This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) in order to calculate the effect size of statin therapy in changing plasma cortisol concentrations. Following a systematic search in Medline, SCOPUS, Web of Science and Google Scholar databases (by up to March 01, 2015), 7 eligible RCTs were selected. Random-effects meta-analysis suggested a significant increase in plasma cortisol concentrations following statin therapy (WMD: 6.34%, 95% CI: 1.80, 10.87, p=0.006). Subgroup analysis confirmed the significance of the effect with lipophilic statins comprising atorvastatin, simvastatin, and lovastatin (WMD: 7.00%, 95% CI: 2.21, 11.79, p=0.004) but not with hydrophilic statins (rosuvastatin and pravastatin) (WMD: 0.60%, 95% CI: -13.46, 14.66, p=0.933). In the meta-regression analysis, changes in plasma cortisol concentrations following statin therapy were found to be independent of treatment duration. Results of this meta-analysis of RCTs suggest a significant elevation in plasma cortisol levels following statin therapy.

• Klíčová slova
• Cortisol level, Meta-analysis, Randomized controlled trial, Statin,
• MeSH
• hydrokortison krev   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• statiny farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• hydrokortison MeSH
• statiny MeSH

Extracorporeal cardiopulmonary resuscitation is a promising treatment for refractory out-of-hospital cardiac arrest. Three recent randomized trials (ARREST trial, Prague OHCA study, and INCEPTION trial) that addressed the clinical benefit of extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest yielded seemingly diverging results. The evidence for extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest, derived from three recent randomized controlled trials, is not contradictory but rather complementary. Excellent results can be achieved with a very high level of dedication, provided that strict selection criteria are applied. However, pragmatic implementation of extracorporeal cardiopulmonary resuscitation does not necessarily lead to improved outcome of refractory out-of-hospital cardiac arrest. Centres that are performing extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest or aspire to do so should critically evaluate whether they are able to meet the pre-requisites that are needed to conduct an effective extracorporeal cardiopulmonary resuscitation programme.

• Klíčová slova
• Efficacy and effectiveness, Extracorporeal cardiopulmonary resuscitation, Randomized controlled trials, Review,
• MeSH
• kardiopulmonální resuscitace * MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• zástava srdce mimo nemocnici * terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Placebo effects emerging from the expectations of relatives, also known as placebo by proxy, have seldom been explored. The aim of this study was to investigate whether in a randomized controlled trial (RCT) there is a clinically relevant difference in long-term outcome between very preterm infants whose parents assume that verum (PAV) had been administered and very preterm infants whose parents assume that placebo (PAP) had been administered. The difference between the PAV and PAP infants with respect to the primary outcome-IQ at 5 years of age-was considered clinically irrelevant if the confidence interval (CI) for the mean difference resided within our pre-specified ±5-point equivalence margins. When adjusted for the effects of verum/placebo, socioeconomic status (SES), head circumference and sepsis, the CI was [-3.04, 5.67] points in favor of the PAV group. Consequently, our study did not show equivalence between the PAV and PAP groups, with respect to the pre-specified margins of equivalence. Therefore, our findings suggest that there is a small, but clinically irrelevant degree to which a preterm infant's response to therapy is affected by its parents' expectations, however, additional large-scale studies are needed to confirm this conjecture.

• Klíčová slova
• long-term outcome, placebo by proxy, preterm infants, randomized controlled trial,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: In patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ≥ 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements. METHODS: A phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization period of 24-36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80-94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80-94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment. DISCUSSION: Despite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2017-002138-22 . Registered on 8 August 2017.

• Klíčová slova
• Beta-blocker, Landiolol, Randomized controlled trial, Sepsis, Septic shock, Tachycardia,
• MeSH
• antiarytmika škodlivé účinky   terapeutické užití   MeSH
• beta blokátory škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• jednotky intenzivní péče * MeSH
• klinické zkoušky, fáze IV jako téma MeSH
• krevní tlak účinky léků   MeSH
• lidé MeSH
• močovina škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• morfoliny škodlivé účinky   terapeutické užití   MeSH
• multicentrické studie jako téma MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma MeSH
• septický šok diagnóza   farmakoterapie   patofyziologie   MeSH
• srdeční frekvence účinky léků   MeSH
• vazokonstriktory terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antiarytmika MeSH
• beta blokátory MeSH
• landiolol MeSH Prohlížeč
• močovina MeSH
• morfoliny MeSH
• vazokonstriktory MeSH

BACKGROUND: Weight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is an unmet clinical need. OBJECTIVE: Identification of predictive factors associated with successful weight loss after sequential exercise in women with obesity. METHODS: The study will consist of a 2-stage analytical approach, including a predictive validation study and a 2:1 randomized cross-over controlled trial. Women aged 25-45 years with obesity (BMI>30) will be included in the study. The intervention will consist of a progressive protocol of aerobic exercise on a treadmill and a bicycle ergometer. We will measure weight loss in terms of fat mass (FM) and fat-free mass (FFM), metabolic flexibility (MetFlex) as ΔRQ (change in respiratory quotient (VCO2/VO2) between basal and insulin-stimulated state during glucose clamp), insulin sensitivity, glucose tolerance, hemoglobin A1c, microbiome composition, and metabolomic signatures. RESULTS: Recruitment for the trial began in January 2024. A total of 12 participants were enrolled and randomized. Among them 6 participants have completed the first phase of the A-arm and 6 participants have completed the control period of the B-arm and their intervention is ongoing. Recruitment is ongoing. We expect the preliminary data from this study to be completed in 2026. CONCLUSIONS: This intervention will investigate whether whole body and gut MetFlex can be further explored and used as ex ante predictors of successful weight loss following exercise intervention, providing proof of concept and paving the way for personalized lifestyle interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06329349; https://clinicaltrials.gov/study/NCT06329349. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/67570.

• Klíčová slova
• diabetes, endocrinology, exercise, gut microbiota, metabolic flexibility, obesity, overweight, physical activity, protocol, randomized control trial, validation study, weight loss,
• MeSH
• cvičení fyziologie   MeSH
• diabetes mellitus 2. typu prevence a kontrola   MeSH
• dospělí MeSH
• hmotnostní úbytek fyziologie   MeSH
• inzulinová rezistence MeSH
• klinické křížové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita * terapie   metabolismus   MeSH
• randomizované kontrolované studie jako téma MeSH
• výsledek terapie MeSH
• životní styl * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

OBJECTIVES: To determine the quality of Doppler images of the fetal middle cerebral artery (MCA) and umbilical artery (UA) using an objective scale, and to determine the reliability of this scale, within a multicenter randomized controlled trial (Revealed versus concealed criteria for placental insufficiency in unselected obstetric population in late pregnancy (Ratio37)). METHODS: The Ratio37 trial is an ongoing randomized, open-label, multicenter controlled study of women with a low-risk pregnancy recruited at 20 weeks. Doppler measurements of the fetal MCA and UA were performed at 37 weeks. Twenty patients from each of the six participating centers were selected randomly, with two images evaluated per patient (one each for the MCA and UA). The quality of a total of 240 images was evaluated by six experts, scored on an objective scale of six items. Inter- and intrarater reliability was assessed using the Fleiss-modified kappa statistic for ordinal scales. RESULTS: On average, 89.2% of MCA images and 85.0% of UA images were rated as being of perfect (score of 6) or almost perfect (score of 5) quality. Kappa values for intrarater reliability of quality assessment were 0.90 (95% CI, 0.88-0.92) and 0.90 (95% CI, 0.88-0.93) for the MCA and UA, respectively. The corresponding inter-rater reliability values were 0.85 (95% CI, 0.81-0.89) and 0.84 (95% CI, 0.80-0.89), respectively. CONCLUSION: The quality of MCA and UA Doppler ultrasound images can be evaluated reliably using an objective scale. Over 85% of images, which were obtained by operators from a broad range of clinical practices within a multicenter study, were rated as being of perfect or almost perfect quality. Intra- and inter-rater reliability of quality assessment was very good. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

• Klíčová slova
• Doppler, middle cerebral artery, quality control, randomized multicenter trial, reliability, umbilical artery,
• MeSH
• arteria cerebri media diagnostické zobrazování   embryologie   MeSH
• arteriae umbilicales diagnostické zobrazování   embryologie   MeSH
• dospělí MeSH
• lidé MeSH
• plod krevní zásobení   diagnostické zobrazování   embryologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• reprodukovatelnost výsledků MeSH
• ultrasonografie dopplerovská normy   MeSH
• ultrasonografie prenatální normy   MeSH
• zajištění kvality zdravotní péče MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• multicentrická studie MeSH

BACKGROUND: Fever is associated with brain injury after cardiac arrest. It is unknown whether fever management with a feedback-controlled device impacts patient-centered outcomes in cardiac arrest patients. This trial aims to investigate fever management with or without a temperature control device after out-of-hospital cardiac arrest. METHODS: The TEMP-CARE trial is part of the 2 × 2 × 2 factorial Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial, a randomized, international, multicenter, parallel-group, investigator-initiated, superiority trial that will evaluate sedation strategies, temperature management, and blood pressure targets simultaneously in nontraumatic/nonhemorrhagic out-of-hospital cardiac arrest patients following hospital admission. For the temperature management component of the trial described in this protocol, patients will be randomly allocated to fever management with or without a feedback-controlled temperature control device. For those managed with a device, if temperature ≥37.8°C occurs within 72 h post-randomization the device will be started targeting a temperature of ≤37.5°C. Standard fever treatment, as recommended by local guidelines, including pharmacological agents, will be provided to participants in both groups. The two other components of the STEPCARE trial evaluate sedation and blood pressure strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. A physician blinded to the intervention will determine the neurological prognosis following European Resuscitation Council and European Society of Intensive Care Medicine guidelines. The primary outcome is all-cause mortality at six months post-randomization. To detect a 5.6% absolute risk reduction (90% power, alpha .05), 3500 participants will be enrolled. Secondary outcomes include poor functional outcome at six months, intensive care-related serious adverse events, and overall health status at six months. CONCLUSION: The TEMP-CARE trial will investigate if post-cardiac arrest management of fever with or without a temperature control device affects patient-important outcomes after cardiac arrest.

• Klíčová slova
• cardiac arrest, feedback‐controlled device, fever, randomized controlled trial, temperature management,
• MeSH
• horečka * terapie   MeSH
• kardiopulmonální resuscitace * MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• randomizované kontrolované studie jako téma MeSH
• tělesná teplota MeSH
• terapeutická hypotermie * přístrojové vybavení   MeSH
• zástava srdce mimo nemocnici * terapie   komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND: Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement is an evidence-based approach to improve the quality of RCTs reporting. OBJECTIVE: To evaluate the reporting quality of published RCTs concerning multiple sclerosis from 2000 to 2015 according to a checklist based on the CONSORT statement. METHODS: Electronic databases were searched for English-language RCTs involving patients with multiple sclerosis (MS). Trials were considered eligible when participants were randomly assigned to at least two medicinal treatment arms and included patients with MS. Quality of reporting was assessed using a 39-item questionnaire based on the CONSORT checklist. Articles were grouped in three 5-year periods and comparisons were made using descriptive statistics. RESULTS AND CONCLUSION: The search identified 102 eligible articles for analysis. 20 of the 38 items of the checklist (52.6%) were addressed in 75% or more of the studies. Reporting of more than 75% of CONSORT items (>75% CONSORT compliance) was increased during the three five-year time periods from 2000 to 2015 (p<0.05). CONCLUSIONS: Quality of reporting in RCTs focusing on multiple sclerosis is showing improvement over time, but still remains unsatisfactory. Further improvement of reporting is necessary to assess the validity of clinical research.

• Klíčová slova
• CONSORT, Multiple sclerosis, Randomized controlled trials,
• MeSH
• impakt faktor časopisů MeSH
• lidé MeSH
• periodika jako téma MeSH
• publikování normy   MeSH
• randomizované kontrolované studie jako téma normy   MeSH
• roztroušená skleróza terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments. OBJECTIVES: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. RESULTS: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. CONCLUSIONS: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

• Klíčová slova
• fosmetpantotenate, pantothenate kinase-associated neurodegeneration, randomized controlled trial, treatment,
• MeSH
• činnosti denního života MeSH
• dvojitá slepá metoda MeSH
• Hallervordenův-Spatzův syndrom * farmakoterapie   genetika   MeSH
• kyselina pantothenová analogy a deriváty   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• fosmetpantotenate MeSH Prohlížeč
• kyselina pantothenová MeSH

BACKGROUND: Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. METHODS: REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1-5, followed by dexamethasone 10 mg on days 6-10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. DISCUSSION: We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. TRIAL REGISTRATION: EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020.

• Klíčová slova
• ARDS, COVID-19, Dexamethasone, Protocol, Randomised controlled trial, Ventilator-free days,
• MeSH
• dexamethason škodlivé účinky   MeSH
• dospělí MeSH
• farmakoterapie COVID-19 * MeSH
• kvalita života MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma MeSH
• SARS-CoV-2 MeSH
• syndrom dechové tísně * diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Názvy látek
• dexamethason MeSH