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1.
Rev Fac Cien Med Univ Nac Cordoba ; 77(4): 363-366, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33351369

RESUMO

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak originated in Wuhan (China) rapidly turned into a pandemic. Due to a national compulsive decree of quarantine, office visits for chronic disease control were delay. Hypopituitarism includes all clinical conditions that result in partial or complete failure of the pituitary gland's ability to secrete hormones. Pituitary insufficiency per se has been associated with an increase in both morbidity and mortality, particularly due to cardiovascular disease, which is an important risk factor for COVID-19 disease severity. OBJECTIVE: To report the first case of SARS-CoV-2 infection in a patient with hypopituitarism, discuss the implications of the treatments the patient was taking and grade up the value of telemedicine in the present scenario. METHODS: Report of the clinical record of a patient with hypopituitarism and infection with SARS-CoV-2. RESULTS: During the span of the infection, the patient remained on the same hormonal therapeutic scheme (thyroid, gonadal and adrenal axis). The dose of hydrocortisone was not changed during the course of the infection as she was asymptomatic. We use telemedicine to control and advise her on the treatment. CONCLUSION: Health care professionals should carefully follow up on the evolution of patients with hypopituitarism to provide them a safer outcome. The use of telemedicine as a methodology for selected patients acquires relevance in the present epidemiological context.


Assuntos
/complicações , Hipopituitarismo/tratamento farmacológico , Infecções Assintomáticas , Feminino , Humanos , Hidrocortisona/uso terapêutico , Hipopituitarismo/complicações
3.
Artigo em Inglês | MEDLINE | ID: mdl-33071957

RESUMO

Introduction: Italy, since the end of February 2020, is experiencing the corona virus disease 2019 (COVID-19) pandemic that may present as an acute respiratory infection. We report on COVID-19 pneumonia in the context of a complex case of Cushing's disease (CD). Case Report: A 67-year-old man with CD, who was admitted to our hospital, presented with signs and symptoms of adrenal insufficiency with persistent hypotension and glycemia toward the lower limits. We progressively withdrew almost all treatments for diabetes and CD (pasireotide and metyrapone), and i.v. hydrocortisone was necessary. A tendency to hyperkalemia was probably associated to enoxaparin. We summarized the many possible interactions between medications of Cushing's syndrome (CS) and COVID-19. Conclusion: Adrenal insufficiency might be a clinical challenge that needs a prompt treatment also in CS patients during COVID-19 infection. We should consider the possibility to titrate or temporary halt medical therapies of CS in the context of COVID-19 infection. Unexpected hyperkalemia in CS patients under treatment with heparin might be the signal of aldosterone suppression.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Síndrome de Cushing/tratamento farmacológico , Hidrocortisona/uso terapêutico , Metirapona/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Anti-Inflamatórios/uso terapêutico , Antimetabólitos/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Síndrome de Cushing/complicações , Síndrome de Cushing/virologia , Gerenciamento Clínico , Humanos , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia
4.
Cochrane Database Syst Rev ; 10: CD013101, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045104

RESUMO

BACKGROUND: Corticosteroids are routinely given to children undergoing cardiac surgery with cardiopulmonary bypass (CPB) in an attempt to ameliorate the inflammatory response. Their use is still controversial and the decision to administer the intervention can vary by centre and/or by individual doctors within that centre. OBJECTIVES: This review is designed to assess the benefits and harms of prophylactic corticosteroids in children between birth and 18 years of age undergoing cardiac surgery with CPB. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and Conference Proceedings Citation Index-Science in June 2020. We also searched four clinical trials registers and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included studies of prophylactic administration of corticosteroids, including single and multiple doses, and all types of corticosteroids administered via any route and at any time-point in the perioperative period. We excluded studies if steroids were administered therapeutically. We included individually randomised controlled trials (RCTs), with two or more groups (e.g. multi-drug or dose comparisons with a control group) but not 'head-to-head' trials without a placebo or a group that did not receive corticosteroids. We included studies in children, from birth up to 18 years of age, including preterm infants, undergoing cardiac surgery with the use of CPB. We also excluded studies in patients undergoing heart or lung transplantation, or both; studies in patients already receiving corticosteroids; in patients with abnormalities of the hypothalamic-pituitary-adrenal axis; and in patients given steroids at the time of cardiac surgery for indications other than cardiac surgery. DATA COLLECTION AND ANALYSIS: We used the Covidence systematic review manager to extract and manage data for the review. Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We resolved disagreements by consensus or by consultation with a third review author. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We found 3748 studies, of which 888 were duplicate records. Two studies had the same clinical trial registration number, but reported different populations and interventions. We therefore included them as separate studies. We screened titles and abstracts of 2868 records and reviewed full text reports for 84 studies to determine eligibility. We extracted data for 13 studies. Pooled analyses are based on eight studies. We reported the remaining five studies narratively due to zero events for both intervention and placebo in the outcomes of interest. Therefore, the final meta-analysis included eight studies with a combined population of 478 participants. There was a low or unclear risk of bias across the domains. There was moderate certainty of evidence that corticosteroids do not change the risk of in-hospital mortality (five RCTs; 313 participants; risk ratio (RR) 0.83, 95% confidence interval (CI) 0.33 to 2.07) for children undergoing cardiac surgery with CPB. There was high certainty of evidence that corticosteroids reduce the duration of mechanical ventilation (six RCTs; 421 participants; mean difference (MD) 11.37 hours lower, 95% CI -20.29 to -2.45) after the surgery. There was high-certainty evidence that the intervention probably made little to no difference to the length of postoperative intensive care unit (ICU) stay (six RCTs; 421 participants; MD 0.28 days lower, 95% CI -0.79 to 0.24) and moderate-certainty evidence that the intervention probably made little to no difference to the length of the postoperative hospital stay (one RCT; 176 participants; mean length of stay 22 days; MD -0.70 days, 95% CI -2.62 to 1.22). There was moderate certainty of evidence for no effect of the intervention on all-cause mortality at the longest follow-up (five RCTs; 313 participants; RR 0.83, 95% CI 0.33 to 2.07) or cardiovascular mortality at the longest follow-up (three RCTs; 109 participants; RR 0.40, 95% CI 0.07 to 2.46). There was low certainty of evidence that corticosteroids probably make little to no difference to children separating from CPB (one RCT; 40 participants; RR 0.20, 95% CI 0.01 to 3.92). We were unable to report information regarding adverse events of the intervention due to the heterogeneity of reporting of outcomes. We downgraded the certainty of evidence for several reasons, including imprecision due to small sample sizes, a single study providing data for an individual outcome, the inclusion of both appreciable benefit and harm in the confidence interval, and publication bias. AUTHORS' CONCLUSIONS: Corticosteroids  probably do not change the risk of mortality for children having heart surgery using CPB at any time point. They probably reduce the duration of postoperative ventilation in this context, but have little or no effect on the total length of postoperative ICU stay or total postoperative hospital stay. There was inconsistency in the adverse event outcomes reported which, consequently, could not be pooled. It is therefore impossible to provide any implications and policy-makers will be unable to make any recommendations for practice without evidence about adverse effects. The review highlighted the need for well-conducted RCTs powered for clinical outcomes to confirm or refute the effect of corticosteroids versus placebo in children having cardiac surgery with CPB. A core outcome set for adverse event reporting in the paediatric major surgery and intensive care setting is required.


Assuntos
Corticosteroides/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Inflamação/prevenção & controle , Adolescente , Corticosteroides/efeitos adversos , Viés , Procedimentos Cirúrgicos Cardíacos/mortalidade , Ponte Cardiopulmonar/mortalidade , Causas de Morte , Criança , Pré-Escolar , Dexametasona/uso terapêutico , Máquina Coração-Pulmão/efeitos adversos , Mortalidade Hospitalar , Humanos , Hidrocortisona/uso terapêutico , Lactente , Recém-Nascido , Inflamação/etiologia , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação , Metilprednisolona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos
7.
Life Sci ; 261: 118366, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32871182

RESUMO

AIMS: Intensive care unit-acquired weakness (ICU-AW) is a complex spectrum of disability that delays recovery of critically ill-immobilized patients with sepsis. Much discrepancy remain on the use of corticosteroids and their impact on muscle regeneration in critical illness management. Therefore, the aim of this study is to investigate whether hydrocortisone (HCT) modulates muscle mass turnover in ICU-AW induced by sepsis with limb immobilization (SI). MAIN METHODS: Sepsis by cecal ligation puncture (CLP) with forelimb-immobilization were performed in rats. The study consisted of four groups: Sham (left forelimb-immobilization), Sham HCT (left forelimb-immobilization + HCT), SI (CLP + left forelimb-immobilization) and SI HCT (CLP + left forelimb-immobilization + HCT). Motor force, blood and muscle sampling were assessed. KEY FINDINGS: HCT prevented body weight loss associated with SI and attenuated systemic and muscular inflammation. Besides, myosin was restituted in SI HCT group in conjunction to muscle mass and strength restoration. Pro-hypertrophic calcineurin (PP2B-Aß) and nuclear factor of activated T-cells C3 (NFATc3) but not protein kinase B (Akt) were re-activated by HCT. Finally, pro-atrophic extracellular signal-regulated kinases (ERK1/2) and p38 mitogen-activated protein kinases (p38) but not nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) were inhibited in SI HCT group. SIGNIFICANCE: This study unravels new molecular events thought to control muscle protein synthesis in ICU-AW induced by sepsis and limb immobilization. HCT has a potential to fine-tune muscle-signaling pathways and to reduce the negative outcomes of ICU-AW.


Assuntos
Extremidades/patologia , Hidrocortisona/uso terapêutico , Imobilização , Unidades de Terapia Intensiva , Debilidade Muscular/tratamento farmacológico , Atrofia Muscular/tratamento farmacológico , Sepse/complicações , Transdução de Sinais , Animais , Peso Corporal , Modelos Animais de Doenças , Hidrocortisona/farmacologia , Hipertrofia , Mediadores da Inflamação/sangue , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , Debilidade Muscular/sangue , Debilidade Muscular/complicações , Atrofia Muscular/sangue , Atrofia Muscular/complicações , Miosinas/metabolismo , Fatores de Transcrição NFATC/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos Wistar , Sepse/sangue
8.
JAMA ; 324(13): 1298-1306, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32876689

RESUMO

Importance: Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option. Objective: To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure. Design, Setting, and Participants: Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board. Interventions: Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73). Main Outcomes and Measures: The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay. Results: The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, -8.6% [95.48% CI, -24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment. Conclusions and Relevance: In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02517489.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidrocortisona/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Insuficiência Respiratória/terapia , Idoso , Anti-Inflamatórios/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Estado Terminal , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Hidrocortisona/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/etiologia , Falha de Tratamento
9.
JAMA ; 324(13): 1330-1341, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32876694

RESUMO

Importance: Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support. Objective: To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. Design, Setting, and Participants: Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance-weighted fixed-effect analysis using risk ratios. Exposures: Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients). Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events. Results: A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as "low" for 6 of the 7 mortality results and as "some concerns" in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo. Conclusions and Relevance: In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.


Assuntos
Corticosteroides/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Glucocorticoides/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Causas de Morte , Infecções por Coronavirus/mortalidade , Estado Terminal , Dexametasona/uso terapêutico , Humanos , Hidrocortisona/uso terapêutico , Metilprednisolona/uso terapêutico , Pandemias , Pneumonia Viral/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Crit Care Resusc ; 22(3): 191-199, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32900325

RESUMO

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.


Assuntos
Anti-Inflamatórios/economia , Anti-Inflamatórios/uso terapêutico , Hidrocortisona/economia , Hidrocortisona/uso terapêutico , Choque Séptico/tratamento farmacológico , Análise Custo-Benefício , Feminino , Humanos , Masculino , New South Wales , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Choque Séptico/mortalidade
12.
Am J Trop Med Hyg ; 103(4): 1635-1639, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828135

RESUMO

The COVID-19 pandemic is showing an exponential growth, mandating an urgent need to develop an effective treatment. Indeed, to date, a well-established therapy is still lacking. We aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) added to standard care in patients with COVID-19. This was a multicenter, randomized controlled trial conducted at three major university hospitals in Egypt. One hundred ninety-four patients with confirmed diagnosis of COVID-19 were included in the study after signing informed consent. They were equally randomized into two arms: 97 patients administrated HCQ plus standard care (HCQ group) and 97 patients administered only standard care as a control arm (control group). The primary endpoints were recovery within 28 days, need for mechanical ventilation, or death. The two groups were matched for age and gender. There was no significant difference between them regarding any of the baseline characteristics or laboratory parameters. Four patients (4.1%) in the HCQ group and 5 (5.2%) patients in the control group needed mechanical ventilation (P = 0.75). The overall mortality did not differ between the two groups, as six patients (6.2%) died in the HCQ group and 5 (5.2%) died in the control group (P = 0.77). Univariate logistic regression analysis showed that HCQ treatment was not significantly associated with decreased mortality in COVID-19 patients. So, adding HCQ to standard care did not add significant benefit, did not decrease the need for ventilation, and did not reduce mortality rates in COVID-19 patients.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Acetaminofen/uso terapêutico , Adulto , Cefalosporinas/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Esquema de Medicação , Reposicionamento de Medicamentos , Egito , Feminino , Humanos , Hidrocortisona/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Respiração Artificial , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
13.
Trials ; 21(1): 734, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831155

RESUMO

OBJECTIVES: Primary objective: To estimate the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization. Secondary objectives: To examine whether the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization varies between subgroups related to treatment characteristics, disease severity at the time of randomization, patient characteristics, or risk of bias. To examine the effect of corticosteroids compared with usual care or placebo on serious adverse events. STUDY DESIGN: Prospective meta-analysis of randomized controlled trials. Both placebo-controlled and open-label trials are eligible. PARTICIPANTS: Hospitalised, critically ill patients with suspected or confirmed COVID-19. INTERVENTION AND COMPARATOR: Intervention groups will have received therapeutic doses of a steroid (dexamethasone, hydrocortisone or methylprednisolone) with IV or oral administration immediately after randomization. The comparator groups will have received standard of care or usual care or placebo. MAIN OUTCOME: All-cause mortality up to 28 days after randomization. SEARCH METHODS: Systematic searching of clinicaltrials.gov , EudraCT, the WHO ISRCTN registry, and the Chinese clinical trials registry. Additionally, research and WHO networks will be asked for relevant trials. RISK OF BIAS ASSESSMENTS: These will be based on the Cochrane RoB 2 tool, and will use structured information provided by the trial investigators on a form designed for this prospective meta-analysis. We will use GRADE to assess the certainty of the evidence. STATISTICAL ANALYSES: Trial investigators will provide data on the numbers of participants who did and did not experience each outcome according to intervention group, overall and in specified subgroups. We will conduct fixed-effect (primary analysis) and random-effects (Paule-Mandel estimate of heterogeneity and Hartung-Knapp adjustment) meta-analyses. We will quantify inconsistency in effects between trials using I2 statistics. Evidence for subgroup effects will be quantified by ratios of odds ratios comparing effects in the subgroups, and corresponding interaction p-values. Comparisons between subgroups defined by trial characteristics will be made using random-effects meta-regression. Comparisons between subgroups defined by patient characteristics will be made by estimating trial-specific ratios of odds ratios comparing intervention effects between subgroups then combining these using random-effects meta-analysis. Steroid interventions will be classified as high or low dose according to whether the dose is greater or less than or equal to 400 mg hydrocortisone per day or equivalent. We will use network meta-analysis methods to make comparisons between the effects of high and low dose steroid interventions (because one trial randomized participants to both low and high dose steroid arms). PROSPERO REGISTRATION NUMBER: CRD42020197242 FULL PROTOCOL: The full protocol for this prospective meta-analysis is attached as an additional file, accessible from the Trials website (Additional file 1). To expedite dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol for the systematic review.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Glucocorticoides/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Corticosteroides/uso terapêutico , Betacoronavirus , Estado Terminal , Dexametasona/uso terapêutico , Humanos , Hidrocortisona/uso terapêutico , Metilprednisolona/uso terapêutico , Pandemias , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Int J Biol Sci ; 16(13): 2382-2391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760206

RESUMO

COVID-19 is a public health emergency that has rapidly spread to over 200 countries and regions, and no effective treatment has been established to date. Severe and critical cases have been associated with higher mortality due to acute respiratory distress syndrome (ARDS) and cytokine storm. Based on the novelty and recent emergence of COVID-19, no effective treatment regimen has been identified, thus prompting clinicians to engage in drug repurposing to address the immediate therapeutic need. This study focused on the molecular target angiotensin-converting enzyme 2 (ACE2) of SARS-CoV-2 and screened a group of ACE2 agonists by bioinformatics. Glucocorticoids are a type of ACE2 activator. We verified the efficacy of nine chemicals on regulating ACE2 expression in human GES-1, an upper digestive tract epithelial cell line, and THP-1, a human monocyte cell line, and found that several glucocorticoids imparted activating effects on ACE2 in both cell lines. The drugs triciribine and kinetin riboside activate ACE2 expression or inhibit IL-6 production in macrophages to some extent. In addition, we compared the efficacies of several glucocorticoids. Hydrocortisone showed the strongest effect on ACE2 activation, followed by prednisolone, dexamethasone, and methylprednisolone. We retrospectively analyzed the therapeutic efficacy of nine severe or critical patients from a cohort of 90 COVID-19 cases, who received medium to small doses of glucocorticoids from our integrated medical team in Wuhan. Seven out of nine patients revealed significant improvement in clinical parameters and chest CT images. This study provides experimental and clinical evidence that medium-to-low-dose glucocorticoids may play a protective role in the respiratory and digestive systems by activating ACE2 and suppressing cytokine storm.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Glucocorticoides/uso terapêutico , Interleucina-6/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Adenosina/uso terapêutico , Adulto , Idoso , Antivirais/uso terapêutico , Betacoronavirus , Linhagem Celular , Linhagem Celular Tumoral , Infecções por Coronavirus/metabolismo , Citocinas/metabolismo , Células Epiteliais/virologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hidrocortisona/uso terapêutico , Cinetina/uso terapêutico , Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Monócitos/virologia , Pandemias , Pneumonia Viral/metabolismo , Estudos Retrospectivos , Ribonucleosídeos/uso terapêutico , Transcriptoma
15.
Cochrane Database Syst Rev ; 8: CD013202, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32813884

RESUMO

BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is a leading cause of mortality and long-term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell-based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials. OBJECTIVES: To determine the efficacy and safety of stem cell-based interventions for the treatment of hypoxic-ischaemic encephalopathy (HIE) in newborn infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June 2020), Embase (1980 to 8 June 2020), and CINAHL (1982 to 8 June 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing 1) stem cell-based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell-based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell-based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell-based interventions other than MSCs. DATA COLLECTION AND ANALYSIS: For each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence. MAIN RESULTS: Our search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studies we excluded. AUTHORS' CONCLUSIONS: There is currently no evidence from randomised trials that assesses the benefit or harms of stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.


Assuntos
Hipóxia-Isquemia Encefálica/terapia , Transplante de Células-Tronco , Anti-Inflamatórios/uso terapêutico , Sangue Fetal/citologia , Humanos , Hidrocortisona/uso terapêutico , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido
17.
Buenos Aires; s.n; 16 jun. 2020.
Não convencional em Espanhol | LILACS, BRISA/RedTESA | ID: biblio-1116497

RESUMO

CONTEXTO CLÍNICO: La Enfermedad por el Coronavirus 2019 (COVID­19, por su sigla en inglés Coronavirus Disease 2019) es una enfermedad respiratoria de humanos producida por un nuevo coronavirus identificado con la sigla SARS-CoV-2. El 11 de marzo de 2020 la Organización Mundial de la Salud (OMS) declaro la COVID-19 como una pandemia. Desde ese momento hasta el 15 de junio su circulación se ha reportado en 205 países reportándose más de 7.800.000 casos y la muerte 430.000 personas. El período de incubación de la infección es de 2 a 14 días. La mayor parte de los contagios se producen persona a persona, siendo altamente transmisible.(3) La clínica varía desde casos asintomáticos a cuadros febriles con tos y dificultad respiratoria, neumonía y distrés respiratorio. También puede acompañarse de alteraciones gastrointestinales. En los casos con mal pronóstico, el paciente presenta un importante deterioro respiratorio en 4-8 días. Las imágenes radiológicas muestran generalmente neumonía focal o generalizada semejante al síndrome de distress respiratorio agudo. (3) La mayoría de los casos graves requieren ingreso hospitalario, siendo mayoritariamente casos primarios en pacientes de edad avanzada y con comorbilidades (diabetes, enfermedad crónica renal, hipertensión, enfermedad cardiaca y enfermedad pulmonar crónica). La tasa media de letalidad de los pacientes ingresados a UTI es cercana al 49%, siendo los valores más elevados en pacientes masculinos de más de 50 años con comorbilidades múltiples. Actualmente el tratamiento de la COVID­19 es sintomático y de sostén no existiendo hasta el momento tratamiento farmacológico específico curativo. Debido a la evidencia que sugiere que el daño pulmonar agudo observado en la infección por SARS-CoV-2 estaría asociada a la activación de las células inmunes circulantes, incluyendo células T y las citoquinas que conducen a un síndrome de liberación de citoquinas (similar al síndrome de activación macrofágica y hemofagocítico) por lo que se plantea que el uso de corticoides sistémicos podría disminuir la mortalidad y/o necesidad de soporte ventilatorio invasivo. TECNOLOGÍA: Los glucocorticoides (GCS) son una familia de medicamentos antiinflamatorios e inmunomoduladores que se utilizan en el tratamiento de diversas patologías cuyo principal componente etiopatogénico es la inflamación. Dentro de los mecanismos de acción propuestos se encuentran: inhibición de citoquinas inflamatorias (IL-1 y IL-2), inhibición de la migración de leucocitaria, inhibición de la desgranulación de mastocitos, depleción linfocitaria (principalmente linfocitos T), incremento de citoquinas anti-inflamatorias (IL-10). Dentro de las alternativas para la administración sistémica se pueden mencionar a la hidrocortisona, dexametasona, betametasona, prednisona, prednisolona, metilprednisolona y deflazacort. Todos ellos difieren principalmente en el grado de actividad mineralocorticorticoide y vida media. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de corticoides sistémicos en COVID­19. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y recomendaciones de diferentes organizaciones de salud. RESULTADOS: Se incluyeron un ECA, una RS, dos estudios observacionales, un documento de evaluación de tecnología sanitaria, 12 guías de práctica clínica, recomendaciones de organismos gubernamentales o sociedades científicas acerca del uso de corticoides sistémicos en pacientes con diagnóstico de COVID­19. CONCLUSIONES: Evidencia de alta calidad proveniente de los resultados de un ensayo clínico aleatorizado aún no publicado sugiere que el uso de corticoides sistémicos se asocia a una disminución en el riesgo de mortalidad principalmente en pacientes con requerimientos de oxigeno suplementario o asistencia mecánica invasiva. Evidencia de muy baja calidad también sugiere que podría tener el mismo beneficio en aquellos pacientes con COVID-19 que presentan síndrome de distrés respiratorio agudo. Múltiples ensayos clínicos aleatorizados en pacientes con cuadros moderados o severos se encuentran en curso. Las guías de práctica clínica de diferentes sociedades internacionales y organismos gubernamentales que lo recomiendan indican su utilización para el tratamiento de pacientes con criterios de síndrome de distrés respiratorio agudo. Si bien no se encontraron estudios de costo-efectividad en Latinoamérica, el costo total del tratamiento al igual que su impacto presupuestario sería muy bajo.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Betametasona/uso terapêutico , Dexametasona/uso terapêutico , Hidrocortisona/uso terapêutico , Metilprednisolona/uso terapêutico , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Avaliação em Saúde , Análise Custo-Benefício
18.
Zhonghua Nei Ke Za Zhi ; 59(6): 451-459, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32486586

RESUMO

Objective: To evaluate the effect of corticosteroids on the prognosis of patients with septic shock. Method: In order to compare administration of corticosteroids with placebo or standard supportive care in adults with septic shock, clinical randomized controlled trials (RCT) were searched and selected, according to inclusion and exclusion criteria. A systemic assessment and meta-analysis was performed using RevMan 5.3. Result: A total of 16 RCTs enrolling 6 896 patients were finally included in present analysis. The corticosteroids group included 3 448 patients, and the control group included 3 448 patients. The 28-day mortality in corticosteroids group and control group were 28.6% and 31.2%, respectively (P=0.16). The 90-day mortality, the mortality in intensive care unit (ICU) and the mortality in the hospital between corticosteroids group and control group were 31.7% vs. 34.0% (P=0.16), 37.5% vs. 37.5% (P=0.87), and 41.0% vs. 43.9% (P=0.35) respectively, which indicated that corticosteroids could not improve the mortality of patients with septic shock. Subgroup analyses showed that hydrocortisone combined with hydrocortisone could reduce the 28-day mortality, and the 28-day mortality in corticosteroids group and control group were 37.7% and 43.3%, respectively (P=0.02). However, other types of corticosteroids had no influence on 28-day mortality. The incidence of gastrointestinal hemorrhage and super-infections showed no statistical difference in corticosteroids group and control group. However, incidence of hyperglycemia was significantly increased in corticosteroids group, 27.1% vs. 25% (P<0.000 1). Conclusion: Corticosteroids could not improve the mortality of patients with septic shock, and simultaneously, significantly increase incidence of hyperglycemia. Corticosteroids have no influence on the incidence of gastrointestinal hemorrhage and super-infections. Subgroup analyses showed that hydrocortisone combined with hydrocortisone could reduce the 28-day mortality.


Assuntos
Corticosteroides/uso terapêutico , Hidrocortisona/uso terapêutico , Choque Séptico/tratamento farmacológico , Corticosteroides/administração & dosagem , Adulto , China/epidemiologia , Hemorragia Gastrointestinal , Humanos , Hidrocortisona/administração & dosagem , Hiperglicemia/epidemiologia , Incidência , Unidades de Terapia Intensiva , Prognóstico , Choque Séptico/mortalidade
19.
Internist (Berl) ; 61(6): 565-572, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32394073

RESUMO

BACKGROUND: The central circadian pacemaker in the suprachiasmatic nucleus and interaction of clock genes with the hypothalamus pituitary adrenal axis are responsible for very distinct cortisol concentrations. Unphysiologically high doses of glucocorticoids that do not follow the circadian rhythm lead to increased rates of morbidity, mortality and reduced quality of life. OBJECTIVES: Does a switch to modified-release hydrocortisone in multimorbid elderly patients offer benefits compared to a conventional therapy regime? METHODS: Evaluation, analysis and discussion of statistics, recent research results and expert advice. RESULTS: Overdosage and unphysiological timing of cortisol administration result in higher incidences of obesity, hypertension, hyperglycemia, coronary heart disease and cardiac events. Body weight, body mass index and HbA1c decline with Plenadren® (Shire Pharmaceuticals Ireland Limited, Dublin, Ireland) treatment compared to conventional therapy. CD16+ natural killer cells and natural killer cytotoxycity are reduced, and the incidence of respiratory-tract infections is increased, with conventional therapy compared to Plenadren®. Cortisol influences sleep pattern and sleep quality by its circadian secretion. CONCLUSION: Novel modified-release hydrocortisone preparations offer diverse benefits with regard to their effect on metabolism, cardiovascular risk, immunity and sleep, which might be beneficial in particular in multimorbid elderly.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Ritmo Circadiano/fisiologia , Glucocorticoides/uso terapêutico , Terapia de Reposição Hormonal/métodos , Hidrocortisona/uso terapêutico , Insuficiência Adrenal/metabolismo , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/metabolismo , Qualidade de Vida , Resultado do Tratamento
20.
Iran J Immunol ; 17(1): 87-93, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32224544

RESUMO

BACKGROUND: Drugs used in cancer treatment specifically kill T regulatory cells. OBJECTIVE: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). MATERIALS: We evaluated the percentages of regulatory T cells by flow cytometry. Soluble CTLA-4 (sCTLA-4) in plasma was evaluated by ELISA assay. RESULTS: Increased percentages of CD4+CD25+ T cells, CD4+CD39+ T cells, CD4+Foxp3+ T cells, and CD4+CD25High T cells were observed in children with ALL in comparison to healthy controls. In addition, the ALL patients with >12 months of therapy showed increased CD4+CD39+ T cells compared to the ALL patients with ≤12 months and healthy controls. Similarly, the CD4+CD25+ T cells and CD4+Foxp3+ T cells increased according to maintenance therapy time. CONCLUSION: Our results showed increased percentages of regulatory T cells in pediatric ALL patients despite chemotherapy, which might be compromising the anti-leukemic cellular immune response.


Assuntos
Quimioterapia de Manutenção/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Hidrocortisona/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Vincristina/uso terapêutico
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