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Zdenek Racil,
Martina Toskova,
Iva Kocmanova, Lucie Buresova,
Michal Kouba,
Lubos Drgona,
Lucia Masarova,
Tomas Guman,
Elena Tothova,
Julia Gabzdilova,
Kristina Forsterova,
Jan Haber,
Barbora Ziakova,
Eva Bojtarova,
Monika Rolencova,
Shira Timilsina,
Petr Cetkovsky,
Jiri Mayer
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ABSTRACT: Abstract The objective of this retrospective, multicenter study was to evaluate the efficacy and safety of micafungin as empirical antifungal therapy during febrile neutropenia (FN) in 73 hematological patients from 6 centers in two countries. All patients received 100 mg of micafungin/day. The overall favorable response rate (RR) was 64.8% when the resolution of fever during neutropenia was included in the response criteria and 84.5% when excluded. A significantly lower favorable RR in patients with persistent fever and non-specific pulmonary infiltrates compared to patients with persistent fever only (82.8 vs. 52.4%, respectively; p = 0.011) was not found when resolution of fever was not included in the composite endpoint criteria (93.1 vs. 78.6%, respectively; p = 0.180). Breakthrough fungal disease developed in 2.7% patients. Treatment was discontinued in 16.4% of cases. Only one patient (1.4%) discontinued therapy due to an adverse event. Posaconazole prophylaxis improved favorable RR when defervescence was included as composite endpoint criteria (p = 0.047), but not when it was excluded (p = 0.485). However, neutrophil recovery did not influence favorable RR (p = 0.803 and p = 0.112, respectively). These data suggest that micafungin is safe and effective as an empirical therapy in patients with FN.
Leukemia & lymphoma 10/2012; · 2.40 Impact Factor
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Zdenek Racil,
Jana Winterova,
Michal Kouba,
Pavel Zak,
Ludmila Malaskova, Lucie Buresova,
Martina Toskova,
Martina Lengerova,
Iva Kocmanova,
Barbora Weinbergerova,
Shira Timilsina,
Monika Rolencova,
Petr Cetkovsky,
Jiri Mayer
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ABSTRACT: The objective of this retrospective study was to evaluate results from voriconazole therapeutic drug monitoring (TDM) in haematological patients in routine clinical practice. Between 2005 and 2010, 1228 blood samples were obtained from 264 haematological patients (median 3 samples/patient; range 1-27) receiving voriconazole for targeted/preemptive treatment of invasive aspergillosis (IA) (46.3% of samples), empirical therapy (12.9%) or prophylaxis (40.8%). A high-pressure liquid chromatography assay was used to analyse voriconazole concentrations. Clinical and laboratory data were analysed retrospectively. The median of the detected voriconazole plasma concentration was 1.00 μg ml(-1) (range <0.20-13.47 μg ml(-1) ). Significant inter- and intra-patients variability of measured concentrations (81.9% and 50.5%) were identified. With the exception of omeprazole administration, there was no relevant relationship between measured voriconazole concentrations and drug dose, route administration, age, gender, CYP2C19*2 genotype, gastrointestinal tract abnormality, administration via nasogastric tube, serum creatinine, and liver enzymes. However, per patient analysis identified significant role of individual voriconazole dose and drug form change on measured plasma concentration. Measured voriconazole concentrations did not correlate with the treatment outcome of patients with IA. We only identified a limited number of adverse events related to voriconazole therapy; however, the median plasma concentration was not different from concentrations measured in samples without reported toxicity. Our retrospective study has suggested that routine monitoring of voriconazole plasma concentrations has probably only a limited role in daily haematological practice.
Mycoses 03/2012; 55(6):483-492. · 2.25 Impact Factor
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Zdenek Racil,
Iva Kocmanova,
Martina Toskova, Lucie Buresova,
Barbora Weinbergerova,
Martina Lengerova,
Monika Rolencova,
Jana Winterova,
Kristyna Hrncirova,
Pavlina Volfova,
Jana Skrickova,
Jiri Mayer
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ABSTRACT: We evaluated the performance of a galactomannan (GM) assay in bronchoalveolar lavage (BAL) fluid compared to serum samples for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological diseases.
Two hundred and fifty-five bronchoscopies were performed on 230 patients. Bronchial and alveolar samples from BAL fluid as well as serum samples were analyzed in the GM assay.
Twenty-eight cases of IPA (11%) were diagnosed. The sensitivity, specificity, positive predictive value, and negative predictive value of the GM assay using a cut-off of 0.5 were 57.1%, 99.3%, 94.1%, and 92.5%, respectively, for the alveolar sample; 44.0%, 99.3%, 91.7%, and 91.4%, respectively, for the bronchial sample; and 60.7%, 100%, 100%, and 92.9%, respectively, for serum. The highest sensitivity (78.6%) with good specificity (98.6%) was obtained with a 'triple detection' of GM in bronchial, alveolar, and serum samples. Neutropenia and antifungal therapy for only 24h increased the sensitivity, while antifungal treatment for ≥ 2 days decreased assay performance. Moreover, a trend towards a higher volume of aspirated fluid in GM-negative BAL (p=0.092) was observed.
In contrast to recently published data, we found only moderate sensitivity, but high specificity and high positive predictive value of the detection of GM in BAL fluid. In addition, neutropenia, antifungal therapy, and BAL standardization affected GM assay performance.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 12/2011; 15(12):e874-81. · 2.17 Impact Factor
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American Journal of Hematology 10/2011; · 4.67 Impact Factor
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International journal of hematology 09/2011; 94(3):303-6. · 1.17 Impact Factor
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American Journal of Hematology 09/2011; 86(9):800-3. · 4.67 Impact Factor
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Leukemia & lymphoma 02/2011; 52(2):331-4. · 2.40 Impact Factor
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ABSTRACT: The Czech Breast Cancer Screening Programme (CBCSP) was initiated in September 2002 by establishing a network of accredited centres. The aim of this article is to describe progress in the programme quality over time after the inception of the organised programme.
The CBCSP is monitored using an information system consisting of three principal components: 1) the national cancer registry, 2) a screening registry collecting data on all screening examinations, further assessments and final diagnoses at accredited programme centres, and 3) administrative databases of healthcare payers. Key performance indicators from the European Guidelines have been adopted for continuous monitoring.
Breast cancer incidence in the Czech Republic has steadily been increasing, however with a growing proportion of less advanced stages. The mortality rate has recently stabilised. The screening registry includes 2,083,285 records on screening episodes between 2002 and 2008. In 2007-2008, 51% of eligible women aged 45-69 were screened. In 2008, the detection rates were 6.1 and 3.7 per 1,000 women in initial and subsequent screening respectively. Corresponding recall rates are 3.9% and 2.2%, however, it is necessary to pay attention to further assessment performed during the screening visits. Benign to malignant open biopsy ratio was 0.1. Of invasive cases detected in screening, 35.6% was less than 10 mm in diameter. Values of early performance indicators, as measured by both crude and standardized estimates, are generally improving and fulfil desirable targets set by European Guidelines.
Mammography screening in the Czech Republic underwent successful transformation from opportunistic prevention to an organised programme. Values of early indicators confirm continuous improvement in different aspects of process quality. Further stimulation of participation through invitation system is necessary to exploit the full potential of screening mammography at the population level.
BMC Public Health 01/2011; 11:288. · 2.00 Impact Factor
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ABSTRACT: We have evaluated the contribution of the 1,3-beta-d-glucan (BG) assay for the screening of invasive fungal infections (IFIs) in patients with haematological malignancies. Serum samples from patients at risk of IFI were collected twice a week and retrospectively tested using the BG assay. BG screening was performed on 1143 samples from 91 patients during 104 anticancer treatment cycles. Proven and probable cases of IFI occurred in 9 (8.7 %) treatment cycles. Depending on the criterion of positivity used (1x >60 pg ml(-1), 1x >80 pg ml(-1), 2x >60 pg ml(-1) or 2x >80 pg ml(-1)) the sensitivity and specificity were 89, 89, 67 and 44 %, and 20, 48, 33 and 56 %, respectively. Although the test was marked as positive in 82, 68, 54 and 45 % of all the treatment cycles, in the majority of cases, these positivities were probably false. The major limit of the BG test was an extremely low positive predictive value (10 to 12 %). We have analysed mucositis, candida colonization, bacteraemia, use of antimicrobials, erythrocyte and thrombocyte filtered blood products, collecting tubes or sampling via venous catheters. Even though no factor is a major source of BG, it could at least partially influence BG assay performance. Thus, BG detection has a limited usefulness as a screening method for IFIs in patients with haematological malignancies.
Journal of Medical Microbiology 09/2010; 59(Pt 9):1016-22. · 2.50 Impact Factor
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American Journal of Hematology 07/2010; 85(7):525-8. · 4.67 Impact Factor
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American Journal of Hematology 05/2010; 85(5):386-9. · 4.67 Impact Factor
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Ludek Pour,
Hana Svachova,
Zdenek Adam,
Martina Almasi, Lucie Buresova,
Tomas Buchler,
Lucie Kovarova,
Pavel Nemec,
Miroslav Penka,
Jiri Vorlicek,
Roman Hajek
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ABSTRACT: Angiogenesis plays a significant role in the pathogenesis of multiple myeloma (MM). We have measured concentrations of angiogenesis activators, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and hepatocyte growth factor (HGF), and inhibitors, including endostatin, thrombospondin-1 (TSP-1), and angiostatin in the peripheral and bone marrow blood of MM patients at diagnosis and after high-dose chemotherapy. We have analyzed 96 patients with secretory MM. Serial measurements of angiogenesis factors/inhibitors were analyzed in the plasma by subgroups based on the best treatment response. Concentrations of angiogenic factors were determined in the peripheral blood and bone marrow plasma. There were significant decreases of VEGF and HGF levels and a significant increase in TSP-1 concentrations in the bone marrow plasma of patients who achieved complete or very good partial response in contrast to those who had partial or no response. VEGF and HGF levels decrease but those of TSP-1 increase after successful treatment for MM, indicating a reduction in the rate of angiogenesis.
Annals of Hematology 09/2009; 89(4):385-9. · 2.62 Impact Factor
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ABSTRACT: Varicella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population.
We studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m2 was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently.
A total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment.
Varicellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.
Clinical Lymphoma & Myeloma 05/2009; 9(2):151-3. · 1.13 Impact Factor
