate hazards ratio (HR) and estimate the association between baseline conditions and the risk of developing pneumococcal pneumonia. Maximum incidences (per 1000 person-years) appeared among patients with history of prior pneumonia (14.6), nursing home residents (12.8), persons with immunodeficiency/asplenia (7.7) and patients with chronic pulmonary disease (7.6). In multivariable analysis, age (HR: 1.05), nursing home residence (HR: 4.59), history of prior pneumonia (HR: 3.58), stroke (HR: 2.50), chronic heart disease (HR: 1.53), chronic pulmonary disease (HR: 4.09), diabetes mellitus (HR: 1.66), smoking (HR: 1.69) and immunosuppressive medication (HR: 1.87) appeared significantly associated with an increased risk of pneumococcal pneumonia. Our data support that nursing home residence, chronic pulmonary disease and immunocompromising conditions are the underlying conditions most strongly associated with an increasing risk of pneumococcal pneumonia in older adults. This data underline the need for better prevention strategies among these persons.
    No preview · Article · Jun 2015 · Infection
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    ABSTRACT: Background: Pneumococcal infections remain a major health problem worldwide. This study analysed the distribution of distinct Streptococcus pneumoniae serotypes causing invasive pneumococcal disease (IPD) among all-age population in the region of Tarragona (Spain) throughout 2006-2009. Methods: An amount of 237 strains were evaluated, of which 203 (85.7%) were isolated from blood cultures, 14 (5.9%) from pleural fluids, 13 (5.5%) from CSF samples and 7 (3%) from other sterile sites. Forty-seven cases (19.8%) were children ≤ 14 years, 94 (39.7%) were patients 15-64 years and 96 (40.5%) were patients ≥ 65 years. Results: Seven serotypes (1, 3, 6A, 7F, 12F, 14 and 19A) caused almost two thirds (63.3%) of cases among all-age patients. Serotype 1 was the most common serotype among children (44.7%) and among people 15-64 years (21.3%), whereas serotype 19A was the most common among people ≥ 65 years (12.5%).Among all-age population, serotype-vaccine coverage for the distinct pneumococcal polysaccharide vaccine (PPV) and conjugate vaccines (PCVs) were 17.3% for the PCV7, 49.8% for the PCV10, 73% for the PCV13 and 80.2% for the PPV23 (p < 0.001). Among children, vaccine-serotype coverage was 23.4% for the PCV7, 72.3% for the PCV10 and 83% for the PCV13. Among people ≥ 65 years, vaccine-serotype coverage was 62.5% for the PCV13 and 68.8% for the PPV23. Conclusion: A considerable proportion of IPD cases among our population would not be covered by the current pneumococcal vaccines.
    No preview · Article · Feb 2015 · Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia
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    ABSTRACT: An epidemiological study was conducted on all cases of invasive pneumococcal disease (IPD) diagnosed in Tarragona, Spain, between 1 January 2006 and 31 December 2009. A total of 286 IPD cases were observed, which was an overall incidence of 21.2 episodes per 100,000 persons-year (95% CI: 16.6-26.9). Incidence rates were 26.3/100,000 (95% CI: 14.4-44.3) among children, 12.2/100,000 (95% CI: 8.2-17.6) among patients between 15-64 years and 59.6/100,000 (95% CI: 40.0-85.8) in those ≥ 65 years. Overall lethality rate was 7.3% (none in children, 3.4% among patients 15-64 years, and 14.8% among patients ≥ 65 years; p < 0.001).
    No preview · Article · Jan 2015 · Enfermedades Infecciosas y Microbiología Clínica
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    ABSTRACT: Introduction: Data available about the epidemiology of stroke is limited. This study investigated incidence and lethality of ischaemic stroke among the general population over 60 years in the region of Tarragona. Patients and methods: Population-based cohort study that included 27,204 individuals >= 60 years assigned to nine Primary Care Centers in the Tarragones county (Catalonia, Spain), who were prospectively followed between December 1st, 2008 and November 30th, 2011. During follow-up, all episodes of ischaemic stroke were recruited among cohort members. Only confirmed ischaemic cases (confirmed by neuroimaging and validated alter checking hospital medical records) were included. Results: An amount of 343 confirmed cases of ischaemic stroke were observed, which means a global incidence rate of 453 episodes per 100,000 persons/year (95% confidence interval = 408-504). Incidence was higher among men than in women (531 vs 392 per 100,000; p < 0.001) and increases substantially with increasing age (195 vs 517 vs 1,006 per 100,000 in 60-69 years, 70-79 years and >= 80 years, respectively; p < 0.001). Incidence was eight times greater among persons with history of prior ictus as compared with those without history of ictus (2,962 vs 340 per 100,000; p < 0.001). Overall lethality rate was 13%, reaching 21% among patients >= 80 years. Conclusion: Morbid-mortality by ischaemic ictus remains considerable among our population. Preventive measures and more efficacious therapies are imperative.
    No preview · Article · Nov 2014 · Revista de neurologia
  • Angel Vila-Corcoles · Olga Ochoa-Gondar

    No preview · Article · Sep 2014 · The Lancet Infectious Diseases
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    ABSTRACT: Background Cerebrovascular benefits using the 23-valent pneumococcal polysaccharide vaccine (PPV23) are controversial. This study assessed clinical effectiveness of PPV23 in preventing ischemic stroke in people older than 60 years. Methods We conducted a population-based cohort study involving 27,204 individuals of 60 years or older in Tarragona, Spain, who were prospectively followed from December 01, 2008, until November 30, 2011. Outcomes were neuroimaging-confirmed ischemic stroke, 30-day mortality from stroke, and all-cause death. Pneumococcal vaccination effectiveness was evaluated by Cox regression analyses, estimating hazard ratios (HRs) adjusted for age, sex, comorbidities, and influenza vaccine status. Results Cohort members were followed for a total of 76,033 person-years, of which 29,065 were for vaccinated subjects. Overall, 343 cases of stroke, 45 deaths from stroke, and 2465 all-cause deaths were observed. Pneumococcal vaccination did not alter the risk of stroke (multivariable HR: 1.04; 95% confidence interval [CI]: .83-1.30; P = .752), death from stroke (HR: 1.14; 95% CI: .61-2.13; P = .686), and all-cause death (HR: .97; 95% CI: .89-1.05; P = .448). In analyses focused on people with and without a history of cerebrovascular disease, the PPV23 did not emerge effective in preventing any analyzed event, but influenza vaccine emerged independently associated with a reduced risk of death from stroke (HR: .51; 95% CI: .28-.93; P = .029) and all-cause death (HR: .73; 95% CI: .67-.81; P < .001). Conclusions Our data support that the PPV23 does not provide benefit against ischemic stroke, but it also supports a beneficial effect of influenza vaccine in reducing specific- and all-cause mortality risk in the general population older than 60 years.
    No preview · Article · Jul 2014 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
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    ABSTRACT: Background: The benefits of using the 23-valent pneumococcal polysaccharide vaccine (PPV23) are controversial. This study assessed clinical effectiveness of PPV23 in preventing community-acquired pneumonia (CAP) among the general population aged ≥ 60 years. Methods: This was a population-based cohort study involving 27 204 individuals aged ≥ 60 years in Tarragona, Spain, who were prospectively followed from 1 December 2008 until 30 November 2011. Primary outcomes were hospitalization for pneumococcal CAP (bacteremic and nonbacteremic cases) and all-cause CAP. All CAP cases were radiographically confirmed and validated by checking clinical records. Cox regression was used to evaluate the association between pneumococcal vaccination and the risk of each outcome. Results: Cohort members were followed for a total of 76 033 person-years (29 065 person-years for vaccinated subjects). Incidence rates (per 1000 person-years) were 0.21 for bacteremic pneumococcal CAP (0.14 vs 0.26 among vaccinated and unvaccinated subjects, respectively), 1.45 for nonbacteremic pneumococcal CAP (1.46 vs 1.44), and 7.51 for all-cause CAP (7.19 vs 7.71). In primary analyses including all cohort members, PPV23 did not appear to be effective against any analyzed outcome. However, a beneficial effect emerged in sensitive and stratified analyses. After multivariable adjustments, as compared with those never vaccinated, recent vaccination with PPV23 (<5 years ago) was associated with reduced risks of bacteremic pneumococcal CAP (hazard ratio [HR], 0.38; 95% confidence interval [CI], .09-1.68), nonbacteremic pneumococcal CAP (HR, 0.52; 95% CI, .29-.92), overall pneumococcal CAP (HR, 0.49; 95% CI, .29-.84), and all-cause CAP (HR, 0.75; 95% CI, .58-.98). Conclusions: Our data support a protective effect of recent PPV23 vaccination (within previous 5 years) against both pneumococcal and all-cause CAP.
    Full-text · Article · Feb 2014 · Clinical Infectious Diseases
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    ABSTRACT: Background Cardiovascular benefits using the 23-valent pneumococcal polysaccharide vaccine (PPV23) are controversial. This study assessed clinical effectiveness of PPV23 in preventing acute myocardial infarction in people over 60-years. Methodology We conducted a population-based cohort study involving 27,204 individuals ≥60 years-old in Tarragona, Spain, who were prospectively followed from 01/12/2008 until 30/11/2011. Outcomes were hospitalization for AMI, 30-day mortality from AMI and all-cause death. Cox regression was used to evaluate the association between pneumococcal vaccination and the risk of each outcome. Results Cohort members were followed for a total of 76,033 person-years, of which 29,065 were for vaccinated subjects. Overall, 359 cases of AMI, 55 deaths from AMI and 2465 all-cause deaths were observed. Pneumococcal vaccination did not alter the risk of AMI (multivariable hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.76–1.18; p = 0.630), death from AMI (HR: 1.32; 95% CI: 0.76–2.28; p = 0.321) and all-cause death (HR: 0.97; 95% CI: 0.89–1.05; p = 0.448). In analyses focused on people with and without history of prior coronary artery disease, pneumococcal vaccination did not emerge effective in preventing any analyzed event. Conclusions This study supports that PPV23 does not provide any relevant benefit against AMI in the general population over 60 years, as in primary as well as in secondary prevention, although it is underpowered to exclude a small benefit of vaccination against rare outcomes.
    No preview · Article · Jan 2014 · Vaccine
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    ABSTRACT: This study compares the ability of two simpler severity rules (classical CRB65 vs. proposed CORB75) in predicting short-term mortality in elderly patients with community-acquired pneumonia (CAP). A population-based study was undertaken involving 610 patients ≥65 years old with radiographically confirmed CAP diagnosed between 2008 and 2011 in Tarragona, Spain (350 cases in the derivation cohort, 260 cases in the validation cohort). Severity rules were calculated at the time of diagnosis, and 30-day mortality was considered as the dependent variable. The area under the receiver operating characteristic curves (AUC) was used to compare the discriminative power of the severity rules. Eighty deaths (46 in the derivation and 34 in the validation cohorts) were observed, which gives a mortality rate of 13.1 % (15.6 % for hospitalized and 3.3 % for outpatient cases). After multivariable analyses, besides CRB (confusion, respiration rate ≥30/min, systolic blood pressure <90 mmHg or diastolic ≤60 mmHg), peripheral oxygen saturation (≤90 %) and age ≥75 years appeared to be associated with increasing 30-day mortality in the derivation cohort. The model showed adequate calibration for the derivation and validation cohorts. A modified CORB75 scoring system (similar to the classical CRB65, but adding oxygen saturation and increasing the age to 75 years) was constructed. The AUC statistics for predicting mortality in the derivation and validation cohorts were 0.79 and 0.82, respectively. In the derivation cohort, a CORB75 score ≥2 showed 78.3 % sensitivity and 65.5 % specificity for mortality (in the validation cohort, these were 82.4 and 71.7 %, respectively). The proposed CORB75 scoring system has good discriminative power in predicting short-term mortality among elderly people with CAP, which supports its use for severity assessment of these patients in primary care.
    No preview · Article · Nov 2013 · Infection
  • Angel Vila-Corcoles

    No preview · Article · May 2013 · JAMA Internal Medicine
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    ABSTRACT: Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.
    Full-text · Article · Apr 2013 · PLoS ONE
  • Angel Vila-Corcoles · Olga Ochoa-Gondar
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    ABSTRACT: Streptococcus pneumoniae remains a major cause of morbidity and mortality throughout the world. To date, after the introduction of routine childhood immunization, elderly people (i.e., persons aged 65 years or older) suffer the greatest burden of pneumococcal disease in developed countries. At present, two anti-pneumococcal vaccines are available for use in adults: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent protein-polysaccharide conjugate vaccine (PCV13). This article reviews current data about the burden of pneumococcal disease in the elderly, as well as evidence for immunogenicity, clinical efficacy, and possible cost-effectiveness of both vaccines. The main advantage of PCV13 is that it may be more effective than PPV23, but a major limitation is that it is directed against strains that are likely to be greatly reduced in the population since its introduction in childhood immunization. The main disadvantage of PPV23 is that it may be less effective than PCV13 against vaccine-type infections but a major advantage is that it may provide protection against ten additional serotypes. To date, expert committees have not changed recommendations for pneumococcal vaccination in adults. However, at present, they are evaluating different alternatives (basically, maintaining PPV23, changing from PPV23 to PCV13 in some groups, or adding PCV13 for all or some target adult population subgroups). Critical data (clinical efficacy reported in ongoing trials and magnitude of indirect effects of pediatric PCV13 programs) needed to make a well-informed decision could be available during 2013. Considering all concerns over indirect effects and replacement strains following the use of polysaccharide-based vaccines, efforts should be directed toward developing vaccines, such as protein-based pneumococcal vaccines, with potential serotype-independent protection. Meanwhile, according to current recommendations, PPV23 should continue to be used for high-risk adults and all elderly people (with and without additional high-risk conditions). Although it is only moderately effective, it has a considerable serotype coverage and at-risk persons can benefit from the vaccination. High-risk individuals could also obtain a benefit from adding PCV13, but more data are needed before a universal recommendation can be made.
    No preview · Article · Feb 2013 · Drugs & Aging
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    ABSTRACT: Purpose Updating epidemiological studies to document current incidences of pneumococcal diseases are greatly needed in the current era of new pneumococcal conjugate vaccines (PCVs). The aim of this study is to analyze the incidence and distribution of different serotypes causing pneumococcal infections among the pediatric population in southern Catalonia, Spain, throughout the 2002–2009 PCV7 eras. Methods A population-based surveillance study was conducted among children aged ≤14 years in the region of Tarragona (Catalonia, Spain) during the period 2002–2009. All cases of pneumococcal infections (invasive and non-invasive cases) were included in the study. Incidence rates (per 100,000 population-year) and prevalence of infections caused by serotypes included in different PCV formulations were calculated for the 2002–2005 and 2006–2009 periods. Results Globally, across the total 2002–2009 period, the incidence of pneumococcal infections was 48.2 per 100,000 children-year (22.4 and 25.8 for invasive and non-invasive infections, respectively). Between 2002–2005 and 2006–2009, the incidence rates largely decreased among children aged
    No preview · Article · Sep 2012 · Infection
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    ABSTRACT: The effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) is controversial, especially among people with high-risk conditions. This study assessed the clinical effectiveness of vaccination against pneumonia among patients with chronic pulmonary diseases. We conducted a population-based case-control study including 96 non-immunocompromised patients with clinical diagnosis of chronic pulmonary disease (chronic bronchitis, emphysema and/or asthma), aged 50 y or older, with radiographically confirmed pneumococcal pneumonia (19 bacteremic and 77 nonbacteremic cases) and 192 outpatient control subjects with similar chronic pulmonary diseases (matched by primary care center, age, sex and main comorbidity). Adjusted odds ratios (ORs) for vaccination were calculated using conditional logistic regression, controlling for by underlying conditions. Pneumococcal vaccination did not alter significantly the risk of overall pneumococcal pneumonia [adjusted OR: 0.71; 95% confidence interval (CI): 0.37-1.39]. Point estimates of vaccine effectiveness was the maximum against bacteremic pneumococcal pneumonia due to vaccine-serotypes, although neither reached statistical significance (adjusted OR: 0.51; 95% CI: 0.03-8.19). Vaccination pointed to a smaller benefit against nonbacteremic pneumococcal pneumonia (adjusted OR: 0.66; 95% CI: 0.33-1.34). Pneumococcal vaccination was associated with a non-statistically significant reduction in the risk of all pneumococcal pneumonia among persons 75 y or older (adjusted OR: 0.45; 95% CI: 0.16-1.27), but no apparent protective effect emerged among people 50-74 y (adjusted OR: 1.48; 95% CI: 0.62-3.56). The effectiveness of the PPV-23 in preventing pneumonia among patients with chronic pulmonary disease is uncertain. Our results point to PPV-23 having little or null effect against pneumococcal pneumonia in such patients, but definitive conclusions cannot be established based on our data.
    Preview · Article · May 2012 · Human Vaccines & Immunotherapeutics
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    ABSTRACT: Conflicting results have been recently reported evaluating the relationship between pneumococcal vaccination and the risk of thrombotic vascular events. This study assessed the clinical effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23) against acute myocardial infarction and ischaemic stroke in older adults. Population-based prospective cohort study conducted from December 1, 2008 until November 30, 2009, including all individuals ≥ 60 years-old assigned to nine Primary Care Centres in Tarragona, Spain (N = 27,204 individuals). Primary outcomes were hospitalisation for acute myocardial infarction and/or ischaemic stroke. All cases were validated by checking clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by Multivariable Cox proportional-hazard models (adjusted by age, sex, influenza vaccine status, presence of comorbidities and cardiovascular risk factors). Cohort members were followed for a total of 26,444 person-years, of which 34% were for vaccinated subjects. Overall incidence rates (per 1000 person-years) were 4.9 for myocardial infarction and 4.6 for ischaemic stroke. In the multivariable analysis, vaccination was associated with a marginally significant 35% lower risk of stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.42-0.99; p = 0.046). We found no evidence for an association between pneumococcal vaccination and reduced risk of myocardial infarction (HR: 0.83; 95% CI: 0.56-1.22; p = 0.347). Our data supports a benefit of PPV23 against ischaemic stroke among the general population over 60 years, suggesting a possible protective role of pneumococcal vaccination against some acute thrombotic events.
    Full-text · Article · Mar 2012 · BMC Public Health
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    Angel Vila-Corcoles · Olga Ochoa-Gondar

    Preview · Chapter · Mar 2012