RESUMO
Objective To observe the toxicity of low concentration Mn2+ compound combined with autophagy inhibitor chloroquine on nerve cell line PC12 cells for long-term and its mechanism. Methods PC12 cells at logarithmic growth stage were treated with 0 (control), 5, 10, 25, 50, 100, and 200 μM manganous chloride, and 5, 10, 25, 50, and 100 μM chloroquine for 24 h, respectively. The effect of manganous chloride and chloroquine on cell viability was detected by MTT assay. The combined effect of the two compounds on cell viability was determined at 24, 48 and 72 h, respectively. The mitochondrial respiratory function was further examined to explore the possible toxicity mechanism of manganous chloride and chloroquine. Results Compared with the control group, manganous chloride and chloroquine alone had inhibitory effect on cells survival in a concentration-dependent manner. Manganous chloride and chloroquine at concentrations of 40 μM and 2.5 μM, respectively, had no significant effect on cell survival. Compared with the control group, administration of 2.5 μM chloroquine alone for 24, 48 and 72 h did not significantly change cell survival and mitochondrial respiratory function. Treatment of cells with manganous chloride alone at the concentration of 40 μM for 72 h did affect mitochondrial respiratory function. However, the cell survival and mitochondrial respiratory function in the combined administration of manganous chloride and chloroquine for 72 h were significant decreased (P< 0.05). Conclusion The long-term combination of low-concentration manganous chloride and chloroquine produced an additive cytotoxicity on PC12 cells, and the toxicity mechanism may be related to the damage of mitochondrial function.
RESUMO
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.
Assuntos
Terapêutica , Protocolos Clínicos , COVID-19 , Infecções Bacterianas , Fidelidade a Diretrizes , PandemiasRESUMO
ABSTRACT OBJECTIVE Assess the correlation between the sales of two drugs with no proven efficacy against covid-19, ivermectin and chloroquine, and other relevant variables, such as Google® searches, number of tweets related to these drugs, number of cases and deaths resulting from covid-19. METHODS The methodology adopted in this study has four stages: data collection, data processing, exploratory data analysis, and correlation analysis. Spearman's method was used to obtain cross-correlations between each pair of variables. RESULTS The results show similar behaviors between variables. Peaks occurred in the same or near periods. The exploratory data analysis showed shortage of chloroquine in the period corresponding to the beginning of advertising for the application of these drugs against covid-19. Both drugs showed a high and statistically significant correlation with the other variables. Also, some of them showed a higher correlation with drug sales when we employed a one-month lag. In the case of chloroquine, this was observed for the number of deaths. In the case of ivermectin, this was observed for the number of tweets, cases, and deaths. CONCLUSIONS The results contribute to decision making in crisis management by governments, industries, and stores. In times of crisis, as observed during the covid-19 pandemic, some variables can help sales forecasting, especially Google® and tweets, which provide a real-time analysis of the situation. Monitoring social media platforms and search engines would allow the determination of drug use by the population and better prediction of potential peaks in the demand for these drugs.
RESUMO OBJETIVO Investigar a correlação entre as vendas de dois medicamentos sem eficácia comprovada no tratamento de covid-19, ivermectina e cloroquina, e outras variáveis relevantes: pesquisas no Google®, número de tweets relacionados aos medicamentos, casos e óbitos decorrentes da covid-19. MÉTODOS A metodologia adotada neste estudo se divide em quatro partes: coleta de dados; processamento dos dados; análise exploratória; e análise de correlação. Foi utilizado o método de Spearman para obter as correlações cruzadas entre cada par de variáveis. RESULTADOS Os resultados mostram similaridade entre os comportamentos das variáveis. Os picos ocorreram em períodos iguais ou próximos. A análise exploratória dos dados apontou que houve falta de cloroquina no período correspondente ao início das divulgações sobre a aplicação desses medicamentos para o tratamento da covid-19. Ambos os medicamentos apresentaram correlação alta e estatisticamente significativa com as demais variáveis analisadas. Também foi observado que algumas delas apresentaram maior correlação com as vendas de medicamentos quando assumiram defasagem temporal de um mês. No caso da cloroquina, isso ocorreu com a variável óbitos. No caso da ivermectina, ocorreu com as variáveis número de tweets, casos e óbitos. CONCLUSÕES Os resultados observados contribuem para a tomada de decisão durante a gestão de crises por parte de governo, indústrias e comércios. Em momentos de crises, como observado durante a pandemia, as variáveis mostraram que são capazes de auxiliar na previsão de vendas, em especial o Google® e os tweets, que proporcionam uma análise em tempo real da situação. Acompanhar as redes sociais e mecanismos de busca permitiria detecção de uso pela população e melhor previsão de potenciais picos de demanda desses medicamentos.
Assuntos
Ivermectina , Cloroquina , Ferramenta de Busca , Pandemias , Mídias Sociais , SARS-CoV-2 , COVID-19 , InfodemiaRESUMO
Background & objectives: The spread of drug-resistant Plasmodium falciparum ( Pf) poses a serious threat to the control and elimination of malaria. The objective of this study was to detect the molecular biomarkers of antimalarial drug resistance in Pf in patients visiting a tertiary care hospital in Assam. Methods: Malaria was first detected in fever cases using microscopy and a rapid diagnostic test (RDT), and then confirmed using PCR. Pf chloroquine resistance transporter (Pfcrt), Pf multidrug resistance-1 (Pfmdr-1), and single-nucleotide polymorphisms linked to delayed parasite clearance after treatment with artemisinin MAL 10-688956 and MAL 13-1718319 and Kelch-13 propeller (PfK-13) genes were evaluated by PCR-restriction fragment length polymorphism (RFLP). Results: Sixty nine cases of malaria were found among 300 cases of fever. Of these, 54 were positive for Pf, 47 of which were confirmed by PCR. Pfcrt-K76T mutation was seen in 96.6 per cent and Pfmdr1-N86Y mutation in 84.2 per cent of cases. Mutation was not detected in MAL10 and MAL13 genes. Sequence analysis of Kelch-13 gene showed the presence of a novel mutation at amino acid position 675. Statistically, no significant association was found between the molecular biomarkers and demographic profile, clinical presentation and outcome of the cases. Interpretation & conclusions: Molecular surveillance is essential to assess the therapeutic efficacy of the drugs against circulating Pf isolates in Assam which are found to be highly resistant to CQ. The role of the new mutation found in the Kelch-13 gene in the development of artemisinin resistance in Assam needs to be thoroughly monitored in future research.
RESUMO
@#Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 – 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.
RESUMO
Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.
RESUMO
AIM: To explore the possible mechanism of propofol in alleviating pruritus induced by subcutaneous injection of chloroquine in rats. METHODS: The pruritus model of chloroquine in SD rats was established and the administration time was determined. 18 rats with successful pruritus model induced by subcutaneous injection of chloroquine were randomly divided into NS group, I group and P group. Normal saline 80 μL/kg, fat emulsion 80 μL/kg and propofol 0.8 mg/kg were injected through internal jugular vein catheter 5 minutes after subcutaneous injection of chloroquine. Another 6 rats were randomly selected as group C, and the same volume of normal saline as the other 3 groups was injected subcutaneously in the back of the neck and through the internal jugular vein catheter. The rats were killed 16 minutes after the corresponding drugs were injected into the internal jugular vein. The expressions of TRPV1 and CB1 receptors in the spinal cord were detected by Western blot. RESULTS: Compared with NS group and I group, the expression level of TRPV1 receptor in the spinal cord of P group rats was significantly increased (P<0.01), while there was no statistically significant difference between C group, NS group, and I group; The expression level of CB1 receptor was significantly higher than that of group C, NS, and I (P<0.05), while there was no statistically significant difference between group C, NS, and I. CONCLUSION: Propofol can significantly alleviate pruritus caused by subcutaneous injection of chloroquine in rats, which may exert an antipruritic effect by increasing the expression of TRPV1 and CB1 receptors in the spinal cord of rats.
RESUMO
Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ‑resistant genotype in the study area.
A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.
Assuntos
Humanos , Cloroquina , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase , Resistência a MedicamentosRESUMO
Abstract Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.
Resumo A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.
RESUMO
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.
RESUMO
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
Assuntos
Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Análise de Sobrevida , Cloroquina , COVID-19/terapia , HidroxicloroquinaRESUMO
Abstract Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.
Resumo A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.
Assuntos
Plasmodium falciparum/genética , Antimaláricos/farmacologia , Paquistão , Proteínas de Membrana Transportadoras/genética , Resistência a Medicamentos/genética , Proteínas de Protozoários/genética , Cloroquina/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , AlelosRESUMO
Abstract Nitric oxide (NO) is an abundant mediator which is demonstrated to be involved in pruritus. Assuming that the increased NO also mediates chloroquine-induced pruritus, which is a frequent complication seen in the chronic chloroquine treatment, the current study aimed to investigate the effect of quercetin and the role of NO in chloroquine-induced pruritus in C57BL/6 mice. Model was created with subcutaneous chloroquine (400µg/site) injection to the nape of the mice. Effect of quercetin and role of NO were investigated with administration of quercetin, and co-administration with L-NAME, 7-NI and L-arginine before chloroquine injection. Locomotor activity was assessed by activity cage and number of the scratching bouts after chloroquine injection was recorded for 30 minutes. Our results show that quercetin significantly reduced scratching bouts at the doses of 10, 20, 40 and 80 mg/kg. Locomotor activity was decreased at the 40 and 80 mg/kg doses of quercetin. Additionally, decrease of the number of scratching bouts by quercetin prevented by L-arginine treatment, while L-NAME and 7-NI enhanced the anti-pruritic effect of sub-effective doses of quercetin. Therefore, our study demonstrated that acute injection of quercetin significantly diminished chloroquine-induced scratching behavior, and this effect is partly mediated by inhibition of neuronal nitric oxide synthase enzyme.
Assuntos
Animais , Masculino , Camundongos , Prurido/induzido quimicamente , Quercetina/efeitos adversos , Cloroquina/administração & dosagem , Óxido Nítrico/agonistas , Atividade MotoraRESUMO
Systemic lupus erythematosus (SLE) is a chronic and potentially fatal autoimmune disease. There are clinical differences between women and men and among age groups. Its treatment involves a heterogeneous group of drugs. The objective was to determine the pharmacological treatment patterns in a group of patients with SLE and compare them according to sex, age group and geographic region. This was a cross-sectional study that identified outpatient drugs used in patients with SLE from a population database of Colombians affiliated with the Colombian Health System. Sociodemographic and pharmacological variables were considered. Descriptive and bivariate analyses were performed. A total of 4307 patients with SLE were identified (median age, 44.2 years; 89.4% women). Disease-modifying antirheumatics were the most prescribed drugs (90.5%), especially chloroquine (54.4%), which predominated in all age groups and geographical regions. Hydroxychloroquine and methotrexate were the predominant prescribed drugs for women, while corticosteroids, chloroquine, azathioprine, and mycophenolate were the predominant prescribed drugs for men. The use of corticosteroids (prednisolone and prednisone) decreased with increasing age. Differences were found in the prescription of drugs for patients with SLE between women and men and among geographic regions and age groups. The use of chloroquine predominated over hydroxychloroquine, contrasting with clinical practice guidelines.
El lupus eritematoso sistémico (LES) es una enfermedad autoinmune crónica y potencialmente mortal. Existen diferencias clínicas entre mujeres y hombres, y entre grupos de edad. Su tratamiento involucra un grupo heterogeneo de medicamentos. El objetivo fue determinar los patrones de tratamiento farmacológico de un grupo de pacientes con LES y compararlos según el sexo, los grupos de edad y las regiones geograficas. Estudio de corte transversal que identifico los medicamentos de uso ambulatorio empleados en pacientes con LES, a partir de una base de datos poblacional de colombianos afiliados al Sistema de Salud de Colombia. Se consideraron variables sociodemográficas y farmacologicas. Se realizo un análisis descriptivo y bivariado. Se identificó a 4.307 pacientes con LES, con una mediana de edad 44,2 anË os y un 89,4% mujeres. Los medicamentos modificadores de enfermedad reumatica fueron los mas prescritos (90,5%), en especial cloroquina (54,4%), el cual predomino en todos los grupos de edad y las regiones geográficas. La hidroxicloroquina y el metotrexato predominaron en mujeres, mientras que los corticosteroides, la cloroquina, la azatioprina y el micofenolato, en hombres. Con el aumento de la edad disminuyo el uso de corticoides (prednisolona y prednisona). Se encontraron diferencias en la prescripción de los medicamentos empleados en los pacientes con LES entre mujeres y hombres, regiones geográficas y grupos etarios. El uso de cloroquina predomino sobre la hidroxicloroquina, en contraste con lo recomendado por las guías de practica clínica.
Assuntos
Humanos , Masculino , Feminino , Adulto , Cloroquina , Doenças da Pele e do Tecido Conjuntivo , Doenças do Tecido Conjuntivo , Compostos Heterocíclicos de Anéis Fundidos , Compostos Heterocíclicos , Lúpus Eritematoso SistêmicoRESUMO
In December 2019, a new coronavirus originating from the city of Wuhan in China started an epidemic that brought many countries into chaos and despair. SARS-CoV-2, as identified, gave rise to the severe acute respiratory syndrome called COVID-19. Its transmission happens through droplets of saliva, hand or contaminated surfaces. Since its discovery, COVID-19 has led many to death, therefore, researchers from around the world have joined efforts to develop strategies to contain the virus. In this race, drugs such as Chloroquine and Hydroxychloroquine have become possible options for showing an antiviral effect, however, studies contest their efficiency, generating uncertainties. Therefore, other alternatives have been investigated in this context, and the study of medicinal plants has been the target of research for the treatment of COVID-19 in search of bioactive natural products that can exert an antiviral action. The study aimed to analyze the published literature on COVID-19 (SARS-CoV-2) and its relationship with medicinal plants. Bibliographical survey. So far, no specific treatment against the disease has been found, only supportive, with drugs that aim to improve the individual's immune system and ensure that the virus does not replicate, for example, there are options such as chloroquine, hydroxychloroquine, remdesivir and convalescent plasma. On the other hand, studies have revealed that medicinal plants such as garlic, among others, showed efficiency in modulating proteins with a view to preventing viral replication and improving immunity against COVID-19. So far, there are no drugs that are completely safe and have been shown to have activity against the new coronavirus (SARS-CoV-2). However, medicinal plants can contribute to the development of specific therapies against SARS-CoV-2 in a safe and effective way.
Em dezembro de 2019, um novo coronavírus originário da cidade de Wuhan, na China, iniciou uma epidemia que levou muitos países ao caos e ao desespero. O SARS-CoV-2, conforme identificado, deu origem à síndrome respiratória aguda grave chamada COVID-19. Sua transmissão acontece através de gotículas de saliva, mãos ou superfícies contaminadas. Desde sua descoberta, o COVID-19 levou muitos à morte, por isso, pesquisadores de todo o mundo uniram esforços para desenvolver estratégias para conter o vírus. Nesta corrida, medicamentos como Cloroquina e Hidroxicloroquina tornaram-se opções possíveis por apresentarem efeito antiviral, porém, estudos contestam sua eficiência, gerando incertezas. Portanto, outras alternativas têm sido investigadas nesse contexto, e o estudo de plantas medicinais tem sido alvo de pesquisas para o tratamento da COVID- 19 em busca de produtos naturais bioativos que possam exercer ação antiviral. O estudo teve como objetivo analisar a literatura publicada sobre COVID-19 (SARS-CoV-2) e sua relação com plantas medicinais. Levantamento bibliográfico. Até o momento, não foi encontrado nenhum tratamento específico contra a doença, apenas de suporte, com medicamentos que visam melhorar o sistema imunológico do indivíduo e garantir que o vírus não se replique, por exemplo, há opções como cloroquina, hidroxicloroquina, remdesivir e convalescença plasma. Por outro lado, estudos revelaram que plantas medicinais como o alho, entre outras, mostraram eficiência na modulação de proteínas visando prevenir a replicação viral e melhorar a imunidade contra a COVID-19. Até o momento, não existem medicamentos completamente seguros e que tenham demonstrado atividade contra o novo coronavírus (SARS-CoV-2). No entanto, as plantas medicinais podem contribuir para o desenvolvimento de terapias específicas contra o SARS-CoV-2 de forma segura e eficaz.
En diciembre de 2019, un nuevo coronavirus originario de la ciudad de Wuhan, en China, inició una epidemia que sumió a muchos países en el caos y la desesperación. El SARS-CoV- 2, tal y como fue identificado, dio lugar al síndrome respiratorio agudo severo denominado COVID-19. Su transmisión se produce a través de gotitas de saliva, de las manos o de superficies contaminadas. Desde su descubrimiento, el COVID-19 ha llevado a muchos a la muerte, por lo que investigadores de todo el mundo han aunado esfuerzos para desarrollar estrategias de contención del virus. En esta carrera, fármacos como la Cloroquina y la Hidroxicloroquina se han convertido en posibles opciones por mostrar un efecto antiviral, sin embargo, los estudios refutan su eficacia, generando incertidumbres. Por lo tanto, otras alternativas han sido investigadas en este contexto, y el estudio de las plantas medicinales ha sido el objetivo de la investigación para el tratamiento de COVID-19 en busca de productos naturales bioactivos que puedan ejercer una acción antiviral. El estudio tuvo como objetivo analizar la literatura publicada sobre el COVID-19 (SARS-CoV-2) y su relación con las plantas medicinales. Estudio bibliográfico. Hasta el momento, no se ha encontrado un tratamiento específico contra la enfermedad, sólo de soporte, con fármacos que buscan mejorar el sistema inmunológico del individuo y asegurar que el virus no se replique, por ejemplo, existen opciones como la cloroquina, hidroxicloroquina, remdesivir y plasma convaleciente. Por otro lado, estudios han revelado que plantas medicinales como el ajo, entre otras, mostraron eficacia en la modulación de proteínas con vistas a impedir la replicación viral y mejorar la inmunidad contra el COVID-19. Hasta el momento, no existen medicamentos que sean completamente seguros y que hayan demostrado tener actividad contra el nuevo coronavirus (SARS-CoV-2). Sin embargo, las plantas medicinales pueden contribuir al desarrollo de terapias específicas contra el SARS-CoV-2 de forma segura y eficaz.
Assuntos
Plantas Medicinais/imunologia , SARS-CoV-2/efeitos dos fármacos , Antivirais/antagonistas & inibidores , Antivirais/uso terapêutico , Vacinas Virais/antagonistas & inibidores , Cloroquina/uso terapêutico , Síndrome Respiratória Aguda Grave/virologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Pandemias/prevenção & controle , Alho/imunologia , COVID-19/epidemiologia , Hidroxicloroquina/uso terapêuticoRESUMO
Introducción: El paludismo es una enfermedad febril aguda potencialmente mortal causada por parásitos transmitidos por el mosquito Anopheles. El paludismo no falciparum (PNF), producido por otras especies de Plasmodium, está menos documentado en la literatura internacional, a pesar de su prevalencia. Objetivos: Describir aspectos clínicos y epidemiológicos de interés para el tratamiento en pacientes ingresados con diagnóstico de PNF importado, y determinar la relación existente entre la respuesta al tratamiento y otras variables. Métodos: Se realizó un estudio transversal analítico de 89 pacientes adultos con PNF importado, ingresados en el Departamento de Medicina del Instituto de Medicina Tropical Pedro Kourí, entre enero de 1997 a diciembre de 2017. Se determinó la pauta de profilaxis y tratamiento según los criterios de las guías publicadas y los fármacos disponibles en Cuba, y la definición de paludismo complicado según la OMS en 2003. Hubo respuesta demorada al tratamiento, cuando el paciente demoraba más de 7 días en negativizar la gota gruesa. Resultados: Predominaron los pacientes del sexo masculino, y una media de edad de 37,2 años. El 55,1 por ciento de los pacientes provenía de la región de las Américas y en el 85,4 por ciento se aisló Plasmodium vivax. La respuesta al tratamiento fue excelente con los esquemas combinados utilizados a base de cloroquina. Fue significativa la relación existente entre la demorada respuesta al tratamiento con la gravedad del cuadro clínico y el estado no inmune de los pacientes. Conclusiones: El PNF es una importante causa de paludismo importado en pacientes provenientes de áreas endémicas, fundamentalmente de América. Se distingue por parasitemias bajas, un cuadro clínico caracterizado por fiebre, escalofríos, cefaleas y evolución hacia cuadros no complicados. La cloroquina fue el medicamento de elección, aunque la repuesta demorada al tratamiento no justifica su suspensión o variación(AU)
Introduction: Malaria is a potentially fatal acute febrile illness caused by parasites transmitted by the Anopheles mosquito. Non-falciparum malaria (NFM), caused by other Plasmodium species, is less documented in the international literature, despite its prevalence. Objectives: To describe clinical and epidemiological aspects of interest for the treatment of patients hospitalized with a diagnosis of imported NFM, and to determine the relationship between response to treatment and other variables. Methods: It was conducted an analytical cross-sectional study of 89 adult patients with imported NFM, admitted to the Department of Medicine of the Institute of Tropical Medicine Pedro Kourí, between January 1997 to December 2017. The prophylaxis and treatment guideline was determined according to the published guidelines and drugs available in Cuba, and the definition of severe malaria by WHO in 2003. There was delayed response to treatment when the patient took more than 7 days to become negative for thick blood smear. Results: Patients were predominantly male, with a mean age of 37.2 years. Plasmodium vivax was isolated in 85.4 percent of the patients and 55.1 percent were from the Americas region. The response to treatment was excellent with the chloroquine-based combination regimens used. The relationship between the delayed response to treatment and the severity of the clinical picture and the non-immune status of the patients was significant. Conclusions: NFM is an important cause of imported malaria in patients from endemic areas, mainly from the Americas. It is characterized by low parasitemia, clinical manifestations of fever, chills, headache and evolution towards uncomplicated symptoms. Chloroquine was the drug of choice, although the delayed response to treatment does not justify its suspension or variation(AU)
Assuntos
Humanos , Masculino , Feminino , Plasmodium vivax/fisiologia , Malária Vivax/tratamento farmacológicoRESUMO
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.
RESUMO
Resumen Se reporta una paciente en tratamiento con cloroquina para una artritis reumatoidea de aproximadamente diez años de evolución, con una importante dosis acumulada y en quien se documentó deterioro progresivo de la función renal, proteinuria en rango no nefrótico y compromiso muscular proximal en extremidades. En la biopsia renal se encontró a nivel de podocitos cuerpos de cebra. Se descartó enfermedad de Fabry. Se concluyó fosfolipidosis inducida por medicamentos en este caso por cloroquina. Este reporte de caso nos recuerda la importancia de conocer los posibles efectos colaterales de los medicamentos. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2192).
Abstract This is the report of a patient being treated with chloroquine for an approximately 10-year history of rheumatoid arthritis, with a significant cumulative dose and documented progressive kidney function deterioration, non-nephrotic proteinuria and involvement of the proximal muscles of the extremities. The kidney biopsy showed zebra bodies in the podocytes. Fabry disease was ruled out. Medication-induced phospholipidosis was diagnosed, in this case due to chloroquine. This case report reminds us of the importance of being aware of the possible side effects of medications. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2192).
RESUMO
Introduction: Among all therapeutic approaches for COVID-19, most controversies have been raised about the efficacy and safety hydroxychloroquine (HCQ) and chloroquine. We conducted an umbrella review to assess any potential benefits of hydroxychloroquine and chloroquine in treating COVID-19.Methods: We searched the Cochrane Database of Systematic Reviews, PubMed and covid-evidence.org from December 2019 until July 2022. Time to viral clearance, need for mechanical ventilation and mortality were assessed as main efficacy outcomes. The analysis was performed using R package version 4.1.2.Result : Hydroxychloroquine had no benefit in decreasing time to viral clearance at days 7 (RR 0.81; 95% CI 0.63, 1.03) and 14 (RR 1.00; 95% CI 0.90, 1.139). Chloroquine has no statistically significant effect in decreasing the time of viral negativity at days 7 (RR 1.20; 95%CI 0.64, 2.25) and 14 (RR 1.08; 95%CI 0.85, 1.36). There is no difference in the need for mechanical ventilation among hydroxychloroquine plus azithromycin versus standard of care groups. Hydroxychloroquine marginally increased the mortality rate compared to placebo but not statistically significant (RR 1.09; P-value 0.05). Adding azithromycin to hydroxychloroquine had no statistically significant effect of decreasing mortality (RR 0.52; 95%CI 0.13, 2.07). Treatments with hydroxychloroquine increased the risk of adverse effects (RR 2.71; 95%CI 1.66, 4.43; p-value <0.0001). Adding azithromycin to hydroxychloroquine increased the adverse events (RR 1.74; 95% CI 1.27, 2.38). Conclusion: Though access to antivirals is an important challenge in developing countries, the decision to sus-pend hydroxychloroquine and chloroquine in treating COVID-19 appears right
Assuntos
Humanos , Masculino , Feminino , Terapêutica , Cloroquina , COVID-19 , Hidroxicloroquina , PandemiasRESUMO
O presente projeto propõe analisar estratégias argumentativas na circulação de informação envolvendo o uso de cloroquina (difosfato de cloroquina) e hidroxicloroquina (sulfato de hidroxicloroquina) para tratamento da Covid-19 no YouTube Brasil, entre os meses de março a julho de 2020, em perfis da plataforma. Os atores sociais que emergem e o contexto político social no Brasil pandêmico também nos guiam para a construção de uma linha do tempo, em uma sucessão de acontecimentos recentes envolvendo os dois medicamentos, médicos/cientistas e o Governo Federal. Nosso intento é refazer a trajetória das substâncias, os argumentos utilizados para validar a terapêutica para Covid-19 em detrimento de medidas não farmacológicas. Foi construída uma perspectiva biográfica e etnográfica para analisar as tentativas de legitimação desses medicamentos por médicos e pesquisadores durante o primeiro ano da pandemia de Covid-19, bem como foram consultados documentos oficiais do Governo Federal de modo a enriquecer o estudo. Assim, propomos uma reflexão acerca das falas proferidas por médicos e cientistas defensores do uso desses dois medicamentos, recorrendo aos programas de TV repostadas em perfis do YouTube e aos debates em lives, focalizando na análise etnográfica do conteúdo do material. AU
The present project proposes to analyze argumentative strategies in the circulation of information involving the use of chloroquine (chloroquine diphosphate) and hydroxychloroquine (hydroxychloroquine sulfate) for Covid-19 treatment on YouTube Brazil, between the months of March and July 2020, in profiles on the platform. The emerging social actors and the social political context in pandemic Brazil also guide us to construct a timeline, in a succession of recent events involving the two drugs, doctors/scientists, and the federal government. Our intent is to retrace the trajectory of the substances, the arguments used to validate the therapy for Covid-19 in detriment of non-pharmacological measures. A biographical and ethnographic perspective was built to analyze the attempts to legitimize these drugs by doctors and researchers during the first year of the Covid-19 pandemic, as well as official documents from the Federal Government were consulted in order to enrich the study. Thus, we propose a reflection about the speeches given by doctors and scientists who defend the use of these two drugs, resorting to tv shows reposted in YouTube profiles and debates in lives, focusing on the ethnographic analysis of the content of the material. AU