• MeSH
• finanční podpora výzkumu jako téma MeSH
• lidé MeSH
• městské obyvatelstvo MeSH
• mortalita trendy   MeSH
• ozon aplikace a dávkování   škodlivé účinky   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Spojené státy americké MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• hospitalizace statistika a číselné údaje   MeSH
• kardiovaskulární nemoci epidemiologie   etiologie   MeSH
• látky znečišťující vzduch klasifikace   MeSH
• lidé MeSH
• nemoci dýchací soustavy epidemiologie   etiologie   MeSH
• velikost částic MeSH
• znečištění životního prostředí škodlivé účinky   MeSH
• Check Tag
• lidé MeSH

• MeSH
• aktivátory plazminogenu aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• cerebrovaskulární poruchy diagnóza   etiologie   farmakoterapie   MeSH
• injekce intravenózní MeSH
• intrakraniální krvácení MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH
• Geografické názvy
• Spojené státy americké MeSH

BACKGROUND: Chronic lung infections and their treatment pose risks for the development of antimicrobial resistance (AMR) in people with cystic fibrosis (PWCF). In this study, we evaluated the attitudes of healthcare providers' (HCP) and PWCF or their parents' toward AMR within the international CF community. METHODS: HCP and PWCF identified through listservs and CF-related organizations were asked to complete an AMR centered survey, with additional questions on antimicrobial stewardship (AMS) for HCP. Descriptive analyses are reported. RESULTS: The responding 443 HCP and 464 PWCF/Parents were from 30 and 25 countries, respectively. Sixty-two percent of HCP and 56% of PWCF stated they were "very concerned" about AMR, with Pseudomonas spp. and Burkholderia spp. considered the most concerning organisms for both HCP and PWCF/Parents. Non-tuberculous mycobacteria were of greater concern to HCP compared to PWCF/Parents. There was a discrepancy regarding AMR education to PWCF, with 80% of HCP stating having discussed this with PWCF/Parents, but only 50% of PWCF recalling such discussions. CONCLUSION: These results highlight that AMR is relevant to CF HCP and PWCF internationally, indicating that educational tools and research are warranted.

• MeSH
• antibiotická politika * MeSH
• bakteriální léková rezistence * MeSH
• cystická fibróza mikrobiologie   MeSH
• infekce bakteriemi rodu Burkholderia farmakoterapie   MeSH
• lidé MeSH
• pacienti psychologie   MeSH
• průzkumy a dotazníky MeSH
• pseudomonádové infekce farmakoterapie   MeSH
• zdraví - znalosti, postoje, praxe * MeSH
• zdravotnický personál psychologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Several treatment approaches in cystic fibrosis (CF) aim to correct CF transmembrane conductance regulator (CFTR) function; the efficacy of each approach is dependent on the mutation(s) present. A need remains for more effective treatments to correct functional deficits caused by the F508del mutation. METHODS: Two placebo-controlled, phase 2a studies evaluated GLPG2222, given orally once daily for 29 days, in subjects homozygous for F508del (FLAMINGO) or heterozygous for F508del and a gating mutation, receiving ivacaftor (ALBATROSS). The primary objective of both studies was to assess safety and tolerability. Secondary objectives included assessment of pharmacokinetics, and of the effect of GLPG2222 on sweat chloride concentrations, pulmonary function and respiratory symptoms. RESULTS: Fifty-nine and 37 subjects were enrolled into FLAMINGO and ALBATROSS, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.2% (14/48) of subjects in FLAMINGO and 40.0% (12/30) in ALBATROSS; most were mild to moderate in severity and comprised primarily respiratory, gastrointestinal, and infection events. There were no deaths or discontinuations due to TEAEs. Dose-dependent decreases in sweat chloride concentrations were seen in GLPG2222-treated subjects (maximum decrease in FLAMINGO: -17.6 mmol/L [GLPG2222 200 mg], p < 0.0001; ALBATROSS: -7.4 mmol/L [GLPG2222 300 mg], p < 0.05). No significant effects on pulmonary function or respiratory symptoms were reported. Plasma GLPG2222 concentrations in CF subjects were consistent with previous studies in healthy volunteers and CF subjects. CONCLUSIONS: GLPG2222 was well tolerated. Sweat chloride reductions support on-target enhancement of CFTR activity in subjects with F508del mutation(s). Significant improvements in clinical endpoints were not demonstrated. Observed safety results support further evaluation of GLPG2222, including in combination with other CFTR modulators. FUNDING: Galapagos NV. Clinical trial registration numbers FLAMINGO, NCT03119649; ALBATROSS, NCT03045523.

• MeSH
• aktivátory chloridových kanálů aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• aminofenoly * aplikace a dávkování   škodlivé účinky   MeSH
• aplikace orální MeSH
• benzoáty * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• benzopyrany * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• biologická dostupnost MeSH
• chinolony * aplikace a dávkování   škodlivé účinky   MeSH
• cystická fibróza * diagnóza   farmakoterapie   genetika   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé MeSH
• monitorování léčiv MeSH
• mutace MeSH
• pot * chemie   účinky léků   MeSH
• protein CFTR genetika   MeSH
• respirační funkční testy metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy. METHODS: In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1-6 months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI). RESULTS: After 1 month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6 months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r = -0.5376; P < .001 and r = -0.3285; P < .001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β = -0.57, P = .019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581-0.863]; P = .029) were used as classifier, especially in the first 2 months of treatment (0.806 [95% CI 0.665-0.947]; P < .001). CONCLUSIONS: This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.

• MeSH
• aktivátory chloridových kanálů terapeutické užití   MeSH
• aminofenoly terapeutické užití   MeSH
• biologické markery analýza   MeSH
• chinolony terapeutické užití   MeSH
• cystická fibróza * genetika   patofyziologie   terapie   MeSH
• dítě MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• mutace MeSH
• pot chemie   MeSH
• protein CFTR genetika   MeSH
• protein WFDC2 analýza   MeSH
• respirační funkční testy metody   MeSH
• retrospektivní studie MeSH
• usilovný výdechový objem účinky léků   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinická studie MeSH
• práce podpořená grantem MeSH

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme.

• MeSH
• adherence pacienta MeSH
• cystická fibróza psychologie   terapie   MeSH
• dospělí MeSH
• lidé MeSH
• management nemoci MeSH
• péče o umírající * MeSH
• pneumologie výchova   pracovní síly   organizace a řízení   MeSH
• poradní výbory MeSH
• přechod k lékaři pro dospělé organizace a řízení   MeSH
• sociální opora MeSH
• společnosti lékařské MeSH
• transplantace plic MeSH
• zdravotnické plánování MeSH
• zdravotnické služby - potřeby a požadavky * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• Geografické názvy
• Evropa MeSH

Developments in managing CF continue to drive dramatic improvements in survival. As newborn screening rolls-out across Europe, CF centres are increasingly caring for cohorts of patients who have minimal lung disease on diagnosis. With the introduction of mutation-specific therapies and the prospect of truly personalised medicine, patients have the potential to enjoy good quality of life in adulthood with ever-increasing life expectancy. The landmark Standards of Care published in 2005 set out what high quality CF care is and how it can be delivered throughout Europe. This underwent a fundamental re-write in 2014, resulting in three documents; center framework, quality management and best practice guidelines. This document is a revision of the latter, updating standards for best practice in key aspects of CF care, in the context of a fast-moving and dynamic field. In continuing to give a broad overview of the standards expected for newborn screening, diagnosis, preventative treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support, this consensus on best practice is expected to prove useful to clinical teams both in countries where CF care is developing and those with established CF centres. The document is an ECFS product and endorsed by the CF Network in ERN LUNG and CF Europe.

• MeSH
• cystická fibróza komplikace   diagnóza   terapie   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• novorozenecký screening MeSH
• péče o umírající MeSH
• předškolní dítě MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• sociální opora MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH

The minipig provides an excellent experimental model for tooth morphogenesis because its diphyodont and heterodont dentition resemble that of humans. However, little information is available on the processes of tooth development in the pig. The purpose of this study was to classify the early stages of odontogenesis in minipigs from the initiation of deciduous dentition to the late bell stage when the successional dental lamina begins to develop. To analyze the initiation of teeth anlagens and the structural changes of dental lamina, a three-dimensional (3D) analysis was performed. At the earliest stage, 3D reconstruction revealed a continuous dental lamina along the length of the jaw. Later, the dental lamina exhibited remarkable differences in depth, and the interdental lamina was shorter. The dental lamina grew into the mesenchyme in the lingual direction, and its inclined growth was underlined by asymmetrical cell proliferation. After the primary tooth germ reached the late bell stage, the dental lamina began to disintegrate and fragmentize. Some cells disappeared during the process of lamina degradation, while others remained in small islands known as epithelial pearls. The minipig can therefore, inter alia, be used as a model organism to study the fate of epithelial pearls from their initiation to their contribution to pathological structures, primarily because of the clinical significance of these epithelial rests.

• MeSH
• bazální membrána embryologie   MeSH
• buněčná diferenciace fyziologie   MeSH
• dentin embryologie   MeSH
• epitel embryologie   MeSH
• mezoderm embryologie   MeSH
• miniaturní prasata MeSH
• modely u zvířat MeSH
• morfogeneze fyziologie   MeSH
• odontoblasty cytologie   MeSH
• odontogeneze fyziologie   MeSH
• orgán skloviny embryologie   MeSH
• počítačové zpracování obrazu metody   MeSH
• prasata MeSH
• premolár embryologie   MeSH
• proliferace buněk MeSH
• proliferační antigen buněčného jádra analýza   MeSH
• řezáky embryologie   MeSH
• špičák embryologie   MeSH
• zobrazování trojrozměrné metody   MeSH
• zubní zárodek embryologie   MeSH
• zuby mléčné embryologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

The past six decades have seen remarkable improvements in health outcomes for people with cystic fibrosis, which was once a fatal disease of infants and young children. However, although life expectancy for people with cystic fibrosis has increased substantially, the disease continues to limit survival and quality of life, and results in a large burden of care for people with cystic fibrosis and their families. Furthermore, epidemiological studies in the past two decades have shown that cystic fibrosis occurs and is more frequent than was previously thought in populations of non-European descent, and the disease is now recognised in many regions of the world. The Lancet Respiratory Medicine Commission on the future of cystic fibrosis care was established at a time of great change in the clinical care of people with the disease, with a growing population of adult patients, widespread genetic testing supporting the diagnosis of cystic fibrosis, and the development of therapies targeting defects in the cystic fibrosis transmembrane conductance regulator (CFTR), which are likely to affect the natural trajectory of the disease. The aim of the Commission was to bring to the attention of patients, health-care professionals, researchers, funders, service providers, and policy makers the various challenges associated with the changing landscape of cystic fibrosis care and the opportunities available for progress, providing a blueprint for the future of cystic fibrosis care. The discovery of the CFTR gene in the late 1980s triggered a surge of basic research that enhanced understanding of the pathophysiology and the genotype-phenotype relationships of this clinically variable disease. Until recently, available treatments could only control symptoms and restrict the complications of cystic fibrosis, but advances in CFTR modulator therapies to address the basic defect of cystic fibrosis have been remarkable and the field is evolving rapidly. However, CFTR modulators approved for use to date are highly expensive, which has prompted questions about the affordability of new treatments and served to emphasise the considerable gap in health outcomes for patients with cystic fibrosis between high-income countries, and low-income and middle-income countries (LMICs). Advances in clinical care have been multifaceted and include earlier diagnosis through the implementation of newborn screening programmes, formalised airway clearance therapy, and reduced malnutrition through the use of effective pancreatic enzyme replacement and a high-energy, high-protein diet. Centre-based care has become the norm in high-income countries, allowing patients to benefit from the skills of expert members of multidisciplinary teams. Pharmacological interventions to address respiratory manifestations now include drugs that target airway mucus and airway surface liquid hydration, and antimicrobial therapies such as antibiotic eradication treatment in early-stage infections and protocols for maintenance therapy of chronic infections. Despite the recent breakthrough with CFTR modulators for cystic fibrosis, the development of novel mucolytic, anti-inflammatory, and anti-infective therapies is likely to remain important, especially for patients with more advanced stages of lung disease. As the median age of patients with cystic fibrosis increases, with a rapid increase in the population of adults living with the disease, complications of cystic fibrosis are becoming increasingly common. Steps need to be taken to ensure that enough highly qualified professionals are present in cystic fibrosis centres to meet the needs of ageing patients, and new technologies need to be adopted to support communication between patients and health-care providers. In considering the future of cystic fibrosis care, the Commission focused on five key areas, which are discussed in this report: the changing epidemiology of cystic fibrosis (section 1); future challenges of clinical care and its delivery (section 2); the building of cystic fibrosis care globally (section 3); novel therapeutics (section 4); and patient engagement (section 5). In panel 1, we summarise key messages of the Commission. The challenges faced by all stakeholders in building and developing cystic fibrosis care globally are substantial, but many opportunities exist for improved care and health outcomes for patients in countries with established cystic fibrosis care programmes, and in LMICs where integrated multidisciplinary care is not available and resources are lacking at present. A concerted effort is needed to ensure that all patients with cystic fibrosis have access to high-quality health care in the future.

• MeSH
• celosvětové zdraví MeSH
• cystická fibróza genetika   terapie   MeSH
• genetická terapie metody   MeSH
• kvalita života * MeSH
• lidé MeSH
• poskytování zdravotní péče trendy   MeSH
• progrese nemoci * MeSH
• protein CFTR aplikace a dávkování   MeSH
• transplantace plic metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH