Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.363
Filtrar
2.
Syst Rev ; 10(1): 294, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736537

RESUMO

BACKGROUND: Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained. OBJECTIVES: The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs). METHODS: The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used a random-effects model to pool results across studies and Peto's one-step odds ratio (OR) for event rates below 1%. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence. RESULTS: One hundred and six RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95% confidence interval [CI]: 0.76-1.26, 33 trials, 15,942 participants, moderate certainty of evidence). However, there was a moderate certainty of evidence that CQ/HCQ increases the incidence of cardiac complications (RR: 1.62, 95% CI: 1.10-2.38, 16 trials, 9908 participants). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1.63, 95% CI: - 0.4-6.57, 5 trials, 344 participants, very low certainty of evidence). CONCLUSIONS: CQ and HCQ probably do not increase SAEs, with low frequency of these adverse events on malarial and non-malarial conditions. However, they may increase cardiac complications especially in patients with COVID-19. No clear effect of their use on the incidence of retinopathy was observed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020177818.


Assuntos
COVID-19 , Hidroxicloroquina , COVID-19/tratamento farmacológico , Cloroquina/efeitos adversos , Humanos , Hidroxicloroquina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
3.
Trials ; 22(1): 808, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781981

RESUMO

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period. METHODS: We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets. RESULTS: 52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041). CONCLUSIONS: Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331834 . Registered on April 2, 2020.


Assuntos
COVID-19 , Profilaxia Pré-Exposição , Adulto , COVID-19/tratamento farmacológico , Método Duplo-Cego , Humanos , Hidroxicloroquina/efeitos adversos , SARS-CoV-2 , Resultado do Tratamento
4.
Rev Assoc Med Bras (1992) ; 67(7): 979-984, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34817510

RESUMO

OBJECTIVE: With the coronavirus disease 2019 (COVID-19) continuing to spread all over the world, although there is no specific treatment until now, hydroxychloroquine and azithromycin have been reported to be effective in recent studies. Although long-term use of hydroxychloroquine and azithromycin has been reported to cause QT prolongation and malign arrhythmia, there is not enough data about the effect of short-term use on arrhythmia. Therefore, this study aims to assess the effect of hydroxychloroquine alone and hydroxychloroquine + azithromycin on corrected QT (QTc). METHODS: A baseline electrocardiogram and on-treatment baseline electrocardiogram were retrospectively collected in COVID-19 patients who received hydroxychloroquine and/or azithromycin. The QTc interval was calculated, and the baseline and peak QTc intervals were compared. In addition, the peak QTc intervals of monotherapy and combination therapy were compared. RESULTS: Of the 155 patients included, 102 (65.8%) patients were using hydroxychloroquine, and 53 (34.2%) patients were using hydroxychloroquine + azithromycin combination. The use of both hydroxychloroquine alone and hydroxychloroquine + azithromycin combined therapy significantly prolonged the QTc, and the QTc interval was significantly longer in patients receiving combination therapy. QTc prolongation caused early termination in both groups, 5 (4.9%) patients in the monotherapy group and 6 (11.3%) patients in the combination therapy group. CONCLUSION: In this study, patients who received hydroxychloroquine for the treatment of COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc.


Assuntos
COVID-19 , Hidroxicloroquina , Azitromicina/efeitos adversos , COVID-19/tratamento farmacológico , Quimioterapia Combinada , Eletrocardiografia , Humanos , Hidroxicloroquina/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2
6.
J Infect Public Health ; 14(11): 1668-1670, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34627063

RESUMO

Coronavirus disease 2019 (COVID-19), which began in China, caused a global pandemic. Few studies have shown the benefit of hydroxychloroquine (HY) ± azithromycin (AZ) for treating COVID-19. Concerns of QT prolongation and increased risks of torsade's de pointes (TdP) with this combination have been raised since each agent can individually prolong the QT interval. This retrospective, observational study included hospitalized patients treated with HY and AZ from March 2020 to May 2020 at a large community hospital. Serial assessments of the QT interval were performed. Our aim is to evaluate the safety and characterize the change in QTc interval and arrhythmic events in COVID-19 patients treated with HY/AZ. A total of 21 COVID patients who received at least four days of HY and AZ were included in this study. Mean baseline was QTc 403 ms, mean maximum QTc was 440 ms, mean change in QTc was 36 ms. Only one patient (4.8%) developed prolonged QTc > 500 ms. No patient had a change in QTc of 60 ms or more. No patient developed TdP. Fifteen patients (71.4%) had hypoxia on admission, with only two patients (9.5%) required oxygen of 1-2 L at discharge. 80.9% of patients have been discharged home or inpatient rehabilitation.


Assuntos
COVID-19 , Hidroxicloroquina , Azitromicina/efeitos adversos , COVID-19/tratamento farmacológico , Cardiotoxicidade , Humanos , Hidroxicloroquina/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2
7.
Eur Rev Med Pharmacol Sci ; 25(19): 6003-6012, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34661260

RESUMO

OBJECTIVE: The present study aims to identify potential safety signals of chloroquine (CQ) and hydroxychloroquine (HCQ), over the period preceding their repurpose as COVID-19 treatment options, through the analysis of safety data retrieved from the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database. MATERIALS AND METHODS: We performed a disproportionality analysis of FAERS data between the first quarter of 2004 and December 2019 using the OpenVigil2.1-MedDRA software. Disproportionality was quantified using the reporting odds ratio (ROR) and its 95% confidence interval (CIs). The reported mortality of CQ and HCQ was also investigated. RESULTS: The dataset contained 6,635,356 reports. Comparison of the RORs revealed significant differences between CQ and HCQ for the following adverse events: cardiomyopathy, cardiac arrhythmias, retinal disorders, corneal disorders, hearing disorders, headache, hepatic disorders, severe cutaneous reactions, musculoskeletal disorders, and cytopenia. Only CQ was associated with psychotic disorders, suicide, self-injury, convulsions, peripheral neuropathy, and decreased appetite. In multivariable logistic regression, death was more frequently associated with CQ use, advanced age, male sex, co-reported suicide and self-injury, cardiomyopathy, cardiac arrhythmias, and decreased appetite. CONCLUSIONS: Our results confirm previously published evidence and suggest that HCQ has a safer clinical profile compared to CQ, and thus could serve as the drug of choice for future therapeutic purposes.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Cloroquina/efeitos adversos , Hidroxicloroquina/efeitos adversos , United States Food and Drug Administration , COVID-19/tratamento farmacológico , Intervalos de Confiança , Bases de Dados Factuais , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Farmacovigilância , Suicídio , Estados Unidos
8.
Acta Otolaryngol ; 141(11): 989-993, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34694199

RESUMO

BACKGROUND: The effect of Covid-19 infection on nasal mucociliary clearance (MCC) is unknown. AIMS/OBJECTIVES: The aim of this study is to investigate the relationship between Covid-19 and nasal MCC in terms of smoking, Covid-19 symptoms and treatment. METHODS: Thirty-six patients who were hospitalized in the pandemic ward due to Covid-19 and 36 volunteers (Covid-19 negative test result) who presented to the otolaryngology outpatient clinic with non-nasal symptoms were included in this study. The Saccharin test was performed in both groups to evaluate nasal MCC. RESULTS: The patients and control groups were not significantly different in terms of age and gender. The nasal MCC time was significantly higher in the patient group compared to the control group (19.18 ± 10.84 min and 13.78 ± 8.18 min, p = .003). CONCLUSIONS AND SIGNIFICANCE: In this study, we found that Covid-19 prolonged nasal MCC time regardless of age. We suggest that corticosteroids should be included in the treatment of Covid-19, both with its symptom reduction and its positive effect on MCC duration.


Assuntos
COVID-19/fisiopatologia , Depuração Mucociliar/fisiologia , Mucosa Nasal/fisiopatologia , Fumar/fisiopatologia , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Adulto , Amidas/uso terapêutico , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Depuração Mucociliar/efeitos dos fármacos , Pirazinas/uso terapêutico
9.
BMC Health Serv Res ; 21(1): 913, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479563

RESUMO

BACKGROUND: Retinal toxicity is a rare adverse event related to the use of hydroxychloroquine (HCQ). To address this, in 2016, the American Academy of Ophthalmology (AAO) issued guidelines recommending that HCQ not exceed 5 mg/kg/day. We analyzed HCQ prescribing habits at our institution, compared to these guidelines, and used surveys to determine the opinions on these guidelines. We then introduced, in a prospective and non-controlled study, a clinical decision support (CDS) tool into the electronic medical record (EMR) to study how this intervention might affect adherence with or opinions on these guidelines. METHODS: Data were collected pre-intervention (June 2017-January 2019) and post-intervention (March 2019-April 2020). In January 2019 we released our CDS tool. Results were analyzed using descriptive statistics for demographic data and Fisher's exact tests for comparisons of proportions between groups. RESULTS: Pre-intervention, we reviewed 1128 rheumatology charts and 282 dermatology charts. 31.0 and 39.7% respectively (32.8% combined) were prescribed HCQ > 5 .0 mg/kg/day. Post-intervention, we reviewed 1161 rheumatology charts and 110 dermatology charts. 23.0 and 25.5% respectively (23.2% combined) were prescribed HCQ > 5.0 mg/kg/day. Post-intervention, 9.6% fewer patients were prescribed HCQ > 5 mg/kg/day (P < .001). Pre-intervention, we compiled 18 rheumatology surveys and 12 dermatology surveys. Post-intervention, we compiled 16 rheumatology surveys and 12 dermatology surveys. Post-intervention, fewer rheumatologists incorrectly described the AAO weight-based guidelines. Combined, there was an overall reduction but not of statistical significance (P = .47). The majority of providers surveyed believed that the CDS tool was useful (72.2%). CONCLUSIONS: At our academic institution, there remains unfamiliarity with and hesitation to comply with the 2016 AAO guidelines. Prescribed doses often exceed what is recommended in these guidelines. A CDS tool can improve adherence with these guidelines and might improve providers' familiarity with these guidelines.


Assuntos
Antirreumáticos , Dermatologia , Oftalmologia , Reumatologia , Antirreumáticos/efeitos adversos , Registros Eletrônicos de Saúde , Hábitos , Humanos , Hidroxicloroquina/efeitos adversos , Estudos Prospectivos , Estados Unidos
10.
J Assoc Physicians India ; 69(6): 11-12, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34472778

RESUMO

Background, Objective: We studied the effectiveness and safety of Hydroxychloroquine (HCQ) preexposure prophylaxis against COVID-19 in Healthcare workers (HCWs) previous studies being inconclusive due to small sample and lack of risk stratification Design and setting: Prospective, observational, multicenter cohort study in 44 hospitals in 17 Indian states during May-Sept 2020 Participants: 12089 Consenting Doctors, nurses, ancillary staff likely exposed to COVID-19 patients irrespective of whether taking HCQ preexposure prophylaxis (4257) or not(7826) participated,(in 6 data missing) Measurements: Data was collected on a self administered online questionnaire. Statistical analysis was done on SPSS version 20. RESULTS: Age above 45 years, diabetes, hypertension, history of COVID contact were independent risk factors for COVID positivity. HCQ intake did not show an independent association. However, when adjusted for other risk factors, HCQ dose as per Government recommendations, 2-3, 4-5 and 6 or more weeks reduced the probability of COVID positivity by 34%, 48%, 72% respectively. COVID free median survival time was higher in non-diabetics, non-hypertensives, persons below 45 years, with no prior exposure to COVID case and those who took HCQ for more than 6 weeks With modeling extent of risk reduction under different scenarios of risk and HCQ intake was 1-65% . Major adverse events reported were GI disorder, palpitation, giddiness and 140 persons discontinued due to adverse events. LIMITATIONS: Limitation of self reporting by HCWs in online form, minimized by specified options,mandatory fields and telephonic verificationConclusion: The study examined individual risk factors including site variations and found that HCQ 800 mg loading followed by 400 mg weekly, dose for more than 2 weeks, reduced the risk of COVID-19, in HCWs, and is a useful option in low resource settings till vaccines are made accessible to all. TRIAL REGISTRATION: CTRI/2020/05/025183.


Assuntos
COVID-19 , Hidroxicloroquina , COVID-19/tratamento farmacológico , Estudos de Coortes , Pessoal de Saúde , Humanos , Hidroxicloroquina/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Resultado do Tratamento
11.
Trials ; 22(1): 638, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535165

RESUMO

BACKGROUND: Sleep apnea and coronary artery disease are prevalent and relevant diseases. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. Intermittent hypoxia, caused by sleep apnea, leads to inflammation and consequent endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function can help prevent cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the potential cardioprotective effect of these drugs in patients without autoimmune diseases is not clear. Hydroxychloroquine (HCQ) is an immunomodulator used to treat rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and blood glucose levels and has antithrombotic effects. The drug is inexpensive and widely available. Adverse effects of HCQ are rare and occur more frequently with high doses. OBJECTIVE: In this randomized clinical trial, the effect of HCQ treatment on endothelial function will be tested in seniors with sleep apnea. METHODS: We will recruit participants over the age of 65 and with moderate-severe sleep apnea from an ongoing cohort. We chose to use this sample already evaluated for sleep apnea for reasons of convenience, but also because the elderly with sleep apnea are vulnerable to heart disease. Endothelial function will be assessed by examining flow-mediated dilation of the brachial artery, the gold standard method, considered an independent predictor of cardiovascular events in the general population and by peripheral arterial tonometry, the most recent and most easily obtained method. Hydroxychloroquine will be used at a dose of 400 mg/daily for 8 weeks. DISCUSSION: Our study aims to obtain evidence, albeit preliminary, of the efficacy of hydroxychloroquine in improving endothelial function and reducing cardiovascular risk markers. If the improvement occurs, we plan to design a randomized multicenter clinical trial to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04161339 . Registered on November 2019.


Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Síndromes da Apneia do Sono , Idoso , Humanos , Hidroxicloroquina/efeitos adversos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/tratamento farmacológico , Resultado do Tratamento
12.
Z Rheumatol ; 80(8): 699-706, 2021 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-34535818

RESUMO

Inflammatory rheumatic diseases often affect women of childbearing age, for whom pregnancy is still associated with increased risks. At the same time, we are gaining more and more insights into risk factors and preventive strategies, enabling almost all women to have successful pregnancies with few adverse outcomes. The cornerstones are planning of the pregnancy under effective disease control and the modification of individual risk factors. Hydroxychloroquine is once again coming into focus as a compound with multiple positive effects. Recommendations published by the American College of Rheumatology (ACR) provide a practical overview of the evidence. Based on the current state of knowledge, rheumatologists can make a lasting contribution to a positive pregnancy outcome for mother and child.


Assuntos
Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Doenças Reumáticas , Reumatologia , Feminino , Fertilidade , Humanos , Hidroxicloroquina/efeitos adversos , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Doenças Reumáticas/tratamento farmacológico
14.
Rev Cardiovasc Med ; 22(3): 1063-1072, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565108

RESUMO

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.


Assuntos
Assistência Ambulatorial , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Intervenção Médica Precoce , Hidroxicloroquina/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , COVID-19/diagnóstico , COVID-19/mortalidade , Quimioterapia Combinada , Feminino , França , Hospitalização , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
BMC Infect Dis ; 21(1): 805, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384388

RESUMO

BACKGROUND: Since the COVID-19 pandemic, several therapeutic agents have been used in COVID-19 management. However, the results were controversial. Here, we aimed to evaluate the efficacy and safety of hydroxychloroquine (HCQ)/chloroquine (CQ) in COVID-19. METHODS: We retrospectively reviewed the medical charts of patients with COVID-19 admitted to an inpatient ward in Wuhan from 2020/Feb/08 to 2020/Mar/05. Patients with HCQ/CQ and age, gender, disease severity matched ones without HCQ/CQ were selected at a 1:2 ratio. The clinical, laboratory and imaging findings were compared between these two groups. The multivariate linear regression analysis was performed to identify the factors that might influence patients' virus shedding periods (VSPs). RESULTS: A total of 14 patients with HCQ/CQ and 21 matched ones were analyzed. The HCQ/CQ treatment lasted for an average of 10.36 ± 3.12 days. The mean VSPs were longer in the HCQ/CQ treatment group (26.57 ± 10.35 days vs. 19.10 ± 7.80 days, P = 0.020). There were 3 patients deceased during inpatient period, two patients were with HCQ/CQ treatment (P = 0.551). In the multivariate linear regression analysis, disease durations at admission (t = 3.643, P = 0.001) and HCQ/CQ treatment (t = 2.637, P = 0.013) were independent parameters for patients' VSPs. One patient with CQ had recurrent first-degree atrioventricular block (AVB) and obvious QTc elongation, another one complained about dizziness and blurred vision which disappeared after CQ discontinuation. One patient with HCQ had transient AVB. CONCLUSIONS: In summary, we identify that the HCQ/CQ administration is not related to less mortality cases at later phase of COVID-19. More studies are needed to explore whether HCQ/CQ treatment would lead to SARS-Cov-2 RNA clearance delay or not.


Assuntos
COVID-19 , Hidroxicloroquina , COVID-19/tratamento farmacológico , Cloroquina , Humanos , Hidroxicloroquina/efeitos adversos , Pandemias , RNA Viral , Estudos Retrospectivos , SARS-CoV-2
16.
Int J Clin Pract ; 75(11): e14710, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34370370

RESUMO

AIMS: Hydroxychloroquine (HCQ) is using as a repurposed drug in considerable proportion of COVID-19 patients. However, being a substrate of cytochrome P450 (CYP) enzymes of CYP3A4/5, CYP2C8 and CYP2D6, the safety and efficacy of this drug may be affected by the coadministration of respective CYP inhibitors, substrates or inducer drugs. It was aimed to identify potential clinically significant drug-drug interaction (DDI) pairs of HCQ. METHODS: Inhibitors, substrates and inducer drugs lists of CYP enzymes of interest from international well-recognised evidence-based drug interaction resources were used to identify potential clinically significant pharmacokinetic DDI pairs of HCQ. RESULTS: Among 329 identified interacting drugs that predicted to cause clinically significant DDIs of HCQ, 45 (13.7%), 43 (13.1%) and 123 (37.4%) unique DDI pairs were identified from the FDA, Stockley's and Flockhart lists, respectively. Of interest, 55 (16.7%) DDI pairs were recognised by all three resources. At least, 29 (8.8%) severe DDI pairs were identified predicted to cause severe toxicity of HCQ in patients with COVID-19. When comparing these interactions with Liverpool DDI lists, it was found that out of 423 total interactions, 238 (56.3%) and 94 (22.2%) unique DDI pairs were identified from all three resources and Liverpool DDI lists, respectively. Of interest, only three (0.7%) DDI pairs were recognised by both the three international resources and Liverpool DDI lists of HCQ. CONCLUSION: Using HCQ has clinical debate whether it should or should not continue in COVID-19 patients, however, potential clinically significant DDIs identified in this study may optimise safety or efficacy of HCQ in considerable proportion of patients.


Assuntos
COVID-19 , Hidroxicloroquina , COVID-19/tratamento farmacológico , Interações Medicamentosas , Humanos , Hidroxicloroquina/efeitos adversos
17.
Int J Clin Pract ; 75(11): e14737, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34388303

RESUMO

BACKGROUND: Whether hydroxychloroquine (HCQ) use could reduce lesser risk of bacterial infections is unknown. We aimed to conduct a retrospective cohort propensity-matching study to investigate the association between HCQ use and the incidence of bacterial pneumonia in rheumatic patients. METHODS: The Longitudinal Health Insurance Database (LHID) from Taiwan National Health Insurance Research Database (NHIRD) of 23 million Taiwanese populations was used. We included patients who were newly diagnosed with rheumatic and immune disease (ICD-9-CM codes 696.0, 710, 714) within 2000-2012. HCQ users and non-users were then matched according to age, sex, urbanisation level, monthly income, comorbidities and medications in the ratio of 1:1 by the propensity score matching. Cox proportional hazard model was used to evaluate the risk of bacterial pneumonia in rheumatic patients who used HCQ and who did not use HCQ. RESULTS: There were total 3285 patients with rheumatic and immune disease enrolled. The cumulative incidence curve of patients with the use of HCQ sulphate had no difference to that of patient without the use of HCQ sulphate in propensity score-matched cohort, (Log-rank test: P = .5). However, patients who used HCQ sulphate for more than 1400 average use days had a lesser risk of bacterial pneumonia (adjusted HR = 0.55, 95% CI = 0.35, 0.89) in the cohort matched, with regarding HCQ non-users as a reference. CONCLUSION: Rheumatic patients taking HCQ had no overall significant differences of bacterial pneumonia incidences compared with rheumatic patients not taking HCQ. HCQ used more than >1400 days or lupus patients using HCQ was associated with lower risk of bacterial pneumonia.


Assuntos
Antirreumáticos , Pneumonia Bacteriana , Antirreumáticos/efeitos adversos , Estudos de Coortes , Humanos , Hidroxicloroquina/efeitos adversos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos
18.
Artigo em Inglês | MEDLINE | ID: mdl-34360449

RESUMO

The purpose of this study is to evaluate the relationship between hydroxychloroquine (HCQ) and diabetic retinopathy (DR) via the national health insurance research database (NHIRD) of Taiwan. All patients with newly diagnosed type 2 diabetes (n = 47,353) in the NHIRD (2000-2012) were enrolled in the study. The case group consists of participants with diabetic ophthalmic complications; 1:1 matching by age (±1 year old), sex, and diagnosis year of diabetes was used to provide an index date for the control group that corresponded to the case group (n = 5550). Chi-square test for categorical variables and Student's t-test for continuous variables were used. Conditional logistic regression was performed to estimate the adjusted odds ratio (aOR) of DR. The total number of HCQ user was 99 patients (1.8%) in the case group and 93 patients (1.7%) in the control group. Patients with hypertension (aOR = 1.21, 95% CI = 1.11-1.31) and hyperlipidemia (aOR = 1.65, 95% CI = 1.52-1.79) significantly increased the risk of diabetic ophthalmic complications (p < 0.001). Conversely, the use of HCQ and the presence of rheumatoid diseases did not show any significance in increased risk of DR. HCQ prescription can improve systemic glycemic profile, but it does not decrease the risk of diabetic ophthalmic complications.


Assuntos
Antirreumáticos , Artrite Reumatoide , Diabetes Mellitus Tipo 2 , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hidroxicloroquina/efeitos adversos , Fatores de Risco , Taiwan/epidemiologia
19.
J Healthc Eng ; 2021: 5556207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336157

RESUMO

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.


Assuntos
Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , Mortalidade Hospitalar , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , COVID-19/fisiopatologia , Análise por Conglomerados , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacos , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Complement Ther Med ; 62: 102768, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34418550

RESUMO

OBJECTIVES: To study the efficacy and safety of Withania somnifera (WS, Ashwagandha) in the prophylaxis against COVID-19 in high risk health care workers (HCW) in comparison to hydroxychloroquine (HCQ). To evaluate the general physical and mental health benefits of Ashwagandha. METHODS: A 16 week randomized prospective, open-label, parallel efficacy, two arm, multi-centre study. The primary efficacy measure was 'failure of prophylaxis' as confirmed COVID-19 by quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) at any time during the study period. This study on 400 participants from three centres was designed to establish non-inferiority for WS to HCQ for prophylaxis against COVID-19 at 80 % power and significance p < 0.025, one-sided. The interim analysis was carried out on 160 participants after completion of 8 weeks. RESULTS: Participants in both the arms were well-matched at the baseline characteristics. Forty participants in the HCQ group and 26 participants in the WS group reported mild AE. The symptoms of confirmed COVID-19 were found to be 3.7 % (95 % CI 1.3-10.5 %) in the HCQ and 1.3 % (95 % CI 0.02-6.7 %) in the WS arm amongst the first 160 participants completing 8 weeks. CONCLUSION: Our intent was to explore a safer option to HCQ. We report that WS was not found inferior to HCQ and its efficacy was within the 15 % non-inferiority margin set a priori. WS as an immunomodulator has other clinical benefits including reducing mental stress. The final report of this study is expected by end of August 2021.


Assuntos
COVID-19 , Withania , Adulto , COVID-19/prevenção & controle , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Withania/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...