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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 797-804, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105475

RESUMO

OBJECTIVE: To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines. METHODS: Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8. RESULTS: ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC50 values were 2.795, 4.020, 5.432 and 4.755 µmol/L, respectively. The activity assays of Caspase-3/7 and Caspase-9 showed that their relative activity was increased gradually in proportion to the drug concentration with the statistically significant difference (r=0.9648, r=0.9377, r=0.9318; r=0.9087, r=0.9431, r=0.8914). MDC staining results showed that the number of autophagic vacuoles increased with the rise of ROC-325 concentration (r=0.9565, r=0.9373, r=0.9233). ROC-325 could increase the expression of apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62 and LC3-Ⅱ/LC3-Ⅰ), but decrease the expression of Beclin-1 detected by Western blot. The CCK-8 assay showed that ROC-325 combined with bortezomib had synergistic effect on the inhibition of drug resistant cell line RPMI 8226-BTZ100. CONCLUSION: ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.


Assuntos
Mieloma Múltiplo , Apoptose , Autofagia , Bortezomib/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Hidroxicloroquina/análogos & derivados
2.
Medicine (Baltimore) ; 100(22): e26238, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087909

RESUMO

RATIONALE: Acute acalculous cholecystitis (AAC) is an extremely rare manifestation of systemic lupus erythematous (SLE). In previous reports, most of the patients were already diagnosed cases of SLE upon confirmation of AAC. PATIENT CONCERNS: A 24-year-old female who initially presented with fever and acute right upper quadrant abdominal pain. She had no medical history. DIAGNOSES: Abdominal ultrasonography and computed tomography (CT) showed gallbladder thickening with pericholecystic edema without gallstones or sludge, demonstrating acalculous cholecystitis. She revealed discoid rash on the both shin. Laboratory tests revealed pancytopenia. The titer of antinuclear antibody (ANA) was 1:1280. Anti-dsDNA antibody, anti-phospholipid antibody, anti-Sm antibody test, and proteinuria in 24 hours were positive. Both C3 and C4 were low. Echocardiography and chest CT showed pericardial effusion and pleural effusion. Using the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria, the score was 31. We thought AAC of this case that was one of the initial manifestations of SLE. INTERVENTIONS: The patient was treated with high-dose prednisolone (1 mg/kg) and hydroxychloroquine 400 mg. OUTCOMES: After 4 days of administration of high-dose corticosteroid therapy, symptoms rapidly improved. After 35 days of the treatment, her symptoms and disease activity of SLE were markedly improved. LESSONS: Although AAC being the initial manifestation of SLE is very rare, prompt diagnosis and management with corticosteroids precluded surgical intervention. Physicians need to be cognizant of AAC as a disease flare and as a rare initial manifestation of SLE.


Assuntos
Colecistite Acalculosa/etiologia , Vesícula Biliar/patologia , Lúpus Eritematoso Sistêmico/complicações , Colecistite Acalculosa/diagnóstico , Doença Aguda , Adulto , Idoso , Anticorpos Antinucleares/sangue , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Criança , Quimioterapia Combinada , Ecocardiografia/métodos , Feminino , Vesícula Biliar/diagnóstico por imagem , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Derrame Pericárdico/diagnóstico , Derrame Pleural/diagnóstico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Proteinúria/diagnóstico , Proteinúria/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Ultrassonografia/métodos , Adulto Jovem
3.
Artigo em Inglês | MEDLINE | ID: mdl-34073254

RESUMO

This paper aims to analyze the ethical challenges in experimental drug use during the early stage of the COVID-19 pandemic, using Germany as a case study. In Germany uniform ethical guidelines were available early on nationwide, which was considered as desirable by other states to reduce uncertainties and convey a message of unity. The purpose of this ethical analysis is to assist the preparation of future guidelines on the use of medicines during public health emergencies. The use of hydroxychloroquine, remdesivir and COVID-19 convalescent plasma in clinical settings was analyzed from the perspective of the ethical principles of beneficence, non-maleficence, justice and autonomy. We observed that drug safety and drug distribution during the pandemic affects all four ethical principles. We therefore recommend to establish ethical guidelines (i) to discuss experimental treatment options with patients from all population groups who are in urgent need, (ii) to facilitate the recording of patient reactions to drugs in off-label use, (iii) to expand inclusion criteria for clinical studies to avoid missing potentially negative effects on excluded groups, and (iv) to maintain sufficient access to repurposed drugs for patients with prior conditions.


Assuntos
COVID-19 , Hidroxicloroquina , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , COVID-19/tratamento farmacológico , COVID-19/terapia , Análise Ética , Alemanha/epidemiologia , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Pandemias , SARS-CoV-2
4.
Medicine (Baltimore) ; 100(22): e25688, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087822

RESUMO

RATIONALE: Hydroxychloroquine has excellent anti-inflammatory and immunomodulatory effects as one of the antimalarial drugs. In particular, hydroxychloroquine was once widely used as a treatment for the new coronavirus pneumonia epidemic in 2020. Retinopathy caused by hydroxychloroquine is normally irreversible, but little attention has been paid to it. PATIENT CONCERNS: A 38-year-old young Chinese woman was taking oral hydroxychloroquine 400 mg daily to control lupus disease activity for six years after the diagnosis of systemic lupus erythematosus (SLE). She did not have any history of eye disease and was admitted to the hospital with a sudden blurring of both eyes. DIAGNOSES: The diagnosis of retinal macular degeneration caused by hydroxychloroquine was made after excluding other interfering diseases based on the patient's long-term use of hydroxychloroquine and the results of the eye examination. INTERVENTIONS: The patient was discontinued from hydroxychloroquine. To control the recurrence of SLE, she was given intravenous methylprednisolone, oral tacrolimus and mycophenolate. Meanwhile, she was asked to take extra care of her eyes and to come to the hospital every three months to have her vision checked. OUTCOMES: The patient's blurred vision improved one week later. Three months later, her vision examination showed no further decline (0.4 in the right eye and 0.6 in the left eye). Meanwhile, the SLE disease activity index (SLEDAI) decreased from six points to five points currently. LESSONS: Retinopathy caused by hydroxychloroquine is irreversible and there is no particularly effective treatment. Discontinuation of hydroxychloroquine, better daily eye protection, and regular vision checks are the keys to preventing retinopathy. Although hydroxychloroquine causing retinal toxicity was mentioned several years ago, the rate and severity of retinal toxicity require further research. How to get more patients to take care of their eyes requires continuous and increased education by doctors.


Assuntos
Anti-Inflamatórios/efeitos adversos , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Doenças Retinianas/induzido quimicamente , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Acuidade Visual
5.
Medicine (Baltimore) ; 100(22): e25919, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087834

RESUMO

ABSTRACT: Most of the reports about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children reported mild-to-moderate disease manifestations. However, recent reports explored a rare pediatric multisystem syndrome possibly associated with SARS-CoV-2 infection termed multisystem inflammatory syndrome in children (MIS-C).The study prospectively enrolled 5 patients with clinical and laboratory evidence of MIS-C associated with SARS-CoV-2 infection. They were admitted to the pediatric intensive care unit (PICU). Their clinical presentation, laboratory, and outcome were described.All patients shared similar clinical presentations such as persistent documented fever for more than 3 days, respiratory symptoms, gastrointestinal involvement, and increased inflammatory markers (CRP, ESR, and ferritin). Three patients had concurrent positive coronavirus disease 2019 (COVID-19) infection, and the other 2 patients had contact with suspected COVID-19 positive patients. They were all managed in the PICU and received intravenous immunoglobulin, systemic steroid, and hydroxychloroquine. The hospital stays ranged between 3 and 21 days. One patient died due to severe multiorgan failures and shock, and the other 4 patients were discharged with good conditions.Pediatric patients with SARS-CoV-2 are at risk for MIS-C. MIS-C has a spectrum of clinical and laboratory presentations, and the clinicians need to have a high index of suspicion for the diagnosis and should initiate its early treatment to avoid unfavorable outcomes. Long-term follow-up studies will be required to explore any sequelae of MIS-C, precisely the cardiovascular complications.


Assuntos
COVID-19/epidemiologia , COVID-19/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulinas/uso terapêutico , Mediadores da Inflamação/metabolismo , Unidades de Terapia Intensiva Pediátrica , Tempo de Internação , Masculino , Estudos Prospectivos , SARS-CoV-2 , Arábia Saudita/epidemiologia , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico
6.
Eur Rev Med Pharmacol Sci ; 25(10): 3923-3932, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34109607

RESUMO

Angiotensin converting enzyme 2 (ACE2) has potentially conflicting roles in health and disease. COVID-19 coronavirus binds to human cells via ACE2 receptor, which is expressed on almost all body organs. Boosting the ACE2 receptor levels on heart and lung cells may provide more cellular enter to virus thereby worsening the infection. Therefore, among the drug targets, ACE2 is suggested as a vital target of COVID-19 therapy. This hypothesis is based on the protective role of the drugs acting on ACE2. Therefore, this review discusses the impact and challenges of using ACE2 as a target in the current therapy of COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Antivirais/química , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/química , Alanina/metabolismo , Alanina/uso terapêutico , Enzima de Conversão de Angiotensina 2/metabolismo , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/metabolismo , Antivirais/uso terapêutico , Azitromicina/química , Azitromicina/metabolismo , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Humanos , Hidroxicloroquina/química , Hidroxicloroquina/metabolismo , Hidroxicloroquina/uso terapêutico , SARS-CoV-2/isolamento & purificação , Vitamina D/química , Vitamina D/metabolismo , Vitamina D/uso terapêutico
7.
BMC Ophthalmol ; 21(1): 209, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975575

RESUMO

BACKGROUND: One of the major side effects of Hydroxychloroquine (HCQ) is retinopathy. The aim of this study was to evaluate the Optical coherence tomography angiography (OCTA) parameters in a group of patients who have Hydroxychloroquine-induced retinopathy based on Multifocal electroretinography (mfERG) with a group who do not have retinopathy. METHOD: This is a Cross-Sectional Study. In this study, patients with Rheumatoid arthritis (RA) or Systemic lupus erythematosus (SLE) who had been taking Hydroxychloroquine for at least 7 years were included. MfERG and OCTA imaging were performed for all patients. Patients were divided into Normal mfERG and Abnormal mfERG groups based on mfERG results. OCTA parameters were studied in these two groups. RESULT: Sixty-one patients (61 eyes) were included. Forty-one patients had SLE and 20 patients had RA. Forty patients (66.7%) had Abnormal mfERG. The mean vascular density (VD) in Superficial capillary plexus (SCP) layer was not significantly different between Normal mfERG and Abnormal mfERG groups (P-Value> 0.05). Mean VD in SCP layer was not significantly different between Normal mfERG and Abnormal mfERG groups (P-Value> 0.05). In RA subgroup, mean VD in SCP layer in PeriFovea region in Abnormal mfERG group was significantly lower than normal group (P-Value < 0.05). Mean VD in deep capillary plexus (DCP) layer in Whole Image, Superior Hemi, Inferior Hemi, PeriFovea area in Abnormal mfERG group was significantly lower than normal group (P-Value < 0.05). This discrepancy was also observed in the RA subgroup but not in the SLE subgroup. The mean of none of the parameters of foveal avascular zone (FAZ) (mm2), Flow Area of Outer Retina (mm2) and Flow Area of Choriocapillaris (mm2) were not statistically significant between the groups Abnormal mfERG and Normal mfERG. (p-value> 0.05). CONCLUSION: VD in the DCP layer decreased in abnormal mfERG patients compared to patients with normal mfERG. But it seems that VD in SCP layer, FAZ Area and Flow Area are similar in both groups. OCTA may be used as a non-invasive tool in the diagnosis of early stages of HCQ-induced retinopathy, especially in RA patients, but further studies are needed.


Assuntos
Hidroxicloroquina , Tomografia de Coerência Óptica , Estudos Transversais , Angiofluoresceinografia , Humanos , Hidroxicloroquina/efeitos adversos , Vasos Retinianos/diagnóstico por imagem
8.
Am J Gastroenterol ; 116(4): 692-699, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33982938

RESUMO

INTRODUCTION: Famotidine has been posited as a potential treatment for coronavirus disease 2019 (COVID-19). We compared the incidence of COVID-19 outcomes (i.e., death and death or intensive services use) among hospitalized famotidine users vs proton pump inhibitors (PPIs) users, hydroxychloroquine users, or famotidine nonusers separately. METHODS: We constructed a retrospective cohort study using data from COVID-19 Premier Hospital electronic health records. The study population was COVID-19 hospitalized patients aged 18 years or older. Famotidine, PPI, and hydroxychloroquine exposure groups were defined as patients dispensed any medication containing 1 of the 3 drugs on the day of admission. The famotidine nonuser group was derived from the same source population with no history of exposure to any drug with famotidine as an active ingredient before or on the day of admission. Time at risk was defined based on the intention-to-treat principle starting 1 day after admission to 30 days after admission. For each study comparison group, we fit a propensity score model through large-scale regularized logistic regression. The outcome was modeled using a survival model. RESULTS: We identified 2,193 users of PPI, 5,950 users of the hydroxychloroquine, 1,816 users of famotidine, and 26,820 nonfamotidine users. After propensity score stratification, the hazard ratios (HRs) for death were as follows: famotidine vs no famotidine HR 1.03 (0.89-1.18), vs PPIs: HR 1.14 (0.94-1.39), and vs hydroxychloroquine: 1.03 (0.85-1.24). Similar results were observed for the risk of death or intensive services use. DISCUSSION: We found no evidence of a reduced risk of COVID-19 outcomes among hospitalized COVID-19 patients who used famotidine compared with those who did not or compared with PPI or hydroxychloroquine users.


Assuntos
COVID-19/tratamento farmacológico , Famotidina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Estudos de Coortes , Feminino , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Cochrane Database Syst Rev ; 5: CD015043, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34029377

RESUMO

BACKGROUND: The role of vitamin D supplementation as a treatment for COVID-19 has been a subject of considerable discussion. A thorough understanding of the current evidence regarding the effectiveness and safety of vitamin D supplementation for COVID-19 based on randomised controlled trials is required. OBJECTIVES: To assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 in comparison to an active comparator, placebo, or standard of care alone, and to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, Web of Science and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 11 March 2021. SELECTION CRITERIA: We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating vitamin D supplementation for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies investigating preventive effects, or studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)). DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (ROB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the following prioritised outcome categories: individuals with moderate or severe COVID-19: all-cause mortality, clinical status, quality of life, adverse events, serious adverse events, and for individuals with asymptomatic or mild disease: all-cause mortality, development of severe clinical COVID-19 symptoms, quality of life, adverse events, serious adverse events. MAIN RESULTS: We identified three RCTs with 356 participants, of whom 183 received vitamin D. In accordance with the World Health Organization (WHO) clinical progression scale, two studies investigated participants with moderate or severe disease, and one study individuals with mild or asymptomatic disease. The control groups consisted of placebo treatment or standard of care alone. Effectiveness of vitamin D supplementation for people with COVID-19 and moderate to severe disease We included two studies with 313 participants. Due to substantial clinical and methodological diversity of both studies, we were not able to pool data. Vitamin D status was unknown in one study, whereas the other study reported data for vitamin D deficient participants. One study administered multiple doses of oral calcifediol at days 1, 3 and 7,  whereas the other study gave a single high dose of oral cholecalciferol at baseline. We assessed one study with low risk of bias for effectiveness outcomes, and the other with some concerns about randomisation and selective reporting. All-cause mortality at hospital discharge (313 participants) We found two studies reporting data for this outcome. One study reported no deaths when treated with vitamin D out of 50 participants, compared to two deaths out of 26 participants in the control group (Risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.13). The other study reported nine deaths out of 119 individuals in the vitamin D group, whereas six participants out of 118 died in the placebo group (RR 1.49, 95% CI 0.55 to 4.04]. We are very uncertain whether vitamin D has an effect on all-cause mortality at hospital discharge (very low-certainty evidence). Clinical status assessed by the need for invasive mechanical ventilation (237 participants) We found one study reporting data for this outcome. Nine out of 119 participants needed invasive mechanical ventilation when treated with vitamin D, compared to 17 out of 118 participants in the placebo group (RR 0.52, 95% CI 0.24 to 1.13). Vitamin D supplementation may decrease need for invasive mechanical ventilation, but the evidence is uncertain (low-certainty evidence). Quality of life We did not find data for quality of life. Safety of vitamin D supplementation for people with COVID-19 and moderate to severe disease We did not include data from one study, because assessment of serious adverse events was not described and we are concerned that data might have been inconsistently measured. This study reported vomiting in one out of 119 participants immediately after vitamin D intake (RR 2.98, 95% CI 0.12 to 72.30). We are very uncertain whether vitamin D supplementation is associated with higher risk for adverse events (very low-certainty). Effectiveness and safety of vitamin D supplementation for people with COVID-19 and asymptomatic or mild disease We found one study including 40 individuals, which did not report our prioritised outcomes, but instead data for viral clearance, inflammatory markers, and vitamin D serum levels. The authors reported no events of hypercalcaemia, but recording and assessment of further adverse events remains unclear. Authors administered oral cholecalciferol in daily doses for at least 14 days, and continued with weekly doses if vitamin D blood levels were > 50 ng/mL. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID-19. The evidence for the effectiveness of vitamin D supplementation for the treatment of COVID-19 is very uncertain. Moreover, we found only limited safety information, and were concerned about consistency in measurement and recording of these outcomes. There was substantial clinical and methodological heterogeneity of included studies, mainly because of different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes. There is an urgent need for well-designed and adequately powered randomised controlled trials (RCTs) with an appropriate randomisation procedure, comparability of study arms and preferably double-blinding. We identified 21 ongoing and three completed studies without published results, which indicates that these needs will be addressed and that our findings are subject to change in the future. Due to the living approach of this work, we will update the review periodically.


Assuntos
COVID-19/tratamento farmacológico , Calcifediol/administração & dosagem , Colecalciferol/administração & dosagem , Vitaminas/administração & dosagem , 25-Hidroxivitamina D 2/sangue , Corticosteroides/uso terapêutico , Adulto , Azitromicina/uso terapêutico , Viés , COVID-19/sangue , COVID-19/mortalidade , Causas de Morte , Ceftriaxona/uso terapêutico , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapêutico , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Deficiência de Vitamina D/diagnóstico
11.
BMC Nephrol ; 22(1): 198, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039299

RESUMO

BACKGROUND: Individuals with end-stage kidney disease (ESKD) on dialysis are vulnerable to contracting COVID-19 infection, with mortality as high as 31 % in this group. Population demographics in the UAE are dissimilar to many other countries and data on antibody responses to COVID-19 is also limited. The objective of this study was to describe the characteristics of patients who developed COVID-19, the impact of the screening strategy, and to assess the antibody response to a subset of dialysis patients. METHODS: We retrospectively examined the outcomes of COVID19 infection in all our haemodialysis patients, who were tested regularly for COVID 19, whether symptomatic or asymptomatic. In addition, IgG antibody serology was also performed to assess response to COVID-19 in a subset of patients. RESULTS: 152 (13 %) of 1180 dialysis patients developed COVID-19 during the study period from 1st of March to the 1st of July 2020. Of these 81 % were male, average age of 52​ years and 95 % were on in-centre haemodialysis. Family and community contact was most likely source of infection in most patients. Fever (49 %) and cough (48 %) were the most common presenting symptoms, when present. Comorbidities in infected individuals included hypertension (93 %), diabetes (49 %), ischaemic heart disease (30 %). The majority (68 %) developed mild disease, whilst 13 % required critical care. Combinations of drugs including hydroxychloroquine, favipiravir, lopinavir, ritonavir, camostat, tocilizumab and steroids were used based on local guidelines. The median time to viral clearance defined by two negative PCR tests was 15 days [IQR 6-25]. Overall mortality in our cohort was 9.2 %, but ICU mortality was 65 %. COVID-19 IgG antibody serology was performed in a subset (n = 87) but 26 % of PCR positive patients (n = 23) did not develop a significant antibody response. CONCLUSIONS: Our study reports a lower mortality in this patient group compared with many published series. Asymptomatic PCR positivity was present in 40 %. Rapid isolation of positive patients may have contributed to the relative lack of spread of COVID-19 within our dialysis units. The lack of antibody response in a few patients is concerning.


Assuntos
Anticorpos Antivirais/sangue , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , COVID-19/complicações , Falência Renal Crônica/complicações , Pandemias , Diálise Renal , SARS-CoV-2/imunologia , Corticosteroides/uso terapêutico , Adulto , Anticorpos Antivirais/biossíntese , Antivirais/uso terapêutico , Infecções Assintomáticas , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/imunologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Comorbidade , Busca de Comunicante , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/imunologia , Masculino , Pessoa de Meia-Idade , Isolamento de Pacientes , Estudos Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Taxa de Sobrevida , Avaliação de Sintomas , Resultado do Tratamento , Emirados Árabes Unidos/epidemiologia , Viremia/diagnóstico
12.
J Nepal Health Res Counc ; 19(1): 1-9, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33934125

RESUMO

BACKGROUND: The global spread of COVID-19 and the lack of definite treatment have caused an alarming crisis in the world. We aimed to evaluate the outcome and potential harmful cardiac effects of hydroxychloroquine and azithromycin compared to hydroxychloroquine alone for COVID-19 treatment. METHODS: PubMed, Medline, Google Scholar, Cochrane Library, clinicaltrials.gov, and World Health Organization clinical trial registry were searched using appropriate keywords and identified six studies using PRISMA guidelines. The quantitative synthesis was performed using fixed or random effects for the pooling of studies based on heterogeneities. RESULTS: The risk of mortality (RR=1.16; CI: 0.92-1.46) and adverse cardiac events (OR=1.06; CI: 0.82-1.37) demonstrated a small increment though of no significance. There were no increased odds of mechanical ventilation (OR=0.84; CI: 0.33-2.15) and significant QTc prolongation (OR=0.84, CI: 0.59-1.21). Neither the critical QTc threshold (OR=1.92, CI: 0.81-4.56) nor absolute ?QTc ?60ms (OR=1.95, CI:0.55-6.96) increased to the level of statistical significance among hydroxychloroquine and azithromycin arm compared to hydroxychloroquine alone, but the slightly increased odds need to be considered in clinical practice. CONCLUSIONS: The combination of hydroxychloroquine and azithromycin leads to small increased odds of mortality and cardiac events compared to hydroxychloroquine alone. The use of hydroxychloroquine and azithromycin led to increased odds of QT prolongation, although not statistically significant.


Assuntos
Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Azitromicina/efeitos adversos , COVID-19/mortalidade , Doenças Cardiovasculares/mortalidade , Quimioterapia Combinada , Humanos , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , SARS-CoV-2
13.
BMJ Open ; 11(5): e042943, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958335

RESUMO

OBJECTIVE: To understand the outcome of hospitalised patients from Mumbai City, which had the highest number of COVID-19 cases in India. DESIGN: Observational study with follow-up. SETTING: Data extraction from medical records of patients with COVID-19 admitted to Nair Hospital & TN Medical College, Mumbai, India. PARTICIPANTS: 689 patients with COVID-19 were admitted in the hospital from 26 March 2020 to 11 May 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: In-hospital mortality; joint effect of comorbidity and age on the risk of dying. RESULTS: A total of 689 patients (median age 44 years) admitted with RT-PCR-confirmed COVID-19 were included in the study. Of these, 77.36% of patients were discharged alive while 22.64% died. 11.61% required some kind of oxygen support while 2.8% of patients required intensive care unit admissions. Older age (HR 2.88, 95% CI 2.09 to 3.98), presence of comorbidities (HR 2.56, 95% CI 1.84 to 3.55), history of hypertension (HR 3.19, 95% CI 1.67 to 6.08), and presence of symptoms at the time of admission (HR 3.21, 95% CI 1.41 to 7.26) were associated with increased risk of in-hospital mortality. Treatment with a combination of azithromycin with hydroxychloroquine, antiviral or steroid compared with no treatment did not alter the disease course and in-hospital mortality. The combined effect of old age and presence of comorbid conditions was more pronounced in women than men. CONCLUSIONS: In-hospital patients were younger, less symptomatic with lesser need of ventilators and oxygen support as compared with many western countries. TRIAL REGISTRATION: Not applicable (observational study, not a clinical trial).


Assuntos
COVID-19 , Adulto , Idoso , Comorbidade , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Hidroxicloroquina , Índia/epidemiologia , Masculino , SARS-CoV-2
14.
Pan Afr Med J ; 38: 225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046130

RESUMO

Liver damage during COVID-19 disease has been described in numerous studies. Its mechanism is poorly understood. It is mainly reserved for severe forms and is manifested by abnormalities of the hepatic assessment and more particularly cytolysis. Particular attention must be paid to patients with chronic liver disease, both in terms of follow-up and treatment. We wanted to know the evolution of COVID-19 and its treatment, on the liver function of a 27-year-old patient followed for chronic non-cirrhotic hepatitis B at the Hassan II University Hospital in Fez. Our patient had stopped the antiviral B treatment and presented COVID-19 infection with minimal to moderate impairment. The initial evaluation showed cytolysis at 4 times upper limit of normal (ULN). Management consisted in the immediate resumption of Tenofovir in combination with hydroxychloroquine (HCQ) and azythromycin with good clinical and biological evolution.


Assuntos
Antivirais/administração & dosagem , COVID-19/complicações , Hepatite B Crônica/fisiopatologia , Adulto , Azitromicina/administração & dosagem , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Hospitais Universitários , Humanos , Hidroxicloroquina/administração & dosagem , Testes de Função Hepática , Masculino , Marrocos , Tenofovir/administração & dosagem
15.
BMJ ; 373: n1038, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975825

RESUMO

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.


Assuntos
COVID-19/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Reposicionamento de Medicamentos/métodos , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Azitromicina/uso terapêutico , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Ceftriaxona/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Combinação de Medicamentos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Enoxaparina/uso terapêutico , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Lactente , Recém-Nascido , Pacientes Internados , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Ritonavir/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , Segurança , Espanha/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Vitamina D/uso terapêutico , Adulto Jovem
16.
JAMA ; 325(17): 1755-1764, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33944875

RESUMO

Importance: Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear. Objective: To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission. Design, Setting, and Participants: ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019. Interventions: Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80). Main Outcomes and Measures: The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin. Results: Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred. Conclusions and Relevance: Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01881308.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Metotrexato/administração & dosagem , Exacerbação dos Sintomas , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/patologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Leflunomida/administração & dosagem , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Radiografia , Sulfassalazina/administração & dosagem , Ultrassonografia
18.
Front Immunol ; 12: 580147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936026

RESUMO

The coronavirus disease 2019 (COVID-19) is widely spread and remains a global pandemic. Limited evidence on the systematic evaluation of the impact of treatment regimens on antibody responses exists. Our study aimed to analyze the role of antibody response on prognosis and determine factors influencing the IgG antibodies' seroconversion. A total of 1,111 patients with mild to moderate COVID-19 symptoms admitted to Leishenshan Hospital in Wuhan were retrospectively analyzed. A serologic SARS-CoV-2 IgM/IgG antibody test was performed on all the patients 21 days after the onset of symptoms. Patient clinical characteristics were compared. In the study, 42 patients progressed to critical illness, with 6 mortalities reported while 1,069 patients reported mild to moderate disease. Advanced age (P = 0.028), gasping (P < 0.001), dyspnea (P = 0.024), and IgG negativity (P = 0.006) were associated with progression to critical illness. The mortality rate in critically ill patients with IgG antibody was 6.45% (95% CI 1.12-22.84%) and 36.36% (95% CI 12.36-68.38%) in patients with no IgG antibody (P = 0.003). Symptomatic patients were more likely to develop IgG antibody responses than asymptomatic patients. Using univariable analysis, fever (P < 0.001), gasping (P = 0.048), cancer (P < 0.001), cephalosporin (P = 0.015), and chloroquine/hydroxychloroquine (P = 0.021) were associated with IgG response. In the multivariable analysis, fever, cancer, cephalosporins, and chloroquine/hydroxychloroquine correlated independently with IgG response. We determined that the absence of SARS-CoV-2 antibody IgG in the convalescent stage had a specific predictive role in critical illness progression. Importantly, risk factors affecting seropositivity were identified, and the effect of antimalarial drugs on antibody response was determined.


Assuntos
Anticorpos Antivirais/imunologia , Antimaláricos/efeitos adversos , COVID-19/imunologia , Imunoglobulina G/imunologia , Adolescente , Adulto , Idoso , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/mortalidade , Cefalosporinas/efeitos adversos , China , Cloroquina/efeitos adversos , Convalescença , Feminino , Febre/complicações , Febre/virologia , Humanos , Hidroxicloroquina/efeitos adversos , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/complicações , Neoplasias/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Soroconversão , Testes Sorológicos
19.
PLoS One ; 16(5): e0251048, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34033655

RESUMO

BACKGROUND: COVID-19 is a multisystemic disorder that frequently causes acute kidney injury (AKI). However, the precise clinical and biochemical variables associated with AKI progression in patients with severe COVID-19 remain unclear. METHODS: We performed a retrospective study on 278 hospitalized patients who were admitted to the ward and intensive care unit (ICU) with COVID-19 between March 2020 and June 2020, at the University Hospital, São Paulo, Brazil. Patients aged ≥ 18 years with COVID-19 confirmed on RT-PCR were included. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We evaluated the incidence of AKI, several clinical variables, medicines used, and outcomes in two sub-groups: COVID-19 patients with AKI (Cov-AKI), and COVID-19 patients without AKI (non-AKI). Univariate and multivariate analyses were performed. RESULTS: First, an elevated incidence of AKI (71.2%) was identified, distributed across different stages of the KDIGO criteria. We further observed higher levels of creatinine, C-reactive protein (CRP), leukocytes, neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) in the Cov-AKI group than in the non-AKI group, at hospital admission. On univariate analysis, Cov-AKI was associated with older age (>62 years), hypertension, CRP, MCV, leucocytes, neutrophils, NLR, combined hydroxychloroquine and azithromycin treatment, use of mechanical ventilation, and vasoactive drugs. Multivariate analysis showed that hypertension and the use of vasoactive drugs were independently associated with a risk of higher AKI in COVID-19 patients. Finally, we preferentially found an altered erythrocyte and leukocyte cellular profile in the Cov-AKI group compared to the non-AKI group, at hospital discharge. CONCLUSIONS: In our study, the development of AKI in patients with severe COVID-19 was related to inflammatory blood markers and therapy with hydroxychloroquine/azithromycin, with vasopressor requirement and hypertension considered potential risk factors. Thus, attention to the protocol, hypertension, and some blood markers may help assist doctors with decision-making for the management of COVID-19 patients with AKI.


Assuntos
Injúria Renal Aguda/diagnóstico , COVID-19/patologia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Azitromicina/uso terapêutico , Brasil/epidemiologia , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/virologia , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Vasodilatadores/efeitos adversos , Vasodilatadores/uso terapêutico , Adulto Jovem
20.
Virol J ; 18(1): 102, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034765

RESUMO

BACKGROUND: Although more than a year past since COVID-19 was defined, there is no specific treatment yet. Since COVID-19 management differs over time, it is hard to determine which therapy is more efficacious. In this study, we aimed to evaluate the efficacy of the regimen with Favipiravir (FPV) and determine if the timing of FPV addition offers any improvement. METHODS: A retrospective observational case-controlled cohort study was performed between March and September 2020, including adults with COVID-19 in a single-center in Turkey. We categorized patients into age-sex matched three groups, group 1 (n = 48) and group 2 (n = 48) included patients treated with the combination of FPV plus Hydroxychloroquine (HQ) early and late, respectively. Group 3 (n = 48) consisted of patients on HQ monotherapy. In Group 2, if the respiratory or clinic condition had not improved sufficiently, FPV was added on or after day 3. RESULTS: We found that starting FPV early had an impact on PCR negativity and the progression of the disease. 'No progression' was defined as the absence of a new finding in the control radiological examination and the absence of accompanying clinical deterioration. Also, the decrease in C-reactive protein (CRP) was greater in Group 1 than Group 3 (p < 0.001). However, we found that early initiation of FPV treatment did not have a positive effect on the estimated survival time. CONCLUSIONS: According to this retrospective study results, we believe that for better clinical outcomes, FPV treatment should be started promptly to enhance antiviral effects and improve clinical outcomes.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Pirazinas/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Idoso , COVID-19/fisiopatologia , COVID-19/virologia , Estudos de Casos e Controles , Esquema de Medicação , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento
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