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2.
Ned Tijdschr Geneeskd ; 1642020 09 03.
Artigo em Holandês | MEDLINE | ID: mdl-33030329

RESUMO

Since the first reports in mid-January of a serious new viral respiratory infection, COVID-19, and the identification of SARS-CoV-2 as the cause of this disease, researchers work intensely on developing a vaccine that can protect individuals against serious disease and that can limit the spread of the virus. Vaccine developers are using a range of platform technologies to do this, each with advantages and disadvantages. Close to 30 vaccines are now in clinical testing. The first results are encouraging, but in order to properly assess the merits of the different vaccines, we must wait for the results of phase 3 trials. The first phase 3 trials have started in July 2020.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais , Ensaios Clínicos Fase III como Assunto , Saúde Global , Humanos
4.
Virol J ; 17(1): 141, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972430

RESUMO

BACKGROUND: The COVID-19 causing coronavirus is an enveloped RNA virus that utilizes an enzyme RNA dependent RNA polymerase for its replication. Favipiravir (FVP) triphosphate, a purine nucleoside analog, inhibits that enzyme. We have conducted this systematic review and meta-analysis on efficacy and safety of the drug FVP as a treatment for COVID-19. METHODS: Databases like Pubmed, Pubmed Central, Scopus, Embase, Google Scholar, preprint sites, and clinicaltirals.gov were searched. The studies with the standard of care (SOC) and FVP as a treatment drug were considered as the treatment group and the SOC with other antivirals and supportive care as the control group. Quantitative synthesis was done using RevMan 5.4. Clinical improvement, negative conversion of reverse transcription-polymerase chain reaction (RT-PCR), adverse effects, and oxygen requirements were studied. RESULTS: We identified a total of 1798 studies after searching the electronic databases. Nine in the qualitative studies and four studies in the quantitative synthesis met the criteria. There was a significant clinical improvement in the FVP group on the 14th day compared to the control group (RR 1.29, 1.08-1.54). Clinical deterioration rates were less likely in the FVP group though statistically not significant (OR 0.59, 95% CI 0.30-1.14) at the endpoint of study (7-15 days). The meta-analysis showed no significant differences between the two groups on viral clearance (day 14: RR 1.06, 95% CI 0.84-1.33), non-invasive ventilation or oxygen requirement (OR 0.76, 95% CI 0.42-1.39), and adverse effects (OR 0.69, 0.13-3.57). There are 31 randomized controlled trials (RCTs) registered in different parts of the world focusing FVP for COVID-19 treatment. CONCLUSION: There is a significant clinical and radiological improvement following treatment with FVP in comparison to the standard of care with no significant differences on viral clearance, oxygen support requirement and side effect profiles.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pirazinas/uso terapêutico , Amidas/efeitos adversos , Antivirais/efeitos adversos , Betacoronavirus/enzimologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/virologia , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Bases de Dados Factuais , Inibidores Enzimáticos/uso terapêutico , Humanos , Pandemias , Pneumonia Viral/virologia , Pirazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrão de Cuidado , Resultado do Tratamento
6.
Ther Innov Regul Sci ; 54(5): 1236-1255, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32865809

RESUMO

Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB's instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial's scientific integrity.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/tratamento farmacológico , Confiabilidade dos Dados , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , China , Comitês de Monitoramento de Dados de Ensaios Clínicos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Fatores de Tempo , Resultado do Tratamento
7.
Trials ; 21(1): 766, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891160

RESUMO

OBJECTIVES: To investigate the potential efficacy of Acacia Senegal extract Gum Arabic (GA) supplementation as immunomodulatory and anti-inflammatory dietary intervention among newly diagnosed COVID 19 Sudanese patients. To study the effect of GA on the level of cytokines, TNFα, IL8, IL6 IL10, CRP and the viral load. Secondary outcomes will be the effect of GA oral intake on mortality rate and days of hospital admission. TRIAL DESIGN: Quadruple blind, randomized placebo-controlled clinical trial Phase II & III. Prospective, two-arm, parallel-group, randomised (1:1 allocation ratio) superiority trial of oral GA among seropositive COVID-19 patients. PARTICIPANTS: Inclusion criteria: COVID-19 infected (newly diagnosed) as proved by real-time PCR within 72 hours of PCR. Age 8-90 years Both genders Exclusion criteria: Intubated patients on parenteral treatment Allergy to Gum Arabic The study will be conducted in COVID Isolation Centres and Soba University Hospital Khartoum State Sudan. INTERVENTION AND COMPARATOR: Experimental: Intervention Group This arm will receive 100% natural Gum Arabic provided in a powder form in 30-grams-dose once daily for four weeks Placebo Comparator: Control group: This group will be provided with pectin powder provided as one-gram-dose once daily for four weeks Both GA and placebo will be in addition to standard care treatment based on local clinical guidelines. MAIN OUTCOMES: Mean change from baseline score of Immune Response to end of the trial. Changes of the level of Tumor Necrosis Factor (TNFα), interleukin IL8, IL6, and IL10 from the baseline values (Four weeks from the start of randomization). Mortality rate: The percentage of deaths among COVID 19 patients received Gum Arabic compared to placebo (Four weeks from the start of randomization]). RANDOMISATION: Randomization (1:1 allocation ratio) and will be conducted using a sequence of computer-generated random numbers by an independent individual. Each participating centre will be assigned a special code generated by the computer. The randomization will be kept by the PI and a research assistant. BLINDING (MASKING): Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 110 eligible patients will be randomly assigned to either GA (n=55) or placebo (n=55) groups. TRIAL STATUS: Protocol Version no 2, 30th June 2020. Recruitment will start on 15th September 2020. The intended completion date is 15th January 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04381871 . Date of trial registration: 11 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
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Goma Arábica/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Criança , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Goma Arábica/efeitos adversos , Interações entre Hospedeiro e Microrganismos , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Br J Nurs ; 29(16): 948-953, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32901559

RESUMO

This article discusses the background to the current COVID-19 pandemic. The specific features of the causative pathogen (SARS-CoV-2) are outlined, together with a 'whistlestop' revision of immunological principles. The article goes on to discuss the principles and mechanisms of immunisation and the stages of vaccine development. The current situation in relation to the race to develop a vaccine against COVID-19 is incorporated and the immunological principles being adapted by the top contenders are outlined. These include new approaches based on genetic sequencing. Finally, the importance of understanding theoretical principles and the potential practical implications for nurses who will be at the coalface, reassuring patients and delivering vaccines, is addressed.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/enfermagem , Humanos , Pneumonia Viral/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinas Virais
9.
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
11.
BMC Med Res Methodol ; 20(1): 220, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867708

RESUMO

BACKGROUND: Because of unknown features of the COVID-19 and the complexity of the population affected, standard clinical trial designs on treatments may not be optimal in such patients. We propose two independent clinical trials designs based on careful grouping of patient and outcome measures. METHODS: Using the World Health Organization ordinal scale on patient status, we classify treatable patients (Stages 3-7) into two risk groups. Patients in Stages 3, 4 and 5 are categorized as the intermediate-risk group, while patients in Stages 6 and 7 are categorized as the high-risk group. To ensure that an intervention, if deemed efficacious, is promptly made available to vulnerable patients, we propose a group sequential design incorporating four factors stratification, two interim analyses, and a toxicity monitoring rule for the intermediate-risk group. The primary response variable (binary variable) is based on the proportion of patients discharged from hospital by the 15th day. The goal is to detect a significant improvement in this response rate. For the high-risk group, we propose a group sequential design incorporating three factors stratification, and two interim analyses, with no toxicity monitoring. The primary response variable for this design is 30 day mortality, with the goal of detecting a meaningful reduction in mortality rate. RESULTS: Required sample size and toxicity boundaries are calculated for each scenario. Sample size requirements for designs with interim analyses are marginally greater than ones without. In addition, for both the intermediate-risk group and the high-risk group, the required sample size with two interim analyses is almost identical to analyses with just one interim analysis. CONCLUSIONS: We recommend using a binary outcome with composite endpoints for patients in Stage 3, 4 or 5 with a power of 90% to detect an improvement of 20% in the response rate, and a 30 day mortality rate outcome for those in Stage 6 or 7 with a power of 90% to detect 15% (effect size) reduction in mortality rate. For the intermediate-risk group, two interim analyses for efficacy evaluation along with toxicity monitoring are encouraged. For the high-risk group, two interim analyses without toxicity monitoring is advised.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Interpretação Estatística de Dados , Pneumonia Viral/terapia , Projetos de Pesquisa , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Avaliação de Resultados em Cuidados de Saúde , Pandemias
13.
Ann Hematol ; 99(10): 2357-2366, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32808106

RESUMO

Rituximab monotherapy is widely used for follicular lymphoma. However, there are no established predictors for response or response duration. We analyzed the long-term prognostic relevance of pre-treatment absolute blood counts of lymphocytes with subsets and monocytes in 265 follicular lymphoma patients, uniformly treated with rituximab without chemotherapy, in two Nordic Lymphoma Group trials. There were 265 previously untreated, stage II-IV follicular lymphoma patients with a median follow-up of over 10 years. Absolute B cell counts ≥ median (0.09 × 109/L) were an independent predictor for shorter time to next treatment or death (multivariable analysis P = 0.010). In univariate analysis, absolute monocyte counts ≥ median (0.5 × 109/L) did not correlate with time to next treatment or death, but with inferior overall survival (P = 0.034). Absolute T cell or T cell subset counts were not predictive for outcome. High absolute B cell counts, possibly reflecting circulating lymphoma cells, have an unfavorable impact on time to next treatment or death in patients treated with rituximab without chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Linfócitos B , Imunossupressores/uso terapêutico , Contagem de Linfócitos , Linfoma Folicular/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Conjuntos de Dados como Assunto , Feminino , Seguimentos , Humanos , Interferon alfa-2/administração & dosagem , Estimativa de Kaplan-Meier , Subpopulações de Linfócitos , Linfoma Folicular/sangue , Masculino , Pessoa de Meia-Idade , Monócitos , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Rituximab/administração & dosagem , Adulto Jovem
14.
PLoS One ; 15(8): e0236021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745082

RESUMO

BACKGROUND: The National Lung Screening Trial (NLST) demonstrated that annual screening with low dose CT in high-risk population was associated with reduction in lung cancer mortality. Nonetheless, the leading cause of mortality in the study was from cardiovascular diseases. PURPOSE: To determine whether the used machine learning automatic algorithms assessing coronary calcium score (CCS), level of liver steatosis and emphysema percentage in the lungs are good predictors of cardiovascular disease (CVD) mortality and incidence when applied on low dose CT scans. MATERIALS AND METHODS: Three fully automated machine learning algorithms were used to assess CCS, level of liver steatosis and emphysema percentage in the lung. The algorithms were used on low-dose computed tomography scans acquired from 12,332 participants in NLST. RESULTS: In a multivariate analysis, association between the three algorithm scores and CVD mortality have shown an OR of 1.72 (p = 0.003), 2.62 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively, and an OR of 1.12 (p = 0.044) for level of liver steatosis. Similar results were shown for the incidence of CVD, OR of 1.96 (p < 0.0001), 4.94 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively. Also, emphysema percentage demonstrated an OR of 0.89 (p < 0.0001). Similar results are shown for univariate analyses of the algorithms. CONCLUSION: The three automated machine learning algorithms could help physicians to assess the incidence and risk of CVD mortality in this specific population. Application of these algorithms to existing LDCT scans can provide valuable health care information and assist in future research.


Assuntos
Doenças Cardiovasculares/mortalidade , Aprendizado de Máquina , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Ensaios Clínicos Fase III como Assunto , Vasos Coronários/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Enfisema/diagnóstico , Enfisema/epidemiologia , Enfisema/etiologia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Feminino , Humanos , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/epidemiologia
16.
PLoS One ; 15(8): e0237175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790757

RESUMO

Patients' vitamin intake is often not documented and is therefore not considered sufficiently in studies of prescribed medication in patients with amyotrophic lateral sclerosis (ALS). We aimed to determine the prevalence of vitamin use by participants in ALS clinical trials. Data about demographics, disease severity (ALS Functional Rating Scale) and concomitant medication were obtained from the Pooled Resource Open-Access ALS Clinical Trials Database, which contains records from more than 6000 ALS patients who participated in 23 phase II/III clinical trials. Information about vitamin intake for all study subjects was coded into major categories. Clinical data of vitamin users and nonusers were compared, and regression analysis was used to explore the associations among clinical parameters, vitamin use and two measures of disease progression. From the 40.996 available medication records from 6274 subjects, 7338 (17.9%) concerned vitamins. One or more vitamins were used by 3331 subjects (53.1%). Most common was vitamin E, vitamin C and multivitamins. Patients who did and did not take vitamins did not differ in terms of disease progression and ALS Functional Rating Scale score. Patients who took vitamins were younger, were more often female, had a shorter time between onset and diagnosis, had shorter disease duration and more frequently had limb-onset types. Disease progression rate and disease aggressiveness were not associated with vitamin use. Despite unclear evidence, the use of vitamins in ALS is common. However, rapid progression was not observed to be associated with vitamin use.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Vitaminas/administração & dosagem , Adulto , Idoso , Esclerose Amiotrófica Lateral/epidemiologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vitaminas/uso terapêutico
17.
Bull Cancer ; 107(7-8): 830-842, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32758364

RESUMO

Immune checkpoint inhibitors (ICI) have revolutionized oncological management in several tumor types, allowing prolonged tumoral responses. Thus, they are administered over long periods of time and can give specific autoimmune adverse reactions that may have a potential impact on quality of life (QoL). Most of phase III trials with ICI have included an assessment of QoL. In metastatic setting, in comparison with chemotherapy or targeted therapies, they indicate an absence of degradation of the QoL scores or even an improvement of these scores. In adjuvant setting, the deterioration of QoL scores is not clinically significant, regardless of the ICI used. In addition, there is no impairment of quality of life in patients with prolonged treatment duration. However, the measurement of QoL under ICI remains a challenge because of the specificities of these treatments and adapted measurement scales are being developed to improve the assessment of the impact of these treatments on patients' QoL.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Imunoterapia Adotiva/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Qualidade de Vida , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Inquéritos Epidemiológicos , Humanos , Imunoterapia Adotiva/efeitos adversos , Terapia de Alvo Molecular/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
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