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1.
PLoS One ; 15(10): e0233938, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095803

RESUMO

BACKGROUND: Onion is one of the most commonly used plants in the traditional medicine for the treatment of various diseases. We recently demonstrated the anti-inflammatory properties of onion bulb extract (OBE) in reducing colitis severity in mice when administered at the same time of colitis induction. However, whether onion can reverse established colitis or even prevent its development has not been investigated. HYPOTHESIS: To test 1. whether OBE can reduce colitis severity when given either before (preventative approach) or after (treatment approach) colitis induction and if so, 2. what are the mechanisms by which onion can achieve these effects. METHODS: Colitis was induced by dextran sulfate sodium (DSS) administration using treatment and preventative approaches. The severity of the inflammation was determined by the gross and histological assessments. The colonic level/activity of pro-inflammatory molecules and immune cell markers was assessed by immunofluorescence and western blotting analysis. In vitro neutrophil superoxide release and survival was assessed by chemilumenecense and Annexin-V/7AAD assays respectively. RESULTS: OBE treatment significantly reduced colitis severity in both approaches, the colonic expression/activity profile of pro-inflammatory molecules, inhibited WKYMVm-induced superoxide release, and increased spontaneous apoptosis of neutrophils in vitro. CONCLUSIONS: OBE can be used as an effective option in the prevention and/or the treatment of established colitis.


Assuntos
Anti-Inflamatórios/administração & dosagem , Colite/tratamento farmacológico , Cebolas/química , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Índice de Gravidade de Doença , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(43): e22879, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120830

RESUMO

Cerebral edema is a frequent and serious complication in traumatic brain injury (TBI) patients. The objective is to study the effect of dexamethasone in patients with brain contusions, and to assess its effect on the vasogenic component of the pericontusional edema.Prospective-observational study to quantify, using magnetic resonance imaging, the volume of the edema before and after 10 days of dexamethasone in patients with brain contusions. Using diffusion tensor imaging, we have examined the effect of dexamethasone on fractional anisotropy (FA) and apparent diffusion coefficient (ADC). To assess changes, the pre- and post-treatment values for each patient were compared using a paired-samples Student t test.We included 30 TBI patients, 15 in each group. The volume of the vasogenic edema in the group of patients treated with dexamethasone decreased from 22 to 19 mL and this decrease was statistically significant (P < .05). Nevertheless, in the non-steroids group the volume of the vasogenic edema increased from 11 to 15 mL. There was a significant decrease in the ADC value (from 1.78-1.59; P < .05); and a significant increase in the FA value (0.09-0.11; P < .05) in the patients treated with dexamethasone.Using diffusion tensor imaging we have shown in a selected group of TBI patients with vasogenic pericontusional edema, a reduction of edema volume, a decrease in the ADC and an increase in the FA after treatment with dexamethasone. However, we have no data if such results are beneficial in terms of improving functional outcome.


Assuntos
Anti-Inflamatórios/uso terapêutico , Edema Encefálico/tratamento farmacológico , Lesões Encefálicas Traumáticas/complicações , Dexametasona/uso terapêutico , Imagem de Tensor de Difusão/métodos , Adulto , Idoso , Anisotropia , Anti-Inflamatórios/administração & dosagem , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Estudos de Casos e Controles , Dexametasona/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia
3.
Medicine (Baltimore) ; 99(43): e22926, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120848

RESUMO

RATIONALE: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies directed against the activity of factor VIII (FVIII) and presents with prolonged bleeding. 5.7% of systemic lupus erythematosus (SLE) patients are affected by AHA. PATIENT CONCERNS: A 51-year-old female patient with SLE presenting with the fatigue and spontaneous clinical bleeding symptoms such as hematuria and ecchymoses for 1 week. DIAGNOSIS: Laboratory examinations revealed prolongation of the activated partial thromboplastin time (APTT) (65.7 s), decreased FVIII activity (1.4%), and a titer of FVIII inhibitors of 8.5 Bethesda units/mL. INTERVENTIONS: Transfusion of recombinant human FVIII (ADVATE) in combination with intravenous methylprednisolone, cyclophosphamide, plasmapheresis, and fresh frozen plasma successfully stopped the bleeding and reduced the level of FVIII inhibitor. OUTCOMES: The size of the hematoma slowly decreased. The skin ecchymosis was gradually absorbed, the hemoglobin count increased, and the coagulation index gradually improved. There was no new bleeding or bleeding site. The patient was discharged and transferred to a local hospital for hospice care. LESSONS: AHA in a patient with SLE is rare. Once it occurs, it can be life-threatening. Clinicians should remain aware that because some cases of AHA may have features of SLE, appropriate distinction and diagnosis of these different but associated diseases is necessary.


Assuntos
Coagulantes/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/etiologia , Lúpus Eritematoso Sistêmico/complicações , Administração Intravenosa , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Testes de Coagulação Sanguínea/métodos , Coagulantes/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Equimose/diagnóstico , Equimose/etiologia , Fator VIII/administração & dosagem , Feminino , Hematúria/diagnóstico , Hematúria/etiologia , Hemofilia A/terapia , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/métodos , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Plasma , Plasmaferese/métodos , Resultado do Tratamento
5.
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
6.
J Crohns Colitis ; 14(Supplement_3): S785-S790, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32959882

RESUMO

Infusion centres are a central part in the management of patients with inflammatory bowel disease [IBD] and could be a source of transmission of SARS-COV-2. Here we aimed to develop global guidance for best practices of infusion centres for IBD patients and to determine the impact of the COVID-19 pandemic on these centres. Under the auspices of the International Organization for the Study of Inflammatory Bowel Disease [IOIBD], a task force [TF] was formed, an online survey was developed to query infusion centre protocols during COVID-19, and recommendations were made, based on TF experience and opinion. Recommendations focus mainly on patients screening, infusion centres re-organization, personnel protection, and protocol modifications such as shortening infusion duration or replacing it with subcutaneous alternatives. Implementing these recommendations will hopefully reduce exposure of both IBD patients and care givers to SARS-COV-2 and improve the function and safety of infusion centres during the COVID-19 pandemic as well as potential future threats.


Assuntos
Instituições de Assistência Ambulatorial/normas , Assistência Ambulatorial/normas , Anti-Inflamatórios/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Controle de Infecções/normas , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adulto , Comitês Consultivos , Assistência Ambulatorial/métodos , Anti-Inflamatórios/uso terapêutico , Protocolos Clínicos , Infecções por Coronavirus/complicações , Esquema de Medicação , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Saúde Global , Pesquisas sobre Serviços de Saúde , Humanos , Controle de Infecções/métodos , Doenças Inflamatórias Intestinais/complicações , Infusões Intravenosas , Quimioterapia de Manutenção/métodos , Quimioterapia de Manutenção/normas , Pneumonia Viral/complicações
7.
J Oleo Sci ; 69(10): 1257-1271, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32908093

RESUMO

This research work aimed to prepare and optimize "self-nanoemulsifying drug delivery system (SNEDDS)" by applying full factorial design (FFD) to improve solubilization and subsequently antiinflammatory efficacy of flufenamic acid (FLF). Suitable excipients were screened out based on the maximum solubility of FLF. FFD was applied using lipid (X1) and surfactant (X2) as independent variables against droplet size (Y1, nm), zeta potential (Y2, mV) and polydispersity index (PDI, Y3). Desirability function identified the main factors influencing the responses and possible interactions. Moreover, the optimized formulation (OFS1) was characterized and compared with pure FLF suspension. The prepared formulations (FS1-FS9) showed the size, PDI and zeta potential of 14.2-110.7 nm, 0.29-0.62 and -15.1 to -28.6 mV, respectively. The dispersion and emulsification of all formulations meted out within 2 min suggesting immediate release and successful solubilization. The optimized formulation OFS1 demonstrated ~ 85% drug release within 1 h which was significantly higher (p ˂ 0.05) than FLF suspension. The hemolysis study negated the probable interaction with blood cells. Eventually, improved anti-inflammatory efficacy was envisaged which might be attributed to increased drug solubility and absorption. The present nanocarrier could be a promising approach and alternative to conventional dosage form.


Assuntos
Anti-Inflamatórios/administração & dosagem , Sistemas de Liberação de Medicamentos , Emulsões , Ácido Flufenâmico/administração & dosagem , Nanopartículas , Formas de Dosagem , Composição de Medicamentos , Desenho de Fármacos , Liberação Controlada de Fármacos , Excipientes , Tamanho da Partícula , Solubilidade , Tensoativos
8.
JAMA ; 324(13): 1317-1329, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32876697

RESUMO

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Assuntos
Anti-Inflamatórios/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Hidrocortisona/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Respiração Artificial/estatística & dados numéricos , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Hidrocortisona/efeitos adversos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Choque/tratamento farmacológico , Choque/etiologia , Resultado do Tratamento
9.
Medicine (Baltimore) ; 99(35): e21934, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871935

RESUMO

RATIONALE: We report a case of central retinal artery occlusion (CRAO) accompanied by choroidal folds in a patient positive for myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA). PATIENT CONCERNS: The study involved a 67-year-old female patient who presented at the Department of Ophthalmology, Osaka Medical College, Takatsuki-City, Osaka, Japan on October 24, 2016 after becoming aware of a sudden decrease of visual acuity (VA) in her right eye. Other than suffering with scleritis 6-months previous, there was no obvious past history. DIAGNOSIS: Upon examination, the VA in her right eye was hand motion, and the anterior segment of that eye showed thinning of the superior sclera. Macular edema in the inner retina and cherry red spots were observed in the ocular fundus, and optical coherence tomography (OCT) findings showed hyperreflectivity of the inner retina and choroidal folds. Fluorescein angiography (FA) examination of the fundus showed scattered areas of no retinal perfusion, and indocyanine green angiography (IA) findings of the fundus indicated a possible choroidal circulatory disturbance in her right eye. Blood test findings revealed the patient to be positive for MPO-ANCA. Based on the above findings, the patient was diagnosed with CRAO and choroidal circulatory disturbance due to ANCA-associated vasculitis. INTERVENTIONS: For treatment, steroid semi-pulse therapy was initiated. OUTCOMES: Post treatment initiation, the fundus features and choroidal folds gradually improved, and her VA slightly improved to 0.08. LESSONS: Based on the FA, IA, and OCT findings, the present case was considered to have CRAO accompanied by choroidal circulatory disturbance due to ANCA-associated vasculitis, a rare disease that may be complicated by choroidal circulatory disturbances.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Doenças da Coroide/etiologia , Oclusão da Artéria Retiniana/etiologia , Idoso , Anti-Inflamatórios/administração & dosagem , Azatioprina/administração & dosagem , Doenças da Coroide/diagnóstico por imagem , Doenças da Coroide/tratamento farmacológico , Feminino , Angiofluoresceinografia , Glucocorticoides/administração & dosagem , Humanos , Prednisolona/administração & dosagem , Pulsoterapia , Oclusão da Artéria Retiniana/diagnóstico por imagem , Oclusão da Artéria Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica , Baixa Visão/etiologia
10.
J Environ Pathol Toxicol Oncol ; 39(3): 213-224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865913

RESUMO

Asthma is a chronic, serious allergic inflammatory disease in the airway. The inflammation in the airway is induced by the allergic T-helper 2 cells (Th2 cells), which leads to unfettered production of inflammatory cytokines. The accretion of inflammatory cells in the airway also speeds up the secretion of reactive oxygen species (ROS) and suppresses antioxidative processes. Hence, the present work aimed to study the antiasthmatic efficacy of betulin and its effect in suppressing the inflammatory markers of ovalbumin (OVA) challenged asthmatic mice. The observed results revealed that the levels of inflammatory cells including neutrophils, eosinophils, lymphocytes, and macrophages were effectively decreased by betulin treatment; furthermore, the inflammatory markers IL-4, IL-5, IL-13, and TNF-α levels were notably suppressed by betulin administration in OVA-challenged asthmatic mice. Similarly, the oral administration of betulin showed a reduction in IgE level and elevation in the IFN-γ level in bronchoalveolar lavage fluid (BALF). The elevated levels of antioxidant enzymes like catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were observed in betulin treated mice. Furthermore, reduced levels of reactive oxygen species like NO2, NO3, and MDA were noted in the betulin treated group. Consistently, airway hyperreactivity (AHR) was depleted in the betulin administered group compared with the OVA-challenged asthmatic group. Betulin treatment was revealed to have noteworthy antiasthmatic effects mediated by the suppression of production of inflammatory cells and the expression of other inflammatory markers. Furthermore, the elevation in the level of antioxidant markers helped to disclose the original regulatory mode of betulin on asthma treatment.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Triterpenos/uso terapêutico , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/imunologia , Asma/metabolismo , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Eosinófilos/citologia , Feminino , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo , Testes de Função Respiratória , Triterpenos/administração & dosagem
11.
J Environ Pathol Toxicol Oncol ; 39(3): 225-234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865914

RESUMO

Asthma is marked by chronic irritation in the airway lumen of the lungs due to the accretion of inflammatory cells that influence the regular inhalation process. An extended buildup of inflammation leads to oxidative pressure and the repression of antioxidant functions. In the current study, a potential compound, boldine, was tested for the containment of provocative markers along the path of antiasthmatic activity in an ovalbumin (OVA)-induced asthmatic mice model. As an effect, the boldine (10 and 20 mg/kg) treatment suppressed inflammatory cells such as eosinophil, macrophage, neutrophil, lymphocyte, and other inflammatory markers in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. Likewise, immunoglobulin E (IgE) levels were drastically condensed in the serum of boldine-treated animals. Levels of enzymatic and nonenzymatic antioxidants, such as superoxide dismutase (SOD) and glutathione (GSH), were upregulated in the boldine treatment group compared to the asthmatic control group, which displays the antioxidant effects of boldine on asthmatic animals. Interestingly, the reactive oxygen species (ROS) and malonaldehyde (MDA) levels were repressed in the BALF of boldine-treated mice groups. Therefore, the effects of boldine are significant for the management of asthma, reducing the accrual of inflammatory cells, along with other inflammatory markers, while improving antioxidant markers and containing ROS. Hence, boldine may be an option for clinical trials of chronic asthma management.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Aporfinas/uso terapêutico , Asma/tratamento farmacológico , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Aporfinas/administração & dosagem , Asma/imunologia , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/análise , Modelos Animais de Doenças , Eosinófilos/citologia , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Espécies Reativas de Oxigênio/metabolismo , Testes de Função Respiratória
12.
J Environ Pathol Toxicol Oncol ; 39(3): 235-245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865915

RESUMO

Ulcerative colitis (UC) is an intractable ailment, in which may chronic inflammations/ulcerations may develop in the mucosal lining of the colon with multiple recurrences. Various drugs such as steroids, immunosuppressants, and antibiotics are extensively used to treat UC. The patients suffer from adverse effects of these advanced drugs. So, they need a harmless therapeutic agent from natural sources. The therapeutic D-carvone has an anti-inflammatory action against the investigational colon cancer models. Therefore, we analyzed the effect of D-carvone on dextran sulfate sodium (DSS) provoked colitis model in mice as follows: Group I: noncolitis healthy control mice; Group II: ulcerative colitis mice models; Group III: D-carvone (40 mg/kg) + ulcerative colitis models; Group IV: sulfasalazine (50 mg/kg) + ulcerative colitis models. On the 8th day, the experimental study was terminated and serum samples and colon tissues were processed for further analysis. The effect of D-carvone at different concentration was studied on the LPS challenged RAW 264.7 cell lines. The D-carvone (40 mg/kg) treatment maintained the colon length and decreased disease activity index (DAI) score in UC animals. The increased antioxidant enzymes status and decreased oxidative stress and pro-inflammatory markers were noted in the D-carvone (40 mg/ kg) + UC mice. Histopathological study of colon tissue of D-carvone (40 mg/kg) treated UC mice displayed less mucosal damage and improved crypt integrity and goblet cells compared with DSS only provoked mice. The im-munohistochemical expression of iNOS and COX-2 was drastically diminished in the D-carvone treated UC mice. D-carvone (40 mg/kg) treatment appreciably diminished the LPS provoked NO production and pro-inflammatory modulators in the RAW 264.7 macrophage cell lines. These findings proved that D-carvone has a potential therapeutic effect to prevent LPS induced inflammation in in vitro cells and chemically induced ulcerative colitis in vivo models.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Monoterpenos Cicloexânicos/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Macrófagos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Animais , Anti-Inflamatórios/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Monoterpenos Cicloexânicos/administração & dosagem , Sulfato de Dextrana , Modelos Animais de Doenças , Lipopolissacarídeos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7
13.
N Z Med J ; 133(1520): 120-124, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994602

RESUMO

Spontaneous bleeding in the head and neck region is exceedingly rare, particularly in the absence of trauma or an underlying disorder. We describe a case of an atraumatic lingual haematoma in an 88-year-old male presenting with threatened airway obstruction. The only risk factor our patient had was Aspirin use. Our patient was able to be managed conservatively with observation in the hospital's high dependency unit (HDU) and intravenous steroid (Dexamethasone) and antibiotic (Amoxicillin + Clavulanic acid) therapy. We discuss this case to highlight the importance of recognising an impending airway emergency in the setting of deep space bleeding or swelling.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Hematoma/complicações , Língua/patologia , Administração Intravenosa , Idoso de 80 Anos ou mais , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Quimioterapia Combinada/métodos , Hematoma/tratamento farmacológico , Humanos , Masculino , Língua/irrigação sanguínea , Resultado do Tratamento
14.
Am Heart J ; 228: 81-90, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32866928

RESUMO

Recurrent pericarditis (RP) occurs in 15% to 30% of patients following a first episode, despite standard treatment with nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids; many patients become dependent on corticosteroids. Rilonacept (KPL-914), an interleukin-1α and ß inhibitor, is in development for the treatment of RP. RHAPSODY, a double-blind, placebo-controlled, randomized-withdrawal (RW) pivotal Phase 3 trial (NCT03737110), enrolls patients 12 years or older presenting with at least a third pericarditis episode, pericarditis pain score ≥4 (11-point numeric rating scale [NRS]), and C-reactive protein ≥1 mg/dL at screening. After a subcutaneous loading dose (adults, 320 mg; children, 4.4 mg/kg), all patients receive blinded weekly subcutaneous rilonacept (adults, 160 mg; children, 2.2 mg/kg) during the run-in period. Patients must taper and discontinue concomitant pericarditis medications during the blinded run-in period and achieve clinical response (C-reactive protein ≤0.5 mg/dL and weekly average NRS ≤2.0 during the 7 days prior to and including the day of randomization) by end of the run-in (while on rilonacept monotherapy) to be randomized to either continued rilonacept or placebo in the RW period. Primary efficacy end point was time to adjudicated pericarditis recurrence during the RW period; secondary efficacy end points were proportion of patients maintaining clinical response, percentage of days with NRS ≤2, and percentage of patients with no-to-minimal pericarditis symptoms at week 16 of the RW period. Safety evaluations include adverse event monitoring, physical examinations, and laboratory tests. The RHAPSODY trial will evaluate the efficacy and safety of rilonacept in the treatment of RP to improve outcomes and patient health-related quality of life.


Assuntos
Monitoramento de Medicamentos/métodos , Pericardite , Qualidade de Vida , Proteínas Recombinantes de Fusão , Prevenção Secundária/métodos , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Interleucina-1alfa/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Masculino , Pericardite/diagnóstico , Pericardite/tratamento farmacológico , Pericardite/fisiopatologia , Pericardite/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos
15.
Trials ; 21(1): 790, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933552

RESUMO

OBJECTIVES: We investigate the effects of Licorice (Glycyrrhiza glabra L.) root extract, an anti-inflammatory natural medicine, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in patients with confirmed COVID-19 that are moderately ill. TRIAL DESIGN: This is a single-center, open-label, randomized, clinical trial with parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: Both male and female patients with ≥18 years of age (≥ 35 kg of weight), admitted at the Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Bandar Abbas for treatment, screened for the following criteria. INCLUSION CRITERIA: 1. Confirmed diagnosis of SARS-CoV-2 infection (via polymerase chain reaction [PCR] and/or antibody test). 2. Presenting as moderate COVID-19 pneumonia (via chest computed tomography (CT) and/or X-ray) requiring hospitalization. 3. Hospitalized ≤48 hours. 4. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs. 4. Treatment with Investigational and antiviral therapy in a clinical study within one month before randomization. 5. History of allergy to Licorice. 6. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19 along with a Licorice-based herbal preparation (D-Reglis ®, Irandarouk Pharmaceutical Company, Iran) at a dose of 760 mg three times a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. MAIN OUTCOMES: The recovery rate of clinical symptoms, including fever, dry cough, and tiredness, as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein, are evaluated as primary outcomes within seven days of randomization. Time to improvement of clinical and paraclinical features and length of stay in a hospital, along with the incidence of adverse reactions are also evaluated as the secondary outcomes within seven days of randomization. RANDOMIZATION: An electronic table of random numbers will be used to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the simple randomization method. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is "IRCT20200506047323N2", https://www.irct.ir/trial/47990 . The registration date is 31 May 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.


Assuntos
Infecções por Coronavirus , Glycyrrhiza , Pandemias , Extratos Vegetais , Raízes de Plantas , Pneumonia Viral , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Monitoramento de Medicamentos/métodos , Feminino , Hospitalização , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
16.
Trials ; 21(1): 794, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938496

RESUMO

OBJECTIVES: In some patients, acute, life-threatening respiratory injury produced by viruses such as SARS-CoV and other viral pneumonia are associated with an over-exuberant cytokine release. Elevated levels of blood IL-6 had been identified as a one of the risk factors associated with severe COVID-19 disease. Anti-IL6 inhibitors are among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients. At present, their use is prioritized to patients with severe interstitial pneumonia (Brescia-COVID Scale-COVID 2-3) with hyperinflammation as determined by the presence of elevated IL6 and/or d-dimer, or progressive d-dimer increase, in patients who otherwise are subsidiary to ICU admission. However, many uncertainties remain on the actual role of anti-IL6 inhibitors in this setting, and whether current use and timing is the right one. There is the hypothesis that the use of anti-IL6 inhibitors at an earlier state during the hyperinflammatory syndrome would be beneficial and may avoid progressing to ARDS. On the other hand, the standard of care has changed and nowadays the use of corticosteroids has become part of the SOC in the treatment of COVID-19 pneumonia. Our limited experience suggests that better treatment outcomes can be achieved when combining IL6-inhibitors (e.g. sarilumab) with corticosteroids. The aim of the present study is to evaluate if an earlier therapeutic intervention with sarilumab plus SOC (including corticosteroids) may be more effective than current standard of care alone, in preventing progression to respiratory failure in COVID-19 infected patients with interstitial pneumonia. This study will also provide supportive evidence to that provided by currently ongoing studies on the efficacy and safety of sarilumab in this clinical context. TRIAL DESIGN: A phase two multi-center randomised controlled trial (RCT) with two parallel arms (1:1 ratio). PARTICIPANTS: They will be hospitalized patients, of at least 18 years of age, with severe COVID-19 who have positive RT-PCR test and have radiographic evidence of pulmonary infiltrates by imaging or rales/crackles on exam and SpO2 ≤ 94% on room air that requires supplemental oxygen. Patients must present elevation of inflammatory parameters (IL-6 > 40 pg/mL or d-dimer >1.0 mcg/ml) or, alternatively, progressive worsening in at least two of these inflammatory parameters in the prior 24-48h: CRP, LDH, serum ferritin, lymphopenia, or d-dimer. EXCLUSION CRITERIA: high oxygen requirements (including face mask with reservoir, non-invasive mechanical ventilation or high flow nasal cannula, or mechanical ventilation), admission to ICU, pregnancy or lactation, allergy or hypersensitivity to sarilumab or corticoesteroids, immunosuppressive antibody therapy within the past 5 months, AST/ALT values > 10 x ULN, neutropenia (< 0.5 x 109/L), severe thrombocytopenia (< 50 x 109/L), sepsis caused by an alternative pathogen, diverticulitis with risk of perforation or ongoing infectious dermatitis. The study will be conducted in several hospitals in Spain. INTERVENTION AND COMPARATOR: Patients randomised to the experimental arm will receive sarilumab + methylprednisolone plus SOC for COVID-19. Patients included in the control arm will receive methylprednisolone plus SOC for COVID-19. Corticosteroids will be given to all patients at a 1mg/kg/d of methylprednisolone for at least 3 days. Clinical follow-up visits will be performed at 3, 5, and 15 days after treatment randomization. Patients in the control group (SOC group without sarilumab) progressing to Brescia- COVID 2-3 plus inflammatory markers, will be given the option to be rescued with sarilumab at the same doses and, in that case, be included in an open-label phase and be followed up for additional weeks (with visits at 3, 7 and 15 days after sarilumab rescue administration). Patients randomly assigned to sarilumab therapy at baseline progressing to Brescia-COVID 2-3 will be rescued according to local clinical practice protocols. A final follow-up visit will be conducted for all patients at day 29 from randomization, regardless of initial treatment assignment. MAIN OUTCOMES: Primary end point is the proportion of patients progressing to either severe respiratory failure (Brescia-COVID ≥2), ICU admission, or death. RANDOMIZATION: Randomization codes were produced by means of the PROC PLAN of the SAS system, with a 1:1 assignment ratio, stratifying by centre and using blocks multiple of 2 elements. The randomization schedule will be managed through the eCRF in a concealed manner. BLINDING (MASKING): All study drugs will be administered as open label. No blinding methods will be used in this trial. NUMBERS TO BE RANDOMISED (SIMPLE SIZE): The target sample size will be 200 COVID-19 patients, who will be allocated randomly to control arm (100) and treatment arm (100). TRIAL STATUS: Protocol Code: SARTRE Protocol Date: May 05th 2020. Version: 2.0 The study has been approved by the Spanish Competent Authority (AEMPS) as a low intervention clinical trial. Start of recruitment: August, 2020 End of recruitment: May, 2021 TRIAL REGISTRATION: Identifier: EudraCT Number: 2020-002037-15 ; Registration date: 26 May 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
Anticorpos Monoclonais Humanizados , Betacoronavirus , Infecções por Coronavirus , Síndrome da Liberação de Citocina/prevenção & controle , Pandemias , Pneumonia Viral , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Ensaios Clínicos Fase II como Assunto , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/imunologia , Feminino , Humanos , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Interleucina-6/antagonistas & inibidores , Resultado do Tratamento
17.
Medicine (Baltimore) ; 99(36): e21911, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899023

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection is a recently emerged viral infection causing predominantly mild upper respiratory symptoms. However, in some instances, it might result in acute respiratory distress syndrome (ARDS) that poses a significant mortality risk. ARDS is postulated to be mediated by a surge of pro-inflammatory cytokines and chemokines, leading to a dysregulated hyper inflammatory response. Colchicine being an anti-inflammatory agent, might mitigate this dysregulated response. Thus, in the absence of therapeutic options available to manage coronavirus disease 2019 (COVID-19), it is imperative to ascertain the effect of colchicine on improving outcomes in COVID-19 patients. METHOD: We will perform a systematic review including a search of the following databases: PubMed, EMBASE, MEDLINE, Clinicaltrials.gov, Cochrane library, and google scholar since inception. We will include randomized controlled trials exploring the effect of colchicine on the efficacy and safety outcomes of COVID-19 patients. Subsequently, we will perform a meta-analysis utilizing the random-effects to ascertain the effect of colchicine on reducing COVID-19 related mortality (primary endpoint) and other efficacy and safety outcomes. RESULTS: Our review results are anticipated in early 2021 (based on the completion of several ongoing randomized controlled trial). Our review results will be published in a peer-reviewed journal. CONCLUSION: This systematic review and meta-analysis, is exploring the effect of colchicine on the efficacy and safety outcomes of COVID-19 patients. If colchicine proved to be effective, it would be a significant milestone in the management of COVID-19, a disease with limited available therapeutic options. PROSPERO REGISTRATION NUMBER: CRD42020191086.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colchicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Betacoronavirus , Colchicina/administração & dosagem , Colchicina/efeitos adversos , Humanos , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
18.
Medicine (Baltimore) ; 99(36): e22070, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899074

RESUMO

BACKGROUND: A number of recent studies have investigated the optimal dosage and timing of dexamethasone in total hip arthroplasty (THA) but have inconsistent findings. Therefore, we designed the randomized controlled research to look for the optimal intravenous dexamethasone dose for the treatment of early postoperative pain after the THA. METHODS: The Declaration of Helsinki principles was followed and the Consolidated Standards of Reporting Trials guidelines for randomized controlled trials was adhered in this study. The First Medical Center in People's Liberation Army General Hospital approved the study (2020-089). After written informed consent was obtained, patients aged between 18 and 80 years with Physical Status I to III of American Society of Anesthesiologists, scheduled for primary unilateral THA, were included in this present work. Randomization is the use of a computer-formed list via a secretary, at a ratio of 1:1:1. The major end points were pain scores at 24 hours, 48 hours, and 72 hours after surgery, with visual analog scale (VAS) utilized at rest, and at 45 degrees passive hip flexion. The secondary outcomes involved the total consumption of morphine, opioid-related side effects, hip range of motion, inflammation markers, and the length of hospital stay. RESULTS: We assumed that the patients who received 3 doses of dexamethasone intravenously possessed the best postoperative results compared to those who received 1 or 2 doses of the dexamethasone. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5864).


Assuntos
Anti-Inflamatórios/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Dexametasona/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Estudos de Casos e Controles , Dexametasona/uso terapêutico , Humanos , Mediadores da Inflamação/metabolismo , Tempo de Internação , Pessoa de Meia-Idade , Morfina/efeitos adversos , Entorpecentes/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Amplitude de Movimento Articular , Escala Visual Analógica , Adulto Jovem
19.
Trials ; 21(1): 772, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907638

RESUMO

OBJECTIVES: The main aim of the study is to evaluate the efficacy of a single dose of sarilumab, in subcutaneous administration, in hospitalised patients with moderate to early severe COVID-19 infection compared to the current standard of care, to prevent progression to systemic hyperinflammatory status. Our hypothesis is that use of subcutaneous sarilumab in early stages (window of opportunity) of COVID-19 moderate-severe pneumonia can prevent higher oxygenation requirements through non-invasive and invasive mechanical ventilation and decrease in-hospital stays, as well as death rate. The secondary objectives of the study are to evaluate the safety of sarilumab through hospitalisation and up to day 14 after discharge, compared to the control arm as assessed by incidence of serious and non serious adverse events (SAEs). In addition, as an exploratory objective, to compare the baseline clinical and biological parameters, including serum IL-6 levels, of the intervention population against controls of the same pandemic outbreak (using a propensity score) to search for markers that identify the best candidates for the treatment with subcutaneous IL-6R inhibitors and to attempt an approximation in the temporal frame of the "window of opportunity" TRIAL DESIGN: SARCOVID is an investigator-initiated single center randomised proof of concept study. PARTICIPANTS: Patients treated at the Hospital Universitario La Princesa, Madrid, Spain requiring hospitalisation will be consecutively recruited, meeting all inclusion criteria and none of the exclusion criteria Inclusion criteria a. Age >18, <80 years old b. COVID-19 infection documented by a positive RT-PCR test or, in absence of a RT-PCR positive test, case definition of COVID 19 infection/pneumonia as per local protocol and the presence of a positive serologic test (IgM/IgA by ELISA) c. Documented interstitial pneumonia requiring admission and at least two of the following parameters: 1) Fever ≥ 37.8°C (tympanic) 2) IL-6 in serum ≥ 25 pg/mL (in the absence of a previous dose of prednisone or equivalent> 1 mg / kg) or PCR> 5mg/dL 3) Lymphocytes <600 cells/mm3 4) Ferritin> 300 µg/L that doubles in 24 hours 5) Ferritin> 600 µg/L in the first determination and LDH> 250 U/L 6) D-dimer (> 1 mg/L) d. Informed verbal consent or requested under urgent conditions, documented in the electronic medical record. Exclusion criteria a. Patients who require mechanical ventilation at the time of inclusion. b. AST / ALT values > 5 folds the ULN. c. Absolute neutrophil count below 500 cells/mm3 d. Absolute platelet count below 50,000 cells/mm3 e. Documented sepsis or high suspicion of superimposed infection by pathogens other than COVID-19. f. Presence of comorbidities that can likely lead to an unfavourable result according to clinical judgment. g. Complicated diverticulitis or intestinal perforation. h. Current skin infection (eg, uncontrolled dermopiodermitis). i. Immunosuppressive anti-rejection therapy. j. Pregnancy or lactation. k. Previous treatment with tocilizumab or sarilumab. l. Patients participating in another clinical trial for SARS-CoV-2 infection. m. Patients with known hypersensitivity or contraindication to sarilumab or excipients. INTERVENTION AND COMPARATOR: The intervention group, sarilumab plus standard of care, will receive 400 mg single dose treatment with Sarilumab (Kevzara), 2 subcutaneous injections 200mg each in a pre-filled syringe. Treatment with drugs or procedures in routine clinical practice that the clinician responsible for the patient deems necessary is allowed. The control group will receive drugs or procedures in routine clinical practice according to the best standard of care as per local protocol. MAIN OUTCOMES: Primary Outcome Measures 1. Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation compared to baseline (Score ranges 1-7) 1. Death; 2. Hospitalised, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalised, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalised, requiring supplemental oxygen; 5. Hospitalised, not requiring supplemental oxygen - but in need of ongoing medical care (COVID-19 related or otherwise) 6. Hospitalised, not requiring supplemental oxygen - no longer requires ongoing medical care (independent) 7. Not hospitalised 2. Duration of hospitalisation: Days from the date of enrolment to the date of discharge 3. Number of deaths at the end of study RANDOMISATION: Randomisation to treatment arms sarilumab plus standard of care or standard of care in a 2:1 ratio will be performed by the Clinical Research and Clinical Trials Unit (CRCTU) at the Hospital using a table of random numbers, an internet-based randomisation tool. After checking that all inclusion criteria are met and none of the exclusion criteria, CRCTU will communicate the recruiting investigator the assigned treatment. BLINDING (MASKING): This study is unblinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 30 patients treated by COVID-19 infection who require hospitalisation: 20 will receive sarilumab plus Standard of Care and 10 will receive Standard of Care. TRIAL STATUS: The Protocol version number is 2, as of 6th April 2020, with amendment 1, as of 7th May 2020. The recruitment is ongoing. Recruitment started on April 13th 2020 and is anticipated to be completed by November 2020. TRIAL REGISTRATION: This trial was first registered in the European Union Clinical Trials Register on 4 April 2020, EudraCT Number 2020-001634-36 . Then, posted on ClinicalTrials.gov on 22 April 2020, Identifier: NCT04357808 . 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 International Council Harmonization guidelines: https://www.ich.org/page/efficacy-guidelines .


Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Admissão do Paciente , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Esquema de Medicação , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudo de Prova de Conceito , Ensaios Clínicos Controlados Aleatórios como Assunto , Espanha , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Pain Physician ; 23(4S): S239-S270, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32942786

RESUMO

BACKGROUND: Multiple randomized controlled trials (RCTs) and systematic reviews have been conducted to summarize the evidence for administration of local anesthetic (lidocaine) alone or with steroids, with discordant opinions, more in favor of equal effect with local anesthetic alone or with steroids. OBJECTIVE: To evaluate the comparative effectiveness of lidocaine alone and lidocaine with steroids in managing spinal pain to assess superiority or equivalency. STUDY DESIGN: A systematic review of RCTs assessing the effectiveness of lidocaine alone compared with addition of steroids to lidocaine in managing spinal pain secondary to multiple causes (disc herniation, radiculitis, discogenic pain, spinal stenosis, and post-surgery syndrome). METHODS: This systematic review was performed utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for literature search, Cochrane review criteria, and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) to assess the methodologic quality assessment and qualitative analysis utilizing best evidence synthesis principles, and quantitative analysis utilizing conventional and single-arm meta-analysis. PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1966 through December 2019. The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. OUTCOME MEASURES: A hard endpoint for the primary outcome was defined as the proportion of patients with 50% pain relief and improvement in function. Secondary outcome measures, or soft endpoints, were pain relief and/or improvement in function. Effectiveness was determined as short-term if it was less than 6 months. Improvement that lasted longer than 6 months, was defined as long-term. RESULTS: Based on search criteria, 15 manuscripts were identified and considered for inclusion for qualitative analysis, quantitative analysis with conventional meta-analysis, and single-arm meta-analysis. The results showed Level II, moderate evidence, for short-term and long-term improvement in pain and function with the application of epidural injections with local anesthetic with or without steroid in managing spinal pain of multiple origins. LIMITATIONS: Despite 15 RCTs, evidence may still be considered as less than optimal and further studies are recommended. CONCLUSION: Overall, the present meta-analysis shows moderate (Level II) evidence for epidural injections with lidocaine with or without steroids in managing spinal pain secondary to disc herniation, spinal stenosis, discogenic pain, and post-surgery syndrome based on relevant, high-quality RCTs. Results were similar for lidocaine, with or without steroids.


Assuntos
Corticosteroides/administração & dosagem , Lidocaína/administração & dosagem , Dor Lombar/tratamento farmacológico , Manejo da Dor/métodos , Corticosteroides/efeitos adversos , Anestésicos Locais/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Humanos , Injeções Epidurais , Reprodutibilidade dos Testes
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