V třetí části přehledového sdělení se podrobně zabýváme indikacemi maturogeneze a možnými alternativami ošetření. Dále je podrobně popsán samotný doporučený klinický protokol, s velkým důrazem na praktické provedení v praxi praktického zubního lékaře. Výplachový protokol a intrakanalikulární medikace je upravena tak, aby došlo k dostatečné dezinfekci kořenového systému a zároveň co nejmenšímu poškození dentinu a kmenových buněk podílejících se na vzniku nové tkáně. Jsou zmíněny na trhu dostupné materiály, které jsou vhodné pro maturogenezi včetně jejich výhod a nevýhod. V neposlední řadě je popsáno hodnocení úspěchu provedené terapie a charakterizace nově vzniklé tkáně.

In the third article, the indications of revascularization treatment and possible alternative treatment options are considered. Furthermore, step-by-step clinical protocol in detail is described, with emphasis on clinical execution in every-day office of general practicioners. Irrigation protocol and intracanal medication is adjusted to obtain adequate disinfection of root canal system and at the same time the damage to dentin and stem cells is decresed. The materials which are suitable for revascularization treatment including their pros and cons are mentioned. Finally, the assesment of therapy outcomes and characterization of newly formed tissue are described.

• Keywords
• Biodentin, MTA zátka, krevní sraženina, mineral trioxide aggregate,
• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Apexification * methods   MeSH
• Dentinogenesis physiology   MeSH
• Child MeSH
• Drug Combinations MeSH
• Outcome Assessment, Health Care methods   MeSH
• Calcium Hydroxide therapeutic use   MeSH
• Clinical Protocols MeSH
• Humans MeSH
• Pulp Capping and Pulpectomy Agents MeSH
• Dental Pulp Necrosis * therapy   MeSH
• Oxides therapeutic use   MeSH
• Platelet-Rich Plasma MeSH
• Root Canal Irrigants MeSH
• Regeneration physiology   MeSH
• Regenerative Endodontics MeSH
• Guided Tissue Regeneration methods   MeSH
• Silicates therapeutic use   MeSH
• Aluminum Compounds therapeutic use   MeSH
• Calcium Compounds therapeutic use   MeSH
• Root Canal Therapy * methods   MeSH
• Tooth Injuries therapy   MeSH
• Root Canal Filling Materials therapeutic use   MeSH
• Dental Cements MeSH
• Tooth Root growth & development   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Východisko. Cílem retrospektivní studie je posouzení výsledků mezinárodního léčebného protokolu LCH II u dětí s histiocytózou z Langerhansových buněk (LCH) léčených ve FN Motol. Metody a výsledky. V období od listopadu 1995 do prosince 2003 bylo léčeno 46 dětí s poměrem pohlaví CH:D 29:17 a průměrným věkem v době diagnózy 6 roků 8 měsíců. Monosystémové onemocnění mělo 28 dětí (60,9 %). Nejčastěji byl postižen skelet (23x) s predominancí lebky (16x). Primární léčbou u monosystémového onemocnění byl chirurgický výkon. Recidiva u 5 dětí byla úspěšně léčena protokolem LCH II – LR (3x) a LCH III – LR /G2/ (2x). Multisystémovou formou trpělo 18 pacientů (39,1 %). Šest bylo léčeno protokolem pro nízké riziko (LCH II – LR) a 12 schématem pro vysoké riziko (LCH II – HR) v nerandomizované větvi s etoposidem. Recidiva onemocnění byla prokázána u 10 pacientů. Devět z nich dosáhlo 2. nebo 3. kompletní remisi (CR) monoterapií 2-chlorodeoxyadenosinem a 1 dítě je v 2. CR po léčbě schématem LCH II – HR. Radioterapie byla indikována u 2 dětí po excizi ložiska v kosti a 1x jako doplňující modalita u recidivy. Celkově žije v 1. CR 29 dětí (63,0 %), 2. CR 14 (30,4 %) a 3. CR 2 pacienti (4,4 %). Jedno dítě zemřelo na progresi základního onemocnění. U žádného z pacientů nebyly pozorovány závažné vedlejší účinky chemoterapie. Průměrná doba sledování je 5 roků 8 měsíců (rozmezí 9 měsíců – 9 roků 6 měsíců). Závěry. LCH II je bezpečný a účinný léčebný protokol. Z výsledků je však zřejmá potřeba další modifikace terapie u skupiny pacientů s multisystémovým postižením, vyžadující další klinické studie.

Background. The aim of study was to evaluate outcome of international treatment protocol LCH II for children with Langerhans cell histiocytosis treated in FN Motol. Methods and Results. Between November 1995 and December 2003, 46 children were treated, sex ratio M:F 29:17 and median age at diagnosis 6 years 8 months. 28 children (60.9%) suffered from monosystem disease with majority of bone lesions (23 times) with skull predominance (16 times). Surgery was primary treatment modality for monosystem disease. Five children with recurrence were successfully treated by protocol LCH II – LR (3x) and LCH III – LR /G2/, respectively. Eighteen children (39.1%) suffered from multisystem disease. 6 out of 18 patients were treated according to low-risk protocol LCH II – LR and 12 children by high-risk scheme LCH II – HR at the nonrandomized branch included etoposide. Recurrence was revealed in 11 patients and 10 of them reached 2nd or 3rd complete remission (CR) by 2 – chlorodeoxyadenosine (CDA) monotherapy, and 1 child reached 2nd CR by LCH II – HR scheme. Two children underwent irradiation after bone lesion excision as well as 1 child as supplemental treatment. Totally, 29 children (63.0 %) achieved 1st CR, 14 (30.4 %) 2nd CR, 2 (4.4 %) 3rd CR, and 1 child died because of LCH progression. There were no severe side effects of chemotherapy. Follow-up median time was 5 years 8 months (range 9 months – 9 years 6 months). Conclusions. LCH II protocol is safe and effective. Results revealed that treatment of patients with multisystem disease might demand some treatment modification.

• MeSH
• Child MeSH
• Etoposide administration & dosage   pharmacology   MeSH
• Research Support as Topic MeSH
• Histiocytosis, Langerhans-Cell etiology   drug therapy   surgery   MeSH
• Humans MeSH
• Prednisone administration & dosage   MeSH
• Antineoplastic Agents administration & dosage   therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols administration & dosage   pharmacology   adverse effects   MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Vinblastine administration & dosage   pharmacology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH

Východisko. Akutní myeloidní leukémie (AML) je u dětí vzácné onemocnění, jehož výsledky léčby dlouho zaostávaly za úspěchy terapie dětské akutní lymfoblastické leukémie. Současné velmi intenzivní léčebné protokoly a pokroky v podpůrné léčbě prognózu dětí s AML významně zlepšily. Daní intenzivní léčbě je vysoký výskyt toxických komplikací. Hlavní příčinou selhání léčby zůstává relaps leukémie. V České republice byla léčba AML u dětí sjednocena v roce 1993 podle německého protokolu AML-BFM 93. Metody a výsledky. Výsledky léčby byly hodnoceny u 61 pacientů. Kompletní remise byla dosažena u 73,8 % dětí. Pravděpodobnost 5letého přežití do selhání (EFS) byla 42,3 % a celkového přežití 45,3 %. Děti standardního rizika měly významně lepší prognózu (EFS 62,5 %) než děti vysokého rizika (EFS 29,7 %) (p=0,03). Nejvýznamnějším prognostickým faktorem byla časná odpověď na léčbu definovaná redukcí blastů v kostní dřeni 2 týdny od zahájení terapie.Alogenní transplantace krvetvorných buněk neznamenala signifikantní zlepšení výsledků léčby dětí vysokého rizika ve srovnání s chemoterapií. Závěry. Výsledky léčby dětí s AML jsou v České republice srovnatelné s výsledky předních světových pracovních skupin. Cílem léčby podle nového protokolu AML-BFM 98 je zvýšení úspěšnosti v dosažení remise snížením počtu časných smrtí.

Background. Acute myeloid leukemia (AML) in children is rare. Although more resistant to chemotherapy than acute lymphoblastic leukemia, its responsiveness and survival rates have considerably improved during the last 15 years by virtue of intensification of chemotherapy and due to the better supportive care. Relapses still remain the main cause of treatment failure. Management of children with AML was unified in the Czech Republic in 1993 according to AML-BFM 93 Study protocol. Methods and Results. Treatment results were evaluated in 61 patients, of whom 45 (73.8%) achieved complete remission. Five-year event-free-survival (EFS) was found in 42.3%, and overall survival was 45.3%. Prognosis of the standard-risk patients was significantly better than in the high-risk group (EFS 62.5% vs. 29.7%, p=0.03). The most important prognostic factor was the early treatment response. Compared to chemotherapy, allogeneic stem-cell transplantation did not significantly improve the outcome of high-risk patients. Conclusions. Treatment results of children with AML in the Czech Republic are comparable to those achieved by leading leukemia study groups in the world. The aim of the next study is to increase the complete-remission rate by reducing early deaths.

• MeSH
• Leukemia, Myeloid, Accelerated Phase diagnosis   classification   therapy   MeSH
• Cytogenetic Analysis MeSH
• Child MeSH
• Risk Assessment MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Radiotherapy MeSH
• Hematopoietic Stem Cell Transplantation MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Review MeSH
• Comparative Study MeSH
• Geographicals
• Czech Republic MeSH

U 48 pacientů bylo provedeno 110 protokolárních biopsii v 1., 3. a 12. měsíci po transplantaci kadaverózní ledviny. Bioptické vzorky byly hodnoceny podle kritérií Banfřské klasifikace. Hlavní příčinou nestability štěpu v 1. a 3. měsíci byly podle očekávání akutní klinické rejekce (78,2 %), které se vyskytovaly ve všech známých morfologických obrazech. . Akutní tubulární nefropatie byla zjištěná u 13 % nestabilních štěpů, hraniční změny a známky nefi'otoxicity u 8,7 % případů. Zvláštní pozornost byla věnována výskytu subklinické rejekce a toxických projevů u stabilních štěpů. VI. a 3. měsíci jsme zjistili u 36,1 % stabilních štěpů subklinickou rejekci tubulointersticiálního a vaskulámího typu. Akutní skóre subklinické rejekce měřené součtem glomerulámích, tubulámích, vaskulámích a intersticiálních změn bylo nižší než u rejekce klinické. Toxické reakce jsme zaznamenali u 14,2 % respektive 19,5 % biopsii z 1. respektive 3. měsíce a u 27,2 % biopsií z 12. měsíce. U více než poloviny prokázaných toxických reakcí jsme nezjistili zvýšenou hladinu imunosuprese ani známky dysfunkce štěpu. V bíopsíích z 12. měsíce bylo 45,5 % vzorků s obrazem chronické transplantační nefi-opatie mírného stupně. Většina těchto případů jevila klinicky velmi dobrou funkci. U 18,1 % vzorků byla zjištěna chronická transplantační nefropatie středního stupně s klinicky dobrou funkcí ledviny. Normální morfologický obraz byl zjištěn u 36,4 % vzorků. V souboru protokolárních biopsii transplantovaných ledvin jsme v časném potransplantačním období prokázali vysoké zastoupení subklinické rejekce a současně i vysoké zastoupení nefrotoxických reakcí. Protokolární biopsie je spolehlivou metodou ke zjištění příčin klinicky němého i klinicky manifestního poškození štěpu.

Fourty eight patients with cadaveric kidney allografts treated by cyclosporin A (CSA) or tacrolimus (FK506) underwent protocol graft biopsies at 1, 3 and 12 months after transplantation, and 110 biopsy specimens were obtained. Histologic diagnosis was made according to the Banff schehie. The main cause of the graft instability at 1 and 3 months was acute clinical rejection, these biopsies showed all known histological patterns of tubulointersticial and vascular rejection. Acute tubular nephropathy was found in 13% and borderline changes or nephrotoxicity in 8.7% of instable grafts. Specifically, we focused on the occurence of subclinical rejection and toxic reactions in stable renal allografts. Of these, 36.1% showed histological patterns of acute tubulointersticial and vascular rejection. The Banff score of subclinical rejection was significantly lower than in clinically apparent rejection. CSA and tacrolimus nephrotoxicity were seen in 14.2%, 19.5% and 27.2% of specimens at 1, 3 and 12 months, respectively. In over one half of the identified cases of nephrotoxicity neither increased level of immunosuppresion nor features of allograft dysfunction were foimd. At 12 months, 45.5% of specimens showed mild chronic transplant nephropathy and 18.1% moderate chronic transplant nephropathy. Normal morphology was found in 36.4% of biopsies. We found a high prevalence of subclinical rejection and nephrotoxicity in the studied cohort. We conclude that protocol biopsy is a reliable method in the diagnosis of clinically silent, as well as clinically apparent, disorders of the transplanted kidney.

• MeSH
• Biopsy MeSH
• Humans MeSH
• Kidney Diseases pathology   MeSH
• Postoperative Complications diagnosis   MeSH
• Graft Rejection pathology   MeSH
• Kidney Transplantation MeSH
• Transplantation Immunology MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH

Východisko. Akutní lymfoblastická leukémie (ALL) je nejčastějším zhoubným onemocněním dětského věku. Prognóza dětí s ALL zaznamenala v posledních 40 letech významné zlepšení. Autoři analyzují výsledky léčby dětí s ALL v České republice, které byly v první polovině 90. let minulého století léčeny podle protokolu ALL-BFM 90. Metody a výsledky. Do studie byly zařazeny děti a dospívající ve věku 0–18 let, u nichž byla diagnózaALL stanovena v jednom z 10 center v období červen 1990 – květen 1996. Pacienti byli rozděleni do 3 odlišně léčených rizikových skupin standardního, středního a vysokého rizika podle velikosti iniciální nádorové masy, časné odpovědi na léčbu a genotypu leukémie. Délka chemoterapie byla 2 roky. Do studie bylo zařazeno 366 dětí s non-B ALL a výsledky léčby byly hodnotitelné u 352 dětí. Při mediánu sledování 7,3 roku byla pravděpodobnost přežití do selhání (EFS) pro celou skupinu 71,3%a pravděpodobnost celkového přežití 76,4%. EFS byl 80,3%pro standardní riziko (n=132), 74 % pro střední riziko (n=181) a 28,2 % pro skupinu vysokého rizika (n=39). Relaps postihl 17,8 % pacientů. Závěry. Sedmiletý EFS 71,3 % znamená zlepšení (p=0,0045) výsledků léčby ve srovnání s předchozím protokolem ALL-BFM 83 (EFS 62 %). Výsledky léčby jsou srovnatelné s výsledky předních světových pracovních skupin léčby dětské leukémie.

Background. Prognosis of children with acute lymphoblastic leukaemia (ALL) – the most common cancer in childhood, has improved remarkably over the last 40 years. The authors report the treatment outcome in children with ALL cured according to ALL-BFM 90 Study protocol in the Czech Republic during the first half of nineties. Methods and Results. Children aged 0–18 years were included into the study in 10 centers between 1990 to 1996. Patients were classified into standard-risk (SR), medium-risk (MR) and high-risk (HR) group according to initial leukaemic burden, early treatment response, and genotype of leukaemia. Duration of the chemotherapy was two years. Treatment results were evaluated in 352 children. With a median follow-up of 7.3 years, event-free-survival (EFS) was 71.3 % and overall survival 76.4 %. EFS was 80.3 %, 74 % and 28.2 % in SR, MR and HR group, respectively. Relapse was diagnosed in 17.8 % of the patients. Conclusions. The treatment outcome of children with ALL improved significantly (p=0.0045) compared to the previous study ALL-BFM 83 (EFS 62 %). These results are comparable to those achieved by leading leukaemia study groups in the world.

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis   drug therapy   mortality   MeSH
• Cytogenetic Analysis methods   MeSH
• Humans MeSH
• Prednisone administration & dosage   MeSH
• Prognosis MeSH
• Antineoplastic Agents administration & dosage   therapeutic use   MeSH
• Antineoplastic Protocols MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH

Krvácanie z horného gastrointestinálneho traktu (GIT) je zriedkavá, ale život kardiochirurgického pacienta ohrozujúca príhoda. V Kardiocentre v Banskej Bystrici sme zaviedli gastrofibroskopické vyšetrenie a liečbu lézií do štandardného protokolu prípravy pac. na operáciu. Cieľ práce: Posúdiť oprávnenosť nášho postupu. Metodika: Retrospektívna analýza 957 pac. operovaných v období máj 1995 - január 2002, rozdelených do skupiny A (151 pac, vyšetrení iba pri pozitívnej anamnéze) a B (806 pac. štandardne vyšetrovaní). Výsledky: Významný rozdiel v incidencii pooperačných komplikácií medzi skupinou A (5,9 %) a B (1,1 %, p < 0,05). Mortalita v skupine A 1,3 % voči nulovej mortalite v skupine B. Iba 2 (11 % voči 16 pac. - 89 %) pacienti S pooperačnou komplikáciou mali pozitívnu anamnézu vredovej choroby. Exitovaní pacienti mali negatívnu anamnézu a neboli predoperačné vyšetrení. V skupine B bola vysoká incidencia predoperačných lézií horného GIT (35 % voči 9 % - p < 0,01), ktoré boU gastroenterologicky preHečené. Väčšina (230 - 82 %) z 281 pacientov s pozitívnym predoperačným nálezom mala negatívnu anamnézu. Záver: Prax gastrofibroskopicky vyšetrovať pred operáciou srdca iba pacientov s pozitívnou anamnézou vredovej choroby nedokáže odhaliť nemé lezie, ktoré sa manifestujú pooperačné. Gastrofibroskopické vyšetrenie a preliečenie zistených lézií by sa malo stať štandardnou súčasťou protokolu prípravy všetkých pacientov pred operáciou srdca.

We introduced a gastrofibroscopy into a standard preoperative protocol for all patients indicated to the cardiac surgery. Aim of the study: Validation of our protocol. Material and methods: 957 consecutive patients operated on from May 1995 to January 2002 were divided to group A - gastrofibroscopy only for patients with positive history or clinical signs of peptic ulcer (151 pts.) and group B - patients with gastrofibroscopy as a standard procedure (806 pts). Results: Significant difference in incidence of peptic ulcer complications between groups (A - 5.9% versus B - 1.1%, p < 0.05). Related mortality was 1.37o in-group A versus 0% in-group B. Positive history of peptic ulcer had only two patients (11% of 18) with postoperative complication. In-group B we found high incidence of peptic defects (B - 35% versus A - 9%, p < 0.01) requiring treatment by gastroenterologist. Majority (230 of 281 - 82%) of pts. with preoperative positive defect had negative history of a peptic ulcer. Conclusions: Current tendency to perform gastrofibroscopic examination only in patients with positive history of peptic ulcer is not able to detect „silent" lesions. Perioperative treatment with H2 blockers fails to prevent the manifestation of peptic ulcer complication. Gastrofibroscopy should be a routine part of the preoperative protocol in cardiac surgery.

• MeSH
• Gastrointestinal Hemorrhage diagnosis   epidemiology   MeSH
• Gastroscopy MeSH
• Cardiac Surgical Procedures MeSH
• Humans MeSH
• Peptic Ulcer complications   MeSH
• Postoperative Care MeSH
• Preoperative Care MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH

• MeSH
• Hodgkin Disease pathology   therapy   MeSH

BACKGROUND: Where it has been determined that a resident in a nursing home living with dementia loses decisional capacity, nursing home staff must deliver care that is in the person's best interests. Ideally, decisions should be made involving those close to the person, typically a family carer and health and social care providers. The aim of the Family Carer Decisional Support intervention is to inform family carers on end-of-life care options for a person living with advanced dementia and enable them to contribute to advance care planning. This implementation study proposes to; 1) adopt and apply the intervention internationally; and, 2) train nursing home staff to deliver the family carer decision support intervention. METHODS: This study will employ a multiple case study design to allow an understanding of the implementation process and to identify the factors which determine how well the intervention will work as intended. We will enrol nursing homes from each country (Canada n = 2 Republic of Ireland = 2, three regions in the UK n = 2 each, The Netherlands n = 2, Italy n = 2 and the Czech Republic n = 2) to reflect the range of characteristics in each national and local context. The RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework will guide the evaluation of implementation of the training and information resources. Our mixed methods study design has three phases to (1) establish knowledge about the context of implementation, (2) participant baseline information and measures and (3) follow up evaluation. DISCUSSION: The use of a multiple case study design will enable evaluation of the intervention in different national, regional, cultural, clinical, social and organisational contexts, and we anticipate collecting rich and in-depth data. While it is hoped that the intervention resources will impact on policy and practice in the nursing homes that are recruited to the study, the development of implementation guidelines will ensure impact on wider national policy and practice. It is our aim that the resources will be sustainable beyond the duration of the study and this will enable the resources to have a longstanding relevance for future advance care planning practice for staff, family carers and residents with advanced dementia.

• MeSH
• Dementia * therapy   MeSH
• Humans MeSH
• Caregivers MeSH
• Terminal Care * methods   MeSH
• Nursing Homes MeSH
• Advance Care Planning * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by 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 through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

• MeSH
• COVID-19 complications   therapy   MeSH
• Length of Stay MeSH
• Dexamethasone administration & dosage   MeSH
• Glucocorticoids administration & dosage   MeSH
• Equivalence Trials as Topic MeSH
• Clinical Trials, Phase II as Topic MeSH
• Humans MeSH
• Multicenter Studies as Topic MeSH
• Disease Progression MeSH
• Randomized Controlled Trials as Topic MeSH
• SARS-CoV-2 MeSH
• Respiratory Distress Syndrome etiology   therapy   MeSH
• Respiration, Artificial * MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Clinical Trial Protocol 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.

• MeSH
• COVID-19 * MeSH
• Dexamethasone adverse effects   MeSH
• Adult MeSH
• COVID-19 Drug Treatment MeSH
• Quality of Life MeSH
• Humans MeSH
• Multicenter Studies as Topic MeSH
• Prospective Studies MeSH
• Randomized Controlled Trials as Topic MeSH
• SARS-CoV-2 MeSH
• Respiratory Distress Syndrome * diagnosis   drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH