BACKGROUND: Data regarding real-life effectiveness of any treatment may improve clinical decision-making. The aim of this study was to evaluate real-life effectiveness of tyrosin-kinase inhibitors, bevacizumab and pemetrexed as first-line treatments in patients with advanced/metastatic non-small cell lung cancer (NSCLC). METHODS: We analyzed data of 2157 patients of the Czech TULUNG Registry of patients with advanced/metastatic NSCLC who received modern-era treatments between 2011 and 2018. Patients treated with gefitinib, erlotinib, afatinib, bevacizumab (+ maintenance), pemetrexed (+ maintenance) as first-line therapy were included in the study. A systematic literature search separately identified clinical trials suitable for calculation of comparator pooled OS and PFS for each regimen. For each subgroup, basic characteristics and survival data (Kaplan-Meier estimates) are shown. We propose the "index of real-life effectiveness" (IRE), a ratio of real-life OS/PFS and comparator pooled OS/PFS. Univariate and multivariate logistic regression identified factors were associated with longer OS (ie, IRE>1.1). RESULTS: Survival analysis showed median OS of 23 months for erlotinib, 29.3 months for afatinib, 19.6 months for gefitinib, 12.2 months for pemetrexed, 17.5 months for pemetrexed maintenance, 15.8 months for bevacizumab and 15.8 months for bevacizumab maintenance. Calculated IREs for OS for the regimens were: erlotinib 1.013, afatinib 1.184, gefitinib 0.736, pemetrexed 1.188, pemetrexed maintenance 1.294, bevacizumab 1.178, and bevacizumab maintenance 1.189. Multivariate regression analysis showed that these factors were associated with longer OS: lower PS for afatinib; lower PS, absence of adverse events and female sex for bevacizumab; and lower PS and female sex for pemetrexed. CONCLUSIONS: This study clearly demonstrated that real-life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems, and comparison between TULUNG data and pooled survival data from trials showed higher real-life effectiveness for most of the studied first-line regimens. Lower ECOG PS, younger age, female sex and adverse events were associated with longer survival in most regimens. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Comparison between TULUNG data and pooled survival data from trials showed higher real-life effectiveness for most of the studied first-line regimens; for most regimens, lower ECOG PS, younger age, female sex and adverse events were associated with longer survival. WHAT THIS STUDY ADDS: Real-life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems.

• Klíčová slova
• Anticancer treatment, non-small cell lung cancer, progression-free survival, real-life effectiveness, tyrosinkinase inhibitors,
• MeSH
• analýza přežití MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic farmakoterapie   mortalita   patologie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   mortalita   patologie   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• registrace MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies. OBJECTIVE: To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. METHODS: We assessed the MASK-air® data of European users with self-reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales-VASs), and a combined symptom-medication score (CSMS). We applied Bayesian mixed-effects models, with clustering by patient, country and pollen season. RESULTS: We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT-tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = -12.1;-2.8), lower VAS Work (average difference = 5.0; 95%CrI = -8.5;-1.5), and a lower CSMS (average difference = 3.7; 95%CrI = -9.3;2.2). When compared to SCIT, SLIT-tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = -17.2;-2.8), lower VAS Work (average difference = 7.8; 95%CrI = -15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = -18.5;0.2). CONCLUSION: In patients with grass pollen allergy, SLIT-tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally-harmonised standards for performing and reporting real-world data in AIT are needed to better understand its 'real-world' effectiveness.

• Klíčová slova
• allergic rhinitis, immunotherapy, mobile health, patient-reported outcomes, real-life data analysis,
• Publikační typ
• časopisecké články MeSH

Human health risk assessment of chemical mixtures is complex due to the almost infinite number of possible combinations of chemicals to which people are exposed to on a daily basis. Human biomonitoring (HBM) approaches can provide inter alia information on the chemicals that are in our body at one point in time. Network analysis applied to such data may provide insight into real-life mixtures by visualizing chemical exposure patterns. The identification of groups of more densely correlated biomarkers, so-called "communities", within these networks highlights which combination of substances should be considered in terms of real-life mixtures to which a population is exposed. We applied network analyses to HBM datasets from Belgium, Czech Republic, Germany, and Spain, with the aim to explore its added value for exposure and risk assessment. The datasets varied in study population, study design, and chemicals analysed. Sensitivity analysis was performed to address the influence of different approaches to standardise for creatinine content of urine. Our approach demonstrates that network analysis applied to HBM data of highly varying origin provides useful information with regards to the existence of groups of biomarkers that are densely correlated. This information is relevant for regulatory risk assessment, as well as for the design of relevant mixture exposure experiments.

• Klíčová slova
• HBM4EU, chemical mixtures, clustering, combined exposure, human biomonitoring, mixture risk assessment, network analysis,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Risankizumab has been approved for the treatment of moderate-to-severe plaque psoriasis; however, real-life data are limited. Our objectives were to evaluate the effectiveness and safety of risankizumab and its impact on the quality of life of patients with psoriasis in a real-world setting. METHODS: We retrospectively analyzed 154 patients from 18 centers in the Czech Republic who had undergone biologic therapy with risankizumab for moderate-to-severe plaque psoriasis. Baseline characteristics included data on comorbidities, demographics, previous therapies, Dermatology Life Quality Index (DLQI) score, and Psoriasis Area and Severity Index (PASI) score. The proportion of patients achieving a 90% improvement in their PASI score from baseline (PASI 90) and complete resolution (PASI 100) after 16, 28, and 52 weeks was analyzed. RESULTS: A total of 95 men and 59 women with mean body mass index (BMI) of 29.6 were enrolled in our analysis. The mean age of the patients was 48.5 years and the mean time from diagnosis until initiation of risankizumab therapy was 22.5 years. After 16 weeks, 63.8 and 44.7% patients achieved PASI 90 and PASI 100 responses, respectively. Improvement continued with time, and the proportion of patients with PASI 90 and PASI 100 responses increased to 82.4 and 67.6%, respectively, at week 52. A significant reduction was observed over time in the DLQI. Patients achieving PASI 100 response at week 16 had a higher reduction in the DLQI score than those with PASI 90 response (- 15.9 vs. - 11.8). PASI 90 and PASI 100 responses were independent of the BMI and previous biologic therapy. No new safety issues were identified. CONCLUSIONS: In this patient population, risankizumab was effective and safe in a real-world setting, and a high number of patients achieved PASI 90 and PASI 100 responses. A higher reduction in the DLQI was seen in patients with PASI 100 response, which supports the evidence that this value should be the new therapeutic goal.

• Klíčová slova
• Psoriasis, Real-life, Registry, Risankizumab,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient-reported outcomes by mobile technology offers the possibility to better understand real-life burden of CRS. METHODS: This study reports on the cross-sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients. Patient characteristics of mSC users were analysed as well as the level of disease control based on VAS global rhinosinusitis symptom score and adapted EPOS criteria. RESULTS: The mSC cohort represents a heterogeneous group of CRS patients with a diverse pattern of major symptoms. Approximately half of patients reported nasal polyps. 47.3% of all CRS patients were uncontrolled based on evaluation of VAS global rhinosinusitis symptom score compared to 40.9% based on adapted EPOS criteria. The impact of CRS on sleep quality and daily life activities was significantly higher in uncontrolled versus well-controlled patients. Half of patients had a history of FESS (functional endoscopic sinus surgery) and reported lower symptom severity compared to patients without a history of FESS, except for patients with a history of more than 3 procedures. Patients with a history of FESS reported higher VAS levels for impaired smell. CONCLUSION: Real-life data confirm the high disease burden in uncontrolled CRS patients, clearly impacting quality of life. Sinus surgery improves patient-reported outcomes, but not in patients with a history of more than 3 procedures. Mobile technology opens a new era of real-life monitoring, supporting the evolution of care towards precision medicine.

• Klíčová slova
• Mobile health technology, nasal polyp, patient-reported outcome measure, real-world evidence, visual analogue scale,
• MeSH
• chronická nemoc MeSH
• kvalita života MeSH
• lidé MeSH
• nosní polypy * epidemiologie   MeSH
• průřezové studie MeSH
• rýma * diagnóza   epidemiologie   MeSH
• sinusitida * diagnóza   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: International guidelines recommend at least three months anticoagulation in all patients after acute venous thromboembolism (VTE) and suggest those with unprovoked events be considered for indefinite anticoagulation if the risk of recurrence is high and the risk of bleeding during treatment non-high. Other authors have recently argued against using a dichotomy unprovoked/provoked events to decide on anticoagulation duration and suggest instead using overall risk factors present in each patient as the basis for deciding. AIM: This sub-analysis of the WHITE study aimed at assessing the reasons for the treatment decisions taken by doctors in different countries. RESULTS: 1240 patients were recruited in 7 countries (China, Czechia, Poland, Portugal, Russia, Slovakia, and Tunisia). Anticoagulation was extended in 51.7% and 49.3% of patients with unprovoked or provoked events (n.s.); stopped in 15.4% versus 28.9% (P < .0001), and changed to antithrombotic drugs (sulodexide or aspirin) in 32.9% versus 21.8% (P < .0001). In the 430 subjects with isolated distal deep vein thrombosis (IDDVT) anticoagulation was stopped in 34.4%, continued in 37.0% (mainly those with post-thrombotic syndrome [PTS]) and switched to antithrombotics in the balance. High risk of recurrence was the most prevalent reason (>83% of cases) given to continue anticoagulation, regardless of nature and site of the index events, followed by risk of bleeding and presence of PTS signs. CONCLUSION: On average, attending physicians estimated the risk of recurrence in real life conditions, and the consequent therapeutic decision, using all the information available, not limiting to the location or nature of the index event.

• Klíčová slova
• anticoagulants, anticoagulation, antithrombotics, aspirin, sulodexide, venous thromboembolism,
• MeSH
• antikoagulancia terapeutické užití   MeSH
• hemokoagulace fyziologie   MeSH
• incidence MeSH
• lidé MeSH
• rizikové faktory MeSH
• žilní tromboembolie epidemiologie   etiologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Čína epidemiologie   MeSH
• Názvy látek
• antikoagulancia MeSH

OBJECTIVE: Several aspects of rituximab (RTX) retreatment in rheumatoid arthritis (RA) need to be further elucidated. The aim of this study was to describe the effect of repeated courses of RTX on disease activity and to compare 2 retreatment strategies, fixed-interval versus on-flare retreatment, in a large international, observational, collaborative study. METHODS: In the first analysis, patients with RA who received at least 4 cycles with RTX were included. In the second analysis, patients who received at least 1 RTX retreatment and for whom information about the strategy for retreatment was available were identified. Two retreatment strategies (fixed-interval vs on-flare) were compared by fitting-adjusted, mixed-effects models of 28-joint Disease Activity Score (DAS28) over time for first and second retreatment. RESULTS: A total of 1530 patients met the eligibility criteria for the first analysis. Significant reductions of mean DAS28 between the starts of subsequent treatment cycles were observed (at start of first treatment cycle: 5.5; second: 4.3; third: 3.8; and fourth: 3.5), suggesting improved response after each additional cycle (p < 0.0001 for all pairwise comparisons). A total of 800 patients qualified for the second analysis: 616 were retreated on flare and 184 at fixed interval. For the first retreatment, the fixed-interval retreatment group yielded significantly better results than the on-flare group (estimated marginal mean DAS28 = 3.8, 95% CI 3.6-4.1 vs 4.6, 95% CI 4.5-4.7, p < 0.0001). Similar results were found for the second retreatment. CONCLUSION: Repeated treatment with RTX leads to further clinical improvement after the first course of RTX. A fixed-interval retreatment strategy seems to be more effective than on-flare retreatment.

• Klíčová slova
• RETREATMENT, RHEUMATOID ARTHRITIS, RITUXIMAB,
• MeSH
• antirevmatika terapeutické užití   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• opakovaná terapie MeSH
• registrace MeSH
• revmatoidní artritida diagnóza   farmakoterapie   MeSH
• rituximab terapeutické užití   MeSH
• senioři MeSH
• stupeň závažnosti nemoci 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
• Názvy látek
• antirevmatika MeSH
• rituximab MeSH

BACKGROUND: Biologics have greatly improved psoriasis management. However, primary and secondary non-response to treatment requires innovative strategies to optimize outcomes. OBJECTIVE: To describe the use of combined treatment of biologics with conventional systemic agents or phototherapy in daily clinical practice. METHODS: We collected data on frequency of use, demographics, treatment characteristics and drug survival of biologics combined with conventional systemic agents or phototherapy in five PSONET registries. RESULTS: Of 9922 biologic treatment cycles, 982 (9.9%) were identified as combination treatment. 72.9% of treatment cycles concerned concomitant use of methotrexate, 25.3% concerned concomitant UVB therapy, acitretin or cyclosporin and 1.8% concerned combined treatment with PUVA, fumaric acids or a second biologic. Substantial variation was detected in type and frequency of combination treatments prescribed across registries. Patients initiated on combined treatment had generally severe disease and were affected with psoriasis for many years. The extent to which patients had been priory treated with biologic monotherapy and the proportion of patients affected with psoriatic arthritis differed between registries. Survival rates for etanercept, adalimumab, infliximab and ustekinumab with methotrexate ranged between 43 and 92%, 28 and 83%, 65 and 87% and 53 and 77%, respectively, across registries after one year with no consistent superior survival for a particular biologic. Longest survival on a biologic combined with methotrexate, acitretin or cyclosporin was 103, 78 and 34 months, respectively. CONCLUSION: Methotrexate was the most commonly used concomitant treatment for patients on a biologic. Wide geographical variations in treatment selection and persistence of combination treatment exist. Data derived from ongoing studies may help to determine whether combined treatment is superior to biologic monotherapy.

• MeSH
• acitretin terapeutické užití   MeSH
• adalimumab terapeutické užití   MeSH
• biologické přípravky terapeutické užití   MeSH
• cyklosporin terapeutické užití   MeSH
• dermatologické látky terapeutické užití   MeSH
• etanercept terapeutické užití   MeSH
• fumaráty terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• kombinovaná farmakoterapie MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• psoriáza terapie   MeSH
• PUVA terapie * MeSH
• registrace MeSH
• stupeň závažnosti nemoci MeSH
• ustekinumab terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Itálie MeSH
• Izrael MeSH
• Nizozemsko MeSH
• Rakousko MeSH
• Názvy látek
• acitretin MeSH
• adalimumab MeSH
• biologické přípravky MeSH
• cyklosporin MeSH
• dermatologické látky MeSH
• etanercept MeSH
• fumaráty MeSH
• fumaric acid MeSH Prohlížeč
• infliximab MeSH
• methotrexát MeSH
• ustekinumab MeSH

The study aimed to assess prognostic significance of del(13q14), del(17p13), t(4;14)(p16;q32), and amp(1q21) in newly diagnosed myeloma patients treated mostly with thalidomide-based therapies. All genetic abnormalities except del(13q14) were independent prognostic factors associated with shortened progression-free survival (PFS) and overall survival (OS). Patients with no abnormalities, one abnormality, and ≥2 abnormalities had a median PFS of 41.8, 17.0, and 10.0 months, respectively; a median OS was not reached, 48.0 and 23.3 months, respectively. According to the presence of amp(1q21), t(4;14)(p16;q32), and del(17p13) and the International Staging System (ISS), we stratified patients into low-risk, intermediate-risk and high-risk groups. A median PFS was 52.9, 25.6, and 10.0 months, respectively; a median OS was not reached, 64.0 and 25.0 months, respectively. In conclusion, our study confirmed the prognostic value of cytogenetic changes and showed that prognostic models based on ISS and cytogenetic studies should include not only del(17p13) and t(4;14)(p16;q32), but also amp(1q21).

• Klíčová slova
• Multiple myeloma, cytogenetic abnormalities, prognosis, thalidomide,
• MeSH
• analýza přežití MeSH
• chromozomální delece * MeSH
• duplikace chromozomů * MeSH
• hybridizace in situ fluorescenční MeSH
• incidence MeSH
• lidé MeSH
• lidské chromozomy, pár 1 MeSH
• lidské chromozomy, pár 14 MeSH
• lidské chromozomy, pár 17 MeSH
• lidské chromozomy, pár 4 MeSH
• mnohočetný myelom epidemiologie   genetika   mortalita   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• translokace genetická * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Polsko epidemiologie   MeSH

INTRODUCTION: Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted. METHODS AND ANALYSIS: Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank. PROSPERO REGISTRATION NUMBERS: CRD42020132990, CRD42020171624.

• Klíčová slova
• asthma, paediatric thoracic medicine, paediatrics, thoracic medicine,
• MeSH
• bronchiální astma * farmakoterapie   MeSH
• dítě MeSH
• hospitalizace MeSH
• lidé MeSH
• systematický přehled jako téma MeSH
• výzkumný projekt MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH