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1.
Vopr Virusol ; 66(1): 40-46, 2021 03 07.
Artículo en Ruso | MEDLINE | ID: mdl-33683064

RESUMEN

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Enfermedad Coronaria/tratamiento farmacológico , Coagulación Intravascular Diseminada/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Arteriosclerosis Intracraneal/tratamiento farmacológico , Acetilcisteína/uso terapéutico , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Fibrilación Atrial/virología , Azitromicina/uso terapéutico , /patología , Estudios de Cohortes , Comorbilidad , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/virología , Dabigatrán/uso terapéutico , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/mortalidad , Coagulación Intravascular Diseminada/virología , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/mortalidad , Hipertensión/virología , Indoles/uso terapéutico , Interferón alfa-2/uso terapéutico , Arteriosclerosis Intracraneal/diagnóstico , Arteriosclerosis Intracraneal/mortalidad , Arteriosclerosis Intracraneal/virología , Masculino , Persona de Mediana Edad , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Rivaroxabán/uso terapéutico , /patogenicidad , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
3.
Medicine (Baltimore) ; 100(4): e24475, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530261

RESUMEN

ABSTRACT: To evaluate the antiviral effect and safety of arbidol and Lianhuaqingwen Capsule (LH) in treating patients with Coronavirus disease 2019 (COVID-19).108 patients with COVID-19 were divided into 2 groups, including 40 patients in the arbidol group and 68 patients in the arbidol + LH group. Patients in the arbidol + LH group received 200 mg of arbidol and 1400 mg of LH per 8 hour, and the arbidol group was given 200 mg arbidol per 8 hour. Blood routine examination, blood biochemistry detection, SARS-CoV-2 nucleic acid detection, and chest CT scans were performed to evaluate the clinical effects between the 2 groups.No statistically significant differences were observed between the 2 groups in terms of preoperative characteristics including the baseline characteristics, laboratory indicators, and chest CT. On day 7 after admission, patients in the arbidol + LH group showed a higher level of Lymphocytes count, and a lower level of serum amyloid A and C-reactive protein levels (P < .05). Moreover, the median time from admission to the first negative result of the SARS-CoV-2 nucleic acid detection was shorter in the arbidol + LH group (P < .05). Analysis based on CT scan results showed a better extinction of lung inflammation in the arbidol + LH group. No apparent side effects were found in both groups. No patients were transferred to the intensive care unit (ICU) treatment.Arbidol combined with LH treatment may be more effective in improving the prognosis and accelerating the SARS-CoV-2 clearance in patients with COVID-19.


Asunto(s)
/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Indoles/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Cápsulas , Quimioterapia Combinada , Femenino , Humanos , Masculino , Medicina China Tradicional , Persona de Mediana Edad , Neumonía Viral/virología , Estudios Retrospectivos
4.
Medicine (Baltimore) ; 100(2): e23923, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33466134

RESUMEN

ABSTRACT: Coronavirus disease 2019 (COVID-19) is an emerging disease caused by severe acute respiratory syndrome coronavirus 2; no specific effective medication to treat the disease has been identified to date. We aimed to investigate the administered medications and intervention times for patients who completely recovered from COVID-19.This single-center, retrospective, observational study included 55 patients with COVID-19 who were transferred to Shenyang Sixth People's Hospital between January 20 and March 15, 2020. Data on demographics, symptoms, laboratory indicators, treatment processes, and clinical outcomes were collected. Administered drugs and intervention times were compared in 47 and 8 patients with mild and severe symptoms, respectively.All 55 patients recovered. Fifty-three patients (96.36%) received antiviral therapy, including 45 in the mild group (median treatment: 14 days; 17 received umifenovir) and all 8 severe-group patients (median treatment: 17.5 days; 4 received lopinavir/ritonavir). Twenty-nine patients (52.72%) were administered antibiotics, including 21 in the mild group (median treatment: 13.5 days; 15 received moxifloxacin) and all 8 in the severe group (median treatment: 9 days; 2 received linezolid). Moreover, 7 patients (12.72%) were treated with glucocorticoids and 9 (16.36%) with immunomodulators.Given the 100% recovery rate, early administration of antiviral drugs can be considered. Umifenovir may benefit patients with mild symptoms, while lopinavir/ritonavir may benefit those with severe symptoms. Prophylactic administration of common antibiotics may reduce the risk of co-infection. The use of glucocorticoids is usually not necessary. Randomized, double-blind, and controlled trials remain necessary for more accurate conclusions.


Asunto(s)
/tratamiento farmacológico , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , China , Femenino , Glucocorticoides/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Indoles/uso terapéutico , Linezolid/uso terapéutico , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Moxifloxacino/uso terapéutico , Estudios Retrospectivos , Ritonavir/uso terapéutico
6.
Anticancer Res ; 41(2): 551-556, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33517260

RESUMEN

Treatment of metastatic prostate cancer has evolved significantly over the past decade. Palliative therapy has, historically, consisted of androgen deprivation, chemotherapy and different radiation therapy approaches. More recently, breakthrough therapy with the use of poly-ADP-ribose polymerase (PARP) inhibitors has led to significant improvement in the outcome of patients with metastatic prostate cancer who harbor certain genetic mutations. This concise review focuses on the 3 PARP inhibitors that have shown activity in metastatic prostate cancer.


Asunto(s)
Indazoles/uso terapéutico , Indoles/uso terapéutico , Ftalazinas/uso terapéutico , Piperazinas/uso terapéutico , Piperidinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Proteína BRCA1/genética , Proteína BRCA2/genética , Predisposición Genética a la Enfermedad , Humanos , Indazoles/efectos adversos , Indoles/efectos adversos , Masculino , Mutación , Metástasis de la Neoplasia , Fosfohidrolasa PTEN/genética , Fenotipo , Ftalazinas/efectos adversos , Piperazinas/efectos adversos , Piperidinas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Resultado del Tratamiento
8.
Lancet Respir Med ; 9(1): 96-106, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33412120

RESUMEN

BACKGROUND: In the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial, nintedanib reduced the rate of decline in forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). Patients on stable treatment with mycophenolate for at least 6 months before randomisation could participate. The aim of this subgroup analysis was to examine the efficacy and safety of nintedanib by mycophenolate use at baseline. METHODS: The SENSCIS trial was a randomised, double-blind, placebo-controlled trial, in which patients with SSc-ILD were randomly assigned (1:1) to receive 150 mg of oral nintedanib twice daily or placebo for at least 52 weeks. In a prespecified subgroup analysis, we analysed the primary endpoint of rate of decline in FVC over 52 weeks by mycophenolate use at baseline. In a post-hoc analysis, we analysed the proportion of patients with an absolute decrease in FVC of at least 3·3% predicted at week 52 (proposed minimal clinically important difference estimate for worsening of FVC in patients with SSc-ILD) in subgroups by mycophenolate use at baseline. Adverse events were reported in subgroups by mycophenolate use at baseline. Analyses were done in all participants who received at least one dose of study drug. We analysed the annual rate of decline in FVC using a random coefficient regression model (with random slopes and intercepts) including anti-topoisomerase I antibody status, age, height, sex, and baseline FVC as covariates and terms for baseline-by-time, treatment-by-subgroup, and treatment-by-subgroup-by-time interactions. SENSCIS is registered with ClinicalTrials.gov, NCT02597933, and is now complete. FINDINGS: Between Nov 30, 2015, and Oct 31, 2017, 819 participants were screened and 576 were enrolled, randomly assigned to, and treated with nintedanib (n=288) or placebo (n=288). 139 (48%) of 288 in the nintedanib group and 140 (49%) of 288 in the placebo group were taking mycophenolate at baseline. In patients taking mycophenolate at baseline, the adjusted mean annual rate of decline in FVC was -40·2 mL per year (SE 19·8) with nintedanib and -66·5 mL per year (19·3) with placebo (difference: 26·3 mL per year [95% CI -27·9 to 80·6]). In patients not taking mycophenolate at baseline, the adjusted mean annual rate of decline in FVC was -63·9 mL per year (SE 19·3) with nintedanib and -119·3 mL per year (19·0) with placebo (difference: 55·4 mL per year [95% CI 2·3 to 108·5]). We found no heterogeneity in the effect of nintedanib versus placebo on the annual rate of decline in FVC between the subgroups by mycophenolate use (p value for interaction=0·45). In a post-hoc analysis, the proportion of patients with an absolute decrease in FVC of at least 3·3% predicted was lower with nintedanib than with placebo in both patients taking mycophenolate (40 [29%] of 138 vs 56 [40%] of 140; odds ratio 0·61 [0·37 to 1·01]) and those not taking mycophenolate (59 [40%] of 149 vs 70 [47%] of 148; 0·73 [0·46 to 1·16]) at baseline. The adverse event profile of nintedanib was similar between the subgroups. Diarrhoea, the most common adverse event, was reported in 106 (76%) of 139 patients in the nintedanib group and 48 (34%) of 140 in the placebo group among those taking mycophenolate at baseline, and in 112 (75%) of 149 in the nintedanib group and 43 (29%) of 148 in the placebo group among those not taking mycophenolate at baseline. Over the entire trial period, 19 patients died (ten in the nintedanib group and nine in the placebo group). One death in the nintedanib group was considered to be related to study drug. INTERPRETATION: Nintedanib reduced the progression of interstitial lung disease both in patients with SSc-ILD who were and were not using mycophenolate at baseline, with no heterogeneity in its treatment effect detected between the subgroups. The adverse event profile of nintedanib was similar in the subgroups by mycophenolate use. Our findings suggest that the combination of mycophenolate and nintedanib offers a safe treatment option for patients with SSc-ILD. More data are needed on the benefits of initial combination therapy versus a sequential approach to treatment of SSc-ILD. FUNDING: Boehringer Ingelheim.


Asunto(s)
Indoles/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Ácido Micofenólico/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Indoles/efectos adversos , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Esclerodermia Sistémica/complicaciones , Resultado del Tratamiento
9.
Ann Palliat Med ; 10(1): 707-720, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33440983

RESUMEN

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.


Asunto(s)
Antivirales/uso terapéutico , /terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/farmacología , Alanina/uso terapéutico , Amidas/farmacología , Amidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Azetidinas/farmacología , Azetidinas/uso terapéutico , Cloroquina/farmacología , Cloroquina/uso terapéutico , Combinación de Medicamentos , Humanos , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Indoles/farmacología , Indoles/uso terapéutico , Interferones/farmacología , Interferones/uso terapéutico , Ivermectina/farmacología , Ivermectina/uso terapéutico , Lopinavir/farmacología , Lopinavir/uso terapéutico , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Purinas/farmacología , Purinas/uso terapéutico , Pirazinas/farmacología , Pirazinas/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Ribavirina/farmacología , Ribavirina/uso terapéutico , Ritonavir/farmacología , Ritonavir/uso terapéutico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Tiazoles/farmacología , Tiazoles/uso terapéutico
10.
Mol Immunol ; 130: 104-112, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33309306

RESUMEN

Atopic dermatitis is a severe, chronic relapsing inflammatory disease of the skin with family clustering. It is characterized into acute phase, which is dominated by T helper 2-type immune responses, and chronic phase, which is dominated by T helper 1-type immune responses. Studies have shown that 3,3'-diindolylmethane not only has antitumor effects but also can relieve symptoms of inflammatory diseases by inhibiting the nuclear factor-κB signaling pathway and regulating T cell differentiation. To study the effect of 3,3'-diindolylmethane on atopic dermatitis and the underlying mechanism, a mouse model of acute atopic dermatitis was established using 2,4-dinitrofluorobenzene. After intraperitoneal injection of 3,3'-diindolylmethane, skin erythema and edema in mice were significantly alleviated. Furthermore, 3,3'-diindolylmethane reduced immune activation, probably by inhibiting the secretion of thymic stromal lymphopoietin by keratinocytes. 3,3'-Diindolylmethane also promoted the differentiation of regulatory T cells and inhibited the activation of T helper 2 and T helper 17 cells to reduce atopic dermatitis-related immune responses. However, it showed no significant effect on the differentiation of T helper 1 cells. These results indicate that 3,3'-diindolylmethane has a significant inhibitory effect on T helper 2 cells in the acute phase of atopic dermatitis. Our findings may provide not only more insights into the pathological mechanism of AD, but also a new candidate medicine for it.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Dermatitis Atópica/tratamiento farmacológico , Indoles/uso terapéutico , Linfocitos T/efectos de los fármacos , Enfermedad Aguda , Adulto , Animales , Diferenciación Celular/inmunología , Células Cultivadas , Dermatitis Atópica/inmunología , Modelos Animales de Enfermedad , Femenino , Humanos , Indoles/farmacología , Queratinocitos/efectos de los fármacos , Queratinocitos/fisiología , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Piel/efectos de los fármacos , Piel/inmunología , Linfocitos T/fisiología
11.
Virus Res ; 294: 198262, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33333102

RESUMEN

Coronavirus disease 19 (COVID-19) has posed serious threats to the general population. To relieve the crisis, a comparison of drug effects against COVID-19 is instructive. Between January 27, 2020 and March 21, 2020, a total of 333 patients treated with arbidol, corticosteroids, hydroxychloroquine, lopinavir/ritonavir, or oseltamivir monotherapy, having definite outcomes and serological antibody detection results, were retrospectively analyzed. The hydroxychloroquine group had a significantly reduced duration of hospital stay than the arbidol and corticosteroids groups. The oseltamivir group had a significantly shorter length of hospital stay than the arbidol, corticosteroids, and lopinavir/ritonavir groups. The hydroxychloroquine group had a significantly higher IgM titer than the other four groups and exhibited significantly higher IgG levels than the arbidol, lopinavir/ritonavir, and oseltamivir groups. Our findings indicated that hydroxychloroquine might have the potential for efficient COVID-19 management, while oseltamivir should be prudently considered in combination therapy.


Asunto(s)
/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , /patología , Combinación de Medicamentos , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Indoles/uso terapéutico , Tiempo de Internación , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Oseltamivir/uso terapéutico , Estudios Retrospectivos , Ritonavir/uso terapéutico , /aislamiento & purificación , Adulto Joven
12.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33336780

RESUMEN

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , /tratamiento farmacológico , /terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Amidas/uso terapéutico , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Antiparasitarios/uso terapéutico , Cannabinoides/uso terapéutico , Cloroquina/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Dexametasona/uso terapéutico , Combinación de Medicamentos , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Indoles/uso terapéutico , Interferones/uso terapéutico , Ivermectina/uso terapéutico , Lopinavir/uso terapéutico , Pirazinas/uso terapéutico , Ritonavir/uso terapéutico , Teicoplanina/uso terapéutico , Tetraciclinas/uso terapéutico , Tiazoles/uso terapéutico
13.
Cochrane Database Syst Rev ; 12: CD010966, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33331662

RESUMEN

BACKGROUND: Cystic fibrosis (CF) is a common life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class II CFTR variant F508del (found in up to 90% of people with CF (pwCF)) is the commonest CF-causing variant. The faulty protein is degraded before reaching the cell membrane, where it needs to be to effect transepithelial salt transport. The F508del variant lacks meaningful CFTR function and corrective therapy could benefit many pwCF. Therapies in this review include single correctors and any combination of correctors and potentiators. OBJECTIVES: To evaluate the effects of CFTR correctors (with or without potentiators) on clinically important benefits and harms in pwCF of any age with class II CFTR mutations (most commonly F508del). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Cystic Fibrosis Trials Register, reference lists of relevant articles and online trials registries. Most recent search: 14 October 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) (parallel design) comparing CFTR correctors to control in pwCF with class II mutations. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk of bias and evidence quality (GRADE); we contacted investigators for additional data. MAIN RESULTS: We included 19 RCTs (2959 participants), lasting between 1 day and 24 weeks; an extension of two lumacaftor-ivacaftor studies provided additional 96-week safety data (1029 participants). We assessed eight monotherapy RCTs (344 participants) (4PBA, CPX, lumacaftor, cavosonstat and FDL169), six dual-therapy RCTs (1840 participants) (lumacaftor-ivacaftor or tezacaftor-ivacaftor) and five triple-therapy RCTs (775 participants) (elexacaftor-tezacaftor-ivacaftor or VX-659-tezacaftor-ivacaftor); below we report only the data from elexacaftor-tezacaftor-ivacaftor combination which proceeded to Phase 3 trials. In 14 RCTs participants had F508del/F508del genotypes, in three RCTs F508del/minimal function (MF) genotypes and in two RCTs both genotypes. Risk of bias judgements varied across different comparisons. Results from 11 RCTs may not be applicable to all pwCF due to age limits (e.g. adults only) or non-standard design (converting from monotherapy to combination therapy). Monotherapy Investigators reported no deaths or clinically-relevant improvements in quality of life (QoL). There was insufficient evidence to determine any important effects on lung function. No placebo-controlled monotherapy RCT demonstrated differences in mild, moderate or severe adverse effects (AEs); the clinical relevance of these events is difficult to assess with their variety and small number of participants (all F508del/F508del). Dual therapy Investigators reported no deaths (moderate- to high-quality evidence). QoL scores (respiratory domain) favoured both lumacaftor-ivacaftor and tezacaftor-ivacaftor therapy compared to placebo at all time points. At six months lumacaftor 600 mg or 400 mg (both once daily) plus ivacaftor improved Cystic Fibrosis Questionnaire (CFQ) scores slightly compared with placebo (mean difference (MD) 2.62 points (95% confidence interval (CI) 0.64 to 4.59); 1061 participants; high-quality evidence). A similar effect was observed for twice-daily lumacaftor (200 mg) plus ivacaftor (250 mg), but with low-quality evidence (MD 2.50 points (95% CI 0.10 to 5.10)). The mean increase in CFQ scores with twice-daily tezacaftor (100 mg) and ivacaftor (150 mg) was approximately five points (95% CI 3.20 to 7.00; 504 participants; moderate-quality evidence). At six months, the relative change in forced expiratory volume in one second (FEV1) % predicted improved with combination therapies compared to placebo by: 5.21% with once-daily lumacaftor-ivacaftor (95% CI 3.61% to 6.80%; 504 participants; high-quality evidence); 2.40% with twice-daily lumacaftor-ivacaftor (95% CI 0.40% to 4.40%; 204 participants; low-quality evidence); and 6.80% with tezacaftor-ivacaftor (95% CI 5.30 to 8.30%; 520 participants; moderate-quality evidence). More pwCF reported early transient breathlessness with lumacaftor-ivacaftor, odds ratio 2.05 (99% CI 1.10 to 3.83; 739 participants; high-quality evidence). Over 120 weeks (initial study period and follow-up) systolic blood pressure rose by 5.1 mmHg and diastolic blood pressure by 4.1 mmHg with twice-daily 400 mg lumacaftor-ivacaftor (80 participants; high-quality evidence). The tezacaftor-ivacaftor RCTs did not report these adverse effects. Pulmonary exacerbation rates decreased in pwCF receiving additional therapies to ivacaftor compared to placebo: lumacaftor 600 mg hazard ratio (HR) 0.70 (95% CI 0.57 to 0.87; 739 participants); lumacaftor 400 mg, HR 0.61 (95% CI 0.49 to 0.76; 740 participants); and tezacaftor, HR 0.64 (95% CI, 0.46 to 0.89; 506 participants) (moderate-quality evidence). Triple therapy Three RCTs of elexacaftor to tezacaftor-ivacaftor in pwCF (aged 12 years and older with either one or two F508del variants) reported no deaths (high-quality evidence). All other evidence was graded as moderate quality. In 403 participants with F508del/minimal function (MF) elexacaftor-tezacaftor-ivacaftor improved QoL respiratory scores (MD 20.2 points (95% CI 16.2 to 24.2)) and absolute change in FEV1 (MD 14.3% predicted (95% CI 12.7 to 15.8)) compared to placebo at 24 weeks. At four weeks in 107 F508del/F508del participants, elexacaftor-tezacaftor-ivacaftor improved QoL respiratory scores (17.4 points (95% CI 11.9 to 22.9)) and absolute change in FEV1 (MD 10.0% predicted (95% CI 7.5 to 12.5)) compared to tezacaftor-ivacaftor. There was probably little or no difference in the number or severity of AEs between elexacaftor-tezacaftor-ivacaftor and placebo or control (moderate-quality evidence). In 403 F508del/F508del participants, there was a longer time to protocol-defined pulmonary exacerbation with elexacaftor-tezacaftor-ivacaftor over 24 weeks (moderate-quality evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence that corrector monotherapy has clinically important effects in pwCF with F508del/F508del. Both dual therapies (lumacaftor-ivacaftor, tezacaftor-ivacaftor) result in similar improvements in QoL and respiratory function with lower pulmonary exacerbation rates. Lumacaftor-ivacaftor was associated with an increase in early transient shortness of breath and longer-term increases in blood pressure (not observed for tezacaftor-ivacaftor). Tezacaftor-ivacaftor has a better safety profile, although data are lacking in children under 12 years. In this population, lumacaftor-ivacaftor had an important impact on respiratory function with no apparent immediate safety concerns; but this should be balanced against the blood pressure increase and shortness of breath seen in longer-term adult data when considering lumacaftor-ivacaftor. There is high-quality evidence of clinical efficacy with probably little or no difference in AEs for triple (elexacaftor-tezacaftor-ivacaftor) therapy in pwCF with one or two F508del variants aged 12 years or older. Further RCTs are required in children (under 12 years) and those with more severe respiratory function.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/efectos de los fármacos , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Mutación , Adulto , Aminofenoles/uso terapéutico , Aminopiridinas/uso terapéutico , Benzodioxoles/uso terapéutico , Sesgo , Niño , Combinación de Medicamentos , Humanos , Indoles/uso terapéutico , Fenilbutiratos/uso terapéutico , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Calidad de Vida , Quinolinas/uso terapéutico , Quinolonas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Medicine (Baltimore) ; 99(51): e23547, 2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33371079

RESUMEN

ABSTRACT: This study aims to investigate the clinical characteristics and viral shedding kinetics of asymptomatic patients with coronavirus disease 2019 (COVID-19).The data of 38 asymptomatic patients positive for SARS-CoV-2 nucleic acid were collected from February to March 2020 in Tuanfeng County, Huanggang, Hubei, China. The epidemiology, laboratory examination, chest imaging, viral nucleic acid test results, clinical characteristics, and viral shedding time were summarized in this retrospective study.The study included 20 family members of patients with COVID-19, 10 medical personnel participating in COVID-19 treatment or working in a fever clinic, 6 personnel from quarantine places, 1 individual with a close contact history with confirmed patients, and 1 local epidemic prevention personnel. All were positive for SARS-CoV-2 nucleic acid. The white blood cell (WBC) count, the absolute value of lymphocytes, C-reactive protein (CRP), and D-dimer were normal. Pneumonia manifestations were not found in the chest computed tomography (CT) scan of 36 patients; the remaining 2 cases included a 1-year-old child and a pregnant woman, and they did not undergo chest CT. The viral shedding time was 6 days.All asymptomatic patients with COVID-19 had a history of close contact or exposure. Laboratory tests were normal. Chest imaging did not show any pneumonia manifestation. The viral shedding time was <10 days, which is shorter than that of patients with COVID-19. A timely discovery of such asymptomatic infections is crucial for blocking the spread of the virus and strengthening the prevention and control measures.


Asunto(s)
Infecciones Asintomáticas/epidemiología , Esparcimiento de Virus , Adolescente , Adulto , Infecciones Asintomáticas/terapia , /diagnóstico por imagen , Niño , China/epidemiología , Femenino , Humanos , Indoles/uso terapéutico , Lactante , Masculino , Medicina China Tradicional , Persona de Mediana Edad , Radiografía Torácica , Estudios Retrospectivos , Adulto Joven
15.
BMC Infect Dis ; 20(1): 954, 2020 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-33317461

RESUMEN

BACKGROUND: Treatment of patients with COVID-19 has included supportive care to mainly relief symptoms of the disease. Although World Health Organization (WHO) has not recommended any effective treatments for COVID-19, there are some reports about use of antiviral drugs. The aim of this study is to determine the effect of Arbidol (ARB) on COVID-19 disease. METHODS: Using an open-label randomized controlled trial, we examined the efficacy of ARB in patients with COVID-19 in a teaching hospital. One hundred eligible patients with diagnosis of COVID-19 were recruited in the study and assigned randomly to two groups of either hydroxychloroquine followed by KALETRA (Lopinavir/ritonavir) or hydroxychloroquine followed by ARB. The primary outcome was hospitalization duration and clinical improvement 7 days after admission. The criteria of improvement were relief of cough, dyspnea, and fever. Time to relief from fever was also assessed across the two groups. Without any dropouts, 100 patients were entered into the study for the final analysis at significance level of 0.05. RESULTS: The mean age of patients was 56.6 (17.8) years and 56.2 (14.8) years in ARB and KALETRA groups, respectively. Majority of patients were male across two groups (66 and 54%). The duration of hospitalization in ARB group was significantly less than KALETRA arm (7.2 versus 9.6 days; P = 0.02). Time to relief fever was almost similar across two groups (2.7 versus 3.1 days in ARB and KALETRA arms, respectively). Peripheral oxygen saturation rate was significantly different after 7 days of admission across two groups (94% versus 92% in ARB and KALETRA groups respectively) (P = 0.02). Based on multiple linear regression analysis, IHD, Na level, and oxygen saturation at the time of admission and type of therapy were the independent adjusted variables that determined the duration of hospitalization in patients with COVID-19. CONCLUSION: Our findings showed that Arbidol, compared to KALETRA, significantly contributes to clinical and laboratory improvements, including peripheral oxygen saturation, requiring ICU admissions, duration of hospitalization, chest CT involvements, WBC, and ESR. We suggest further studies on ARB against COVID-19 using larger sample size and multicenter design. TRIAL REGISTRATION: IRCT20180725040596N2 on 18 April 2020.


Asunto(s)
Antivirales/uso terapéutico , Indoles/uso terapéutico , Adulto , Anciano , Combinación de Medicamentos , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Pandemias , Ritonavir/uso terapéutico
16.
Virol J ; 17(1): 162, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-33097047

RESUMEN

OBJECTIVE: We aimed to describe the features of 220 nonemergency (mild or common type) COVID-19 patients from a shelter hospital, as well as evaluate the efficiency of antiviral drug, Arbidol in their disease progressions. METHODS: Basic clinical characteristics were described and the efficacy of Arbidol was evaluated based on gender, age, maximum body temperature of the patients. RESULTS: Basically, males had a higher risk of fever and more onset symptoms than females. Arbidol could accelerate fever recovery and viral clearance in respiratory specimens, particularly in males. Arbidol also contributed to shorter hospital stay without obvious adverse reactions. CONCLUSIONS: In the retrospective COVID-19 cohort, gender was one of the important factors affecting patient's conditions. Arbidol showed several beneficial effects in these patients, especially in males. This study brought more researches enlightenment in understanding the emerging infectious disease.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Indoles/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Betacoronavirus/aislamiento & purificación , China/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Estudios Retrospectivos
17.
Chem Biol Interact ; 331: 109278, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33038329

RESUMEN

Only in the last decade the long-term consequences of sepsis started to be studied and even less attention has been given to the treatment of psychological symptoms of sepsis survivors. It is estimated that 60% of sepsis survivors have psychological disturbances, including depression, anxiety, and cognitive impairment. Although the causative factors remain largely poorly understood, blood-brain barrier (BBB) disturbances, neuroinflammation, and oxidative stress have been investigated. Therefore, we sought to explore if the immunomodulatory and antioxidant selenocompound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) would be able to ameliorate long-term behavioral and biochemical alterations in sepsis survivors male Swiss mice. CMI treatment (1 mg/kg, given orally for seven consecutive days) attenuated depression- and anxiogenic-like behaviors and cognitive impairment present one month after the induction of sepsis (lipopolysaccharide, 5 mg/kg intraperitoneally). Meantime, CMI treatment modulated the number of neutrophils and levels of reactive species in neutrophils, lymphocytes, and monocytes. In addition, peripheral markers of liver and kidneys dysfunction (AST, ALT, urea, and creatinine) were reduced after CMI treatment in post-septic mice. Notably, CMI treatment to non-septic mice did not alter AST, ALT, urea, and creatinine levels, indicating the absence of acute hepatotoxicity and nephrotoxicity following CMI treatment. Noteworthy, CMI ameliorated BBB dysfunction induced by sepsis, modulating the expression of inflammation-associated genes (NFκB, IL-1ß, TNF-α, IDO, COX-2, iNOS, and BDNF) and markers of oxidative stress (reactive species, nitric oxide, and lipid peroxidation levels) in the prefrontal cortices and hippocampi of mice. In conclusion, we unraveled crucial molecular pathways that are impaired in post-septic mice and we present CMI as a promising therapeutic candidate aimed to manage the long-lasting behavioral alterations of sepsis survivors to improve their quality of life.


Asunto(s)
Conducta Animal , Indoles/química , Estrés Oxidativo , Sepsis/patología , Animales , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Conducta Animal/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Depresión/tratamiento farmacológico , Depresión/etiología , Depresión/patología , Modelos Animales de Enfermedad , Indoles/farmacología , Indoles/uso terapéutico , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Lipopolisacáridos/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Locomoción/efectos de los fármacos , Masculino , Ratones , Neutrófilos/citología , Neutrófilos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Sepsis/complicaciones
18.
Medicine (Baltimore) ; 99(41): e22707, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33031343

RESUMEN

RATIONALE: Anlotinib has been proved to be effective in advanced refractory non-small cell lung cancer. PATIENT CONCERNS: A 47-year-old female non-smoker was admitted due to persistent chest tightness for a month. DIAGNOSES: Epidermal growth factor receptor (EGFR) wild-type advanced primary lung adenocarcinoma without brain or bone metastasis. INTERVENTIONS: The patient failed 2 lines of pemetrexed/docetaxel plus carboplatin and third-line erlotinib. Fourth-line anlotinib was administered thereafter. OUTCOMES: The pulmonary lesions showed partial remission 5 months after anlotinib monotherapy. The patient demonstrated a progression-free survival of more than 7 months and an overall survival of >12 months. The adverse events including hypertension and fatigue were well-tolerated. LESSONS: Salvage anlotinib might be a reasonable choice in EGFR wild-type lung adenocarcinoma after failure of chemotherapy. Further well-designed trials are warranted to verify this occasional finding.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Indoles/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Quinolinas/uso terapéutico , Adenocarcinoma/genética , Femenino , Genes erbB-1 , Humanos , Neoplasias Pulmonares/genética , Persona de Mediana Edad , Terapia Recuperativa
19.
Medicine (Baltimore) ; 99(40): e22637, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019486

RESUMEN

INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignancy that progresses rapidly and easily relapses. To the best of our knowledge, advances have been minimal for decades and the first-line treatment is still platinum-etoposide and radiotherapy. However, elderly patients with severe renal failure who suffer from SCLC usually show more serious drug-related side effects. A large proportion of them cannot tolerate the standard treatment, and their prognosis is poorer compared with that of younger patients. Presently, oral etoposide capsules may be accepted as a replaceable option. We report the case of a male patient with SCLC on hemodialysis who was successfully treated with concurrent oral etoposide monotherapy and radiotherapy and achieved excellent outcomes. PATIENT'S CONCERNS: A 63-year-old man with severe renal failure was diagnosed with SCLC. PRIMARY DIAGNOSES: SCLC was diagnosed using transbronchial biopsy. INTERVENTIONS: He received concomitant single-agent oral etoposide (6 cycles) and local radiotherapy. Etoposide 100 mg once daily combined with thoracic radiation treatment (2 Gy/f, total DT: 50 Gy/25 f), was subsequently followed by prophylactic cranial irradiation plus anlotinib. OUTCOMES: The patient achieved complete response after 1 cycle and the subsequent treatment was effective without any kidney damage and other severe side effects. CONCLUSION: Though etoposide capsule is an old drug, its use should be considered in SCLC patients with renal insufficiency undergoing hemodialysis. However, treatment guidelines and research data for such patients are still lacking and further studies are needed. Although recent research focuses mainly on new drugs, some old drugs like etoposide which can bring unexpected positive effects should not be neglected.


Asunto(s)
Etopósido/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Inhibidores de Topoisomerasa II/uso terapéutico , Administración Oral , Terapia Combinada , Irradiación Craneana/métodos , Etopósido/administración & dosificación , Humanos , Indoles/uso terapéutico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Quinolinas/uso terapéutico , Diálisis Renal/métodos , Insuficiencia Renal/terapia , Inhibidores de Topoisomerasa II/administración & dosificación , Resultado del Tratamiento
20.
Medicine (Baltimore) ; 99(36): e22128, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899099

RESUMEN

RATIONALE: Brain metastasis (BM) is a serious complication in non-small cell lung cancer (NSCLC) patients. Pemetrexed is one of the preferred agents in nonsquamous NSCLC with BM; however, the traditional chemotherapy demonstrated limited efficacy partly due to drug resistance and the blood-brain barrier. PATIENT CONCERNS: A 52-year-old male non-smoker was admitted for irritating cough, chest distress, and back pain. DIAGNOSES: Epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative primary lung adenocarcinoma with an asymptomatic solitary BM (cTxNxM1b, IVA). INTERVENTIONS: Pemetrexed (500 mg/m of body surface area) and carboplatin (area under the curve of 5) were firstly administered every 3 weeks for 3 cycles, followed by pemetrexed/carboplatin plus anlotinib (12 mg daily; 2 weeks on and 1 week off) for another 3 cycles. Then maintenance anlotinib monotherapy was continued for a year, without unacceptable adverse events. OUTCOMES: The BM was slightly enlarged after 3 cycles of pemetrexed/carboplatin; however, a complete remission was achieved after the combination therapy. His intracranial progression-free survival was more than 2 years. LESSONS: Pemetrexed/carboplatin plus anlotinib could be considered for the treatment of epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative lung adenocarcinoma with BM. Further well-designed trials are warranted to verify this occasional finding.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Quinasa de Linfoma Anaplásico/metabolismo , Carboplatino/uso terapéutico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Pemetrexed/uso terapéutico , Quinolinas/uso terapéutico
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