Incidence and Risk of Pneumococcal Pneumonia in Adults with Distinct Underlying Medical Conditions: A Population-Based Study.

PURPOSE: This study investigated the incidence of pneumococcal pneumonia requiring hospitalisation among middle-aged and older adults with and without specific underlying medical conditions, evaluating the influence of these conditions in the risk of developing pneumonia. METHODS: Population-based prospective cohort study included 2,025,730 individuals ≥ 50 years around Catalonia, Spain. The Catalonian information system for the development of research in primary care (SIDIAP) was used to establish baseline characteristics of the cohort (comorbidities and underlying medical conditions). Hospitalisations from pneumococcal pneumonia occurred among cohort members between 01/01/2015 and 31/12/2015 were collected from hospital discharge codes of 68 reference Catalonian hospitals. Cox regression was used to estimate the association between baseline conditions and the risk of developing pneumonia. RESULTS: Global incidence rate (IR) of hospitalised pneumococcal pneumonia was 82.8 cases per 100,000 persons-year. Maximum IRs (per 100,000 persons-year) emerged among persons with haematological neoplasia (837.4), immunodeficiency (709.2), HIV infection (474.7), severe renal disease (407.5) and chronic pulmonary disease (305.7). In the multivariable analyses, apart from increasing age, HIV infection (hazard ratio [HR] 6.78), haematological neoplasia (HR 6.30), prior all-cause pneumonia (HR 5.27), immunodeficiency (HR 4.57) and chronic pulmonary disease (HR 2.89) were the conditions most strongly associated with an increasing risk. Pneumococcal vaccination did not emerge associated with a reduced risk in our study population (nor PPsV23 neither PCV13). CONCLUSION: Old age, immunocompromising conditions and chronic pulmonary/respiratory disease are major risk factors for pneumococcal pneumonia in adults. Our data underline the need for better prevention strategies in these persons.

Bupivacaine Toxicity Increases Transmural Dispersion of Repolarization, Developing of a Brugada-like Pattern and Ventricular Arrhythmias, Which is Reversed by Lipid Emulsion Administration. Study in an Experimental Porcine Model.

Unintentional administration of bupivacaine may be associated with electrocardiogram changes that promote the development cardiac arrhythmias. Ventricular repolarization markers (corrected QT, QT dispersion, Tpeak-Tend and Tpeak-Tend dispersion) are useful to predict cardiac arrhythmias. We aim to investigate the effects of bupivacaine on the transmural dispersion of repolarization and their reversion following intravenous lipid emulsion (ILE) administration. Fourteen pigs were anaesthetized with thiopental and sevoflurane and underwent tracheal intubation. After instrumentation, a 4 mg kg-bolus of bupivacaine was administrated followed by an infusion of 100 µg kg-1 min-1. QT interval, QTc:QT corrected by heart rate, Tpeak-to-Tend interval and QT and Tpeak-to-Tend dispersion were determined in a sequential fashion: after bupivacaine (at 1 min, 5 min and 10 min) and after ILE (1.5 mL kg-1 over 1 min followed by an infusion of 0.25 mL kg-1 min-1). Three additional animals received only ILE (control group). Bupivacaine significantly prolonged QT interval (∆:36%), QT dispersion (∆:68%), Tpeak-to-Tend (∆:163%) and Tpeak-to-Tend dispersion (∆:98%), from baseline to 10 min. Dispersion of repolarization was related to lethal arrhythmias [three events, including asystole, sustained ventricular tachycardia (VT)] and repeated non-sustained VT (4/14, 28%). A Brugada-like-ECG pattern was visualized at V1-4 leads in 5/14 pigs (35%). ILE significantly decreased the alterations induced by bupivacaine, with the termination of VT within 10 min. No ECG changes were observed in control group. Bupivacaine toxicity is associated with an increase of transmural dispersion of repolarization, the occurrence of a Brugada-like pattern and malignant VA. ILE reverses the changes in dispersion of repolarization, favouring the disappearance of the Brugada-like pattern and VT.

Prevalence of high, medium and low-risk medical conditions for pneumococcal vaccination in Catalonian middle-aged and older adults: a population-based study.

BACKGROUND: Updated population-based data on the frequency and distribution of risk factors for pneumococcal disease is scarce. This study investigated the prevalence of distinct comorbidities and underlying risk conditions related to an increasing risk of pneumococcal disease among Catalonian middle-aged and older adults. METHODS: Cross-sectional population-based study including 2,033,465 individuals aged 50 years or older registered at 01/01/2015 in the Catalonian Health Institute (Catalonia, Spain). The clinical research database of the Information System for the Development of Research in Primary Care (SIDIAP database) was used to identify high-risk (asplenia and/or immunocompromising conditions) and other increased-risk conditions (chronic pulmonary, cardiac or liver disease, diabetes mellitus, alcoholism and/or smoking) among study subjects. RESULTS: Globally, 980,310 (48.2%) of the 2,033,465 study population had at least one risk condition of suffering pneumococcal disease (55.4% in men vs 42.0% in women, p < 0.001; 41.7% in people 50-64 years vs 54.7% in persons 65 years or older, p < 0.001). An amount of 176,600 individuals (8.7%) had high-risk conditions (basically immunocompromising conditions). On the other hand, 803,710 persons (39.5%) had one or more other risk conditions. In fact, 212,255 (10.4%) had chronic pulmonary diseases, 248,377 (12.2%) cardiac disease, 41,734 (2.1%) liver disease, 341,535 (16.8%) diabetes mellitus, 58,781 (2.9%) alcoholism and 317,558 (15.6%) were smokers. CONCLUSION: In our setting, approximately 50 % of overall persons 50 years or older may be considered at-risk population for pneumococcal disease (almost 10 % have high-risk conditions and 40 % have other risk conditions).

Incidence and risk conditions of ischemic stroke in older adults.

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.

Analysis of the temporal regression of the QRS widening induced by bupivacaine after Intralipid administration. Study in an experimental porcine model.

OBJECTIVE: The principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels, which leads to an increase in the QRS duration. Recently, experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity. We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid. MATERIAL AND METHODS: Twelve pigs were anesthetized with intravenous sodium thiopental 5mg kg(-1) and sevoflurane 1 MAC (2.6%). Femoral artery and vein were canalized for invasive monitoring, analysis of blood gases and determination of bupivacaine levels. After instrumentation and monitoring, a bupivacaine bolus of 4-6 mg kg(-1) was administered in order to induce a 150% increase in QRS duration (defined as the toxic point). The pigs were randomized into two groups of six individuals. Intralipid group (IL) received 1.5 mL kg(-1)of IL over one minute, followed by an infusion of 0.25 mL kg min(-1). Control group (C) received the same volume of a saline solution. The electrocardiographic parameters were recorded, and blood samples were taken after bupivacaine and 1, 5, 10 and 30 minutes after Intralipid/saline administration. RESULTS: Bupivacaine (4.33±0.81 mg/kg in IL group and 4.66±1.15 mg/kg in C group) induced similar electrocardiographic changes in both groups; mean maximal percent increase in QRS interval was 184±62% in IL group, and 230±56% in control group (NS). Lipid administration reversed the QRS widening previously impaired by bupivacaine. After ten minutes of the administration of IL, the mean QRS interval decreased to 132±56% vs. 15±76% relative to the maximum widening induced by bupivacaine, in IL and C group, respectively. CONCLUSION: Intralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine. Time to normalization of electrocardiographic parameters can last more than 10 minutes. While the phenomena of cardiac toxicity persist, resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored.

Epidemiology of Streptococcus pneumoniae causing acute otitis media among children in Southern Catalonia throughout 2007-2013: Incidence, serotype distribution and vaccine's effectiveness.

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.

Comparison of three predictive rules for assessing severity in elderly patients with CAP.

AIM: This study compares the ability of the Pneumonia Severity Index (PSI) and the British Thoracic Society CURB-65 and CRB-65 rules in predicting short-term mortality among elderly patients with community-acquired pneumonia (CAP). METHODS: It is a population-based study including all people over 65 years old with a radiographically confirmed CAP in the region of Tarragona (Spain) between 2002 and 2008. Treatment setting and clinical variables were considered for each patient. PSI, CURB-65 and CRB-65 scores were calculated at the moment of diagnosis and 30-day mortality was considered as a main dependent variable. The rules were compared based on sensitivity, specificity and area under the receiver operating characteristic curve (AUC). RESULTS: Of the total 590 CAP cases, mortality rate was 13.6% (15.3% in hospitalised and 1.4% in outpatient cases; p = 0.001). Mortality increased with increasing PSI score (None in class II, 6,9% in class III, 14,4% in class IV and 29,5% in class V), CURB-65 score (7.5%, 14.5%, 26.7%, 53.3% and 100% for scores 1,2,3,4 and 5 respectively) and CRB-65 score (6.6%, 26.1%, 40.5% and 50% for scores 1,2,3 and 4 respectively). The three rules performed too similarly to predict 30-day mortality, with a ROC area of 0.727 [95% confidence interval (CI): 0.67-0.79] for the PSI, 0.672 (95% CI: 0.61-0.74) for the CURB-65, and 0.719 (95% CI: 0.65-0.78) for the CRB-65. CONCLUSION: Our data shows that the analysed rules perform equally well among elderly people with CAP which supports the recommendation for using the simplified CRB-65 severity score among elderly patients in primary care or emergency visits.

Effects of annual influenza vaccination on winter mortality in elderly people with chronic pulmonary disease.

BACKGROUND: Although there is a general agreement for the recommendation of the influenza vaccine to persons with chronic obstructive pulmonary disease (COPD), the magnitude of clinical effectiveness and benefit from the annual vaccination is controversial. We assessed the effects of annual influenza vaccination on winter mortality in older adults with COPD. METHODS: This prospective cohort study included 1298 Spanish community-dwelling individuals aged 65 years or older with a diagnosis of COPD followed from 1 January 2002 to 30 April 2005. The primary outcome was all-cause death during influenza periods (January-April). Multivariable Cox proportional hazard models adjusted by age, sex and comorbidity were used to evaluate vaccine effectiveness. RESULTS: Influenza vaccination was associated with a non-statistically significant 16% reduction in winter mortality among vaccinated COPD patients [unadjusted hazard ratio (HR): 0.84; 95% confidence interval (CI): 0.60-1.17]. Multivariable analysis showed that there was an insignificant trend towards a reduced mortality in the vaccinated group considering overall influenza periods 2002-2005 (adjusted HR: 0.76; 95% CI: 0.52-1.06; p=0.098). We estimated that, in the total COPD population, one death was prevented for every 187 annual vaccinations (95% CI: 62 to infinity). CONCLUSIONS: Our data suggest benefit from the influenza vaccination and support an annual vaccination strategy for elderly COPD patients.

[C-reactive protein value related to a smoking history and composition of nicotine and tobacco tar]. / Valor de la proteína C reactiva según historia de tabaquismo y composición de nicotina y alquitrán.

INTRODUCTION: The CRP is known to be an acute phase reactant, but with new high sensitivity assay methods it appears that CRP is also a marker of chronic inflammation. This study was to investigate whether smoking acts as a systemic disease and to see if there is a relation between CRP values and smoking. MATERIAL AND METHODS: 762 persons were studied, with a mean age of 41.74+/-10.03 years. 200 were smokers, 344 were non-smokers and 218 were ex-smokers. The following details were noted in the smoking history: cigarette brand, number of cigarettes/day, number of years smoking and milligrams of nicotine and tar. In the case of ex-smokers, the number of years since giving up smoking was noted. The CRP was determined using the high sensitive Tina-Quant assay. Windows SPSS version 11.0 software was used. RESULTS: The CRP values showed statistically significant differences between the smoking and non-smoking groups. A statistically significant increase in CRP was observed in relation to number of cigarettes/day (p=0.001), mg of nicotine (p=0.017), mg of tar (p=0.020) and number of years of smoking (p=0.0001). However, when analysing the relation between CRP and the number of years since giving up smoking, there was a negative curve of 0.02 in the equation, but this was not of statistical significance. CONCLUSIONS: CRP levels rise when there is an increase in number of cigarettes/day, mg of nicotine and tar and years smoking.

Valor de la proteína C reactiva según historia de tabaquismo y composición de nicotina y alquitrán / C-reactive protein value related to a smoking history and composition of nicotine and tobacco tar

Introducción: La PCR se conoce como reactante de fase aguda, pero con los nuevos métodos de análisis ultrasensibles, aparece el concepto de PCR como marcador de inflamación crónica. En este estudio vamos a investigar si el tabaquismo se comporta como una enfermedad sistémica, ver si existe relación entre los valores de la PCR y el tabaquismo. Material y métodos: Se estudian 762 personas de edad media 41,74 (d.s.10,03) años. 200 eran fumadoras, 344 no fumadoras y 218 exfumadoras. En la historia de tabaquismo se recoge: marca de tabaco, número de cigarrillos/ día, duración en años del hábito y milígramos de nicotina y alquitrán. En los exfumadores el número de años de abandono tabáquico. La PCR se determina mediante ensayo Tina – Quant ultrasensible. Se aplica el programa informático SPSS windows versión 11.0 Resultados: Aparecen valores de PCR con diferencias estadísticamente significativas entre los grupos de fumadores y de no fumadores. Se observa un aumento estadísticamente significativo de la PCR en relación con el número de cigarrillos/ día (p = 0,001), con los mg de nicotina (p = 0,017), con los mg de alquitrán (p = 0,020) y con los años de duración del hábito tabáquico (p = 0,001). Sin embargo, al estudiar la relación entre PCR y años de abandono tabáquico se observa una pendiente negativa de la ecuación de 0,02, pero no es estadísticamente significativa. Conclusiones: Los niveles de PCR aumentan al incrementarse el consumo de cigarrillos/día, los mg de nicotina, de alquitrán y la duración del hábito

Introduction: The CRP is known to be an acute phase reactant, but with new high sensitivity assay methods it appears that CRP is also a marker of chronic inflammation. This study was to investigate whether smoking acts as a systemic disease and to see if there is a relation between CRP values and smoking. Material and methods: 762 persons were studied, with a mean age of 41.74 ± 10.03 years. 200 were smokers, 344 were non-smokers and 218 were ex-smokers. The following details were noted in the smoking history: cigarette brand, number of cigarettes/day, number of years’ smoking and milligrams of nicotine and tar. In the case of ex-smokers, the number of years since giving up smoking was noted. The CRP was determined using the high sensitive Tina – Quant assay. Windows SPSS version 11.0 software was used. Results: The CRP values showed statistically significant differences between the smoking and non-smoking groups. A statistically significant increase in CRP was observed in relation to number of cigarettes/day (p = 0.001), mg of nicotine (p = 0.017), mg of tar (p=0.020) and number of years of smoking (p = 0.0001). However, when analysing the relation between CRP and the number of years since giving up smoking, there was a negative curve of 0.02 in the equation, but this was not of statistical significance. Conclusions: CRP levels rise when there is an increase in number of cigarettes/day, mg of nicotine and tar and years’ smoking

Novel mutations in the muscle chloride channel CLCN1 gene causing myotonia congenita in Spanish families.

Mutations in the muscular voltage-dependent chloride channel gene (CLCN1), located at 7q35, lead to recessive and dominant myotonia congenita. We report four novel mutations identified in this gene, after clinical, electromyographic, and genetic studies performed on 13 unrelated families. Two of the four mutations (2512insCTCA and A218T) were identified in families with Thomsen's disease, one (Q658X) in a family with Becker's disease, and the fourth (R669C) in a presumably sporadic patient with the Becker phenotype. Although identification of the mutations allows us to establish some genotype/phenotype correlations, this does not wholly account for the clinical heterogeneity and the inheritance patterns of the disease.

Calpainopathy-a survey of mutations and polymorphisms.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder characterized mainly by symmetrical and selective atrophy of the proximal limb muscles. It derives from defects in the human CAPN3 gene, which encodes the skeletal muscle-specific member of the calpain family. This report represents a compilation of the mutations and variants identified so far in this gene. To date, 97 distinct pathogenic calpain 3 mutations have been identified (4 nonsense mutations, 32 deletions/insertions, 8 splice-site mutations, and 53 missense mutations), 56 of which have not been described previously, together with 12 polymorphisms and 5 nonclassified variants. The mutations are distributed along the entire length of the CAPN3 gene. Thus far, most mutations identified represent private variants, although particular mutations have been found more frequently. Knowledge of the mutation spectrum occurring in the CAPN3 gene may contribute significantly to structure/function and pathogenesis studies. It may also help in the design of efficient mutation-screening strategies for calpainopathies.

Severe limb girdle muscular dystrophy in Spanish gypsies: further evidence for a founder mutation in the gamma-sarcoglycan gene.

Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscular dystrophy with primary gamma-sarcoglycan deficiency, generally associated with a severe clinical course. gamma-sarcoglycan, a 35kDa dystrophin-associated protein, is encoded by a single gene on chromosome 13q12. Six different mutations have been described in that gene, and it has been proved they are the origin of the disease. One of these mutations (C283Y), a G-->A transition in codon 283, was recently and exclusively identified in Gypsy patients from different European countries. We report the study of 11 LGMD2C unrelated Gypsy families (nine Spanish and two Portugese). The muscle biopsies of these patients showed a drastically decreased immunostaining with alpha and gamma-sarcoglycan antibodies. All the patients were homozygous for C283Y missense mutation, and all affected chromosomes (patients and heterozygous relatives) carried the allele 5 (112 bp) of the intragenic microsatellite D13S232. Unexpectedly, this allele is most frequent in the Caucasian population but not in the normal Gypsy population. The clinical severity of all patients demonstrates that the C283Y missense mutation in a homozygous state causes a severe LGMD2C (DMD-like). The elevated number of families ascertained let us assume that LGMD2C is prevalent in the Gypsy population, and that all the families have inherited a founding mutation.

Primoinfección por citomegalovirus en embarazadas de diferente condición socioeconómica / Primary infection by cytomegalovirus in pregnancy women of different socioeconomic conditions

Cytomegalovirus infection is the first cause of viral congenital infections. We studied the incidence of primary cytomegalovirus infection, searching for the presence of antibodies with an ELISA technique, in 939 pregnant women of a low socioeconomic level, attending a public outpatient clinic and 123 pregnant university students, attending a special outpatient clinic for students. The initially seronegative women were tested again during the second and third trimester of pregnancy to identify primary infections. The presence of cytomegalovirus congenital infection in the newborn of infected mothers was investigated isolating the virus in cell cultures from urine samples. There was a higher prevalence of infection among low socioeconomic status women (95 vs 69.9 per cent). Two women (one student and one coming from a low socioeconomic status) had a primary infection and in the newborn of the student, a congenital cytomegalovirus infection was detected. It is concluded that women's socioeconomic condition is not risk factor for cytomegalovirus primary infection during pregnancy

Effect of heterocyclic analogues of triphenylmethane dyes against Trypanosoma cruzi.

Several heterocyclic analogues of triphenylmethane dyes have been synthesized. Their in vitro activity has been evaluated using the epimastigote forms of Trypanosoma cruzi as an assay system. The malachite green and gentian violet dyes previously reported as trypanocidal agents were also tested for comparison. Among the compounds tested, the 2-benzothienyl-bis-(4,4'-dimethylaminophenyl) derivative proved to be the most interesting, because of its high selectivity in killing parasites. The ID50, defined as the concentration which produced 50% reduction in (3H) thymidine incorporation in DNA after 18 hours or in viable parasites after five days of incubation with the above compounds, was 0.2 ng ml-1 and less than 1 ng ml-1, respectively. The relative toxicity, measured by its effect on cultured human HeLa cells, was over 10,000-fold higher. By contrast, gentian violet only showed a ten-fold higher inhibitory effect for T. cruzi. The other derivatives synthesized were active in various degrees. According to these results, a structure-activity relationship for these compounds is proposed.