Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma.

The aim of this study was to assess patterns of CCND3 gene amplification in bladder cancer and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 102 primary bladder tumor samples in which there was enough tissue material to assess CCND3 gene status by fluorescent in situ hybridization (FISH) was the study group. CCND3 gene FISH amplification present in 31.4 percent of bladder carcinomas, was related to tumor progression (p=0.021) and lower time to progression (mean+-SD; 25.75+-15.25 months) as compared to 33.29+-11.0 months in the CCND3 not amplified group (p=0.05). By immunohistochemistry, Cyclin D3 labeling index was higher in the CCND3 amplified group (mean+-SD, 76.69+-27.51) than in not amplified (mean+-SD, 21.57+-7.02) (p less than 0.0001). The univariate survival analysis showed CCND3 gene amplification to be associated to a shorter progression-free survival (p=0.020) together with WHO histological grade (p=0.001) and pT stage category (p less than 0.0001). Cox s regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p= 0.030, RR3.561, 95 percent CI 1.128-11.236) together with pT category (p less than 0.0001, RR5.834, 95 percent CI 2.364-14.395). Our FISH analysis suggests that CCND3 gene amplification is a marker of aggressiveness and might be a predictor of tumor progression in bladder urothelial carcinoma

Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GA2LEN platform. The Galenda project

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA2LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD®) has been established under FileMaker® Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA2LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA2LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments. © 2009 The Authors

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective

State of the climate in 2015

In 2015, the dominant greenhouse gases released into Earth\u2019s atmosphere\u2014carbon dioxide, methane, and nitrous oxide\u2014all continued to reach new high levels. At Mauna Loa, Hawaii, the annual CO2 concentration increased by a record 3.1 ppm, exceeding 400 ppm for the first time on record. The 2015 global CO2 average neared this threshold, at 399.4 ppm. Additionally, one of the strongest El Ni\uf1o events since at least 1950 developed in spring 2015 and continued to evolve through the year. The phenomenon was far reaching, impacting many regions across the globe and affecting most aspects of the climate system. Owing to the combination of El Ni\uf1o and a long-term upward trend, Earth observed record warmth for the second consecutive year, with the 2015 annual global surface temperature surpassing the previous record by more than 0.1\ub0C and exceeding the average for the mid- to late 19th century\u2014commonly considered representative of preindustrial conditions\u2014by more than 1\ub0C for the first time. Above Earth\u2019s surface, lower troposphere temperatures were near-record high. Across land surfaces, record to near-record warmth was reported across every inhabited continent. Twelve countries, including Russia and China, reported record high annual temperatures. In June, one of the most severe heat waves since 1980 affected Karachi, Pakistan, claiming over 1000 lives. On 27 October, Vredendal, South Africa, reached 48.4\ub0C, a new global high temperature record for this month. In the Arctic, the 2015 land surface temperature was 1.2\ub0C above the 1981\u20132010 average, tying 2007 and 2011 for the highest annual temperature and representing a 2.8\ub0C increase since the record began in 1900. Increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 25 February 2015, the lowest maximum sea ice extent in the 37-year satellite record was observed, 7% below the 1981\u20132010 average. Mean sea surface temperatures across the Arctic Ocean during August in ice-free regions, representative of Arctic Ocean summer anomalies, ranged from ~0\ub0C to 8\ub0C above average. As a consequence of sea ice retreat and warming oceans, vast walrus herds in the Pacific Arctic are hauling out on land rather than on sea ice, raising concern about the energetics of females and young animals. Increasing temperatures in the Barents Sea are linked to a community-wide shift in fish populations: boreal communities are now farther north, and long-standing Arctic species have been almost pushed out of the area. Above average sea surface temperatures are not confined to the Arctic. Sea surface temperature for 2015 was record high at the global scale; however, the North Atlantic southeast of Greenland remained colder than average and colder than 2014. Global annual ocean heat content and mean sea level also reached new record highs. The Greenland Ice Sheet, with the capacity to contribute ~7 m to sea level rise, experienced melting over more than 50% of its surface for the first time since the record melt of 2012. Other aspects of the cryosphere were remarkable. Alpine glacier retreat continued, and preliminary data indicate that 2015 is the 36th consecutive year of negative annual mass balance. Across the Northern Hemisphere, late-spring snow cover extent continued its trend of decline, with June the second lowest in the 49-year satellite record. Below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska, increasing by up to 0.66\ub0C decade\u20131 since 2000. In the Antarctic, surface pressure and temperatures were lower than the 1981\u20132010 average for most of the year, consistent with the primarily positive southern annular mode, which saw a record high index value of +4.92 in February. Antarctic sea ice extent and area had large intra-annual variability, with a shift from record high levels in May to record low levels in August. Springtime ozone depletion resulted in one of the largest and most persistent Antarctic ozone holes observed since the 1990s. Closer to the equator, 101 named tropical storms were observed in 2015, well above the 1981\u20132010 average of 82. The eastern/central Pacific had 26 named storms, the most since 1992. The western north Pacific and north and south Indian Ocean basins also saw high activity. Globally, eight tropical cyclones reached the Saffir\u2013Simpson Category 5 intensity level. Overlaying a general increase in the hydrologic cycle, the strong El Ni\uf1o enhanced precipitation variability around the world. An above-normal rainy season led to major floods in Paraguay, Bolivia, and southern Brazil. In May, the United States recorded its all-time wettest month in its 121-year national record. Denmark and Norway reported their second and third wettest year on record, respectively, but globally soil moisture was below average, terrestrial groundwater storage was the lowest in the 14-year record, and areas in \u201csevere\u201d drought rose from 8% in 2014 to 14% in 2015. Drought conditions prevailed across many Caribbean island nations, Colombia, Venezuela, and northeast Brazil for most of the year. Several South Pacific countries also experienced drought. Lack of rainfall across Ethiopia led to its worst drought in decades and affected millions of people, while prolonged drought in South Africa severely affected agricultural production. Indian summer monsoon rainfall was just 86% of average. Extremely dry conditions in Indonesia resulted in intense and widespread fires during August\u2013November that produced abundant carbonaceous aerosols, carbon monoxide, and ozone. Overall, emissions from tropical Asian biomass burning in 2015 were almost three times the 2001\u201314 average