This book endeavours to pinpoint the relations between musical, and especially instrumental, practice and the evolving conceptions of pitch systems. It traces the development of ancient melodic ...notation from reconstructed origins, through various adaptations necessitated by changing musical styles and newly invented instruments, to its final canonical form. It thus emerges how closely ancient harmonic theory depended on the culturally dominant instruments, the lyre and the aulos. These threads are followed down to late antiquity, when details recorded by Ptolemy permit an exceptionally clear view. Dr Hagel discusses the textual and pictorial evidence, introducing mathematical approaches wherever feasible, but also contributes to the interpretation of instruments in the archaeological record and occasionally is able to outline the general features of instruments not directly attested. The book will be indispensable to all those interested in Greek music, technology and performance culture and the general history of musicology.
Adverse effects of biologics used for treating IBD Stallmach, Andreas, MD; Hagel, Stefan, MD; Bruns, Tony, MD
Baillière's best practice & research. Clinical gastroenterology,
04/2010, Letnik:
24, Številka:
2
Journal Article
Recenzirano
In the last decade, biologic agents, in particular anti-TNF agents such as infliximab, adalimumab, and certolizumab have substantially extended the therapeutic armamentarium of inflammatory bowel ...disease (IBD). Additional approaches include biologicals, such as natalizumab, that block leucocyte adhesion; those that target cytokines, such as interleukin-12/23 antibodies; or those that inhibit T-cell signaling, such as interleukin-6 receptor antibodies. However, these drugs have a number of contraindications and side effects, especially when used in combination with classical immunosuppressive agents or corticosteroids. Areas of concern include opportunistic infections, malignancies, and miscellaneous complications such as injection/infusion reactions and autoimmunity and contraindications, such as heart failure and acute infectious diseases. In this review, the indications of biologicals in IBD treatment are briefly reported, and the potential disadvantages of a more active therapeutic approach in IBD are discussed. We have learned in the last decade that anti-TNF-α therapy is an effective and relatively safe treatment option for selected patients that changes the natural course of severe IBD. However, despite these changed therapeutic paradigms and goals in IBD, clinicians should be aware that the powerful immunosuppressive capacity of biologicals necessitates a rigorous long-term safety follow-up.
Summary Objective Mortality and morbidity of Staphylococcus aureus bacteremia (SAB) still remains considerably high. We aimed to evaluate the impact of infectious disease consultation (IDC) on the ...management and outcomes of patients with SAB. Methods We systematically searched 3 publication databases from inception to 31st May 2015 and reference lists of identified primary studies. Results Our search returned 2874 reports, of which 18 fulfilled the inclusion criteria, accounting for 5337 patients. Overall 30-day mortality was 19.95% 95% CI 14.37–27.02 with a significant difference in favour of the IDC group (12.39% vs 26.07%) with a relative risk (RR) of 0.53 95% CI 0.43–0.65. 90-day mortality and relapse risk for SAB were also reduced significantly with RRs of 0.77 95% CI 0.64–0.92 and 0.62 95% CI 0.39–0.99, respectively. Both, the appropriateness of antistaphylococcal agent and treatment duration was improved by IDC (RR 1.14 95% CI 1.08–1.20 and 1.85 95% CI 1.39–2.46, respectively). Follow-up blood cultures and echocardiography were performed more frequently following IDC (RR 1.35 95% CI 1.25–1.46 and 1.98 95% CI 1.66–2.37, respectively). Conclusions Evidence-based clinical management enforced by IDC may improve outcome of patients with SAB. Well-designed cluster-randomized controlled trials are needed to confirm this finding from observational studies.
We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on ...hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34-2.42, HR = 1.81; 95% CI: 1.49-2.20 and HR = 2.42; 95% CI: 1.66-3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2-9.4, 11.5 days; 95% CI: 11.5-11.6 and 13.3 days; 95% CI: 13.2-13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8-5.9) but not hazard of death (1.16; 95% CI: 0.98-1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13-2.35), excess LOS (4.9 days; 95% CI: 1.1-8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae.
Healthcare-associated infections (HAIs) are a major health concern and have substantial effects on morbidity and mortality and increase healthcare costs. We investigated the effect of a hospital-wide ...program for the prevention of HAIs on additional length of stay (LOS).
We analyzed data from a prospective, single-center, quasi-experimental study with two surveillance periods before and after implementation of an infection prevention intervention program. HAI diagnosis was made according to surveillance definition criteria established by the US Centers for Disease Control and Prevention. A multistate model was used to estimate additional LOS for patients with HAI in both surveillance periods.
During the first and second periods, 1,568 and 2,336 HAIs were identified among 26,943 and 35,211 patients, respectively. For HAI patients exclusively treated in a general ward, additional LOS was 8.4 (95% confidence interval, CI: 6.8-10.0) days in the first period and 9.6 (95% CI: 8.3-11.0) days in the second period (p = 0.26). For HAI patients treated in both an intensive care unit (ICU) and a general ward, additional LOS was 8.1 (95% CI: 6.3-9.9) days in the first period to 7.3 (95% CI: 6.1-8.5) days in the second period (p = 0.47).
Healthcare-associated infections prolong LOS. A hospital-wide infection control program did not alter the prolongation of LOS.
Adequate antibiotic treatment is a prerequisite for the successful treatment of systemic infections. Based on accumulating scientific evidence, a fixed dosage regimen can lead to insufficient and ...ineffective antibiotic therapy. Thus, the aim of this study was to develop and validate a simplified, but sensitive method for the simultaneous quantification of antimicrobials by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for the development of personalized therapy regimens using therapeutic drug monitoring.
A method was developed for the simultaneous quantification of 9 antimicrobials (aciclovir, ampicillin, cefuroxime, ciprofloxacin, meropenem, metronidazole, piperacillin, rifampicin, and tazobactam) in lithium-heparin plasma. A simple sample preparation method and a chromatographic run time of 10 minutes enabled the quick processing of the samples. The method was validated according to the guidelines for bioanalytical method validation of the European Medicines Agency and addressed sensitivity, specificity, linearity, accuracy, precision, dilution integrity, carry-over, recovery, matrix effects, and stability.
The chromatographic run time was 10 minutes and antimicrobials eluted at retention times ranging from 1.1 to 2.2 minutes. Calibration curve for all antimicrobials was linear over a range of 1-100 mg/L, and a 2-fold or 5-fold dilution of the samples was possible. The method accuracy ranged from 85.1% to 114.9% for all measured antimicrobials, and the within- and between-run precision values were <11.9% and <16.5% for the lower limit of quantification. No interferences and carry-over were observed. The samples were stable for at least 5 hours at room temperature or in the autosampler (10°C).
The LC-MS/MS method developed in this study is appropriate and practical for the therapeutic drug monitoring of antimicrobials in the daily clinical laboratory practice because of its short analysis time, the need for a small amount of plasma, high specificity, and accuracy.
A prospective cohort study (German Clinical Trial Registry, No. 00005273) was performed to determine pre-admission colonization rates, hospital acquisition risk factors, subsequent infection rates ...and colonization persistence including the respective molecular epidemiology and transmission rates of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (EPE). A total of 342 EPEs were isolated from rectal swabs of 1,334 patients on admission, at discharge and 6 months after hospitalization. Inclusion criteria were patients' age > 18 years, expected length of stays > 48 hours, external referral. The EPEs were characterized by routine microbiological methods, a DNA microarray and ERIC-PCR. EPE colonization was found in 12.7 % of admitted patients, with the highest rate (23.8 %) in patients from nursing homes. During hospitalization, 8.1 % of the patients were de novo EPE colonized, and invasive procedures, antibiotic and antacid therapies were independent risk factors. Only 1/169 patients colonized on admission developed a hospital-acquired EPE infection. Escherichia coli was the predominant EPE (88.9 %), and 92.1% of the ESBL phenotypes could be related to CTX-M variants with CTX-M-1/15 group being most frequent (88.9%). A corresponding β-lactamase could not be identified in five isolates. Hospital-acquired EPE infections in patients colonized before or during hospitalization were rare. The diversity of the EPE strains was much higher than that of the underlying plasmids. In seven patients, transmission of the respective plasmid across different species could be observed indicating that the current strain-based surveillance approaches may underestimate the risk of inter-species transmission of resistance genes.
The spread of carbapenem-non-susceptible Klebsiella pneumoniae strains bearing different resistance determinants is a rising problem worldwide. Especially infections with KPC (Klebsiella pneumoniae ...carbapenemase) - producers are associated with high mortality rates due to limited treatment options. Recent clinical studies of KPC-blood stream infections revealed that colistin-based combination therapy with a carbapenem and/or tigecycline was associated with significantly decreased mortality rates when compared to colistin monotherapy. However, it remains unclear if these observations can be transferred to K. pneumoniae harboring other mechanisms of carbapenem resistance. A three-dimensional synergy analysis was performed to evaluate the benefits of a triple combination with meropenem, tigecycline and colistin against 20 K. pneumoniae isolates harboring different β-lactamases. To examine the mechanism behind the clinically observed synergistic effect, efflux properties and outer membrane porin (Omp) genes (ompK35 and ompK36) were also analyzed. Synergism was found for colistin-based double combinations for strains exhibiting high minimal inhibition concentrations against all of the three antibiotics. Adding a third antibiotic did not result in further increased synergistic effect in these strains. Antagonism did not occur. These results support the idea that colistin-based double combinations might be sufficient and the most effective combination partner for colistin should be chosen according to its MIC.
Abstract
Background
Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients. The aim of this study was to assess current evidence to determine ...whether antiviral therapy is associated with better outcomes in these patients.
Methods
MEDLINE
,
ISI Web of Science
,
Cochrane Database
and ClinicalTrials.gov were searched from inception to 25 May 2020. All clinical studies investigating the effects of antiviral therapy on the outcome of mechanically ventilated ICU patients in whom HSV was detected in the respiratory tract were eligible for inclusion, regardless of study design, publication status or language. Titles and abstracts were reviewed independently by two authors. If the articles seemed eligible, full-text articles were reviewed and data extracted.
We performed a random-effects meta-analysis to estimate relative risks (RRs) with corresponding 95% confidence intervals (CIs). The primary endpoint was hospital all-cause mortality.
Results
Nine studies were included in the meta-analysis (one randomized controlled trial, eight cohort studies). Antiviral treatment was associated with lower hospital mortality (with antiviral treatment, 40.6% (189 out of 465 patients); without, 52.7% (193 out of 366 patients); RR 0.74 0.64, 0.85; eight studies, low quality of evidence). Furthermore, antiviral treatment was associated with lower 30-day mortality (RR 0.75 0.59, 0.94; three studies, very low quality of evidence). We did not observe evidence for differences in ICU mortality (RR 0.73 0.51, 1.05; three studies, very low quality of evidence).
Conclusions
This meta-analysis of the available data shows that antiviral therapy might result in lower hospital and 30-day all-cause mortality in mechanically ventilated ICU patients who are positive for HSV in the respiratory tract. However, this result must be interpreted with great caution due to the high risk of bias and limited number of patients. Large, well-designed randomized controlled clinical trials are urgently needed.
Trial registration
The study was registered in advance on International Prospective Register of Systematic Reviews
(CRD42020180053)
.
Infective endocarditis represents a life-threatening disease with high mortality rates. A fraction of patients receives exclusively conservative antibiotic treatment due to their comorbidities and ...high operative risk, despite fulfilling criteria for surgical therapy. The aim of the present study is to compare outcomes in patients with infective endocarditis and indication for surgical therapy in those who underwent or did not undergo valve surgery.
Three databases were systematically assessed. A pooled analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies with longer follow-up comparing conservative and surgical treatment was performed. A landmark analysis to further elucidate the effect of surgical intervention on mortality was carried out. Four studies with 3003 patients and median follow-up time of 7.6 months were included. Overall, patients with an indication for surgery who were surgically treated had a significantly lower risk of mortality compared with patients who received conservative treatment (hazard ratio HR, 0.27 95% CI, 0.24-0.31,
<0.001). The survival analysis in the first year showed superior survival for patients who underwent surgery when compared with those who did not at 1 month (87.6% versus 57.6%; HR, 0.31 95% CI, 0.26-0.37,
<0.01), at 6 months (74.7% versus 34.6%) and at 12 months (73.3% versus 32.7%).
Based on the findings of this study-level meta-analysis, patients with infective endocarditis and formal indication for surgical intervention who underwent surgery are associated with a lower risk of short- and long-term mortality when compared with conservative treatment.
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