AIMS: To investigate the efficacy and safety of intravitreal Dexamethasone implant (DEX-I) therapy in the treatment of diabetic macular edema (DME) refractory to intravitreal bevacizumab (IVB). MATERIAL AND METHODS: This retrospective and cross-sectional study included 37 eyes of 37 patients who received 3 loading doses of IVB injections for DME with no response and underwent DEX-I implant. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurements and central foveal thickness (CFT) measured by spectral domain optical coherence tomography (SD-OCT) were recorded and compared before DEX-I, at the first week, first, second, third and sixth months. Duration of DME, glycated hemoglobin (HbA1c) levels, DME types and lens status (phakic, pseudophakic) were also recorded. RESULTS: The mean age of the patients was 61.14 ±8.69 years (59.5% male, 40.5% female). 35.1% of the patients had cystoid macular edema, 64.9% had diffuse macular edema and 73 % were phakic and 27% were pseudophakic. BCVA, CFT and IOP values before DEX-I injection were 0.78 ±0.16 LogMAR, 493.73 ±107.6 µm and 13.05 ±2.59 mmHg, respectively. At 6 months after DEX-I, BCVA, CFT and IOP values were 0.64 ±0.11 LogMAR, 397.35 ±59.72 µm and 16.3 ±2.51 mmHg, respectively. In all follow-ups, there was a significant improvement in BCVA, a significant decrease in CFT and a significant increase in IOP compared to pre-injection. Ocular hypertension was observed in 0.8 % of patients and progression of cataract progression in 1% of patients after treatment. CONCLUSION: DEX-I therapy is an effective and safe treatment option for DME refractory to IVB treatment.

• Klíčová slova
• Dexamethasone implant, bevacizumab, cataract, diabetic macular edema, intraocular pressure,
• MeSH
• bevacizumab aplikace a dávkování   škodlivé účinky   MeSH
• dexamethason * aplikace a dávkování   škodlivé účinky   MeSH
• diabetická retinopatie * farmakoterapie   MeSH
• glukokortikoidy aplikace a dávkování   škodlivé účinky   MeSH
• injekce intravitreální * MeSH
• léky implantované * MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární edém * farmakoterapie   etiologie   diagnostické zobrazování   MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• senioři MeSH
• zraková ostrost MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bevacizumab MeSH
• dexamethason * MeSH
• glukokortikoidy MeSH
• léky implantované * MeSH

Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 109/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 109/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 109/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 109/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.

• Klíčová slova
• adults, immune thrombocytopenia, platelets, quality of life, response,
• MeSH
• aplikace orální MeSH
• dospělí MeSH
• idiopatická trombocytopenická purpura * farmakoterapie   MeSH
• inhibitory proteinkinas * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• inhibitory tyrosinkinasy MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet trombocytů MeSH
• proteinkinasa BTK * antagonisté a inhibitory   MeSH
• pyrazoly terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• pyrimidiny aplikace a dávkování   škodlivé účinky   terapeutické užití   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 I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• Názvy látek
• BTK protein, human MeSH Prohlížeč
• inhibitory proteinkinas * MeSH
• inhibitory tyrosinkinasy MeSH
• proteinkinasa BTK * MeSH
• pyrazoly MeSH
• pyrimidiny MeSH

BACKGROUND: Unfractionated heparin is used as the most common anticoagulation for venovenous extracorporeal membrane oxygenation (VV ECMO) patients. However, it is accompanied by frequent bleeding and thrombotic complications. The aim of the study was to demonstrate the feasibility of Enoxaparin anticoagulation for VV ECMO patients. METHODS: This study is a retrospective analysis of VV ECMO patients on continuous intravenous Enoxaparin anticoagulation. The primary outcome was the incidence of bleeding, thrombotic, and neurological complications during ECMO support. The secondary outcome was an analysis of secondary and primary hemostasis profiles. RESULTS: Data from 38 patients were analyzed in this study. The incidence of bleeding complications was 5.3%, for thrombotic complications it was 2.6% and for neurological (bleeding/ischemic events) complications it was 10.5%. The targeted anti-Xa activity of 0.4-0.6 IU/mL was achieved and maintained during whole ECMO period in 28 patients (73.8%), not affecting the hemocoagulation profile represented by APTT-r 1.15 ± 0.2, TT 18.67 ± 3.35 s, PT/INR 1.21 ± 0.19, fibrinogen 5.39 ± 1.49 g/L, antithrombin, and platelet count. Primary hemostasis pathology was diagnosed in all patients by PFA 200 tests Col/EPI 279 ± 38 s and Col/ADP 249 ± 66 s. The running time of ECMO was 7.8 ± 3.4 days. CONCLUSIONS: Enoxaparin anticoagulation appears to be feasible for VV ECMO patients without an increase in adverse events. Further larger-sampled and comparative studies are needed in the future to support our findings.

• Klíčová slova
• anticoagulation, enoxaparin, extracorporeal membrane oxygenation, heparin, primary hemostasis,
• MeSH
• antikoagulancia aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• enoxaparin * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• inhibitory faktoru Xa aplikace a dávkování   terapeutické užití   MeSH
• intravenózní podání MeSH
• krvácení * prevence a kontrola   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• studie proveditelnosti MeSH
• trombóza prevence a kontrola   etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikoagulancia MeSH
• enoxaparin * MeSH
• inhibitory faktoru Xa MeSH

INTRODUCTION: ND0612 is being investigated as a continuous, subcutaneous levodopa/carbidopa infusion, in combination with oral levodopa/carbidopa, for motor fluctuations in Parkinson's disease (PD). One-year data from the ongoing BeyoND study (NCT02726386) showed that the ND0612 regimen was safe and well tolerated and provided a sustained ≥2-h improvement in daily Good ON-time through 12 months of treatment. METHODS: We describe 3-year safety and efficacy outcomes for participants who completed 12 months of ND0612 treatment in the core study period and entered the extension phase. RESULTS: Of the 214 enrolled participants, 120 completed the core 1-year period, and 114 participants continued into the extension phase. Of these, 95/114 (83.3 %) completed 2 years and 77/114 (67.5 %) completed 3 years of study treatment. Key reasons for discontinuation were treatment-emergent adverse events (TEAEs) (n = 5 and n = 11 after 2 and 3 years, respectively) and withdrawal of consent (n = 9 and n = 5, respectively). TEAEs were reported by 105/114 (92.1 %) participants in Year 1, 77/114 (67.5 %) in Year 2, and 73/95 (76.8 %) in Year 3. While most participants experienced infusion site reactions, these led to discontinuation in only five participants during this extension. At Month 36, the mean reduction in OFF-time from baseline was 2.81 h and the increase in Good ON-time was 2.79 h. CONCLUSIONS: Three-year results from this open-label study support the long-term safety, tolerability, and efficacy of ND0612. For participants who entered the extension phase, the high rate of retention supports a favorable benefit-risk ratio of the ND0612 regimen for patients with PD experiencing motor fluctuations.

• Klíčová slova
• Infusion, Levodopa, Motor complications, ND0612, Parkinson's disease,
• MeSH
• antiparkinsonika * aplikace a dávkování   škodlivé účinky   MeSH
• fixní kombinace léků * MeSH
• karbidopa * aplikace a dávkování   MeSH
• levodopa * aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Parkinsonova nemoc * farmakoterapie   MeSH
• senioři MeSH
• subkutánní infuze * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• antiparkinsonika * MeSH
• carbidopa, levodopa drug combination MeSH Prohlížeč
• fixní kombinace léků * MeSH
• karbidopa * MeSH
• levodopa * MeSH

Itaconate, an endogenous immunomodulator from the tricarboxylic acid (TCA) cycle, shows therapeutic effects in various disease models, but is highly polar with poor cellular permeability. We previously reported a novel, topical itaconate derivative, SCD-153, for the treatment of alopecia areata. Here, we present the discovery of orally available itaconate derivatives for systemic and skin disorders. Four sets of prodrugs were synthesized using pivaloyloxymethyl (POM), isopropyloxycarbonyloxymethyl (POC), (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl (ODOL), and 3-(hexadecyloxy)propyl (HDP) pro-moieties pairing with itaconic acid (IA), 1-methyl itaconate (1-MI), and 4-methyl itaconate (4-MI). Among these, POC-based prodrugs (P2, P9, P13) showed favorable stability, permeability, and pharmacokinetics. Notably, P2 and P13 significantly inhibited Poly(I:C)/IFNγ-induced inflammatory cytokines in human epidermal keratinocytes. Oral studies demonstrated favorable pharmacokinetics releasing micromolar concentrations of IA or 4-MI from P2 and P13, respectively. These findings highlight the potential of prodrug strategies to enhance itaconate's cellular permeability and oral bioavailability, paving the way for clinical translation.

• MeSH
• aplikace orální MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• objevování léků MeSH
• prekurzory léčiv * chemie   farmakologie   chemická syntéza   farmakokinetika   MeSH
• sukcináty * chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• itaconic acid MeSH Prohlížeč
• prekurzory léčiv * MeSH
• sukcináty * MeSH

New approaches to the issue of pyrogens in parenteral preparations The article provides a basic understanding of the pathophysiology of exogenous and endogenous pyrogens, particularly in the context of parenteral administration of drugs and the use of medical devices. It explains that pyrogens cause an increase in body temperature by activating the thermoregulatory center in the hypothalamus, with bacterial lipopolysaccharides being the most common source of pyrogenic burden. Contamination of pharmaceuticals with pyrogenic substances can lead to adverse effects, including life-threatening conditions. The text focuses on modern methods for identifying pyrogens, specifically endotoxins, and selecting suitable analytical procedures for their determination. These include in vivo tests on rabbits and the bacterial endotoxin tests, as well as in vitro tests such as the monocyte activation test and the recombinant Factor C test. The work includes a detailed description how to perform these tests, their advantages and disadvantages, and the development of methods for detecting pyrogens in pharmaceuticals. The author explains the reasons of false positive and negative test results, and ilusrates the calculations of threshold endotoxin limits. Information is provided on the new strategy of the European and Czech Pharmacopoeias on this issue, emphasizing efforts to reduce pyrogenic burden and the need to control both microbiological and endotoxin contamination levels.

• Klíčová slova
• Endotoxins, limits., pyrogens, testing,
• MeSH
• endotoxiny analýza   MeSH
• kontaminace léku * prevence a kontrola   MeSH
• lidé MeSH
• parenterální infuze MeSH
• pyrogeny * analýza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• endotoxiny MeSH
• pyrogeny * MeSH

Oral supplementation of sodium, potassium and phosphate ions in extemporaneous preparation The article deals with the possibilities of oral supplementation of three selected ions - sodium, potassium and phosphate, by means of individually prepared medicines. It forms an overview of the most frequently used extemporaneous prescriptions in the University Hospital in Motol. It deals with the description of available raw materials and theoretical characteristics of ions. For selected formulations, the amount of ions is given in both mass and molar terms. The formulas reflect the need for ion supplementation in appropriate doses and appropriate dosage form according to the individual needs of patients.

• Klíčová slova
• individual drug formulation, ions, extemporaneous preparation, supplementation, sodium, potassium, phosphorus,
• MeSH
• aplikace orální MeSH
• draslík * MeSH
• fosfáty * chemie   MeSH
• lidé MeSH
• příprava léků MeSH
• sodík * chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• draslík * MeSH
• fosfáty * MeSH
• sodík * MeSH

UNLABELLED: Safety of injectable dosage forms during their preparation and administration by nurses in hospitals: a literature review Introduction and Aim: Medication errors in hospitals are still frequent and significant for patient safety and associated healthcare costs. Especially, injectable dosage forms pose the high risk. The aim of this study was to review the current literature focused on medication errors related to injectable drug forms during their preparation and administration by nurses in hospitals. METHODS: Databases Medline and Scopus were used for the literature review. Papers dealing with intravenous (i. v.), intramuscular (i. m.), or subcutaneous (s. c.) administration by nurses in hospitals using direct observation method for data collection were searched. Original papers, systematic reviews or meta-analyses published in English by the end of 2022 were included. RESULTS: A total of 334 papers were retrieved, of which 21 studies met the inclusion criteria. 17 studies were observational (8 descriptive, 9 analytical) and 4 interventional. Medication errors were very common, moreover, critical steps of the medication process and possible interventions were identified. CONCLUSION: The results showed that the process of preparing and administering injectable dosage forms is a high-risk process. In the provision of healthcare, relevant measures must be set up to maximise patient safety.

• Klíčová slova
• medication error, nursing staff, hospital, parenteral administration, intravenous administra-tion, medication error, nursing staff, hospital, parenteral administration, intravenous administra-tion.,
• MeSH
• bezpečnost pacientů MeSH
• injekce * MeSH
• lékové formy MeSH
• lidé MeSH
• medikační omyly * prevence a kontrola   statistika a číselné údaje   MeSH
• personál sesterský nemocniční MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• lékové formy MeSH

UNLABELLED: Direct oral anticoagulants from the perspective of Czech pharmacists - opinions, attitudes, confidence, and patient education during dispensing in a pharmacy Introduction and Aim: Pharmacists play an important role in the management of anticoagulation therapy, therefore good knowledge and confidence in care of patients treated with anticoagulation are essential. The aim of this study was to analyse the opinions and attitudes of pharmacists in the Czech Republic towards direct oral anticoagulants (DOACs), their perception of the benefits and risks of DOACs, and the position of pharmacists in educating patients about the basic principles of DOAC treatment in the context of dispensing these medicines in pharmacies. METHODS: An online anonymous questionnaire survey conducted in 2021 among pharmacists of three specific District Pharmacists Associations of the Czech Chamber of Pharmacy. The questionnaire included 32 open- and closed-ended questions, and questions for reporting of the level of agreement using a Likert scale. Descriptive statistics, parametric and non-parametric tests were used to evaluate the data. RESULTS: A total of 162 pharmacists participated (14% return rate), 139 of whom dispensed medicines in a pharmacy in the last year. Respondents working in pharmacies located in any health centre and in hospital pharmacies reported dispensing DOACs more frequently (p < 0.001). The majority of respondents (73%) felt completely or rather confident in providing expert information regarding DOACs. Higher confidence was associated with respondents working in hospital pharmacies or pharmacies located in health centres (p < 0.05), working in clinical pharmacy wards (p < 0.05) and being more likely to dispense DOACs in the pharmacy (p < 0.001). Higher confidence was related to the areas pharmacists discussed with patients during DOAC dispensing, e.g., reasons for using DOACs or how to administer. CONCLUSION: The frequency of dispensing DOACs, type of pharmacy, and working as clinical pharmacist influenced respondents' confidence towards DOACs. Confidence may have influenced the course of DOAC dispensing in the pharmacy. Consolidating the pharmacist's position in patient education during DOAC treatment and strengthening pharmacists' confidence in dispensing DOACs should be therefore considered.

• Klíčová slova
• pharmacists, DOACs, attitude, opinions, education,
• MeSH
• antikoagulancia * terapeutické užití   MeSH
• aplikace orální MeSH
• farmaceuti * MeSH
• lidé MeSH
• postoj zdravotnického personálu * MeSH
• průzkumy a dotazníky MeSH
• vzdělávání pacientů jako téma * MeSH
• zdraví - znalosti, postoje, praxe MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antikoagulancia * MeSH

Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare disease characterized by accumulation of yellowish deposits in the macula. Rarely, it may be complicated by choroidal neovascularization (CNV). Cases with CNV may be confused with occult CNV in age-related macular degeneration. In our case, we will present the visual and anatomical results of a patient with AOVF-related CNV, in which we administered 3 doses of intravitreal ranibizumab (IVR). A 59-year-old female patient, who attended our clinic with the complaint of decreased vision in both eyes, was diagnosed with AOVF-related CNV in both eyes and was treated with 3 doses of IVR for 3 months. Despite the improvement in visual and anatomical functions 1 month after the first dose, vision decreased, and anatomical functions regressed to the pre-injection state in continued injections. IVR therapy is not an appropriate treatment option in the treatment of AOVF-associated CNV.

• Klíčová slova
• adult onset vitelliform dystrophy, anti-VEGF, optic coherence tomography, retinal dystrophy, subretinal deposits,
• MeSH
• Bestova nemoc * farmakoterapie   diagnostické zobrazování   diagnóza   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   MeSH
• inhibitory angiogeneze * aplikace a dávkování   MeSH
• injekce intravitreální * MeSH
• lidé středního věku MeSH
• lidé MeSH
• neovaskularizace choroidey farmakoterapie   diagnostické zobrazování   MeSH
• ranibizumab * aplikace a dávkování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• humanizované monoklonální protilátky MeSH
• inhibitory angiogeneze * MeSH
• ranibizumab * MeSH