PICC-port představuje nový druh dlouhodobého žilního přístupu, který je indikován čím dál častěji z důvodu snížení rizika komplikací při zavádění a výborného estetického efektu ve srovnání s porty hrudními. Jedná se o další generaci portů, která nahradila historicky zaváděné pažní nebo brachiální porty, kdy nevhodně prováděná implantace nevedla k rozšíření jejich používání pro vysoký výskyt komplikací. Při dodržení moderních doporučení se stává PICC-port ve specifických klinických situacích žilním vstupem první volby.
The PICC-port is a novel type of long-term venous access device that is increasingly indicated for use because of the reduced risk of complications during insertion and excellent aesthetic effect when compared with a chest port. It is the next generation of ports that has replaced the previously inserted arm or brachial ports in which inappropriate implantation hindered their widespread use due to high rates of complications. When modern recommendations are followed, the PICC-port can become the first-choice venous access in specific clinical situations.
INTRODUCTION: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). The safety profile and patient preference for conventional versus shorter ocrelizumab infusions were investigated in the ENSEMBLE PLUS study. METHODS: ENSEMBLE PLUS was a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810), comparing outcomes in patients with early-stage relapsing-remitting MS receiving ocrelizumab 600 mg over the approved 3.5-h (conventional) versus 2-h (shorter) infusion. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first randomized dose (RD); the secondary endpoint included IRR frequency at subsequent RDs. RESULTS: At first RD, the number of patients with an IRR in the conventional (101/373; 27.1%) versus shorter (107/372; 28.8%) infusion group was similar (difference, stratified estimates [95% CI]: 1.9% [- 4.4, 8.2]). Most IRRs (conventional: 99.4%; shorter: 97.7%) were mild/moderate. IRR frequency decreased over the course of RDs; three patients discontinued from the shorter infusion arm but continued with conventional infusion. Overall, > 98% of IRRs resolved without sequelae in both groups. Pre-randomization throat irritation was predictive of future throat irritation as an IRR symptom. Adverse events (AEs) and serious AEs were consistent with the known ocrelizumab safety profile. On completion of ENSEMBLE PLUS, most patients chose to remain on (95%) or switch to (80%) shorter infusion. CONCLUSION: ENSEMBLE PLUS demonstrates the safety and tolerability of shorter ocrelizumab infusions. Most patients remained on/switched to shorter infusion after unblinding; IRRs did not strongly influence patient decisions. CLINICAL TRIALS REGISTRATION: Substudy of ENSEMBLE (NCT03085810). REGISTRATION: March 21, 2017.
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * aplikace a dávkování škodlivé účinky MeSH
- imunologické faktory * aplikace a dávkování škodlivé účinky MeSH
- intravenózní infuze MeSH
- lidé středního věku MeSH
- lidé MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
OBJECTIVES: The objective of this study was to develop a population pharmacokinetic model of meropenem in a heterogeneous population of patients with a serious bacterial infection in order to propose dosing optimisation leading to improved achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target. METHODS: A total of 174 meropenem serum levels obtained from 144 patients during therapeutic drug monitoring were analysed using a non-linear mixed-effects modelling approach and Monte Carlo simulation was then used to compare various dosing regimens in order to optimise PK/PD target attainment. RESULTS: The meropenem volume of distribution of the patient population was 54.95 L, while clearance started at 3.27 L/hour and increased by 0.91 L/hour with each 1 mL/s/1.73 m2 of estimated glomerular filtration rate. Meropenem clearance was also 0.31 L/hour higher in postoperative patients with central nervous system infection. Meropenem administration by continuous infusion showed a significantly higher probability of attaining the PK/PD target than a standard 30 min infusion (95.3% vs 49.5%). CONCLUSIONS: A daily meropenem dose of 3 g, 6 g and 10.5 g administered by continuous infusion was shown to be accurate for patients with moderate to severe renal impairment, normal renal function to mild renal impairment and augmented renal clearance, respectively.
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování MeSH
- bakteriální infekce * farmakoterapie MeSH
- biologické modely * MeSH
- dospělí MeSH
- intravenózní infuze MeSH
- lidé středního věku MeSH
- lidé MeSH
- meropenem * farmakokinetika aplikace a dávkování MeSH
- metoda Monte Carlo MeSH
- monitorování léčiv metody MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Melflufen, a first-in-class alkylating peptide-drug conjugate, rapidly enters tumor cells and metabolizes to melphalan. In previous studies, melflufen was administered via central venous catheter (CVC). However, administration by peripheral venous catheter (PVC) may be preferable. PATIENTS AND METHODS: PORT was a two-period, phase 2 crossover study of CVC versus PVC melflufen administration in patients with relapsed/refractory multiple myeloma. Adults with ≥ 2 prior therapies refractory to/intolerant of an immunomodulatory drug and a proteasome inhibitor were randomized 1:1 to weekly oral dexamethasone plus melflufen (40 mg) via CVC or PVC infusion on day 1 of 28-day cycle 1. In cycle 2, patients continued dexamethasone and crossed over to the other melflufen administration route. In cycle 3, all patients received melflufen until progression; PVC or CVC routes were allowed based upon investigator decision. Pharmacokinetic sampling was performed during and after melflufen infusion. Primary endpoints were melphalan pharmacokinetic parameters (Cmax, AUC(0-t), and AUC(0-∞)) and frequency and severity of PVC-related local reactions. RESULTS: The 90% CIs for adjusted geometric mean ratios for pharmacokinetic parameters following CVC versus PVC administration were within the 0.8-1.25 bioequivalence range (Cmax 0.946 [90% CI: 0.849, 1.053]; AUC(0-t) 0.952 [90% CI: 0.861, 1.053]; AUC(0-∞) 0.955 [90% CI: 0.863, 1.058]). In both arms, adverse events were primarily hematological and similar; no phlebitis or local infusion-related reactions occurred. CONCLUSION: Melflufen PVC and CVC administrations are bioequivalent based on melphalan pharmacokinetic parameters. Melflufen via PVC was well tolerated, with no infusion-related reactions or new safety signals and may represent an alternative route of administration.
- MeSH
- dospělí MeSH
- fenylalanin analogy a deriváty aplikace a dávkování farmakokinetika MeSH
- intravenózní infuze MeSH
- intravenózní podání MeSH
- klinické křížové studie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- melfalan aplikace a dávkování terapeutické užití analogy a deriváty MeSH
- mnohočetný myelom * farmakoterapie patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study. METHODS: ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0-16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16-40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented. RESULTS: The 95 patients enrolled were randomised to receive IVIg (N = 47) or placebo (N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4-15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred. CONCLUSIONS: Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors. TRIAL REGISTRATION: ProDERM study (NCT02728752).
- MeSH
- dermatomyozitida * farmakoterapie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- intravenózní imunoglobuliny škodlivé účinky MeSH
- intravenózní infuze MeSH
- lidé MeSH
- myozitida * chemicky indukované MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- MeSH
- Crohnova nemoc farmakoterapie MeSH
- farmakoterapie metody MeSH
- infliximab * aplikace a dávkování MeSH
- injekce subkutánní * MeSH
- intravenózní infuze škodlivé účinky MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé MeSH
- progrese nemoci MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- biologické markery MeSH
- bronchopneumonie * diagnóza epidemiologie komplikace mikrobiologie mortalita terapie MeSH
- cévní přístupy klasifikace MeSH
- chirurgie plic škodlivé účinky MeSH
- intravenózní infuze metody MeSH
- klinická studie jako téma MeSH
- klinické rozhodování MeSH
- lidé MeSH
- pooperační komplikace * diagnóza epidemiologie mikrobiologie mortalita terapie MeSH
- rizikové faktory MeSH
- statistika jako téma MeSH
- výsledek terapie MeSH
- zajištění dýchacích cest metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Jedním z často skloňovaných nežádoucích účinků cetuximabu je infuzní reakce, a to zejména jako anafylaktická reakce při prvním podání této molekuly. Vlastní reakce souvisí s preexistujícími protilátkami IgE proti oligosacharidu α-1,3-galaktóze na molekule cetuximabu. V případě reakcí nižšího stupně - grade 1 a 2 - je možné v aplikaci pokračovat, nicméně v případě grade 3 či 4 je nezbytné aplikaci ukončit a další podávání cetuximabu je obvykle kontraindikováno. Rozšířené premedikační schéma snižuje riziko závažné infuzní reakce v průběhu aplikace cetuximabu a umožňuje převést aplikaci cetuximabu z jednotek intenzivní péče či lůžkových onkologických oddělení na ambulantní chemoterapeutický stacionář, což zvyšuje komfort pro pacienty a současně snižuje náklady na onkologickou léčbu.
One of the frequently discussed side effects of the cetuximab is the infusion-related reaction, more specifically the anaphylaxis during the first application of the cetuximab. The reaction is related to the preexisting IgG antibodies against galactose- α-1,3-galactose which is present on the cetuximab molecule. In the case of grade 1 and 2 reaction the application may continue however in the case of severe (grade 3 and 4) hypersensitivity reaction the infusion has to be discontinued immediately and further use of cetuximab is contraindicated. The extended premedication scheme significantly reduces the risk of severe infusion-related reaction and enables to transfer the first infusion from intensive care units or oncology beds to outpatient clinics which improves patient quality of life and reduces the treatment cost.
