BACKGROUND: Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs. 6 mg dexamethasone intravenously in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19. METHODS: In a multicenter, open-label, randomized trial conducted in nine hospitals in the Czech Republic, we randomized adult patients with ARDS and COVID-19 requiring high-flow oxygen, noninvasive or invasive mechanical ventilation to receive either intravenous high-dose dexamethasone (20 mg/day on days 1-5, 10 mg/day on days 6-10) or standard-dose dexamethasone (6 mg/d, days 1-10). The primary outcome was 28-day ventilator-free days. The five secondary outcomes were 60-day mortality, C-reactive protein dynamics, 14-day WHO (World Health Organization) Clinical Progression Scale score, adverse events and 90-day Barthel index. The long-term outcomes were 180- and 360-day mortality and the Barthel index. The planned sample size was 300, with interim analysis after enrollment of 150 patients. RESULTS: The trial was stopped due to a lack of recruitment, and the follow-up was completed in February 2023. Among 234 randomized patients of 300 planned patients, the primary outcome was available for 224 patients (110 high-dose and 114 standard-dose dexamethasone; median [interquartile range (IQR)] age, 59.0 [48.5-66.0] years; 130 [58.0%] were receiving noninvasive or invasive mechanical ventilation at baseline). The mean number of 28-day ventilator-free days was 8.9 (± 11.5) days for high-dose dexamethasone and 8.0 (± 10.7) days for standard-dose dexamethasone, with an absolute difference of + 0.81 days (95% CI - 2.12-3.73 days). None of the prespecified secondary outcomes, including adverse events, differed between the groups. CONCLUSIONS: Despite not reaching its prespecified enrollment, there was no signal to either benefit or harm high-dose dexamethasone over standard-dose dexamethasone in patients with COVID-19 and moderate-to-severe ARDS. Trial registration Trial registration: ClinicalTrials.gov Identifier: NCT04663555. Registered 10 December 2020, https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 and EudraCT: 2020-005887-70.

• MeSH
• COVID-19 * mortalita   komplikace   MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• farmakoterapie COVID-19 * MeSH
• lidé středního věku MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• syndrom dechové tísně * farmakoterapie   mortalita   MeSH
• umělé dýchání * MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: We examined the clinical effectiveness of molnupiravir in reducing deaths in a real-world cohort of adult patients with COVID-19 during the Omicron outbreak. METHODS: This was a population-wide retrospective cohort study in the Czech Republic. We analyzed all 74 541 patients with an officially registered diagnosis of SARS-CoV-2 infection between 1 January and 31 December 2022, aged 18 years or older, treated with molnupiravir. The primary outcome was 30-day all-cause mortality; the secondary outcome was 30-day COVID-19-related mortality. Hazard ratios (HRs) were estimated using stratified Cox regression and the Fine-Gray model. RESULTS: The use of molnupiravir in adult SARS-CoV-2 positive patients was associated with a lower risk of both 30-day all-cause mortality: adjusted HR 0.58 (95% confidence interval, 0.53-0.64; P < .001) and 30-day COVID-19-related mortality: adjusted HR 0.50 (95% confidence interval, 0.42-0.58; P < .001). The effect of molnupiravir was highly significant regardless of sex, Deyo-Charlson Comorbidity Index score, hospitalization status, COVID-19 vaccination status, and patients older than age 65 years. CONCLUSIONS: In this cohort study, early initiation of molnupiravir was associated with a significant reduction in 30-day all-cause and COVID-19-related mortality in adult SARS-CoV-2 positive patients.

• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

In the last decade, undiagnosed disease programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases. In our single-center study, we have launched a pilot program for pediatric patients with undiagnosed diseases in the second-largest university hospital in the Czech Republic. This study was prospectively conducted at the Department of Pediatrics at University Hospital Brno between 2020 and 2023. A total of 58 Czech patients with undiagnosed diseases were enrolled in the study. All children underwent singleton WES with targeted phenotype-driven analysis. We identified 28 variants, including 11 pathogenic, 13 likely pathogenic, and 4 VUS according to ACMG guidelines, as diagnostic of genetic diseases in 25 patients, resulting in an overall diagnostic yield of 43%. Eleven variants were novel and had not been previously reported in any public database. The overall clinical utility (actionability) enabling at least one type of change in the medical care of the patient was 76%, whereas the average number of clinical implications to individual patient care was two. Singleton WES facilitated the diagnostic process in the Czech undiagnosed pediatric population. We believe it is an effective approach to enable appropriate counseling, surveillance, and personalized clinical management.

• MeSH
• dítě MeSH
• genetické testování metody   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• nediagnostikované nemoci * genetika   diagnóza   epidemiologie   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• sekvenování exomu * metody   MeSH
• vzácné nemoci * genetika   diagnóza   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia. METHODS: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy. CONCLUSIONS: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.

• MeSH
• COVID-19 * MeSH
• dexamethason škodlivé účinky   MeSH
• dospělí MeSH
• farmakoterapie COVID-19 MeSH
• hypoxie MeSH
• lidé MeSH
• pacienti MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

• MeSH
• anestetika intravenózní MeSH
• anestezie * MeSH
• ketogenní dieta * MeSH
• lidé MeSH
• motorické evokované potenciály fyziologie   MeSH
• skolióza * chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• lidé MeSH
• maligní hypertermie * terapie   MeSH
• mutace MeSH
• ryanodinový receptor vápníkového kanálu genetika   MeSH
• vápníkové kanály - typ L MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

In the Czech Republic, the strategic data-based and organizational support for individual regions and for providers of acute care at the nationwide level is coordinated by the Ministry of Health. At the beginning of the COVID-19 pandemic, the country needed to very quickly implement a system for the monitoring, reporting, and overall management of hospital capacities. The aim of this viewpoint is to describe the purpose and basic functions of a web-based application named "Control Centre for Intensive Care," which was developed and made available to meet the needs of systematic online technical support for the management of intensive inpatient care across the Czech Republic during the first wave of the pandemic in spring 2020. Two tools of key importance are described in the context of national methodology: one module for regular online updates and overall monitoring of currently free capacities of intensive care in real time, and a second module for online entering and overall record-keeping of requirements on medications for COVID-19 patients. A total of 134 intensive care providers and 927 users from hospitals across all 14 regions of the Czech Republic were registered in the central Control Centre for Intensive Care database as of March 31, 2021. This web-based application enabled continuous monitoring and decision-making during the mass surge of critical care from autumn 2020 to spring 2021. The Control Center for Intensive Care has become an indispensable part of a set of online tools that are employed on a regular basis for crisis management at the time of the COVID-19 pandemic.

• MeSH
• COVID-19 * MeSH
• lidé MeSH
• pandemie * prevence a kontrola   MeSH
• péče o pacienty v kritickém stavu MeSH
• SARS-CoV-2 MeSH
• strategické plánování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH