INTRODUCTION: Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE). METHODS: The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF - "lack of efficacy" (LE) and "intolerance" (INT). RESULTS: While 263 (43%) of 612 patients received no second AF ("non-switched"), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: -98ml/y in switched and -172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001). CONCLUSION: The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy.

• MeSH
• idiopatická plicní fibróza * farmakoterapie   MeSH
• lidé MeSH
• progrese nemoci MeSH
• pyridony škodlivé účinky   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: There is a lack of data on the long-term effect of nintedanib on survival in specific groups of idiopathic pulmonary fibrosis (IPF) patients with different phenotypes. We investigated the outcomes of nintedanib therapy in an observational study of a large multicentre real-world cohort of IPF patients with various initial characteristics. METHODS: The analysis included IPF patients treated with nintedanib (NIN) and IPF patients not receiving antifibrotic treatment (NAF) enrolled for the EMPIRE registry in 2015-2020. The patients were stratified according to their initial FVC predicted, dyspnoea, UIP pattern and age. All-cause mortality and annual rate of FVC decline were the main endpoints. Cox proportional hazards model for survival assessment and linear mixed-effects model for FVC decline modelling were used. RESULTS: A total of 869 NIN patients and 691 NAF patients were eligible for the analysis. The annual FVC decline rate was significantly different (adjusted values -0.053 l/yr vs -0.122 l/yr; p = 0.001). The adjusted hazard ratio (HR) for mortality was 0.40 (95 % CI 0.3 to 0.53, p < 0.001). The most significant effect of nintedanib was demonstrated in patients with impaired lung function, i.e., with an FVC predicted to be less than 80 % and a NYHA II to IV. Nintedanib therapy also reduced the difference in survival between men and women. CONCLUSIONS: Modelling confirmed that NIN therapy reduced differences in OS between patients with better and worse initial conditions and prognosis. Our results indicate that NIN is particularly beneficial for patients with advanced IPF and more severe phenotypes. TRIAL REGISTRATION: EMPIRE was registered as a non-interventional post-registration study at the State Institute for Drug Control of the Czech Republic under ID 1412080000 on December 8, 2014.

• MeSH
• antifibrotické látky terapeutické užití   MeSH
• časové faktory MeSH
• fenotyp MeSH
• idiopatická plicní fibróza * farmakoterapie   mortalita   patofyziologie   MeSH
• indoly * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• proporcionální rizikové modely MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

There are limited data on referral rates and the number of patients with idiopathic pulmonary fibrosis (IPF) who are eligible for lung transplantation. The aim of the present study was to assess adherence to the consensus of the International Society for Heart and Lung Transplantation (ISHLT) for the referral of patients with IPF among Czech interstitial lung disease (ILD) centers. Czech patients who were diagnosed with IPF between 1999 and 2021 (n = 1584) and who were less than 65 years old at the time of diagnosis were retrospectively selected from the Czech Republic of the European Multipartner Idiopathic Pulmonary Fibrosis Registry (EMPIRE). Nonsmokers and ex-smokers with a body mass index (BMI) of <32 kg/m2 (n = 404) were included for further analyses. Patients with a history of cancer <5 years from the time of IPF diagnosis, patients with alcohol abuse, and patients with an accumulation of vascular comorbidities were excluded. The trajectory of individual patients was verified at the relevant ILD center. From the database of transplant patients (1999-12/2021, n = 541), all patients who underwent transplantation for pulmonary fibrosis (n = 186) were selected, and the diagnosis of IPF was subsequently verified from the patient's medical records (n = 67). A total of 304 IPF patients were eligible for lung transplantation. Ninety-six patients were referred to the transplant center, 50% (n = 49) of whom were referred for lung transplantation. Thirty percent of potentially eligible patients not referred to the transplant center were considered to have too many comorbidities by the reporting physician, 19% of IPF patients denied lung transplantation, and 17% were not referred due to age. Among Czech patients with IPF, there may be a larger pool of potential lung transplant candidates than has been reported to the transplant center to date.

• MeSH
• dodržování směrnic statistika a číselné údaje   MeSH
• dospělí MeSH
• idiopatická plicní fibróza * chirurgie   MeSH
• intersticiální plicní nemoci chirurgie   MeSH
• konziliární vyšetření a konzultace * statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace plic * statistika a číselné údaje   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

• Publikační typ
• abstrakt z konference MeSH

INTRODUCTION: The antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry. PATIENTS/METHODS: Data of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated. RESULTS: During 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN). CONCLUSION: Our real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI.

• MeSH
• idiopatická plicní fibróza * farmakoterapie   MeSH
• lidé MeSH
• plíce MeSH
• registrace MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Kratom, vyskytující se zejména v oblasti jihovýchodní Asie, je specifická rostlina, která je využívaná pro své psychoaktivní účinky. I když je známá v oblasti výskytu již od 18. století, v Evropě se začíná objevovat až v posledních dvou desetiletích. Její hlavní účinnou látkou je alkaloid mitragynin, jehož účinek je vázaný na užitou dávku. Při nižších dávkách působí stimulačně, při vyšších navozuje stavy podobné efektu opioidů, což je dané jeho působením na specifické opioidní receptory. Diskutované jsou zejména možnosti použití kratomu ve specifických oblastech, zejména pak při léčbě bolesti či jako prostředku ke zvládání závislosti na opioidních látkách. Naproti tomu je silně probírán jeho potenciál vyvolávat závislost, riziko poškození organismu jeho užíváním a toxicita. V posledních deseti letech jsme výzkumem tohoto produktu získali data týkající se jeho specifického působení, obsahu alkaloidů a farmakologie. Stále se však jedná o neprobádanou látku, což se odráží i v pohledech na jeho právní status a přístup odborníků k jeho medicínskému použití. V tomto článku se snažíme shrnout známá data o základních vlastnostech kratomu. Zabýváme se zejména jeho ukotvením a rolí v současné kultuře, farmakologickým profilem, potenciálním léčebným efektem, návykovostí, ale i legislativním statusem. Tato data jsme získali detailním prostudováním publikovaných dat, a to zejména z posledních deseti let.

Kratom is a specific plant occurring mainly in Southeast Asia and is used for its psychoactive effects. Although it has been known in the area since 18th century, it has only begun to appear in Europe in the last two decades. Its main active substance is the alkaloid mitragynin, the effect of which is tied to the dose used. At lower doses it acts as a stimulant, at higher doses it induces conditions similar to the effect of opioids, which is due to its action on specific opioid receptors. In particular, the possibilities of using kratom in specific areas are discussed. Especially in the treatment of pain or as a means of managing opioids addiction. On the other hand, its potential to cause addiction, the risk of harm to the body through its use and toxicity are strongly discussed. In the last ten years, we have researched this product to obtain data on its specific action, alkaloid content and pharmacology. However, it is still an unexplored substance, which is also reflected in the views of its legal status and the approach of experts to its medical use. In this article, we try to summarize known data on the basic properties of kratom. We deal mainly with its anchoring and role in the current culture, pharmacological profile, potential therapeutic effect, addictiveness but also legislative status. We obtained these data by a detailed study of published data, especially from the last ten years

• MeSH
• analgetika MeSH
• indolové alkaloidy farmakokinetika   farmakologie   MeSH
• lidé MeSH
• Mitragyna * chemie   škodlivé účinky   toxicita   MeSH
• poruchy spojené s užíváním opiátů MeSH
• rostlinné přípravky MeSH
• zneužívání léků na předpis MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis IPF We analysed the association of common profibrotic polymorphisms in MUC5B mucin 5B rs35705950 and DSP desmoplakin rs2076295 on antifibrotic treatment outcomes in IPF METHODS MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients n 210 139 men 71 women from

• MeSH
• desmoplakiny * genetika   MeSH
• idiopatická plicní fibróza * farmakoterapie   genetika   MeSH
• indoly * terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• pilotní projekty MeSH
• pyridony * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• pirfenidon, nintedanib,
• MeSH
• idiopatická plicní fibróza * diagnóza   epidemiologie   farmakoterapie   terapie   MeSH
• lidé MeSH
• progrese nemoci MeSH
• protinádorové látky aplikace a dávkování   ekonomika   farmakologie   MeSH
• transplantace plic MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

INTRODUCTION: Pirfenidone, an antifibrotic drug, slows-down the disease progression in idiopathic pulmonary fibrosis (IPF) over 12 months, however limited data on the decline of lung function and overall survival (OS) in real-world cohorts on longer follow-up exists. PATIENTS/METHODS: Of the enrolled Czech IPF patients (n = 841) from an EMPIRE registry, 383 (45.5%) received pirfenidone, 218 (25.9%) no-antifibrotic treatment and 240 (28.5%) were excluded (missing data, nintedanib treatment). The 2- and 5-yrs OS and forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO) were investigated at treatment initiation and 6, 12, 18 and 24 months' follow-up. RESULTS: During a 2-yr follow-up, less than a quarter of the patients progressed on pirfenidone as assessed by the decline of ≥10% FVC (17.0%) and ≥ 15% DLCO (14.3%). On pirfenidone, the DLCO (≥10%) declines at 6, 12, 18 and 24 months' and DLCO (≥15%) declines at 6, 18 and 24 months' follow-up were associated with increased mortality. The DLCO decline showed higher predictive value for mortality than FVC decline. In patients with no-antifibrotics, FVC and DLCO declines were not predictive for mortality. Pirfenidone increased 5-yrs OS over no-antifibrotic treatment (55.9% vs 31.5% alive, P = 0.002). CONCLUSION: Our study observed the 2-yrs sustained effect of pirfenidone on the decline of lung function and survival in the real-world patient's IPF cohort. DLCO decline of ≥10% shows a potential as a mortality predictor in IPF patients on pirfenidone, and should be routinely evaluated during follow-up examinations.

• MeSH
• antiflogistika nesteroidní farmakologie   terapeutické užití   MeSH
• idiopatická plicní fibróza diagnóza   farmakoterapie   epidemiologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• progrese nemoci * MeSH
• pyridony farmakologie   terapeutické užití   MeSH
• registrace * MeSH
• respirační funkční testy trendy   MeSH
• senioři MeSH
• vitální kapacita účinky léků   fyziologie   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
• Geografické názvy
• Česká republika MeSH