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Objetivo: verificar a toxicidade do uso medicamentoso da hidroxicloroquina em pacientes. Metodologia: trata-se de uma revisão integrativa de literatura com uma avaliação documental e abordagem descritiva nas bases de dados eletrônicos LILACS, SCIELO e MEDLINE-PUBMED, usando diferentes combinações de descritores, publicados entre os anos de 2015 a 2023, nos idiomas inglês, espanhol e português. Resultados: este estudo revisou 117 artigos científicos, dos quais 67 foram nos Estados Unidos. Além disso, o ano de 2020 obteve 21,2% a mais de publicações em relação ao ano de 2015. Desse modo, notou-se que a prevalência de 44,07% das lesões pelo uso da hidroxicloroquina foi oftálmica, 35,5% foram cardíacas, 14,4%, dermatológicas e as outras demais porcentagens restantes. Conclusão: portanto, os resultados obtidos confirmam a toxicidade da hidroxicloroquina no uso de tratamentos adjacentes.
Introduction: Tto verify the toxicity of the use of hydroxychloroquine medications in patients. Methods: it is an integrative literature review with a documentary evaluation and descriptive approach conducted in the electronic databases LILACS, SCIELO, and MEDLINE-PUBMED, using different combinations of descriptors, published between 2015 and 2023 in English, Spanish, and Portuguese. Results: this study reviewed 117 scientific articles, with 67 of them conducted in the United States. Besides that, 2020 had a 21.2% increase in publications compared to 2015. It was observed that 44.07% of the injuries caused by hydroxychloroquine use were ophthalmic, 35.5% were cardiac, 14.4% were dermatological, and the remaining percentages accounted for other types of injuries. Conclusion: therefore, the obtained results confirm the toxicity of hydroxychloroquine in the use of adjacent treatments.
Subject(s)
Toxicity , Hydroxychloroquine摘要
Originally used as an antimalarial drug,hydroxychloroquine is now widely used in the treatment of rheumatic immune diseases due to its cost-effectiveness,safety,and efficacy.In addition to its immunomodulatory effects,hydroxychloroquine also exhibits anti thrombotic,anti-hypolipidemic,and anti-hypoglycemic properties.Hydroxychloroquine blood levels are correlated with clinical outcomes and adverse reactions,and can reflect patient compliance.However,due to the complex pharmacokinetic profile of hydroxychloroquine,significant inter-individual differences in blood concentration exist even with the administration of the same dosage.This study investigates the factors affecting the blood concentration of hydroxychloroquine in terms of physiological factors,pathological factors,metabolic enzyme gene polymorphisms,and drug-related factors.The aim is to provide a reference for rational clinical use and the development of individualized dosing.
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Objective@#To investigate the application of mycophenolate mofetil (MMF) in oral mucosal pemphigoid and provide a clinical reference.@*Methods@#One case of glucocorticoids combined with MMF in the treatment of oral mucosal pemphigoid was reported, and the clinical application of MMF in oral mucosa-related bullous diseases was discussed.@*Results@#One patient with a clinical diagnosis of “oral mucosal pemphigoid” was treated with methylprednisolone (36 mg, qd, morning dose) or combined hydroxychloroquine sulfate (0.1 g/time, bid) and thalidomide capsules (50 mg, qd, bedtime) and other drugs. The patient’s disease was slowly controlled but prone to recurrence. The treatment regimen was immediately adjusted, i.e., methylprednisolone (36 mg, qd, morning dose) was combined with MMF (0.5 g/time, bid) for 2 weeks, which resulted in ideal lesion healing control. After 8 weeks of methylprednisolone combined with MMF, the dose of methylprednisolone was gradually reduced to 12 mg, qd, and MMF was reduced to 0.5 g, qd, the patient’s symptoms improved significantly, and no obvious lesions were found in the mouth. The dose was then reduced and maintained according to the principle of pemphigoid treatment. Methylprednisolone (8 mg, qd, morning dose) and MMF (0.5 g, qd) have been used for 6 months of maintenance treatment, and they are still being followed up. As yet, the patient’s condition is stable without obvious lesions and new blisters, and no obvious side effects have been observed. A review of the literature shows that MMF is widely used in the field of dermatology to treat a variety of immune diseases, such as connective tissue diseases and autoimmune blistering diseases. According to the reports of adverse reactions to MMF, digestive system reactions are the most common adverse reactions; therefore, patients with active gastrointestinal diseases should be treated with caution, followed by bone marrow suppression, and it is recommended to monitor liver function and blood routine in patients using MMF. The safety and efficacy of MMF for treating pemphigoid involving the skin have been reported in the literature, but oral mucosal doctors still lack experience for treating mucous membrane pemphigoid.@*Conclusions@#As a new immunosuppressant, MMF has high safety and no obvious side effects and can be considered as a combination adjuvant drug for patients with severe clinical disease and refractory oral mucosal pemphigoid.
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Objective:To evaluate the therapeutic effect of intense pulsed light on rosacea.Methods:From December 2022 to April 2023, the Dermatology Department of the Affiliated Hospital of Shaanxi University of Chinese Medicine searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, CBM and other Chinese and English databases to collect clinical randomized controlled studies on intense pulsed light treatment of rosacea for ameta-analysis.Results:A total of 559 patients were included in 6 randomized controlled trials. The efficacy of the combination of strong pulsed light and medication in the treatment of rosacea was significantly better than that of medication alone ( Z=6.15, P<0.001). After subgroup analysis, the combination of strong pulsed light and tetracycline drugs was more effective in treating rosacea than using tetracycline drugs alone ( Z=3.17, P<0.05). The efficacy of the combination of strong pulsed light and minocycline in the treatment of rosacea was better than that of minocycline alone ( Z=2.37, P<0.05), and clinical evaluation showed the improvements of erythema, papules, and pustules. The differences in scores for itching and capillary dilation were statistically significant ( P<0.05). Conclusions:The efficacy of intense pulsed light therapy for rosacea is definite, and its combination with topical or oral medication is superior to that of medication alone. However, the stability of the effect needs to be confirmed by more high-quality randomized controlled trials.
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OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples （50 μL） were precipitated with 200 μL methanol containing the internal standard （100 ng/mL chloroquine）， and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution （phase A） and methanol （phase B） at gradient elution of 0.35 mL/min. The injection volume was 2 μL， and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 （bepotastine）， m/z 336.3→247.1 （hydroxychloroquine）， and m/z 320.2→247.2 （chloroquine）. The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL（ r＝0.999）， and hydroxychloroquine was 50-1 000 ng/mL （r＝0.998）. The intra-assay and inter-assay precisions were both ≤15%， and the accuracy， extraction recovery， matrix effect， and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed， after 2 h and 14 h， the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL； those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL， respectively. The relative infant doses were 1.83% and 0.56%， respectively. CONCLUSIONS The established method is simple， rapid， and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.
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OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples （50 μL） were precipitated with 200 μL methanol containing the internal standard （100 ng/mL chloroquine）， and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution （phase A） and methanol （phase B） at gradient elution of 0.35 mL/min. The injection volume was 2 μL， and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 （bepotastine）， m/z 336.3→247.1 （hydroxychloroquine）， and m/z 320.2→247.2 （chloroquine）. The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL（ r＝0.999）， and hydroxychloroquine was 50-1 000 ng/mL （r＝0.998）. The intra-assay and inter-assay precisions were both ≤15%， and the accuracy， extraction recovery， matrix effect， and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed， after 2 h and 14 h， the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL； those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL， respectively. The relative infant doses were 1.83% and 0.56%， respectively. CONCLUSIONS The established method is simple， rapid， and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.
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COVID-19 pandemic changed the face of global health and brought about new issues in global health security and economy. The World Health Organization published guidelines for clinical management of COVID-19 four months after declaration of COVID-19 as a pandemic. Scholarly reviews and studies from member states within WHO AFRO reveals significant deviation from the WHO published protocols on COVID-19. Assessment of national treatment protocols of 30 of 47 WHO AFRO member states showed widespread inappropriate use of antimicrobial agents for patients, which may worsen the global and concerning threat of antimicrobial resistance. There is need for adopting interventions that optimize antimicrobial use in the context of pre- and post-pandemic preparedness to ensure long-term effectiveness and sustainability for antimicrobials. Treatment guidelines are to be adopted or adapted depending on best clinical evidence available. Non-compliance with guidelines might lead to mismanagement of infectious diseases with attendant negative consequences including antimicrobial resistance and misdirection of critical resources and supplies amongst others.
La pandémie de COVID-19 a changé le visage de la santé mondiale et a soulevé de nouveaux problèmes en matière de sécurité sanitaire et d'économie mondiale. L'Organisation mondiale de la santé a publié des lignes directrices pour la gestion clinique du COVID-19 quatre mois après la déclaration du COVID-19 comme pandémie. Les revues scientifiques et les études des États membres de l'OMS AFRO révèlent un écart significatif par rapport aux protocoles publiés par l'OMS sur le COVID-19. L'évaluation des protocoles nationaux de traitement de 30 des 47 États membres de l'OMS AFRO a révélé une utilisation inappropriée et généralisée d'agents antimicrobiens chez les patients, ce qui pourrait aggraver la menace mondiale et préoccupante de résistance aux antimicrobiens. Il est nécessaire d'adopter des interventions qui optimisent l'utilisation des antimicrobiens dans le contexte de la préparation pré et post-pandémique afin de garantir l'efficacité et la durabilité à long terme des antimicrobiens. Les directives thérapeutiques doivent être adoptées ou adaptées en fonction des meilleures preuves cliniques disponibles. Le non-respect des directives pourrait conduire à une mauvaise gestion des maladies infectieuses avec des conséquences négatives qui en découlent, notamment la résistance aux antimicrobiens et une mauvaise orientation des ressources et fournitures essentielles, entre autres.
Subject(s)
Therapeutics , Clinical Protocols , COVID-19 , Bacterial Infections , Guideline Adherence , Pandemics摘要
Mesmo em emergências sanitárias, quando terapias experimentais são empregadas, é importante prezar pela segurança e eficácia no uso de medicamentos, e a análise de prescrições médicas é uma das maneiras de monitorar aspectos de segurança. Objetivo: Quantificar e classificar as interações medicamentosas potenciais com hidroxicloroquina de acordo com o riscoem prescrições de pacientes com COVID-19 em pacientes com COVID-19 em uso de hidroxicloroquina admitidos em uma unidade de terapia intensiva de um Hospital de Ensino.Metodologia:Este estudo transversal baseou-se na análise de 162 prescrições de 38 pacientes admitidos em uma unidade de terapia intensiva de um Hospital de ensino entre abril e junho de 2020.O Micromedex® e o UpToDate® foram as bases de dados de apoio à conduta clínica utilizadas para estabelecer as interações medicamentosas potenciais. Resultados:A média de dias de internamento foi de 16,1 ± 14,0 e a média de dias em uso de hidroxicloroquina foi de 4,26 ± 1,74. 87,14% das prescrições apresentaram interações medicamentosas potenciais e a mais comum foi entre hidroxicloroquina e azitromicina. 76,4% das prescrições analisadas apresentaram interações medicamentosas potenciais com hidroxicloroquina. 73,5% das prescrições tiverampelo menos uma interação medicamentosa potencial entre medicamentos que prolongam o intervalo QT. Conclusões: Tendo em vista os riscos da exposição de pacientes críticos às interações medicamentosas, este estudo demonstra a necessidade de fortalecer nas instituições hospitalares a cultura de monitoramento de parâmetros de segurança e eficáciano uso de medicamentos, inclusive em terapias experimentais com a utilização de medicamentos off-labelpara minimizar riscos e ampliar possíveis benefícios (AU).
Even in health emergencies, when experimental therapies are employed, it is important to ensure the safety and efficacy of medicines, and the analysis of medical prescriptions is one of the ways to monitor safety aspects.Objective: Quantify and rank potential drug interactions with hydroxychloroquine according to risk in prescriptions of COVID-19 patients taking hydroxychloroquine admitted to an intensive care unit of a TeachingHospital.Methodology: This cross-sectional study was based on the analysis of 162 prescriptions of 38 patients admitted to an intensive care unit of a teaching hospital between April and June 2020. Micromedex® and UpToDate® were the clinical practice support databases used to establish potential drug interactions. Results: The mean number of days of hospitalization was 16.1 ± 14.0 and the mean number of days of days on hydroxychloroquine was 4.26 ± 1.74. 87.14% of the prescriptions presented potential drug interactions and the most common was between hydroxychloroquine and azithromycin. 76.4% of the analyzed prescriptions had potential drug interactions with hydroxychloroquine. 73.5% of prescriptions had at least one potential drug interaction between drugs that prolong the QT interval. Conclusions: In view of the risks of exposure of critically ill patients to drug interactions, this study interactions, this study demonstrates the need to strengthen in hospital institutions the culture of institutions the culture of monitoring safety and efficacy parameters in the use of medicines, including experimental therapies with the use of off-label drugs to minimize risks and increase possible benefits (AU).
Aunque en médio aemergencias sanitarias, cuando son empleadas terapias experimentales, es importante estimar la seguridad y eficacia en el uso de los medicamentos, y el análisis de prescripciones es una de las formas de acompanhar los aspectos de seguridad. Objetivo:Cuantificar y clasificar las interaciones farmacologicas potenciales con hidroxicloroquina de acuerdo com el riesgo em prescripciones de pacientes com Covid-19 em uso de hidroxicloroquina andmitidos em unidad de terapia intensiva de um Hospital Docente. Metodología: Este estudio transversal se asienta en el análisis de 162 prescripciones de 38 pacientes admitidos em uma unidad de terapia intensiva de um Hospital Docente entre abril y junio de 2020. El Micromedex®ï¸y el UpToDate®ï¸fueron las bases de datos de apoyo a la actuación clínica utilizadas para establecer las interacciones farmacológicas potenciales. Resultados:El promedio de días de internamiento fue de 16,1 ± 14,0 y el promedio de días en uso hidroxicloroquina fuede 4,26 ± 1,74. 87,14% de las prescripciones presentaron interacciones farmacológicas potenciales y la más común fue entre hidroxicloroquina y azitromicina. 76,4% de las prescripciones analizadas presentaron interaciones farmacológicas com hidroxicloroquina. 73,5% de las prescripciones tuvierion por lo menos uma interacción farmacológica potencial entre medicamentos que prolongam el intervalo QT. Conclusiones:Tenendo a la vista los riesgos de la exposición de pacientes críticos a las interaciones farmacológicas, este estudio demuestra la necesidad de reforzar em las instituiciones hospitalarias la cultura de monitoreo de parâmetros de seguridade y eficacio em el uso de medicamentos, incluso en terapias experimentales con utilización de medicamentos off-label, para minorar riesgos y ampliar los posibles beneficios (AU).
Subject(s)
Humans , Male , Female , Drug Utilization , Prescriptions , COVID-19/transmission , Hydroxychloroquine/analysis , Intensive Care Units , Cross-Sectional Studies/methods , Data Interpretation, Statistical , Drug Interactions , Hospitals, Teaching摘要
Objetivos. Caracterizar los eventos adversos (EA) asociados a hidroxicloroquina (HQ), azitromicina (AZI), tocilizumab (TOB) e ivermectina (IVM) prescritos como «fuera de etiqueta» en el tratamiento de pacientes hospitalizados por la COVID-19. Materiales y métodos. Se realizó un análisis secundario transversal de la base de datos del sistema de farmacovigilancia del Seguro Social de Salud del Perú (EsSalud) de las notificaciones de EA a HQ, AZI, TOB e IVM provenientes del Hospital Nacional Edgardo Rebagliati Martins de abril a octubre del 2020. Se revisaron las historias clínicas digitales, se estimaron las tasas de reporte de EA y se evaluaron sus características por tipo de fármaco, tiempo de aparición, tipo por órgano-sistema afectado, gravedad y causalidad. Resultados. Se identificaron 154 notificaciones que describen un total de 183 EA posiblemente relacionados con HQ, AZI, TOB e IVM, siendo 8% la tasa de reporte de EA. La mediana de tiempo de aparición de EA fue de 3 días (RIC: 2-5). La mayoría fueron cardiovasculares, destacándose la prolongación del intervalo QT. Se observaron EA hepatobiliares principalmente asociados a TOB. La mayoría de los casos fueron moderados, no obstante, el 10,4% fue grave. Conclusiones. Se identificaron EA potencialmente asociados al uso de HQ, AZI, TOB e IVM contra la COVID-19, siendo los más frecuentes los de tipo cardiovasculares. A pesar de que la AZI, HQ e IVM poseen perfiles conocidos de seguridad, su empleo en la COVID-19 podría incrementar la aparición de EA por los factores de riesgo propios de esta infección. Se sugiere reforzar la vigilancia, especialmente, de TOB.
Objective. To characterize the adverse events (AEs) related to the off-label use of hydroxychloroquine (HQ), azithromycin (AZI), tocilizumab (TOB) and ivermectin (IVM) for the treatment of COVID-19 in hospitalized patients. Materials and Methods. We conducted a secondary cross-sectional analysis of the Peruvian Social Health Insurance (EsSalud) pharmacovigilance system database of AE notifications to HQ, AZI, TOB and IVM in the Edgardo Rebagliati Martins National Hospital from April to October 2020. Information was collected from digital medical records. We estimated AE reporting rates and evaluated their characteristics by drug type, time of occurrence, type by the affected organ-system, severity and causality. Results. We identified 154 notifications describing a total of 183 AE possibly related to HQ, AZI, TOB and IVM; the reporting rate was 8%. The median time of AE occurrence was 3 days (IQR: 2-5). Most were cardiovascular events; prolongation of the QT interval was the most frequent. Hepatobiliary AEs were mainly associated with TOB. Most cases were moderate, however, 10.4% were severe. Conclusions. We found AEs potentially associated with the use of HQ, AZI, TOB and IVM against COVID-19; cardiovascular events were the most frequent. Although AZI, HQ and IVM have known safety profiles, their use against COVID-19 could increase the occurrence of AE due to the risk factors inherent to this infection. Surveillance systems must be improved, especially those for TOB.
Subject(s)
Humans , Male , Female , Insurance, Health摘要
Objective:To evaluate whether there are changes in cone cells in patients with pre-clinical hydroxychloroquine (HCQ) retinopathy using an adaptive optics (AO) retinal camera.Methods:A retrospective case-control study. From May 2020 to July 2020, 46 patients who were treated in Department of Rheumatism and Immunology, Hainan Hospital of PLA General Hospital with rheumatic immune diseases were included. All patients had a history of HCQ use and no obvious abnormality was found in fundus examination; 105 healthy people with similar demographic characteristics without a history of hydroxychloroquine were recruited as the control group were included. All subjects received the routine ophthalmological examination including best corrected visual auity (BCVA), spectral-domain optical coherence tomography (SD-OCT), Fundus autofluorescence (FAF), visual field, endoscopy of the cornea, and the measurement of axial length (AL). The BCVA was performed with the Snellen visual acuity chart, and the result was converted to logarithmic minimum angle of resolution (logMAR) visual acuity for statistic. Among the 46 cases, 6 cases were males and 40 cases were females. Age was (42.02±13.81) years old; logMAR BCVA was 0.063±0.015; AL was (23.95±0.726) mm. Visual field, macular SD-OCT, FAF examination showed no abnormality. The average cumulative dose of HCQ was 522.60 (6-1 728) g. rtx1 AO retinal camera was used to collect fundus images of subjects in four quadrants above the retina, nasal side, lower side and temporal side with 3°centrifugation from the fovea in both eyes. The cone density, cone spacing, cone arrangement regularity and the proportion of the nearest cones with 6 (nn=6) were measured in the four quadrants. The density of cone cells between the left and right eyes in case group and control group were compared by paired t test. The density and spacing of cone cells in each quadrant were compared by t test of two independent samples. Results:Compared with the control group, the cone cell density in the four quadrants of the left eye and the nasal, superior and inferior sides of the right eye in the case group was significantly decreased, and the difference was statistically significant ( t=4.247, 2.107, 4.884, 2.254, 2.643, 4.445, 4.116; P<0.05). The cone spacing in the nasal and temporal sides of the left eye of the patients in the case group was significantly larger than that in the control eye, with statistical significance ( t=2.750, 3.318; P<0.05). Compared with the control group, the regulatign of cone cell arrangement in the left temporal side of the right and left eye in the case group were significantly reduced, the difference was statistically significant ( P=0.002, 0.011). The proportion of nn=6 in the inferior and temporal sides of the right eye decreased significantly in the case group, and the difference was statistically significant ( P=0.006, 0.032). Conclusion:AO retinal imaging can detect the changes of cone cells in the early clinical stage of HCQ retinopathy.
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Objective:To evaluate the effect of perioperative application of hydroxychloroquine on the prognosis of patients undergoing cardiac surgery.Methods:All SLE patients in the Department of Cardiovascular Surgery of the First Affiliated Hospital of Zhengzhou University who took hydroxychloroquine and glucocorticoid for more than 7 days before operation were enrolled in the observation group(28 cases), including 3 males and 25 females, aged(38.3±8.2)years old. Patients who did not use hydroxychloroquine but only used glucocorticoid before operation were included in the control group(24 cases), including 2 males and 22 females, aged(37.9 ±9.8)years old. There was no significant difference in preoperative clinical data between the two groups in terms of sex, age, BMI, course of systemic lupus erythematosus, hemoglobin, albumin, C-reactive protein, ALT, serum creatinine, ejection fraction, diabetes, hypertension, hyperlipidemia, smoking, alcoholism, preoperative atrial arrhythmia, ventricular arrhythmia, atrioventricular block and so on. The constituent ratio of preoperative operation plan was basically the same between the two groups. The postoperative complications and survival of the two groups were compared.Results:There was no significant difference in early clinical indexes between the two groups, such as cardiopulmonary bypass time( t=0.12, P=0.19), chest drainage volume( t=0.30, P=0.77), second thoracotomy hemostasis( χ2=1.17, P=0.46). There was no significant difference in drug-related complications such as new retinopathy, myocardial concentric hypertrophy, atrial arrhythmia( χ2=1.27, P=0.26), ventricular arrhythmia( χ2=0.98, P=0.32), atrioventricular block( χ2=0.06, P=0.82) and other drug-related complications between the observation group and the control group. There was no significant difference between the two groups in postoperative acute heart failure( χ2=1.17, P=0.28), acute liver insufficiency( χ2=1.17, P=0.28), sternal infection and IABP use( χ2=0.47, P=0.50). Compared with the control group, the incidence of acute renal insufficiency after operation was lower in the observation group( χ2=4.51, P=0.04). The incidence of new postoperative pneumonia was lower( χ2=8.26, P=0.01). The length of postoperative antibiotic use, the length of postoperative ICU hospital stay, the postoperative hospital stay and the total cost of hospitalization in the observation group were significantly less than those in the control group( z=2.71, 2.09, 2.02, 2.02, P=0.01, 0.04, 0.04, 0.04). Compared with the control group, the in-hospital mortality rate of patients in the observation group was lower than that in the control group(3.6% vs. 12.5%, χ2=0.47, P=0.50), and the 6-month and 1-year survival rates of the observation group were higher than those of the control group(92.9% vs.83.3%, 92.9% vs.79.2%; χ2=0.41, 2.17; P=0.53, 0.34), but the difference was not statistically significant. Conclusion:Perioperative administration of hydroxychloroquine can significantly reduce the incidence of postoperative acute renal insufficiency and pneumonia, reduce the duration of postoperative antibiotic use, postoperative ICU hospital stay, postoperative hospital stay, and the cost of hospitalization. Hydroxychloroquine may reduce the in-hospital mortality and improve the long-term survival rate after cardiac surgery, but long-term large sample clinical studies are still needed.
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Hydroxychloroquine is widely used in a variety of autoimmune diseases. However, long-term use of hydroxychloroquine can cause severe retinopathy, which has a complex pathogenic mechanism and diverse clinical manifestations, mainly manifested as photoreceptor and retinal pigment epithelial damage and irreversible vision loss. Identifying damage before retinitis pigment epithelium lesions preserve central vision, so early detection is crucial to slow disease progression and reduce vision loss. The development of multimodal imaging technology and the issuance of the latest treatment guidelines provide a powerful tool for the early screening and treatment of hydroxychloroquine retinopathy. Proficient in the latest guidelines for the treatment of hydroxychloroquine can better guide clinicians to do a good job in disease screening and management, recommend risks, safe dosages and appropriate screening procedures to patients and strengthen the prevention of hydroxychloroquine retinopathy, which will help save the vision of more patients and reduce the waste of medical resources.
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@#Introduction: The outbreak of coronavirus disease (COVID-19) in December 2019 called for a rapid solution, leading to repurposing of existing drugs. Due to its immunomodulatory effect and antiviral properties, hydroxychloroquine (HCQ) has been used in early 2020 for treatment of COVID-19 patients. This study was conducted to evaluate the treatment outcome of HCQ monotherapy in Malaysia. Methods: A retrospective cohort study was conducted in COVID-19 ward in Hospital Kuala Lumpur (HKL), from March to April 2020. A total of 446 COVID-19 patients were recruited, only 325 patients were finally included for analysis. Statistical analysis was done using SPSS, with a significant value set at p<0.05. Results: The mean age of the patients were 38.5 ±15.5. They were majority male, (n=210, 64.6%) Malaysian (n=239, 73.5%) and Malay ethnicity (n=204, 62.8%). Ninety-one (28%) patients received HCQ monotherapy. HCQ monotherapy was associated with worse outcome (OR: 10.29, 95% CI 1.17-90.80). There was a significant difference in mean length of stay between those with and without HCQ treatment (t323=5.868, p<0.001, 95% CI, 2.56-5.31). The average length of stay for HCQ treated group was 3.84 days longer than those without treatment. 6.6% of the patient receiving HCQ monotherapy encountered adverse drug effects. Conclusion: Similar to study reported worldwide, our study demonstrated that HCQ did not improve length of stay and the outcome of COVID-19 patients.
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Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.
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Resumo Fundamento Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. Objetivos Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. Métodos Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). Conclusão Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar.
Abstract Background Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. Objectives To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. Methods A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. Results From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). Conclusion COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar.
摘要
Objetivos: Comparar os desfechos clínicos e a sobrevida de pacientes adultos com COVID-19 expostos e não expostos a tratamento medicamentoso com cloroquina e hidroxicloroquina. Método: Trata-se de um estudo de coorte retrospectiva com dados coletados em um hospital de Vitória. Foram incluídos todos os pacientes de enfermarias e Unidade de Terapia Intensiva (UTI) com idade igual ou superior a 18 anos, com diagnóstico confirmado de COVID-19, ou seja, com PCR positivo para a infecção, atendidos no hospital entre 26 de fevereiro a 31 de dezembro de 2020, e com registro de alta hospitalar por motivo de óbito ou não óbito. Aplicou-se a estatística descritiva (frequência absoluta e relativa) e teste do Qui-quadrado e Exato de Fisher para verificar associação entre as variáveis dependentes e independentes, considerando o índice de confiança (IC) de 95%. As variáveis contínuas foram analisadas por meio de medidas de tendência central (mínimo, máximo, média, mediana e desvio padrão). Para avaliar a existência de diferença nas médias com relação ao desfecho do tratamento medicamentoso para as variáveis contínuas, utilizou-se o teste não paramétrico de Mann-Whitney. Aplicou-se o método de Kaplan Meier para comparar o tempo de tratamento e demais variáveis independentes de interesse. Por fim, para analisar o tempo de internação até a ocorrência de óbito, utilizou-se o modelo de regressão de Cox com os respectivos riscos bruto e ajustado. As análises foram realizadas no programa R versão 4.1.2. e, em todas, considerado o nível de significância de 5% e intervalo de confiança de 95% (IC95%). Resultados: A amostra foi composta por 896 indivíduos; a maioria com idade média de 53,4 anos, do sexo feminino, etnia parda, casada, com ensino médio completo, não tabagista. O tempo médio de internação foi de 9,77 dias e 7,13 dias de tratamento medicamentoso para COVID-19. Cerca de 42,1% apresentaram mais de duas comorbidades e as mais prevalentes foram diabetes mellitus tipo 2 (45%), hipertensão arterial (44,9%) e doença pulmonar obstrutiva crônica (14,6%). Durante a internação, 16,4% dos indivíduos precisaram de ventilação mecânica e 51,3% utilizaram cloroquina ou hidroxicloroquina durante a internação. Evoluíram para óbito 99 indivíduos. Ainda, houve a utilização de mais de três medicamentos por 873 pessoas. Na análise bivariada, estiveram associados ao tratamento com cloroquina ou hidroxicloroquina a idade (p=0,0045), ventilação mecânica (p=0,0010), parada cardiorrespiratória (p=0,0010), hipoglicemia (p=0,0310), polifarmácia (p=0,0010) e número de comorbidades (p=0,0010). A taxa de ocorrência de óbitos em pessoas divorciadas (OR: 2,4904; p=0,398; IC 95% 0,9125-0,4438) e viúvas (OR: 1,9823; p=0,0277; IC 95% 0,6842-0,3108) foi maior do que em pessoas casadas. A taxa de ocorrência de óbito entre pessoas com escore qSOFA positivo foi 2,70 (OR: 2,7018; p=0,0009; IC 95% 0,9939-0,2981) vezes maior do que as com escore qSOFA negativo. Na análise de associação entre ventilação mecânica e demais variáveis independentes, entre os indivíduos que não faziam o uso da ventilação mecânica, os viúvos e os que apresentavam qSOFA positivo apresentaram mais chance de óbito. O índice de massa corporal (IMC) elevado apresentou-se como fator protetor, tido que a chance de óbito reduziu em 10,97% para cada aumento de 1 unidade no IMC entre os indivíduos em ventilação mecânica. Por fim, no modelo completo do ajuste de efeitos principais com base nos estratos de ventilação mecânica, para analisar a homogeneidade dos grupos, os resultados encontrados acerca do risco em divorciados, viúvos e qSOFA positivo permaneceram conforme análises anteriores. Conclusão: dos 11% dos pacientes com COVID-19 que evoluíram para o óbito, 6,8% fizeram uso de cloroquina ou hidroxicloroquina. As taxas de sobrevivência apresentaram-se menores em pacientes indígenas, do sexo masculino, viúvos e que fizeram uso de ventilação mecânica. Ainda, o baixo IMC foi considerado fator de risco para a mortalidade em pacientes com COVID-19 em ventilação mecânica, já o estado civil destacou-se como fator protetor em pessoas casadas
Objectives: To compare clinical outcomes and survival of adult patients with COVID19 exposed and not exposed to drug treatment with chloroquine and hydroxychloroquine. Method: This is a retrospective cohort study with data collected in a hospital in Vitória. All patients in wards and Intensive Care Units (ICU) aged 18 years or over, with a confirmed diagnosis of COVID-19, that is, with a positive PCR for the infection, treated at the hospital between February 26th and December 31, 2020, and with a record of hospital discharge due to death or non-death. Descriptive statistics (absolute and relative frequency) and the Chi-square test and Fisher's exact test were applied to verify the association between the outcome and independent variables, considering the confidence index (CI) of 95%. Continuous variables were analyzed using measures of central tendency (minimum, maximum, mean, median and standard deviation). To assess the existence of a difference in means in relation to the outcome of drug treatment for continuous variables, the non-parametric Mann-Whitney test was used. The Kaplan Meier method was applied to compare treatment time and other independent variables of interest. Finally, to analyze the length of hospital stay until death, the Cox regression model was used with the respective crude and adjusted risks. The analyzes were carried out using the R program version 4.1.2. and, in all cases, a significance level of 5% and a confidence interval of 95% (95% CI) were considered. Results: The sample consisted of 896 individuals; the majority with an average age of 53.4 years, female, mixed race, married, with completed high school, non-smokers. The average length of stay was 9.77 days and 7.13 days of drug treatment for COVID-19. Around 42.1% had more than two comorbidities and the most prevalent were type 2 diabetes mellitus (45%), hypertension (44.9%) and chronic obstructive pulmonary disease (14.6%). During hospitalization, 16.4% of individuals required mechanical ventilation and 51.3% used chloroquine or hydroxychloroquine during hospitalization. 99 individuals died. Furthermore, more than three medications were used by 873 people. In the bivariate analysis, age (p=0.0045), mechanical ventilation (p=0.0010), cardiorespiratory arrest (p=0.0010), hypoglycemia (p=0.0310) were associated with treatment with chloroquine or hydroxychloroquine, polypharmacy (p=0.0010) and number of comorbidities (p=0.0010). The rate of death in divorced people (OR: 2.4904; p=0.398; 95% CI 0.9125-0.4438) and widows (OR: 1.9823; p=0.0277; 95% CI 0 .6842-0.3108) was higher than in married people. The rate of death among people with a positive qSOFA score was 2.70 (OR: 2.7018; p=0.0009; 95% CI 0.9939-0.2981) times higher than those with a negative qSOFA score. In the analysis of the association between mechanical ventilation and other independent variables, among individuals who did not use mechanical ventilation, widowers and those with a positive qSOFA were more likely to die. High BMI was a protective factor, as the chance of death reduced by 10.97% for each increase of 1 unit in BMI among individuals on mechanical ventilation. Finally, in the complete main effects adjustment model based on the mechanical ventilation strata, to analyze the homogeneity of the groups, the results found regarding the risk in divorced, widowed and positive qSOFA remained in line with previous analyses. Conclusion: The results demonstrate that the use of chloroquine and hydroxychloroquine by patients with COVID-19 may be related to the occurrence of deaths and did not reduce the chance of mechanical ventilation. Survival rates were lower in indigenous, male, widowed patients who used mechanical ventilation and drug treatment with chloroquine or hydroxychloroquine. Furthermore, the results indicate that chloroquine/hydroxychloroquine are not beneficial in the treatment of COVID-19, however, further studies are necessary
Subject(s)
Humans , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Survival Analysis , Chloroquine , COVID-19/therapy , Hydroxychloroquine摘要
Resumo Fundamento: Revisões sistemáticas anteriores não identificaram benefício do uso da hidroxicloroquina ou da cloroquina em pacientes com COVID-19 não hospitalizados. Após a publicação dessas revisões, os resultados do COPE, o maior ensaio clínico randomizado até hoje, tornaram-se disponíveis. Objetivos: Conduzir uma revisão sistemática e metanálise de ensaios clínicos randomizados (ECRs) para sintetizar as evidências sobre a eficácia e a segurança da hidroxicloroquina e da cloroquina em pacientes com COVID-19 não hospitalizados em comparação a controle ou tratamento padrão. Métodos: As buscas foram conduzidas nos bancos de dados PubMed, Embase, The Cochrane Library e ClinicalTrials.gov, e complementadas por busca manual. Foram realizadas metanálises diretas e avaliações de risco de viés e certeza da evidência, incluindo análise do tamanho ótimo da informação (OIS, optimal information size). Um nível de significância de 0,05 foi adotado na metanálise. PROSPERO: CRD42021265427. Resultados: Oito ECRs com 3219 participantes foram incluídos. As taxas de internação por COVID-19 e de eventos adversos não foram significativamente diferentes entre hidroxicloroquina (5,6% e 5,1%) e controle (7,4% e 20,4%) [risco relativo (RR) 0,77, intervalo de confiança 95% (IC95%), 0,57-1,04, I2: 0%; RR 1,78, IC95% 0,90; 3,52, I2: 93%, respectivamente)]. O OIS (7880) não foi alcançado para hospitalização por COVID-19, independentemente da simulação para a taxa de evento e redução do RR estimados. Conclusão: A evidência de muito baixa qualidade indicou falta de benefício com hidroxicloroquina em prevenir internações por COVID-19. Apesar de ser a revisão sistemática com o maior número de participantes incluídos, o OIS, considerando a resposta à infecção anterior à vacinação, não foi atingido.
Abstract Background: Previous systematic reviews have identified no benefit of hydroxychloroquine and chloroquine in non-hospitalized COVID-19 patients. After publication of these reviews, the results of COPE, the largest randomized trial conducted to date, became available. Objectives: To conduct a systematic review and meta-analyses of randomized clinical trials (RCTs) to synthesize the evidence on the efficacy and safety of hydroxychloroquine and chloroquine for non-hospitalized COVID-19 patients compared to placebo or standard of care. Methods: Searches were conducted in PubMed, Embase, The Cochrane Library, and ClinicalTrials.gov complemented by manual search. Pairwise meta-analyses, risk of bias, and evidence certainty assessments were conducted, including optimal information size analysis (OIS). A level of significance of 0.05 was adopted in the meta-analysis. PROSPERO: CRD42021265427. Results: Eight RCTs with 3,219 participants were included. COVID-19 hospitalization and any adverse events rates were not significantly different between hydroxychloroquine (5.6% and 35.1%) and control (7.4% and 20.4%) (risk ratio, RR, 0.77, 95% confidence interval, CI, 0.57-1.04, I2: 0%; RR 1.78, 95%-CI 0.90; 3.52, I2: 93%, respectively). The OIS (7,880) was not reached for COVID-19 hospitalization, independently of the simulation for anticipated event rate and RR reduction estimate. Conclusion: Evidence of very low certainty showed lack of benefit with hydroxychloroquine in preventing COVID-19 hospitalizations. Despite being the systematic review with the largest number of participants included, the OIS, considering pre-vaccination response to infection, has not yet been reached.
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Abstract Introduction Chloroquine and hydroxychloroquine are antimalarial drugs widely used in the treatment of rheumatic diseases. With the global pandemic caused by the new coronavirus, there was an increase in the prescription of these drugs, which led to a major concern regarding their ototoxic effects. Objectives The objective of the present study was to assess existing scientific evidence about the toxic effects of chloroquine and hydroxychloroquine on the peripheral and/or central auditory system. Data Synthesis A systematic literature review was performed by searching the PubMed (Medline), Scopus, Web of Science, LILACS, and SciELO electronic databases, in a search of articles that fullfiled the predefined inclusion and exclusion criteria. The review was conducted in three phases and, in all of them, analyses were performed by two independent researchers. Disagreements were discussed with a third researcher until a consensus was reached. A total of 437 articles were found and 8 were included in this review. Seven of the included studies reported hearing loss in their samples and presented a diagnostic hypothesis of ototoxicity induced by chloroquine or hydroxychloroquine. The most common type of hearing loss was sensorineural, with varying laterality and degrees of severity. The most frequently used audiological test was pure tone audiometry, and only two studies assessed brainstem evoked responses. Conclusion The scientific evidence compiled in this research showed that chloroquine and hydroxychloroquine have an ototoxic effect in the peripheral auditory system. These drugs can cause cochlear damage, including changes in the stria vascularis and lesions in sensory hair cells.
摘要
Coronavirus disease 2019 (COVID-19) is an acute respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It has various clinical manifestations, from asymptomatic to severe disease with possible multi-organ involvement, with respiratory and vascular systems being the frequent affected. COVID-19 can affect patients with autoimmune diseases including systemic lupus erythematosus (SLE). The concurrent of both diseases may show the similar characteristic which can asa challenge in diagnosis and early therapeutic consideration. We report a case of 53 year-old Balinese woman patient who previously diagnosed with acute respiratory iIlness (Pneumonitis),The patient with past history of SLE since 2005, takes 200 mg hydroxychloroquine (HCQ) and 4 mg methylprednisolone once a day orally without adverse effect. Then she was confirmed with SARS-CoV-2 infection (COVID-19 pneumonitis) concurrent with SLE flare (Lupus pneumonitis). The clinical similarities were fever, dry coughand shortness of breath with the chest X-ray(CXR) was bilateral interstitiil infiltrate. Laboratory results; a positive SARS-CoV-2 polymerase chain reaction test, leucophenia, increased ESR, slightly increased CRP, decreased CD4 and CD8 cell count. Decreasedoxygen saturation, requiring 4 L of oxygen via nasal cannula on admission.She was given therapyofantibiotics, antivirus and other symptomatic. The prior SLE maintenance therapywas continued with increasingmethylprednisolone dose. The patient抯condition was improved and weaned off her oxygen requirements. Shewas dischargedandfollowed by home isolation for 14 days.