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1.
Med. clín (Ed. impr.) ; 156(1): 7-12, ene. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-196134

RESUMO

OBJETIVO: Analizar si existe asociación entre el uso de glucocorticoides a dosis altas y la evolución de la SAFI (saturación/fracción inspirada de oxígeno) o el tiempo hasta el alta, en pacientes hospitalizados por COVID-19. MÉTODOS: Estudio observacional sobre una cohorte de 418 pacientes ingresados en 3 hospitales comarcales de Cataluña (España). Como resultados primarios se estudiaron la evolución de la SAFI en las primeras 48h de tratamiento y el tiempo hasta el alta. Los resultados se compararon entre pacientes tratados y no tratados con glucocorticoides (metilprednisolona 1-2mg/kg/día o dexametasona 20-40mg/día), mediante el análisis de subcohortes emparejadas por múltiples factores clínicos y pronósticos, así como mediante modelos multivariantes de Cox, ajustados por diversos factores pronósticos. El uso simultáneo de diferentes tratamientos para la COVID-19 fue tenido en cuenta, tanto en el emparejamiento de subcohortes como en la regresión de Cox. RESULTADOS: Hubo 187 pacientes con glucocorticoides; de ellos, 25 pacientes pudieron ser emparejados con un número equivalente de pacientes control. En las subcohortes emparejadas, no se apreció diferencia en el tiempo hasta el alta (log-rank: p = 0,291), ni en el cambio en la SAFI a las 48h desde la basal (glucocorticoides: −0,04; controles: +0,37; p = 0,095). Los modelos multivariantes mediante regresión de Cox mostraron un tiempo hasta el alta significativamente más largo en pacientes tratados con glucocorticoides (hazard ratio: 7,26; IC 95%: 3,30-15,95). CONCLUSIONES: No hemos encontrado mejoría en la función respiratoria o tiempo hasta el alta, asociado al uso de glucocorticoides a dosis altas


OBJECTIVE: To analyze whether there is an association between the use glucocorticoids at high doses, and the evolution of saturation/fraction of inspired oxygen (SAFI) or time to discharge, in patients hospitalized with COVID-19. METHODS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia, Spain. As primary outcomes, we studied the evolution of SAFI in the first 48hours of treatment and the time to discharge. The results were compared between patients treated and untreated with glucocorticoids (methylprednisolone 1-2mg/kg/day o dexamethasone 20-40mg/day) through sub-cohort analyses matched for multiple clinical and prognostic factors, as well as through Cox multivariate models adjusted for prognostic factors. The simultaneous use of different treatments for COVID-19 was taken into account, both in sub-cohorts matching and in Cox regression. RESULTS: There were 187 patients treated with glucocorticoids; of these, 25 patients could be matched with an equivalent number of control patients. In the analysis of these matched sub-cohorts, no significant difference was observed in time to discharge (log-rank: p = 0.291) or the increment in SAFI at 48hours of treatment (glucocorticoides: −0.04; controls: +0.37; p = 0.095). Multivariate models using Cox regression showed a significantly longer time to discharge in patients treated with glucocorticoids (hazard ratio: 7.26; 95% IC: 3.30-15.95). CONCLUSIONS: We have not found improvement in respiratory function or time until discharge, associated with the use of glucocorticoids at high doses


Assuntos
Humanos , Masculino , Feminino , Idoso , Glucocorticoides/administração & dosagem , Alta do Paciente , Estudos de Coortes , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Oxigênio/administração & dosagem , Metilprednisolona/administração & dosagem , Dexametasona/administração & dosagem , Síndrome Respiratória Aguda Grave/tratamento farmacológico
2.
Trials ; 22(1): 93, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499916

RESUMO

BACKGROUND: All of the existing medication and surgical therapies currently cannot completely inhibit intracerebral hemorrhage (ICH)-mediated brain damage, resulting in disability in different degrees in the involved patients. Normobaric oxygenation (NBO) was reported attenuating ischemic brain injury. Herein, we aimed to explore the safety and efficacy of NBO on rescuing the damaged brain tissues secondary to acute ICH, especially those in the perihematoma area being threatened by ischemia and hypoxia. METHODS: A total of 150 patients confirmed as acute spontaneous ICH by computed tomography (CT) within 6 h after symptoms onset, will enroll in this study after signing the informed consent, and enter into the NBO group or control group randomly according to a random number. In the NBO group, patients will inhale high-flow oxygen (8 L/min, 1 h each time for 6 cycles daily) and intake low-flow oxygen (2 L/min) in intermittent periods by mask for a total of 7 days. While in the control group, patients will breathe in only low-flow oxygen (2 L/min) by mask for 7 consecutive days. Computed tomography and perfusion (CT/CTP) will be used to evaluate cerebral perfusion status and brain edema. CT and CTP maps in the two groups at baseline and day 7 and 14 after NBO or low-flow oxygen control will be compared. The primary endpoint is mRS at both Day14 post-ICH and the end of the 3rd month follow-up. The secondary endpoints include NIHSS and plasma biomarkers at baseline and Day-1, 7, and 14 after treatment, as well as the NIHSS at the end of the 3rd month post-ICH and the incidence of bleeding recurrence and the mortalities within 3 months post-ICH. DISCUSSION: This study will provide preliminary clinical evidence about the safety and efficacy of NBO on correcting acute ICH and explore some mechanisms accordingly, to offer reference for larger clinical trials in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04144868 . Retrospectively registered on October 29, 2019.


Assuntos
Edema Encefálico/terapia , Lesões Encefálicas/terapia , Hemorragia Cerebral/terapia , Oxigenoterapia/efeitos adversos , Oxigênio/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/diagnóstico , Edema Encefálico/etiologia , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/etiologia , Córtex Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Máscaras , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Oxigenoterapia/instrumentação , Oxigenoterapia/métodos , Imagem de Perfusão/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
3.
Int J Antimicrob Agents ; 57(2): 106265, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33338559

RESUMO

Severe COVID-19 (coronavirus disease 2019) is associated with elevated inflammatory markers, consistent with cytokine release syndrome (CRS). Tocilizumab is an interleukin-6 (IL-6) inhibitor effective in treating CRS secondary to chimeric antigen receptor T-cell (CAR T-cell) therapy. The efficacy of tocilizumab in treating COVID-19 is unknown. This was a retrospective cohort study conducted at two hospitals in northern New Jersey (USA). All patients treated with tocilizumab for confirmed or suspected COVID-19 between 10 March 2020 and 9 April 2020 at the study sites were included. The primary endpoint was clinical improvement on Day 7 after treatment as assessed by respiratory status. Univariate analysis compared data between those who improved and those who did not. A total of 45 severe and critically ill patients treated with tocilizumab for COVID-19 were evaluated. Of the 45 patients, 11 (24.4%), 22 (48.9%) and 12 (26.7%) patients improved, had no change or worsened by Day 7 after treatment, respectively. Lower white blood cell count and lactate dehydrogenase at the time of drug administration as well as shorter time from supplemental oxygen initiation to dosing were significantly associated with clinical improvement in the univariate analysis. In conclusion, tocilizumab administration was associated with a low rate of clinical improvement within 7 days in this cohort of severe and critically ill patients with COVID-19.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , /tratamento farmacológico , /etiologia , Estado Terminal , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Oxigênio/uso terapêutico , Estudos Retrospectivos , Ritonavir/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
4.
Chem Biol Interact ; 334: 109339, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33316227

RESUMO

Clinical trials of thermoheliox application (inhalation with a high-temperature mixture of oxygen and helium, 90 °C) in the treatment of the acute phase of coronavirus infection were conducted. Dynamics of disease development in infected patients (PCR test for the virus) and, dynamics of changes in blood concentration of C-reactive protein, immunoglobulin M, specific immunoglobulin G were studied. High efficiency of thermoheliox in releasing the organism from the virus and stimulating the immune response (thermovaccination effect) was shown. The kinetic model of the process is proposed and analyzed.


Assuntos
/imunologia , Hélio/administração & dosagem , Hipertermia Induzida/métodos , Oxigênio/administração & dosagem , Administração por Inalação , Adulto , Idoso , Anticorpos Antivirais/sangue , Proteína C-Reativa/biossíntese , Temperatura Alta , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Cinética , Pessoa de Meia-Idade , Modelos Imunológicos , Vacinação/métodos
5.
Med Hypotheses ; 146: 110421, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33308935

RESUMO

BACKGROUND: Infection with SARS-CoV-2 is responsible for the COVID-19 crisis affecting the whole world. This virus can provoke acute respiratory distress syndrome (ARDS) leading to overcrowed the intensive care unit (ICU). Over the last months, worldwide experience demonstrated that the ARDS in COVID-19 patients are in many ways "atypical". The mortality rate in ventilated patients is high despite the application of the gold standard treatment (protective ventilation, curare, prone position, inhaled NO). Several studies suggested that the SARS-CoV-2 could interact negatively on red blood cell homeostasis. Furthermore, SarsCov2 creates Reactive Oxygen Species (ROS), which are toxic and generate endothelial dysfunction. Hypothesis/objective(s) We hypothesis that HEMO2Life® administrated intravenously is safe and could help symptomatically the patient condition. It would increase arterial oxygen content despite lung failure and allow better tissue oxygenation control. The use of HEMO2Life® is also interesting due to its anti-oxidative effect preventing cytokine storm induced by the SARS-CoV-2. Evaluation of the hypothesis: Hemarina is based on the properties of the hemoglobin of the Arenicola marina sea-worm (HEMO2Life®). This extracellular hemoglobin has an oxygen capacity 40 times greater than the hemoglobin of vertebrates. Furthermore, the size of this molecule is 250 times smaller than a human red blood cell, allowing it to diffuse in all areas of the microcirculation, without diffusing outside the vascular sector. It possesses an antioxidative property du a Superoxide Dismutase Activity. This technology has been the subject of numerous publications and HEMO2Life® was found to be well-tolerated and did not induce toxicity. It was administered intravenously to hamsters and rats, and showed no acute effect on heart rate and blood pressure and did not cause microvascular vasoconstriction. In preclinical in vivo models (mice, rats, and dogs), HEMO2Life® has enabled better tissue oxygenation, especially in the brain. This molecule has already been used in humans in organ preservation solutions and the patients showed no abnormal clinical signs. CONSEQUENCES OF THE HYPOTHESIS: The expected benefits of HEMO2Life® for COVID-19 patients are improved survival, avoidance of tracheal intubation, shorter oxygen supplementation, and the possibility of treating a larger number of patients as molecular respirator without to use an invasive machine.


Assuntos
/complicações , Hemoglobinas/uso terapêutico , Hipóxia/etiologia , Hipóxia/terapia , Modelos Biológicos , Oxigênio/administração & dosagem , Animais , Cricetinae , Cães , Hemoglobinas/administração & dosagem , Hemoglobinas/metabolismo , Humanos , Hipóxia/fisiopatologia , Injeções Intravenosas , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Pandemias , Ratos , Pesquisa Médica Translacional
6.
Sci Rep ; 10(1): 21775, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311551

RESUMO

There is the urgent need to study the effects of immunomodulating agents as therapy for Covid-19. An observational, cohort, prospective study with 30 days of observation was carried out to assess clinical outcomes in 88 patients hospitalized for Covid-19 pneumonia and treated with canakinumab (300 mg sc). Median time from diagnosis of Covid-19 by viral swab to administration of canakinumab was 7.5 days (range 0-30, IQR 4-11). Median PaO2/FiO2 increased from 160 (range 53-409, IQR 122-210) at baseline to 237 (range 72-533, IQR 158-331) at day 7 after treatment with canakinumab (p < 0.0001). Improvement of oxygen support category was observed in 61.4% of cases. Median duration of hospitalization following administration of canakinumab was 6 days (range 0-30, IQR 4-11). At 7 days, 58% of patients had been discharged and 12 (13.6%) had died. Significant differences between baseline and 7 days were observed for absolute lymphocyte counts (mean 0.60 vs 1.11 × 109/L, respectively, p < 0.0001) and C-reactive protein (mean 31.5 vs 5.8 mg/L, respectively, p < 0.0001).Overall survival at 1 month was 79.5% (95% CI 68.7-90.3). Oxygen-support requirements improved and overall mortality was 13.6%. Confirmation of the efficacy of canakinumab for Covid-19 warrants further study in randomized controlled trials.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Hospitalização , Interleucina-1beta/antagonistas & inibidores , Idoso , /mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Estudos Prospectivos , Taxa de Sobrevida
7.
Med Gas Res ; 10(4): 193-200, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380588

RESUMO

Recent development regarding mixture of H2 (concentration of ~66%) with O2 (concentration of ~34%) for medical purpose, such as treatment of coronavirus disease-19 (COVID-19) patients, is introduced. Furthermore, the design principles of a hydrogen inhaler which generates mixture of hydrogen (~66%) with oxygen (~34%) for medical purpose are proposed. With the installation of the liquid blocking module and flame arresters, the air pathway of the hydrogen inhaler is divided by multiple isolation zones to prevent any unexpected explosion propagating from one zone to the other. An integrated filtering/cycling module is utilized to purify the impurity, and cool down the temperature of the electrolytic module to reduce the risk of the explosion. Moreover, a nebulizer is provided to selectively atomize the water into vapor which is then mixed with the filtered hydrogen-oxygen mix gas, such that the static electricity of a substance hardly occurs to reduce the risk of the explosion. Furthermore, hydrogen concentration detector is installed to reduce the risk of hydrogen leakage. Result shows that the hydrogen inhaler implementing the aforesaid design rules could effectively inhibit the explosion, even ignition at the outset of the hydrogen inhaler which outputs hydrogen-oxygen gas (approximately 66% hydrogen: 34% oxygen).


Assuntos
/terapia , Hidrogênio/administração & dosagem , Nebulizadores e Vaporizadores , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Explosões/prevenção & controle , Humanos , Nebulizadores e Vaporizadores/normas , Oxigenoterapia/normas , Eletricidade Estática/efeitos adversos , Volatilização
8.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370981

RESUMO

A 62-year-old woman presented with a 3-month history of shortness of breath on exertion and dry cough. On examination, she was noted to have fine end-inspiratory crepitations over the upper zone of the lungs. Pulmonary function tests (PFTs) showed a restrictive defect. Initial chest radiography revealed diffuse reticular interstitial shadowing while high-resolution CT scan of the thorax showed fibrotic changes. Avian precipitins were also highly positive for pigeons, parrots and budgerigars. Taking into account these results, the patient was diagnosed with hypersensitivity pneumonitis. Antigen avoidance, oral glucocorticoids and azathioprine achieved an initial improvement in PFTs and symptoms; however, the patient still deteriorated, requiring long-term oxygen therapy. While working the patient up for lung transplantation, rituximab was given to good effect (acting as a bridging therapy) as it achieved symptomatic relief and stabilisation of her PFTs.


Assuntos
Pulmão dos Criadores de Aves/tratamento farmacológico , Tosse/tratamento farmacológico , Dispneia/tratamento farmacológico , Glucocorticoides/farmacologia , Rituximab/uso terapêutico , Animais , Pulmão dos Criadores de Aves/complicações , Pulmão dos Criadores de Aves/diagnóstico , Pulmão dos Criadores de Aves/imunologia , Tosse/diagnóstico , Tosse/imunologia , Resistência a Medicamentos , Dispneia/diagnóstico , Dispneia/imunologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Testes de Função Respiratória , Rituximab/farmacologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370995

RESUMO

A 7-month-old-term male infant presented with cough, tachypnoea, hypoxaemia and post-tussive emesis. Clinical history was significant for respiratory failure and pulmonary hypertension in the neonatal period requiring assisted ventilation, congenital hypothyroidism, mild hypotonia, recurrent respiratory infections, hypoxaemia requiring supplemental oxygen and nasogastric tube feeds. Physical examination showed tachypnoea, coarse bilateral breath sounds and mild hypotonia. Chest radiograph revealed multifocal pulmonary opacities with coarse interstitial markings and right upper lobe atelectasis. Following antibiotic therapy for suspected aspiration pneumonia, chest CT scan was performed and showed multiple areas of pulmonary consolidation and scattered areas of bilateral ground-glass opacities. Genetic studies showed a large deletion of chromosome 14q13.1-14q21.1, encompassing the NK2 homeobox 1 (NKX2-1) gene consistent with a diagnosis of brain-thyroid-lung (BTL) syndrome. Our case highlights the importance of genetic studies to diagnose BTL syndrome in infants with hypothyroidism, hypotonia and lung disease.


Assuntos
Atetose/diagnóstico , Coreia/diagnóstico , Deleção Cromossômica , Cromossomos Humanos Par 14/genética , Hipotireoidismo Congênito/diagnóstico , Hipóxia/genética , Hipotonia Muscular/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Atetose/complicações , Atetose/genética , Atetose/terapia , Coreia/complicações , Coreia/genética , Coreia/terapia , Hipotireoidismo Congênito/complicações , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/terapia , Nutrição Enteral , Hidratação , Testes Genéticos , Humanos , Hipóxia/diagnóstico , Hipóxia/terapia , Lactente , Intubação Gastrointestinal , Pulmão/diagnóstico por imagem , Masculino , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/terapia , Oxigênio/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Fator Nuclear 1 de Tireoide/genética , Tomografia Computadorizada por Raios X
10.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(6): 1025-1030, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33369341

RESUMO

During the COVID-19 epidemic, our national guidelines have suggested that surgical patients should wear a mask to decrease the potential transmission of COVID-19 in the operating room, as long as the condition allows. However, so far, there is no study to discuss the influence of wearing a mask on the ventilation and blood oxygenation status in patients of spontaneous breathing with supplementary oxygen through an anesthetic facemask. This is a before-after study in the same patient, and 10 healthy volunteers were recruited, by testing the arterial blood gas parameters at key time points before and after oxygen inhalation to evaluate the effects of two different supplementary oxygen methods ('disposable medical mask + anesthetic facemask' and 'anesthetic facemask only') on the oxygenation of subjects. Our data demonstrated whether wearing a disposable medical mask or not could effectively increase the oxygen supply of the subjects compared with the basic value before oxygen inhalation; however, compared with the group without mask, the arterial oxygen partial (PaO 2) reduced significantly at each time points when subjects wearing a disposable medical mask. There was no significant difference in other parameters, and our data showed that age growth and smoking had no significant effects on the difference of PaO 2 between the groups with and without masks. This study demonstrates effective oxygen supplementation through anesthetic facemask in subjects with spontaneous breathing who is wearing a disposable medical mask, whose pulse oxygen saturation and arterial oxygen saturation can reach 100% rapidly, and this provides a theoretical basis for the management of patients with disseminated respiratory diseases to wear masks in the operating room; however, the rate and amount of PaO 2 increase are both decreased as compared to those who is not wearing a disposable medical mask during supplementary oxygenation. Whether this difference will affect the clinical outcome needs further study.


Assuntos
Máscaras , Oxigênio/administração & dosagem , Oxigênio/sangue , Voluntários Saudáveis , Humanos , Oximetria
11.
BMC Pulm Med ; 20(1): 324, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33357219

RESUMO

BACKGROUND: It had been shown that High-flow nasal cannula (HFNC) is an effective initial support strategy for patients with acute respiratory failure. However, the efficacy of HFNC for patients with COVID-19 has not been established. This study was performed to assess the efficacy of HFNC for patients with COVID-19 and describe early predictors of HFNC treatment success in order to develop a prediction tool that accurately identifies the need for upgrade respiratory support therapy. METHODS: We retrospectively reviewed the medical records of patients with COVID-19 treated by HFNC in respiratory wards of 2 hospitals in Wuhan between 1 January and 1 March 2020. Overall clinical outcomes, the success rate of HFNC strategy and related respiratory variables were evaluated. RESULTS: A total of 105 patients were analyzed. Of these, 65 patients (61.9%) showed improved oxygenation and were successfully withdrawn from HFNC. The PaO2/FiO2 ratio, SpO2/FiO2 ratio and ROX index (SpO2/FiO2*RR) at 6h, 12h and 24h of HFNC initiation were closely related to the prognosis. The ROX index after 6h of HFNC initiation (AUROC, 0.798) had good predictive capacity for outcomes of HFNC. In the multivariate logistic regression analysis, young age, gender of female, and lower SOFA score all have predictive value, while a ROX index greater than 5.55 at 6 h after initiation was significantly associated with HFNC success (OR, 17.821; 95% CI, 3.741-84.903 p<0.001). CONCLUSIONS: Our study indicated that HFNC was an effective way of respiratory support in the treatment of COVID-19 patients. The ROX index after 6h after initiating HFNC had good predictive capacity for HFNC outcomes.


Assuntos
/terapia , Hipóxia/terapia , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Oxigênio/sangue , Idoso , /fisiopatologia , Cânula , Feminino , Humanos , Hipóxia/fisiopatologia , Hipóxia/virologia , Masculino , Pessoa de Meia-Idade , Pressão Parcial , Taxa Respiratória , Estudos Retrospectivos , Resultado do Tratamento
12.
PLoS One ; 15(12): e0244857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382796

RESUMO

BACKGROUND: Continuous positive airway pressure (CPAP) ventilation may be used as a potential bridge to invasive mechanical ventilation (IMV), or as a ceiling-of-care for persistent hypoxaemia despite standard oxygen therapy, according to UK guidelines. We examined the association of mode of respiratory support and ceiling-of-care on mortality. METHODS: We conducted a retrospective cohort analysis of routinely collected de-identified data of adults with nasal/throat SARs-CoV-2 swab-positive results, at the Calderdale and Huddersfield NHS Foundation Trust between 10th March-19th April 2020 (outcomes determined on 22nd May). FINDINGS: Of 347 patients with SARs-CoV-2 swab-positive results, 294 (84.7%) patients admitted for Covid-19 were included in the study. Sixty-nine patients were trialled on CPAP, mostly delivered by face mask, either as an early ceiling of care instituted within 24 hours of admission (N = 19), or as a potential bridge to IMV (N = 44). Patients receiving a ceiling of care more than 24 hours after admission (N = 6) were excluded from the analysis. Two hundred and fifteen patients (73.1%) maximally received air/standard oxygen therapy, and 45 (15.3%) patients maximally received CPAP. Thirty-four patients (11.6%) required IMV, of which 24 had received prior CPAP. There were 138 patients with an early ceiling-of-care plan (pre-admission/within 24h). Overall, 103(35.0%) patients died and 191(65.0%) were alive at study end. Among all patients trialled on CPAP either as a potential bridge to IMV (N = 44) or as a ceiling-of-care (N = 19) mortality was 25% and 84%, respectively. Overall, there was strong evidence for higher mortality among patients who required CPAP or IMV, compared to those who required only air/oxygen (aOR 5.24 95%CI: 1.38, 19.81 and aOR 46.47 95%CI: 7.52, 287.08, respectively; p<0.001), and among patients with early ceiling-of-care compared to those without a ceiling (aOR 41.81 95%CI: 8.28, 211.17; p<0.001). Among patients without a ceiling of care (N = 137), 10 patients required prompt intubation following failed oxygen therapy, but 44 patients received CPAP. CPAP failure, defined as death (N = 1) or intubation (N = 24), occurred in 57% (N = 25) of patients. But in total, 75% (N = 33) of those started on CPAP with no ceiling of care recovered to discharge-19 without the need for IMV, and 14 following IMV. CONCLUSION: Our data suggest that among patients with no ceiling-of-care, an initial trial of CPAP as a potential bridge to IMV offers a favourable therapeutic alternative to early intubation. In contrast, among patients with a ceiling-of care, CPAP seems to offer little additional survival benefit beyond oxygen therapy alone. Information on ceilings of respiratory support is vital to interpreting mortality from Covid-19. STRENGTHS AND LIMITATIONS OF THIS STUDY: Sample size relatively small.Study sample representative of hospitalised Covid-19 patients in UK.Previously unreported data on role of ceilings-of-care in hospitalised Covid-19 patients.Novel data on use of CPAP separated by indication.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/economia , Hospitalização/economia , Oxigênio/administração & dosagem , Adulto , /epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Trials ; 21(1): 939, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225960

RESUMO

BACKGROUND: Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNß-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNß anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNß was indicated as the key component of a successful therapeutic combination. METHODS: This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNß-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNß-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNß-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNß-1a in COVID-19 patients. DISCUSSION: Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNß-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNß-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment. TRIAL REGISTRATION: EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1a/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , Antivirais/administração & dosagem , Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Gerenciamento de Dados , Feminino , Humanos , Injeções Subcutâneas , Interferon beta-1a/administração & dosagem , Itália/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Mortalidade/tendências , Oxigênio/administração & dosagem , Oxigênio/uso terapêutico , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
14.
Trials ; 21(1): 940, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225990

RESUMO

OBJECTIVES: To assess the effect of prone positioning therapy on intubation rate in awake patients with COVID-19 and acute respiratory failure. TRIAL DESIGN: This is a two-center parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hospital Civil de Guadalajara and Hospital General de Occidente in Mexico for COVID-19 associated acute respiratory failure and in need of supplementary oxygen through high-flow nasal cannula are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the COVID-19 unit who test positive for COVID-19 by PCR-test and in need for oxygen are eligible for inclusion. Randomization starts upon identification of requirement of a fraction of inspired oxygen ≥30% for an oxygen capillary saturation of ≥90% Exclusion criteria: less than 18 years-old, pregnancy, patients with immediate need of invasive mechanical ventilation (altered mental status, fatigue), vasopressor requirement to maintain median arterial pressure >65 mmHg, contraindications for prone positioning therapy (recent abdominal or thoracic surgery or trauma, facial, pelvic or spine fracture, untreated pneumothorax, do-not-resuscitate or do-not-intubate order, refusal or inability of the patient to enroll in the study. INTERVENTION AND COMPARATOR: Patients of the intervention group will be asked to remain in a prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of 92%-95%. For patients in the control group, prone positioning will be allowed as a rescue therapy. Staff intensivists will monitor the patient's status in both groups on a 24/7 basis. All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: Endotracheal intubation rate for mechanical ventilation at 28 days. RANDOMISATION: Patients will be randomly allocated to either prone positioning or control group at 1:1 ratio. Such randomization will be computer generated and stratified by center with permuted blocks and length of 4. BLINDING (MASKING): Due to logistical reasons, only principal investigators and the data analyst will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): With an intubation rate of 60% according to recent reports from some American centers, and assuming a decrease to 40% to be clinically relevant, we calculated a total of 96 patients per group, for a beta error of 0.2, and alpha of 0.5. Therefore, we plan to recruit 200 patients, accounting for minimal losses to follow up, with 100 non-intubated patients in the prone position group and a 100 in the control group. TRIAL STATUS: The local registration number is 048-20, with the protocol version number 2.0. The date of approval is 3rd May 2020. Recruitment started on 3rd May and is expected to end in December 2020. TRIAL REGISTRATION: The protocol was retrospectively registered under the title: "Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure. The PRO-CARF trial" in ClinicalTrials.gov with the registration number: NCT04477655. Registered on 20 July 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
Infecções por Coronavirus/complicações , Intubação Intratraqueal/instrumentação , Oxigênio/uso terapêutico , Pneumonia Viral/complicações , Decúbito Ventral/fisiologia , Insuficiência Respiratória/etiologia , Doença Aguda , Adulto , Betacoronavirus/genética , Cânula/efeitos adversos , Cânula/provisão & distribução , Estudos de Casos e Controles , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Humanos , Intubação Intratraqueal/estatística & dados numéricos , Masculino , México/epidemiologia , Oxigênio/administração & dosagem , Oxigênio/sangue , Oxigênio/provisão & distribução , Pandemias , Posicionamento do Paciente/métodos , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia
16.
Medicine (Baltimore) ; 99(46): e23243, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181713

RESUMO

BACKGROUND: This study uses a method of systematic evaluation to evaluate the safety and effectiveness of heated humidified high-flow nasal cannula (HHHFNC) as an initial ventilation method in the treatment of neonatal respiratory distress syndrome (NRDS) scientifically. In the field of evidence-based medicine, this study provides a theoretical reference and basis for choosing appropriate initial non-invasive ventilation methods in the treatment of NRDS, thereby providing assistance for clinical treatment. METHODS: The main electronic network databases were searched by computer, including 4 Chinese databases: CNKI, WangFang Data, CQVIP, SinoMed and 3 English databases: PubMed, The Cochrane Library and EMBASE, the time range of retrieval from the beginning of each database to September 1, 2020. The content involves all the published randomized controlled trials on the effectiveness of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS. Using a search method that combines medical subject words and free words. Based on the Cochrane risk bias assessment tool, 2 researchers independently screen the literature, and then extract the data we needed in the literature, and cross-check. If it is difficult to decide whether to include literature, then turning to a third researcher for help and making a final decision after discussion, and using RevMan 5.3 and STATA 13.0 to analyze the relative data. RESULTS: Based on the method of meta-analysis, this study analyzes the pre-determined outcome indicators through scientific statistical analysis, and compares the effectiveness and safety of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS. All results will be published in peer-reviewed high-quality professional academic journals. CONCLUSION: Based on evidence-based medicine, this study will obtain the establishing evidence of comparison that the clinical effectiveness and safety of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS through the existing data and data, which provides the evidence support of evidence-based medicine in the treatment of NRDS. OSF REGISTRATION NUMBER: September 17, 2020. osf.io/f6at4 (https://osf.io/f6at4).


Assuntos
Cânula/normas , Protocolos Clínicos , Umidificadores/normas , Oxigenoterapia/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Humanos , Recém-Nascido , Metanálise como Assunto , Ventilação não Invasiva/métodos , Ventilação não Invasiva/normas , Oxigênio/administração & dosagem , Oxigênio/uso terapêutico , Oxigenoterapia/normas , Revisões Sistemáticas como Assunto
17.
Aging (Albany NY) ; 12(20): 19945-19953, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33136555

RESUMO

COVID-19 pneumonia can be severe, with an unpredictable evolution and high mortality prevalence in older patients. The diagnosis is usually performed by RT-PCR or CT chest scan. Lung ultrasonography (LUS) has been proposed as an alternative method to monitor patients with COVID-19 pneumonia. To assess the diagnostic performance of LUS, we performed LUS using a portable device and adapting a protocol already used in Acute Respiratory Syndrome. We used the score obtained with the index we created to assess for LUS diagnostic performance as compared to lung CT chest scan and to predict for oxygen requirements. Daily bedside LUS was easy to perform and microbiologically safe. LUS was 89% sensitive and 100% specific in predicting CT chest scan abnormalities, and 95% sensitive and 67% specific in detecting oxygen requirements. This is the first report on the diagnostic performance of LUS as compared to CT chest scan for the diagnosis of COVID-19 pneumonia and assessments of oxygen requirements by LUS. LUS could help in the orientation of dyspneic patients to intensive care. It could also be proposed when there is limited access to CT scan in the context of a pandemic crisis, or to implement clinical lung examinations for outpatient follow-up.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Ultrassonografia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Pandemias , Testes Imediatos , Estudo de Prova de Conceito , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
18.
Cochrane Database Syst Rev ; 9: CD013708, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32870512

RESUMO

BACKGROUND: Supplemental oxygen is frequently administered to patients with acute respiratory distress syndrome (ARDS), including ARDS secondary to viral illness such as coronavirus disease 19 (COVID-19). An up-to-date understanding of how best to target this therapy (e.g. arterial partial pressure of oxygen (PaO2) or peripheral oxygen saturation (SpO2) aim) in these patients is urgently required. OBJECTIVES: To address how oxygen therapy should be targeted in adults with ARDS (particularly ARDS secondary to COVID-19 or other respiratory viruses) and requiring mechanical ventilation in an intensive care unit, and the impact oxygen therapy has on mortality, days ventilated, days of catecholamine use, requirement for renal replacement therapy, and quality of life. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, CENTRAL, MEDLINE, and Embase from inception to 15 May 2020 for ongoing or completed randomized controlled trials (RCTs). SELECTION CRITERIA: Two review authors independently assessed all records in accordance with standard Cochrane methodology for study selection. We included RCTs comparing supplemental oxygen administration (i.e. different target PaO2 or SpO2 ranges) in adults with ARDS and receiving mechanical ventilation in an intensive care setting. We excluded studies exploring oxygen administration in patients with different underlying diagnoses or those receiving non-invasive ventilation, high-flow nasal oxygen, or oxygen via facemask. DATA COLLECTION AND ANALYSIS: One review author performed data extraction, which a second review author checked. We assessed risk of bias in included studies using the Cochrane 'Risk of bias' tool. We used the GRADE approach to judge the certainty of the evidence for the following outcomes; mortality at longest follow-up, days ventilated, days of catecholamine use, and requirement for renal replacement therapy. MAIN RESULTS: We identified one completed RCT evaluating oxygen targets in patients with ARDS receiving mechanical ventilation in an intensive care setting. The study randomized 205 mechanically ventilated patients with ARDS to either conservative (PaO2 55 to 70 mmHg, or SpO2 88% to 92%) or liberal (PaO2 90 to 105 mmHg, or SpO2 ≥ 96%) oxygen therapy for seven days. Overall risk of bias was high (due to lack of blinding, small numbers of participants, and the trial stopping prematurely), and we assessed the certainty of the evidence as very low. The available data suggested that mortality at 90 days may be higher in those participants receiving a lower oxygen target (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.03 to 3.27). There was no evidence of a difference between the lower and higher target groups in mean number of days ventilated (14.0, 95% CI 10.0 to 18.0 versus 14.5, 95% CI 11.8 to 17.1); number of days of catecholamine use (8.0, 95% CI 5.5 to 10.5 versus 7.2, 95% CI 5.9 to 8.4); or participants receiving renal replacement therapy (13.7%, 95% CI 5.8% to 21.6% versus 12.0%, 95% CI 5.0% to 19.1%). Quality of life was not reported. AUTHORS' CONCLUSIONS: We are very uncertain as to whether a higher or lower oxygen target is more beneficial in patients with ARDS and receiving mechanical ventilation in an intensive care setting. We identified only one RCT with a total of 205 participants exploring this question, and rated the risk of bias as high and the certainty of the findings as very low. Further well-conducted studies are urgently needed to increase the certainty of the findings reported here. This review should be updated when more evidence is available.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Unidades de Terapia Intensiva , Oxigênio/administração & dosagem , Pneumonia Viral/complicações , Respiração Artificial , /terapia , Viés , Catecolaminas/uso terapêutico , Tratamento Conservador , Humanos , Razão de Chances , Pandemias , Terapia de Substituição Renal/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , /virologia , Autoimagem , Fatores de Tempo
19.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L670-L674, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32878480

RESUMO

The severity of coronavirus disease 2019 (COVID-19) is linked to an increasing number of risk factors, including exogenous (environmental) stimuli such as air pollution, nicotine, and cigarette smoke. These three factors increase the expression of angiotensin I converting enzyme 2 (ACE2), a key receptor involved in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the etiological agent of COVID-19-into respiratory tract epithelial cells. Patients with severe COVID-19 are managed with oxygen support, as are at-risk individuals with chronic lung disease. To date, no study has examined whether an increased fraction of inspired oxygen (FiO2) may affect the expression of SARS-CoV-2 entry receptors and co-receptors, including ACE2 and the transmembrane serine proteases TMPRSS1, TMPRSS2, and TMPRSS11D. To address this, steady-state mRNA levels for genes encoding these SARS-CoV-2 receptors were assessed in the lungs of mouse pups chronically exposed to elevated FiO2, and in the lungs of preterm-born human infants chronically managed with an elevated FiO2. These two scenarios served as models of chronic elevated FiO2 exposure. Additionally, SARS-CoV-2 receptor expression was assessed in primary human nasal, tracheal, esophageal, bronchial, and alveolar epithelial cells, as well as primary mouse alveolar type II cells exposed to elevated oxygen concentrations. While gene expression of ACE2 was unaffected, gene and protein expression of TMPRSS11D was consistently upregulated by exposure to an elevated FiO2. These data highlight the need for further studies that examine the relative contribution of the various viral co-receptors on the infection cycle, and point to oxygen supplementation as a potential risk factor for COVID-19.


Assuntos
Infecções por Coronavirus/patologia , Proteínas de Membrana/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Mucosa Respiratória/metabolismo , Serina Endopeptidases/metabolismo , Serina Proteases/metabolismo , Células Epiteliais Alveolares/metabolismo , Animais , Betacoronavirus , Células Cultivadas , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/administração & dosagem , Oxigênio/análise , Pandemias , Receptores Virais/metabolismo , Fatores de Risco , Serina Endopeptidases/genética , Serina Proteases/genética , Índice de Gravidade de Doença
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