INTRODUCTION: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group. PATIENTS AND METHODS: For this prospective observational study, we enrolled 10 consecutive patients treated with NPWT for post-sternotomy DSWI. On the first sampling day, serum and exudate samples were synchronously collected at 0 (pre-dose), 0.5, 1, 2, 3 and 6 h after vancomycin administration. On the following three consecutive days, additional samples were collected, only before vancomycin administration. RESULTS: The ratio of average vancomycin concentration in wound exudate to in serum was higher for free (unbound) (1.51 ± 0.53) than for total (bound + unbound) (0.91 ± 0.29) concentration (p = 0.049). The percentage of free vancomycin was higher in wound exudate than serum (0.79 ± 0.19 vs. 0.46 ± 0.16; p = 0.04). Good vancomycin wound penetration was maintained on the following three days (vancomycin trough exudate-to-serum concentration ratio > 1). The total hospital stay was significantly longer in patients with DSWI (46 ± 11.6 days) versus without DSWI (14 ± 11.7 days) (p < 0.001). There was no in-hospital or 90-day mortality. Two patients experienced late DSWI recurrence. All-cause mortality was 4.8% during a median follow-up of 2.5 years. CONCLUSION: Vancomycin effectively penetrates wound exudate in patients receiving NPWT for DSWI after open-heart surgery.The protocol for this study was registered at ClinicalTrials.gov on July 16, 2024 (NCT06506032).
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování MeSH
- exsudáty a transsudáty metabolismus mikrobiologie MeSH
- infekce chirurgické rány * MeSH
- kardiochirurgické výkony * škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- sternotomie * škodlivé účinky MeSH
- sternum chirurgie MeSH
- terapie ran pomocí řízeného podtlaku * metody MeSH
- vankomycin * aplikace a dávkování farmakokinetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: Systemically administered antibiotics are thought to penetrate the wounds more effectively during negative pressure wound therapy (NPWT).To test this hypothesis total and free antibiotic concentrations were quantified in serum and wound exudate. METHODS: UHPLC-MS/MS methods were developed and validated for the determination of ceftazidime, cefepime, cefotaxime, cefuroxime, cefazolin, meropenem, oxacillin, piperacillin with tazobactam, clindamycin, ciprofloxacin, sulfamethoxazole/trimethoprim (cotrimoxazole), gentamicin, vancomycin, and linezolid. The unbound antibiotic fraction was obtained by ultrafiltration using a Millipore Microcon-30kda Centrifugal Filter Unit. Analysis was performed on a 1.7-μm Acquity UPLC BEH C18 2.1 × 100-mm column with a gradient elution. RESULTS: The validation was performed for serum, exudates and free fractions. For all matrices, requirements were met regarding linearity, precision, accuracy, limit of quantitation, and matrix effect. The coefficient of variation was in the range of 1.2-13.6%.and the recovery 87.6-115.6%, respectively. Among the 29 applications of antibiotics thus far, including vancomycin, clindamycin, ciprofloxacin, oxacillin, cefepime, cefotaxime, cotrimoxazole, and gentamicin, total and free antibiotic concentrations in serum and exudate were correlated. CONCLUSION: This method can accurately quantify the total and free concentrations of 16 antibiotics. Comparison of concentration ratios between serum and exudates allows for monitoring individual antibiotics' penetration capacity in patients receiving NPWT.
- MeSH
- antibakteriální látky MeSH
- cefepim MeSH
- cefotaxim MeSH
- chromatografie kapalinová metody MeSH
- ciprofloxacin MeSH
- exsudáty a transsudáty MeSH
- gentamiciny MeSH
- infekce v ráně * MeSH
- klindamycin MeSH
- kombinace léků trimethoprim a sulfamethoxazol MeSH
- lidé MeSH
- oxacilin MeSH
- sternotomie MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- terapie ran pomocí řízeného podtlaku * MeSH
- vankomycin MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Background: Association between clinical effect and serum concentration of amiodarone (AMI) and its active metabolite desethylamidarone (DEA) in patients after surgical ablation (SA) of atrial fibrillation (AF) has not yet been studied. Aims: We wanted to find a correlation between AMI and DEA serum concentration and maintaining sinus rhythm (SR) after SA of AF. Methods: Sixty eight patients with AF who had undergone surgical ablation between 2014 and 2017 were included in a single-centre, prospective, observational study. Maintaining of SR was evaluated by standard 12-lead ECG and 24-hour Holter ECG monitoring at months 1, 3, 6 and 12 following surgery. Therapeutic monitoring of AMI and DEA concentrations was done to optimize therapy and adverse effects were followed up. Results: We have noticed a high success rate in maintaining of SR (overall 83%). The median of serum concentration of AMI was 0.81 mg/L (range 0.16-2.35 mg/L) and DEA 0.70 mg/l (range 0.19-2.63 mg/L). No significant differences were found in the serum concentratration of AMI, DEA or DEA/AMI concentratration ratios between patients with SR and persistent supraventricular tachyarrhythmia except on the second outpatient visit. We observed significant correlation between serum concentration of DEA and thyroid-stimulating hormone elevation. Conclusion: We confirmed the efficacy of AMI and DEA at the measured serum concentrations. However, analysis of these concentrations alone cannot replace assessment of the clinical response for treatment. Establishment of individual AMI (and DEA) concentrations at which the optimal therapeutic response is achieved seems to be advantageous. Therapeutic monitoring of AMI and DEA is helpful in personalised pharmacotherapy after SA of AF.
- Publikační typ
- časopisecké články MeSH
AIMS: Limited contemporary data are available on the clinical and echocardiographic outcomes after surgery for cardiac papillary fibroelastoma (CPF). The aim of this study was to review the clinical manifestations, pathological characteristics, surgical management, and prognoses of patients with histologically verified CPF, who underwent surgery at our cardiac surgery center from 2008 to 2018. METHODS AND RESULTS: Twelve patients of median age 62 years (28 to 77 years) were treated. Embolic stroke or transient ischemic attack (five patients, 42%) were the only CPF clinical manifestations. Eleven (92%) tumors were localized on the valves, with the aortic valve being the most common tumor site (seven patients; 58%). Multiple factor analysis revealed no independent predictor of CPF-related embolization. Simple shave tumor excision was sufficient in most patients (10 patients, 83%). No operative or tumor-related late mortality during the median follow-up period of 4.7 years (1.1 to 10.2 years) was recorded. Asymptomatic metachronous valve tumor recurrence (in a location different from that of the original tumor) was revealed in two patients (17%) by transesophageal echocardiography (TEE), not detected by transthoracic echocardiography (TTE). One of these two patients underwent repeated surgery for CPF but later suffered a recurrent embolic stroke, due to another tumor recurrence. CONCLUSION: CPF can be safely and effectively treated surgically. TEE is superior to the TTE option in CPF post-operative recurrence detection. There is a clear need for a prospective study to determine criteria for embolization risk stratification and optimum management in patients with CPF.
- MeSH
- dospělí MeSH
- echokardiografie transezofageální MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- následné studie MeSH
- papilární fibroelastom srdce diagnóza mortalita chirurgie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Introduction: Although there is a significant utilization gap of biologic medicines in the EU, many studies estimate equity in patient access to biopharmaceuticals only based on their availability on the national list of reimbursed medicines. Hidden access barriers may facilitate financial sustainability of pharmaceuticals in less affluent EU countries; however, they have rarely been documented in scientific publications. Our objective was to explore these access barriers for tumor necrosis factor (TNF) alpha inhibitors in rheumatoid arthritis (RA) in five Central and Eastern European countries. Methods: A detailed interview guide was developed based on multi-stakeholder workshops and a targeted literature review. In each participant country 3-3-3-3 interviews with payers, rheumatologists, patients/patient representatives, and industry representatives were conducted. Responses were aggregated at a country level and validated by primary investigators in each country. Results: Limited number of RA centers and consequently significant travelling time and cost for patients in distant geographical areas, uneven budget allocation among centers, limited capacity of nurses, narrowed patient population in national financial protocols compared to international clinical guidelines in initiating or continuing biologics, high administrative burden in prescribing biologics and limited health literacy of patients were the most relevant barriers to timely patient access in at least three participant countries. Conclusion: Assessing only the availability of TNF alpha inhibitors on the national list of reimbursed medicines provides limited information about real-world patient access to these medicines. Revealing hidden access barriers may contribute to initiate policy actions which could reduce inequity in patient access.
- Publikační typ
- časopisecké články MeSH
Úvod: Fibrilace síní (FS) je poruchou srdečního rytmu s prevalencí 3,37 % populace, která roste s věkem.1 Pacienti s FS mají vysoké riziko cévní mozkové příhody (CMP) a systémové embolizace (SE), které dále roste, pokud pacient prodělal tranzitorní ischemickou ataku (TIA) nebo CMP. Cíl: Cílem farmakoekonomického hodnocení je porovnání nákladů a přínosů léčby novými perorálními antikoagulancii (novel oral anticoagulants, NOAC) proti warfarinu jako standardu léčby v první linii prevence CMP a SE u pacientů s nevalvulární fibrilací síní. Metody: Markovův model hodnotí nákladovou efektivitu se zohledněním kvality života (CUA) z pohledu plátce zdravotní péče s výsledkem v podobě přírůstkového poměru nákladové efektivity (incremental cost-effectiveness ratio, ICER) na QALY (Quality Adjusted Life Years) a ICER na LYG (Life-Years Gained) pro celoživotní horizont. Populace pacientů vychází z dostupné klinické evidence, zejména ze studií ARISTOTLE, RE-LY, ROCKET-AF, ENGAGE AF-TIMI.2-6 Výsledky: NOAC dle dosažených výsledků představují účinnější variantu léčby než warfarin, dosahují vyšší účinnosti a bezpečnosti za podmínky zachované nákladové efektivity. ICER pro apixaban vs. warfarin vychází na 479 014 Kč/QALY se ziskem 0,184 QALY a 0,177 LYG; dabigatran 150 mg vs. warfarin 582 768 Kč se ziskem 0,121 QALY a 0,099 LYG; edoxaban 60 mg vs. warfarin 563 057 Kč se ziskem 0,149 QALY a 0,129 LYG a konečně rivaroxaban vs. warfarin 664 238 Kč se ziskem 0,126 QALY a 0,102 LYG. Provedená metodická a probabilistická analýza senzitivity potvrdily přidanou hodnotu léčby NOAC ve srovnání se stávající terapií. Závěr: NOAC, v porovnání se současným standardem léčby, kterým je warfarin, mají větší přínos v podobě dosažení celkového přežití, zvýšení kvality života a zabránění vzniku kardiovaskulárních příhod za splnění předpokladu efektivně vynaložených nákladů s výsledkem ICER hluboko pod hranicí ochoty platit 1,2 mil. Kč.
Introduction: Atrial fibrillation (AF) is a cardiac rhythm disorder with a prevalence of 3.37% of the popula- tion, which increases with age.1 AF patients have a high risk of stroke and systemic embolism, which continues to increase when the patient has undergone transient ischemic attack (TIA) or stroke. Objective: The aim of the pharmacoeconomic evaluation is to compare the cost and benefit of NOAC (novel oral anticoagulants) treatment against warfarin treatment as a first-line prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Methods: The Markov model evaluates the cost-effectiveness of prevention from the perspective of a health care payer with the result of incremental cost-effectiveness ratio (ICER) per Quality Adjusted Life Year (QALY) and Life-Year Gained (LYG). The patient population is based on available clinical evidence, especially ARISTOTLE, RE-LY, ROCKET-AF, ENGAGE AF-TIMI.2-6, Results: According to the results, NOAC achieve higher efficacy and safety while maintaining cost effectiveness compared to warfarin. ICER for apixaban vs. warfarin is 479,014 CZK / QALY with 0.184 QALY and 0.177 LYG; dabigatran 150 mg vs. warfarin CZK 582,768 with a profit of 0.121 QALY and 0.099 LYG; edoxaban 60 mg vs. warfarin CZK 563,057 with 0.149 QALY and 0.129 LYG and finally rivaroxaban vs. warfarin 664,238 CZK with 0.126 QALY and 0.102 LYG. Methodological and probabilistic sensitivity analysis were performed and confirmed the added value of NOAC treatment compared to existing therapy.
- Publikační typ
- abstrakt z konference MeSH
