BACKGROUND: Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known. METHODS: EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0-2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union's Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028. DISCUSSION: EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023.

• MeSH
• antitumorózní látky alkylující * terapeutické užití   MeSH
• časové faktory MeSH
• chemoradioterapie metody   MeSH
• doba přežití bez progrese choroby * MeSH
• glioblastom * patologie   farmakoterapie   mortalita   radioterapie   terapie   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kvalita života MeSH
• lidé MeSH
• lomustin * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• multicentrické studie jako téma * MeSH
• nádory mozku * radioterapie   patologie   mortalita   terapie   MeSH
• pragmatické klinické studie jako téma MeSH
• progrese nemoci * MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND: The growing number of patients with type 2 diabetes and prediabetes is a major public health concern. Physical activity is a cornerstone of diabetes management and may prevent its onset in prediabetes patients. Despite this, many patients with (pre)diabetes remain physically inactive. Primary care physicians are well-situated to deliver interventions to increase their patients' physical activity levels. However, effective and sustainable physical activity interventions for (pre)diabetes patients that can be translated into routine primary care are lacking. METHODS: We describe the rationale and protocol for a 12-month pragmatic, multicentre, randomised, controlled trial assessing the effectiveness of an mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED). Twenty-one general practices will recruit 340 patients with (pre)diabetes during routine health check-ups. Patients allocated to the active control arm will receive a Fitbit activity tracker to self-monitor their daily steps and try to achieve the recommended step goal. Patients allocated to the intervention arm will additionally receive the mHealth intervention, including the delivery of several text messages per week, with some of them delivered just in time, based on data continuously collected by the Fitbit tracker. The trial consists of two phases, each lasting six months: the lead-in phase, when the mHealth intervention will be supported with human phone counselling, and the maintenance phase, when the intervention will be fully automated. The primary outcome, average ambulatory activity (steps/day) measured by a wrist-worn accelerometer, will be assessed at the end of the maintenance phase at 12 months. DISCUSSION: The trial has several strengths, such as the choice of active control to isolate the net effect of the intervention beyond simple self-monitoring with an activity tracker, broad eligibility criteria allowing for the inclusion of patients without a smartphone, procedures to minimise selection bias, and involvement of a relatively large number of general practices. These design choices contribute to the trial's pragmatic character and ensure that the intervention, if effective, can be translated into routine primary care practice, allowing important public health benefits. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05351359, 28/04/2022).

• MeSH
• cvičení MeSH
• diabetes mellitus 2. typu * prevence a kontrola   MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• pragmatické klinické studie jako téma MeSH
• praktické lékařství * MeSH
• prediabetes * terapie   MeSH
• randomizované kontrolované studie jako téma MeSH
• sedavý životní styl MeSH
• telemedicína * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH

• Klíčová slova
• pembrolizumab, vibostolimab,
• MeSH
• imunoterapie MeSH
• ipilimumab aplikace a dávkování   farmakologie   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• lidé MeSH
• malobuněčný karcinom * farmakoterapie   mortalita   MeSH
• nádory plic farmakoterapie   mortalita   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   mortalita   MeSH
• nivolumab aplikace a dávkování   farmakologie   MeSH
• pragmatické klinické studie jako téma MeSH
• protokoly antitumorózní kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses. METHODS/DESIGN: The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis. DISCUSSION: In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis. TRIAL REGISTRATION: ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.

• MeSH
• blízká infračervená spektroskopie přístrojové vybavení   metody   MeSH
• jednotky intenzivní péče o novorozence MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• monitorování fyziologických funkcí přístrojové vybavení   metody   MeSH
• mozek diagnostické zobrazování   metabolismus   patologie   MeSH
• mozková hypoxie diagnóza   epidemiologie   terapie   MeSH
• multicentrické studie jako téma MeSH
• novorozenci extrémně nezralí * MeSH
• novorozenec MeSH
• pragmatické klinické studie jako téma MeSH
• randomizované kontrolované studie jako téma MeSH
• terapie náhlých příhod metody   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• dopisy MeSH

BACKGROUND: Intensive care unit (ICU)-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 h of ICU admission may improve muscle function and long-term outcome. METHODS: An assessor-blinded, pragmatic, single-centre randomized controlled trial will be performed. Adults (n = 150) mechanically ventilated for < 48 h from four ICUs who are estimated to need > 7 days of critical care will be randomized (1:1) to receive either standard of care or FES-CE-based intensified rehabilitation, which will continue until ICU discharge. PRIMARY OUTCOME: quality of life measured by 36-Item Short Form Health Survey score at 6 months. SECONDARY OUTCOMES: functional performance at ICU discharge, muscle mass (vastus ultrasound, N-balance) and function (Medical Research Council score, insulin sensitivity). In a subgroup (n = 30) we will assess insulin sensitivity and perform skeletal muscle biopsies to look at mitochondrial function, fibre typing and regulatory protein expression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02864745. Registered on 12 August 2016.

• MeSH
• časové faktory MeSH
• cyklistika * MeSH
• elektrostimulační terapie * škodlivé účinky   MeSH
• ergometrie * MeSH
• jednotky intenzivní péče MeSH
• kosterní svaly inervace   MeSH
• kritický stav MeSH
• kvalita života MeSH
• lidé MeSH
• obnova funkce MeSH
• pragmatické klinické studie jako téma MeSH
• svalová kontrakce * MeSH
• svalová síla * MeSH
• svalová slabost diagnóza   patofyziologie   rehabilitace   MeSH
• výsledek terapie MeSH
• zátěžový test MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Česká republika MeSH

INTRODUCTION: Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock. METHODS: CLASSIC trial is an investigator-initiated, international, randomised, stratified, and analyst-blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health-related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre-defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention-to-treat (ITT) population. DISCUSSION: The CLASSIC trial results will provide important evidence to guide clinicians' choice regarding the IV fluid therapy in adults with septic shock.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• interpretace statistických dat MeSH
• klinické protokoly * MeSH
• kognice MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• péče o pacienty v kritickém stavu MeSH
• pragmatické klinické studie jako téma MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• septický šok mortalita   psychologie   terapie   MeSH
• tekutinová terapie škodlivé účinky   metody   MeSH
• výsledek terapie MeSH
• výzkumný projekt 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
• randomizované kontrolované studie MeSH

• Klíčová slova
• tocilizumab,
• MeSH
• dítě MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• humanizované monoklonální protilátky MeSH
• kongresy jako téma MeSH
• lidé MeSH
• obrovskobuněčná arteritida farmakoterapie   MeSH
• pragmatické klinické studie jako téma MeSH
• randomizované kontrolované studie jako téma MeSH
• receptory interleukinu-6 antagonisté a inhibitory   MeSH
• revmatické nemoci * farmakoterapie   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• srovnávací studie MeSH

BACKGROUND: Randomized clinical trials have proven mechanical thrombectomy (MT) to be a highly effective and safe treatment in acute stroke. The purpose of this study was to compare neurothrombectomy data from the Czech Republic (CR) with data from the HERMES meta-analysis. METHODS: Available nationwide data for the CR from 2016 from the Safe Implementation of Treatments in Stroke-Thrombectomy (SITS-TBY) registry for patients with terminal internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlusions were compared with data from HERMES. CR and HERMES patients were comparable in age, sex, and baseline National Institutes of Health Stroke Scale scores. RESULTS: From a total of 1053 MTs performed in the CR, 845 (80%) were reported in the SITS-TBY. From these, 604 (72%) were included in this study. Occlusion locations were as follows (CR vs HERMES): ICA 22% versus 21% (P=0.16), M1 MCA 62% versus 69% (P=0.004), and M2 MCA 16% versus 8% (P<0.0001). Intravenous thrombolysis was given to 76% versus 83% of patients, respectively (P=0.003). Median onset to reperfusion times were comparable: 232 versus 285 min, respectively (P=0.66). A modified Thrombolysis in Cerebral Infarction score of 2b/3 was achieved in 74% (433/584) versus 71% (390/549) of patients, respectively (OR 1.17, 95% CI 0.90-1.5, P=0.24). There was no statistically significant difference in the percentage of parenchymalhematoma type 2 (OR 1.12, 95% CI 0.66-1.90, P=0.68). A modified Rankin Scale score of 0-2 at 3 months was achieved in 48% (184/268) versus 46% (291/633) of patients, respectively (OR 0.92, 95% CI 0.71-1.18, P=0.48). CONCLUSIONS: Data on efficacy, safety, and logistics of MT from the CR were similar to data from the HERMES collaboration.

• MeSH
• arteria carotis interna diagnostické zobrazování   MeSH
• cévní mozková příhoda diagnostické zobrazování   epidemiologie   terapie   MeSH
• infarkt arteria cerebri media diagnostické zobrazování   epidemiologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pragmatické klinické studie jako téma metody   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stenty * MeSH
• trombektomie škodlivé účinky   metody   trendy   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
• metaanalýza MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12-64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48-72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN27908921; Pre-results.

• MeSH
• analýza nákladů a výnosů MeSH
• antivirové látky ekonomika   terapeutické užití   MeSH
• bolesti hlavy virologie   MeSH
• časové faktory MeSH
• chřipka lidská komplikace   farmakoterapie   prevence a kontrola   MeSH
• činnosti denního života MeSH
• horečka virologie   MeSH
• hospitalizace MeSH
• léky bez předpisu terapeutické užití   MeSH
• léky na předpis terapeutické užití   MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• myalgie virologie   MeSH
• oseltamivir ekonomika   terapeutické užití   MeSH
• péče o sebe MeSH
• pneumonie virologie   MeSH
• pragmatické klinické studie jako téma * MeSH
• určení symptomu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH

• MeSH
• biomedicínský výzkum metody   trendy   MeSH
• diabetes mellitus MeSH
• hodnocení léčiv metody   trendy   využití   MeSH
• klinické zkoušky jako téma * metody   organizace a řízení   využití   MeSH
• lékařská praxe založená na důkazech metody   trendy   MeSH
• lidé MeSH
• ověření koncepční studie MeSH
• pragmatické klinické studie jako téma * klasifikace   metody   využití   MeSH
• randomizované kontrolované studie jako téma * metody   využití   MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH