Search

Prehistoric monuments often constitute evident landmarks and sometimes, after falling into disuse, fascinated local people enough to stimulate speculations about their origin over time. According to legend, the Hill of Udine (NE Italy) was built by Attila the Hun's soldiers, but its origin (natural or anthropogenic) has been debated until now. Our research analyzed five new 40-m long stratigraphic cores, investigating for the first time the total thickness of the hill and compared the data with the available archaeological information. Moreover, we considered other hills and mounds in northern Italy and other European regions where folklore traditions relate their origin to Attila. The geoarchaeological and ethnographic data prove that the Hill of Udine is a Bronze Age anthropogenic mound erected between 1400 and 1150 BCE and that, later, folklore has transformed the ancestral memory of its origin into legend. By measuring 30 m in height and over 400,000 m3 in volume, the flat-topped hill is the largest prehistoric mound in Europe. This discovery reveals unprecedented skills in earth construction and confirms significant anthropogenic modifications of the environment during Bronze Age. [ABSTRACT FROM AUTHOR]

Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success. [ABSTRACT FROM AUTHOR]

Early empiric therapy and adequate resuscitation have been identified as main predictors of outcome in patients with candidemia or bacteremia. Moreover, source control is a major determinant in infectious sites when feasible, as a main technique to reduce microbiological burden. A retrospective, multicenter, cohort study was performed at surgical wards and intensive care units (ICU) of three University Hospitals in Spain between 2010 and 2014, with the aim of improving understanding of the interaction between source control, early antifungal therapy, and use of vasoactives in patients with intra-abdominal candidiasis (IAC). Source control was defined as all physical actions taken to control a focus of infection and reduce the favorable conditions that promote microorganism growth or that maintain the impairment of host defenses. Two hundred and fifty-eight patients with IAC were identified. Sixty-one patients were at ICU for diagnosis. Mortality was higher in the ICU group compared to what was documented for the non-ICU group (35 % vs 19.5 %, p = 0011). Adequate source control within 48 h of diagnosis was achieved in 60 % of the cohort. In multivariate analysis, inadequate source control was identified as the only common risk factor for 30-day mortality in both groups (ICU group OR: 13.78 (95% CI: 2.60-72.9, p = 0.002) and non-ICU group OR: 6.53 (95% CI: 2.56-16.61, p = <0.001). The population receiving both adequate source control and adequate antifungal treatment was the one associated with a higher survival rate, in both the ICU and surgical groups. Source control remains a key element in IAC, inside and outside the intensive care unit. Early antifungal treatment among ICU patients was associated with lower mortality. [ABSTRACT FROM AUTHOR]

The author discusses the improvement process for articles published in "Intensive Care Medicine." Topics discussed include the variables based on potential importance of articles that were introduced into the process and important information on what leads to manuscript downloads or citations. Also discussed is the importance of optimizing manuscript keywords and the association of article types with downloads to help improve downloads.

Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD− patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species ( S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD− patients ( p = 0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p < 0.001); embolization (43.3 % versus 26.1 %, p < 0.001) and congestive heart failure (42 % versus 34.1 %, p = 0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD− and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required. [ABSTRACT FROM AUTHOR]

Purpose: Risk factors for β-lactam antibiotic underdosing in critically ill patients have not been described in large-scale studies. The objective of this study was to describe pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment envisioning empirical dosing in critically ill patients and considering a worst-case scenario as well as to identify patient characteristics that are associated with target non-attainment.Methods: This analysis uses data from the DALI study, a prospective, multi-centre pharmacokinetic point-prevalence study. For this analysis, we assumed that these were the concentrations that would be reached during empirical dosing, and calculated target attainment using a hypothetical target minimum inhibitory concentration (MIC), namely the susceptibility breakpoint of the least susceptible organism for which that antibiotic is commonly used. PK/PD targets were free drug concentration maintained above the MIC of the suspected pathogen for at least 50 % and 100 % of the dosing interval respectively (50 % and 100 % f T (>MIC)). Multivariable analysis was performed to identify factors associated with inadequate antibiotic exposure.Results: A total of 343 critically ill patients receiving eight different β-lactam antibiotics were included. The median (interquartile range) age was 60 (47-73) years, APACHE II score was 18 (13-24). In the hypothetical situation of empirical dosing, antibiotic concentrations remained below the MIC during 50 % and 100 % of the dosing interval in 66 (19.2 %) and 142 (41.4 %) patients respectively. The use of intermittent infusion was significantly associated with increased risk of non-attainment for both targets; creatinine clearance was independently associated with not reaching the 100 % f T( >MIC) target.Conclusions: This study found that-in empirical dosing and considering a worst--case scenario--19 % and 41 % of the patients would not achieve antibiotic concentrations above the MIC during 50 % and 100 % of the dosing interval. The use of intermittent infusion (compared to extended and continuous infusion) was the main determinant of non-attainment for both targets; increasing creatinine clearance was also associated with not attaining concentrations above the MIC for the whole dosing interval. In the light of this study from 68 ICUs across ten countries, we believe current empiric dosing recommendations for ICU patients are inadequate to effectively cover a broad range of susceptible organisms and need to be reconsidered. [ABSTRACT FROM AUTHOR]

Purpose: Risk factors for β-lactam antibiotic underdosing in critically ill patients have not been described in large-scale studies. The objective of this study was to describe pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment envisioning empirical dosing in critically ill patients and considering a worst-case scenario as well as to identify patient characteristics that are associated with target non-attainment. Methods: This analysis uses data from the DALI study, a prospective, multi-centre pharmacokinetic point-prevalence study. For this analysis, we assumed that these were the concentrations that would be reached during empirical dosing, and calculated target attainment using a hypothetical target minimum inhibitory concentration (MIC), namely the susceptibility breakpoint of the least susceptible organism for which that antibiotic is commonly used. PK/PD targets were free drug concentration maintained above the MIC of the suspected pathogen for at least 50 % and 100 % of the dosing interval respectively (50 % and 100 % f T). Multivariable analysis was performed to identify factors associated with inadequate antibiotic exposure. Results: A total of 343 critically ill patients receiving eight different β-lactam antibiotics were included. The median (interquartile range) age was 60 (47-73) years, APACHE II score was 18 (13-24). In the hypothetical situation of empirical dosing, antibiotic concentrations remained below the MIC during 50 % and 100 % of the dosing interval in 66 (19.2 %) and 142 (41.4 %) patients respectively. The use of intermittent infusion was significantly associated with increased risk of non-attainment for both targets; creatinine clearance was independently associated with not reaching the 100 % f T target. Conclusions: This study found that-in empirical dosing and considering a worst-case scenario-19 % and 41 % of the patients would not achieve antibiotic concentrations above the MIC during 50 % and 100 % of the dosing interval. The use of intermittent infusion (compared to extended and continuous infusion) was the main determinant of non-attainment for both targets; increasing creatinine clearance was also associated with not attaining concentrations above the MIC for the whole dosing interval. In the light of this study from 68 ICUs across ten countries, we believe current empiric dosing recommendations for ICU patients are inadequate to effectively cover a broad range of susceptible organisms and need to be reconsidered. [ABSTRACT FROM AUTHOR]

Introduction: Invasive candidiasis (IC) has primarily been studied in intensive care unit (ICU) patients, although, in reality, a vast majority of these infections occur outside of the ICU. The recent publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines also deal with the non-ICU population, but many uncertainties remain on the management of IC, particularly in non-critically ill patients. Methods: The Italian Society of Antimicrobial Therapy, Società Italiana di Terapia Antimicrobica (SITA), produced practical, hospital-wide recommendations on the management of Candida infection in non-immunocompromised patients in the hospital ward. Results and discussion: Our focus is on patient stratification in terms of risk factors for IC and of clinical severity, emphasising a high index of suspicion to ensure early diagnosis, early treatment and de-escalation when a patient is clinically stable, in order to optimise resource allocation. [ABSTRACT FROM AUTHOR]

We describe the case of an intravenous drug user affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection with associated bacteraemia who, while on replacement therapy with methadone, required 11 mg/kg/day daptomycin to achieve trough (C) and peak (C) plasma levels similar to those observed with the standard dosage of 6 mg/kg in healthy volunteers (mean ± standard deviation: C 12.35 ± 0.80 mg/L, C 63.90 ± 8.71 mg/L). Clinical pharmacological advice based on real time therapeutic drug monitoring may be helpful for optimizing daptomycin exposure in these patients. Physicians should take into account that dosages much higher than the standard ones may be needed, probably as a consequence of augmented drug clearance. [ABSTRACT FROM AUTHOR]

Bone and joint infections are recognized as difficult-to-treat infections that result in significant morbidity and mortality among patients and increased healthcare costs. This article presents the recommendations for the diagnosis and management of osteomyelitis and prosthetic joint infections in adults developed by Bone and Joint Infections Committee for the Italian Society of Infectious and Tropical Diseases. It contains data published through to November 2007. An evidence-based scoring system that is used by the Infectious Diseases Society of America was applied to treatment recommendations. [ABSTRACT FROM AUTHOR]

One-third of HIV-infected individuals suffer from chronic hepatitis C virus infection (HCV) in Europe. Recommendations from HCV–HIV International Panel advise current treatment with pegylated interferon plus ribavirin. We assessed the impact of interferon and ribavirin combination in 43 patients between 2002 and 2006. All coinfected patients treated for HCV during the 5-year period were included in retrospective data collection. CD4+ T-lymphocyte count, HAART discontinuation, reasons for treatment interruption and factors correlated to sustained virological response (SVR) were monitored. The mean age was 41 ± 6.7 years; the risk factor for coinfection was intravenous drug abuse in 32/43 (74%). The baseline CD4+ T-lymphocytes cell count was > 500 in 51% (22/43). Genotype 3a represented 51% (22/43); 37% were on HAART at baseline (16/43) and half of patients showed high HCV RNA levels (> 800,000 IU/ml). High rates of treatment discontinuation were observed (27/43, 63%), caused by voluntary interruptions in 52% (14/27) and virological failure in 26% (7/27). The overall population had an SVR of 30%; genotypes 3a and 1 had SVR of 38% and 24%, respectively. The SVR was significantly lower in three groups: high HCV RNA viral load (χ2 = 6, p < 0.0025), CD4+ T-lymphocyte historical nadir <350 cells/mm3 (χ2 = 3.26, p < 0.01) and genotype 1 with high viral load (χ2 = 4.8, p < 0.005). Although factors such as HCV viral load rates and genotype 1 have been confirmed to threaten the response to therapy, we observed a significant response rate when patients had a history of CD4+ T-lymphocyte nadir >350 per mm3. The high dropout rates due to voluntary discontinuations complicated the patients’ case management. [ABSTRACT FROM AUTHOR]

Conversely, CAMB has well-known side effects which may affect almost half of the patients receiving these medications. These side effects may require treatment with additional medications [e.g., paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), promethazine, opiates] and these have side effects of their own. Today, we are able to provide antifungal therapy that does not expose our critically ill patient to potentially severe (or even just unnecessarily uncomfortable) side effects, i.e., the lipid formulation of amphotericin B or echinocandins. [Extracted from the article]

In this paper we study the dynamics of a charged particle in an accelerating field. We make use of a simple perturbation method to derive a general analytic expression of the transfer matrix for the transverse motion. The results have been compared with numerical calculations. In the asymptotic regime, i.e. when the energy gain per cell is small compared to the initial energy, the agreement is very good. [ABSTRACT FROM AUTHOR]

A feasibility study has been carried out for high-precision measurements of two-photon reactions leading to hadrons at the DAΦNE electron-positron collider. This new facility will operate at a c.m. energy of 1.02 GeV and up to a maximum of 1.5 GeV. It will have a luminosity of L⋍5·10 cms, 100 times larger than the present available ee colliders. DAΦNE offers an excellent opportunity to study γγ reactions at low energy with high statistics, using the KLOE detector equipped with electron tagging facilities as described in this report. Among the various topics that one may address in these studies, we concentrate on the following: 1) Precision measurements of the polarizabilities of charged and neutral pions via the two-photon reactions γγ→ππ. These will allow tests of chiral theories and chiral perturbation techniques, as well as other theoretical approaches. 2) Measurements for the first time of the azimuthal correlations of the γγ→ππ and other two-photon reactions. These provide new tests of the validity of chiral and other theories. 3) Formation of the C=+1 light pseudoscalar mesons, π, η and η′. This allows the study of the $$q\bar q$$ and possibly gluonic inner structure of these mesons. For the π its measured radiative width will also improve the currently known lifetime. 4) The possibility to realize a double tagging at DAΦNE will allow reliable measurements of the currently little known total γγ→hadrons cross-section below 1 GeV, to be compared with several models. The physics program described above cannot be realized without tagging the two-photon reactions to suppress the background from ee annihilation channels and other sources. [ABSTRACT FROM AUTHOR]

The design of a synchrotron radiation source dedicated to X-ray lithography is presented. The parameter optimization carried out is based on the lithography requirements, on the radiation spectrum and beam source sizes, and on the machine performances, such as long lifetime, absence of beam instabilities and reliable operation at design current. High-field conventional magnets are proposed for the radiation production. [ABSTRACT FROM AUTHOR]

Pneumocystis jiroveci pneumonia in non-HIV patients is infrequent and characterized by atypical presentations and increased severity. Although hematogenous dissemination from the lungs can lead to extrapulmonary infections, isolation of oocysts from blood in human subjects has not been documented. We report a case of P. jiroveci pneumonia with persistent isolation of oocysts from blood and positivity of P. jiroveci polymerase chain reaction. The patient presented with bilateral diffuse pulmonary nodules and received prolonged treatment with trimethoprim/sulfamethoxazole. [ABSTRACT FROM AUTHOR]

A correction to the article "Risk factors for target non-attainment during empirical treatment with ß-lactam antibiotics in critically ill patients" is presented.

Reports on the use of fluoroquinolones in the treatment of disseminated Mycobacterium avium complex infections in patients with AIDS. Methods; Results; Discussion.