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1.
BMJ ; 372: n526, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649077

RESUMO

CLINICAL QUESTION: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. RECOMMENDATION: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). HOW THIS GUIDELINE WAS CREATED: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. UNDERSTANDING THE NEW RECOMMENDATION: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. UPDATES: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. READERS NOTE: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.


Assuntos
/prevenção & controle , Quimioprevenção , Hidroxicloroquina/farmacologia , Medição de Risco , /epidemiologia , Quimioprevenção/métodos , Quimioprevenção/normas , Tomada de Decisão Clínica/métodos , Humanos , Fatores Imunológicos/farmacologia , Incerteza , Organização Mundial da Saúde
2.
PLoS One ; 16(2): e0247163, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33592050

RESUMO

BACKGROUND: Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers. METHODS: A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection. RESULTS: Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection. CONCLUSION: Two-dose ivermectin prophylaxis at a dose of 300 µg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic.


Assuntos
/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Ivermectina/uso terapêutico , Adulto , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/uso terapêutico , Estudos de Casos e Controles , Quimioprevenção/métodos , Combinação de Medicamentos , Feminino , Humanos , Índia , Ivermectina/administração & dosagem , Masculino , Pessoa de Meia-Idade
3.
Int J Mol Sci ; 22(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498364

RESUMO

The high number of new cancer incidences and the associated mortality continue to be alarming, leading to the search for new therapies that would be more effective and less burdensome for patients. As there is evidence that Se compounds can have chemopreventive activity, studies have begun to establish whether these compounds can also affect already existing cancers. This review aims to discuss the different classes of Se-containing compounds, both organic and inorganic, natural and synthetic, and the mechanisms and molecular targets of their anticancer activity. The chemical classes discussed in this paper include inorganic (selenite, selenate) and organic compounds, such as diselenides, selenides, selenoesters, methylseleninic acid, 1,2-benzisoselenazole-3[2H]-one and selenophene-based derivatives, as well as selenoamino acids and Selol.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Compostos de Selênio/uso terapêutico , Animais , Antineoplásicos/química , Quimioprevenção/métodos , Ensaios Clínicos como Assunto , Humanos , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Compostos de Selênio/química
4.
PLoS One ; 15(12): e0244451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373997

RESUMO

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.


Assuntos
Coinfecção/tratamento farmacológico , Assistência à Saúde/organização & administração , Infecções por HIV/tratamento farmacológico , Implementação de Plano de Saúde , Hanseníase/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Assistência ao Convalescente/organização & administração , Assistência ao Convalescente/estatística & dados numéricos , Antirretrovirais/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Quimioprevenção/métodos , Estudos de Coortes , Coinfecção/microbiologia , Assistência à Saúde/métodos , Assistência à Saúde/estatística & dados numéricos , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por HIV/virologia , Humanos , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Modelos Organizacionais , Mycobacterium leprae/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Equipe de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/estatística & dados numéricos , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Uganda , Adulto Jovem
5.
Int J Mol Sci ; 21(24)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33334002

RESUMO

Polycystic ovary syndrome (PCOS) is characterized by elevated androgen production and subclinical changes in cardiovascular and metabolic risk markers. Total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glucose, and fasting insulin appear to increase specifically in PCOS compared with fertile women. PCOS also confers an increased risk of cardiometabolic disease in later life. Novel biomarkers such as serum's cholesterol efflux capacity and blood-derived macrophage activation profile may assist in more accurately defining the cardiometabolic risk profile in these women. Aldosterone antagonists, androgen receptor antagonists, 5α-reductase inhibitors, and synthetic progestogens are used to reduce hyperandrogenism. Because increased insulin secretion enhances ovarian androgen production, short-term treatment with metformin and other hypoglycemic agents results in significant weight loss, favorable metabolic changes, and testosterone reduction. The naturally occurring inositols display insulin-sensitizing effects and may be also used in this context because of their safety profile. Combined oral contraceptives represent the drug of choice for correction of androgen-related symptoms. Overall, PCOS management remains focused on specific targets including assessment and treatment of cardiometabolic risk, according to disease phenotypes. While new options are adding to established therapeutic approaches, a sometimes difficult balance between efficacy and safety of available medications has to be found in individual women.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Quimioprevenção , Síndrome do Ovário Policístico/complicações , Adulto , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Quimioprevenção/métodos , Anticoncepcionais Orais/farmacologia , Anticoncepcionais Orais/uso terapêutico , Suscetibilidade a Doenças , Feminino , Humanos , Avaliação de Resultados em Cuidados de Saúde , Síndrome do Ovário Policístico/epidemiologia , Medição de Risco , Fatores de Risco
6.
Ann Saudi Med ; 40(6): 462-468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33307734

RESUMO

BACKGROUND: Venous thromboembolism or extensive thrombosis is relatively common in patients with severe COVID-19 infection and has been associated with increased mortality. During the current COVID-19 pandemic, several prophylactic doses and types of low-molecular-weight heparin (LMWH) are being used worldwide; however, there are no high-quality studies or recommendations for an optimal prophylactic LMWH dose. OBJECTIVES: Investigate the relationship between coagulation parameters and the LMWH dose, and mortality and ICU admission in hospitalized patients with severe COVID-19 pneumonia. DESIGN: Retrospective. SETTING: Tertiary care hospital. PATIENTS AND METHODS: Data on clinical features, coagulation parameters and anticoagulant medications of inpatients with severe COVID-19 were collected for the period between 11 March 2020 and 31 April 2020. MAIN OUTCOME MEASURES: Mortality and ICU admission for prophylactic dose LMWH (0.5 mg/kg twice daily) and therapeutic dose LMWH (1 mg/kg twice daily). SAMPLE SIZE: 154 cases. RESULTS: Ninety-eight (63.6%) patients were treated with the LMWH prophylactic dose and 56 (36.4%) patients were treated with the therapeutic dose. Forty-four (44.9%) of 98 patients using the prophylactic dose LMWH died, while 10 (17.9%) of 56 patients using the therapeutic dose LMWH died (P=.001). Mortality was 6.4-fold higher in the prophylactic dose LMWH users than in the therapeutic dose LMWH users (OR=6.5, 95% CI: 2.4-17.6, P<.001). CONCLUSIONS: Therapeutic dosing of LMWH may decrease mortality in patients with severe COVID-19 infected pneumonia. More aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies. LIMITATIONS: Lack of information about bleeding complications. LMWH was not compared with other anticoagulant therapies. There was no comparison between our two groups on the APACHE score. Used different doses of LMWH in different clinics in our hospital. Single-center, retrospective study. CONFLICT OF INTEREST: None.


Assuntos
Quimioprevenção/métodos , Heparina de Baixo Peso Molecular , /isolamento & purificação , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , /mortalidade , /terapia , Relação Dose-Resposta a Droga , Feminino , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Tromboembolia/sangue , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Turquia/epidemiologia
8.
Ann R Coll Surg Engl ; 102(9): 712-716, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32969260

RESUMO

INTRODUCTION: Portal and mesenteric venous thrombosis is a rare but potentially serious complication after laparoscopic sleeve gastrectomy. There are no consistent studies that prove the safety and effectiveness of oral anticoagulant thromboprophylaxis with rivaroxaban after laparoscopic sleeve gastrectomy. The objective was to evaluate the effect of rivaroxaban on the frequency of portal and mesenteric venous thrombosis and its safety profile after laparoscopic sleeve gastrectomy. MATERIALS AND METHODS: This retrospective analysis of prospectively collected data includes all laparoscopic sleeve gastrectomies performed by a single surgeon at Pontificia Universidad Católica de Chile Hospital between January 2009 and June 2019. All patients received low molecular weight heparin thromboprophylaxis during the whole hospital stay. Between July 2012 and June 2019, patients received additional post-discharge thromboprophylaxis with rivaroxaban. Patient demographics, impaired renal, post-surgical portal and mesenteric venous thrombosis, and bleeding episodes were registered. RESULTS: A total of 516 patients were identified; 95 patients were excluded. Results for 421 patients were analysed: 198 received only intrahospital thromboprophylaxis (group 1) and 223 received additional post-discharge thromboprophylaxis with rivaroxaban (group 2). There was no statistically significant difference between the two groups concerning age, sex and body mass index. In group 1, four cases of portal and mesenteric venous thrombosis were registered and no cases were reported in group 2 (p < 0.05). All cases occurred before 30 days after surgery. No bleeding episodes and no adverse reactions were detected in group 2. CONCLUSIONS: Thromboprophylaxis during the whole hospital stay (two to three days), followed by rivaroxaban 10mg once daily for 10 days after discharge (completing in total 13-14 days of prophylaxis), could reduce cases of post-surgical portal and mesenteric venous thrombosis without an increase in bleeding complications.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos , Isquemia Mesentérica/prevenção & controle , Rivaroxabana/uso terapêutico , Adulto , Quimioprevenção/métodos , Feminino , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Masculino , Estudos Retrospectivos
9.
Mil Med Res ; 7(1): 41, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887670

RESUMO

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.


Assuntos
Quimioprevenção/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Alta do Paciente/normas , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto
10.
Mil. med. res. (Lond.) ; 7(41): 1-33, Sept. 04, 2020.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1129883

RESUMO

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients


Assuntos
Humanos , Adulto , Plasma/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Cloroquina/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Quimioprevenção/métodos , Receptores de Interleucina-6/uso terapêutico , Antirretrovirais/uso terapêutico , Pandemias/prevenção & controle , Lopinavir/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Prática Clínica Baseada em Evidências/métodos
11.
Front Med ; 14(5): 674-680, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32761492

RESUMO

We report the clinical and laboratory findings and successful management of seven patients with critical coronavirus disease 2019 (COVID-19) requiring mechanical ventilation (MV). The patients were diagnosed based on epidemiological history, clinical manifestations, and nucleic acid testing. Upon diagnosis with COVID-19 of critical severity, the patients were admitted to the intensive care unit, where they received early noninvasive-invasive sequential ventilation, early prone positioning, and bundle pharmacotherapy regimen, which consists of antiviral, anti-inflammation, immune-enhancing, and complication-prophylaxis medicines. The patients presented fever (n = 7, 100%), dry cough (n = 3, 42.9%), weakness (n = 2, 28.6%), chest tightness (n = 1, 14.3%), and/or muscle pain (n = 1, 14.3%). All patients had normal or lower than normal white blood cell count/lymphocyte count, and chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs. Nucleic acid testing confirmed COVID-19 in all seven patients. The median MV duration and intensive care unit stay were 9.9 days (interquartile range, 6.5-14.6 days; range, 5-17 days) and 12.9 days (interquartile range, 9.7-17.6 days; range, 7-19 days), respectively. All seven patients were extubated, weaned off MV, transferred to the common ward, and discharged as of the writing of this report. Thus, we concluded that good outcomes for patients with critical COVID-19 can be achieved with early noninvasive-invasive sequential ventilation and bundle pharmacotherapy.


Assuntos
Antivirais/administração & dosagem , Infecções por Coronavirus , Estado Terminal/terapia , Ventilação não Invasiva/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Quimioprevenção/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Tomografia Computadorizada por Raios X/métodos , Desmame do Respirador/métodos
12.
PLoS Med ; 17(8): e1003214, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32822362

RESUMO

BACKGROUND: Seasonal malaria chemoprevention (SMC) is now widely deployed in the Sahel, including several countries that are major contributors to the global burden of malaria. Consequently, it is important to understand whether SMC continues to provide a high level of protection and how SMC might be improved. SMC was evaluated using data from a large, household-randomised trial in Houndé, Burkina Faso and Bougouni, Mali. METHODS AND FINDINGS: The parent trial evaluated monthly SMC plus either azithromycin (AZ) or placebo, administered as directly observed therapy 4 times per year between August and November (2014-2016). In July 2014, 19,578 children aged 3-59 months were randomised by household to study group. Children who remained within the age range 3-59 months in August each year, plus children born into study households or who moved into the study area, received study drugs in 2015 and 2016. These analyses focus on the approximately 10,000 children (5,000 per country) under observation each year in the SMC plus placebo group. Despite high coverage and high adherence to SMC, the incidence of hospitalisations or deaths due to malaria and uncomplicated clinical malaria remained high in the study areas (overall incidence rates 12.5 [95% confidence interval (CI): 11.2, 14.1] and 871.1 [95% CI: 852.3, 890.6] cases per 1,000 person-years, respectively) and peaked in July each year, before SMC delivery began in August. The incidence rate ratio comparing SMC within the past 28 days with SMC more than 35 days ago-adjusted for age, country, and household clustering-was 0.13 (95% CI: 0.08, 0.20), P < 0.001 for malaria hospitalisations and deaths from malaria and 0.21 (95% CI 0.20, 0.23), P < 0.001 for uncomplicated malaria, indicating protective efficacy of 87.4% (95% CI: 79.6%, 92.2%) and 78.3% (95% CI: 76.8%, 79.6%), respectively. The prevalence of malaria parasitaemia at weekly surveys during the rainy season and at the end of the transmission season was several times higher in children who missed the SMC course preceding the survey contact, and the smallest prevalence ratio observed was 2.98 (95% CI: 1.95, 4.54), P < 0.001. The frequency of molecular markers of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance did not increase markedly over the study period either amongst study children or amongst school-age children resident in the study areas. After 3 years of SMC deployment, the day 28 PCR-unadjusted adequate clinical and parasitological response rate of the SP + AQ regimen in children with asymptomatic malaria was 98.3% (95% CI: 88.6%, 99.8%) in Burkina Faso and 96.1% (95% CI: 91.5%, 98.2%) in Mali. Key limitations of this study are the potential overdiagnosis of uncomplicated malaria by rapid diagnostic tests and the potential for residual confounding from factors related to adherence to the monthly SMC schedule. CONCLUSION: Despite strong evidence that SMC is providing a high level of protection, the burden of malaria remains substantial in the 2 study areas. These results emphasise the need for continuing support of SMC programmes. A fifth monthly SMC course is needed to adequately cover the whole transmission season in the study areas and in settings with similar epidemiology. TRIAL REGISTRATION: The AZ-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT02211729.


Assuntos
Antimaláricos/administração & dosagem , Características da Família , Malária/epidemiologia , Malária/prevenção & controle , Estações do Ano , Burkina Faso/epidemiologia , Quimioprevenção/métodos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Malária/sangue , Masculino , Mali/epidemiologia
13.
BMJ Case Rep ; 13(8)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747596
14.
Am J Cardiovasc Drugs ; 20(5): 393-403, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32748336

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought many unique pathologies, such as coagulopathy, prompting a desperate need for effective management. COVID-19-associated coagulopathy (CAC) can cause various thromboembolic complications, especially in critically ill patients. The pathogenesis is likely due to endothelial injury, immobilization, and an increase in circulating prothrombotic factors. Data on treatment are limited, although prophylactic anticoagulation is advised in all hospitalized patients. Herein, we have comprehensively reviewed the current literature available on CAC and highlight the pathogenesis, clinical features, and management of CAC.


Assuntos
Transtornos da Coagulação Sanguínea , Quimioprevenção/métodos , Infecções por Coronavirus , Fármacos Hematológicos/farmacologia , Pandemias , Pneumonia Viral , Trombofilia , Betacoronavirus/fisiologia , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Transtornos da Coagulação Sanguínea/prevenção & controle , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Humanos , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Trombofilia/tratamento farmacológico , Trombofilia/virologia
15.
J Transl Med ; 18(1): 322, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847594

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has led to a declaration of a Public Health Emergency of International Concern by the World Health Organization. As of May 18, 2020, there have been more than 4.7 million cases and over 316,000 deaths worldwide. COVID-19 is caused by a highly infectious novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to an acute infectious disease with mild-to-severe clinical symptoms such as flu-like symptoms, fever, headache, dry cough, muscle pain, loss of smell and taste, increased shortness of breath, bilateral viral pneumonia, conjunctivitis, acute respiratory distress syndromes, respiratory failure, cytokine release syndrome (CRS), sepsis, etc. While physicians and scientists have yet to discover a treatment, it is imperative that we urgently address 2 questions: how to prevent infection in immunologically naive individuals and how to treat severe symptoms such as CRS, acute respiratory failure, and the loss of somatosensation. Previous studies from the 1918 influenza pandemic have suggested vitamin D's non-classical role in reducing lethal pneumonia and case fatality rates. Recent clinical trials also reported that vitamin D supplementation can reduce incidence of acute respiratory infection and the severity of respiratory tract diseases in adults and children. According to our literature search, there are no similar findings of clinical trials that have been published as of July 1st, 2020, in relation to the supplementation of vitamin D in the potential prevention and treatment for COVID-19. In this review, we summarize the potential role of vitamin D extra-renal metabolism in the prevention and treatment of the SARS-CoV-2 infection, helping to bring us slightly closer to fulfilling that goal. We will focus on 3 major topics here: 1. Vitamin D might aid in preventing SARS-CoV-2 infection: Vitamin D: Overview of Renal and Extra-renal metabolism and regulation. Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis. Vitamin D: Overview of local immunomodulation in human infectious diseases. Anti-viral infection. Anti-malaria and anti-systemic lupus erythematosus (SLE). 2. Vitamin D might act as a strong immunosuppressant inhibiting cytokine release syndrome in COVID-19: Vitamin D: Suppression of key pro-inflammatory pathways including nuclear factor kappa B (NF-kB), interleukin-6 (IL-6), and tumor necrosis factor (TNF). 3. Vitamin D might prevent loss of neural sensation in COVID-19 by stimulating expression of neurotrophins like Nerve Growth Factor (NGF): Vitamin D: Induction of key neurotrophic factors. .


Assuntos
Quimioprevenção/métodos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Imunomodulação/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Vitamina D/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Suplementos Nutricionais , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/fisiologia , Neuroproteção/efeitos dos fármacos , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Vitamina D/metabolismo , Vitamina D/farmacologia , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/virologia
16.
Am Surg ; 86(9): 1185-1193, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32723180

RESUMO

BACKGROUND: Venous thromboembolism (VTE) remains a serious complication for trauma patients. While early VTE prophylaxis has gained traction, the timing of prophylaxis remains uncertain. We hypothesized that VTE prophylaxis within 24 hours of admission would have lower VTE rates and similar rates of adverse events in seriously injured patients. METHODS: Trauma patients were included from 32 American College of Surgeons verified Level 1 and 2 trauma centers over a 10-year period. Patients with injury severity score (ISS) <15, death or discharge within 48 hours of arrival, or who received no prophylaxis were excluded. RESULTS: 14 096 patients received VTE prophylaxis with an ISS of ≥15. Patients given prophylaxis at <24 hours had fewer VTE events and trended toward fewer serious in-hospital complications. Mortality and return to the operating room were similar across groups. Hospital and intensive care unit length of stay in the <24 hours prophylaxis group was significantly shorter when VTE prophylaxis was initiated earlier. CONCLUSIONS: In severely injured trauma patients with ISS >15, early VTE prophylaxis within 24 hours significantly reduced the risk of VTE as compared with delayed prophylaxis. Early chemoprophylaxis was found to be efficacious in reducing the incidence of VTE; however, the safety of this practice should be evaluated by future prospective studies.


Assuntos
Anticoagulantes/uso terapêutico , Quimioprevenção/métodos , Unidades de Terapia Intensiva/estatística & dados numéricos , Medição de Risco/métodos , Centros de Traumatologia/estatística & dados numéricos , Tromboembolia Venosa/prevenção & controle , Ferimentos e Lesões/complicações , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Ferimentos e Lesões/diagnóstico
17.
Am J Trop Med Hyg ; 103(2): 679-683, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32524945

RESUMO

Mass drug administration (MDA) with azithromycin (AZ) has been used successfully to control trachoma. However, several studies have shown that MDA with AZ has led to the emergence of resistance to AZ in Streptococcus pneumoniae. The emergence of resistance to AZ has also been observed when this antibiotic was combined with the antimalarials used for seasonal malaria chemoprevention (SMC). The development of antibiotic resistance, including resistance to AZ, is sometimes associated with the emergence of a bacterial clone that belongs to a specific serotype. We hypothesize that the increase in resistance of S. pneumoniae observed after 3 years of SMC with AZ might be associated with a change in the distribution of pneumococcal serotypes. Therefore, 698 randomly selected isolates from among the 1,468 isolates of S. pneumoniae obtained during carriage studies undertaken during an SMC plus AZ trial were serotyped. A polymerase chain reaction (PCR) multiplex assay using an algorithm adapted to the detection of the pneumococcal serotypes most prevalent in African countries was used for initial serotyping, and the Quellung technique was used to complement the PCR technique when necessary. Fifty-six serotypes were detected among the 698 isolates of S. pneumoniae. A swift appearance and disappearance of many serotypes was observed, but some serotypes including 6A, 19F, 19A, 23F, and 35B were persistent. The distribution of serotypes between isolates obtained from children who had received AZ or placebo was similar. An increase in AZ resistance was seen in several serotypes following exposure to AZ. Mass drug administration with AZ led to the emergence of resistance in pneumococci of several different serotypes and did not appear to be linked to the emergence of a single serotype.


Assuntos
Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Azitromicina/uso terapêutico , Portador Sadio/microbiologia , Farmacorresistência Bacteriana , Malária/prevenção & controle , Administração Massiva de Medicamentos , Nasofaringe/microbiologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Amodiaquina/uso terapêutico , Burkina Faso , Quimioprevenção/métodos , Pré-Escolar , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Pirimetamina/uso terapêutico , Estações do Ano , Sorogrupo , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/fisiologia , Sulfadoxina/uso terapêutico
18.
Dig Dis Sci ; 65(8): 2181-2186, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32537704

RESUMO

Coronavirus disease of 2019 (COVID-19) can be associated with high morbidity and mortality; patients with severe clinical manifestations may develop significant coagulopathy as well as unexpected thromboembolic complications. In response, centers are increasingly treating selected patients with intermediate-dose prophylactic or even therapeutic dose anticoagulation in order to prevent potentially catastrophic thrombotic complications. With this changing practice, the authors suspect that inpatient gastrointestinal consult teams across the country will be frequently managing COVID-19 patients with gastrointestinal bleeding (GIB). In order to reduce potentially avoidable hospital readmissions for GIB while improving patient outcomes, it is imperative to appropriately risk-stratify patients prior to initiation of anticoagulation. In this review, we discuss how to appropriately identify high-risk patients for GIB and how to mitigate GIB risk with proton-pump inhibitor co-therapy, medication reconciliation, and Helicobacter pylori testing and treating in this complex and morbid population.


Assuntos
Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea , Infecções por Coronavirus/sangue , Hemorragia Gastrointestinal , Pneumonia Viral/sangue , Inibidores da Bomba de Prótons/uso terapêutico , Risco Ajustado/métodos , Anticoagulantes/administração & dosagem , Betacoronavirus/isolamento & purificação , Transtornos da Coagulação Sanguínea/prevenção & controle , Transtornos da Coagulação Sanguínea/virologia , Quimioprevenção/métodos , Quimioprevenção/normas , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Pandemias
19.
PLoS Negl Trop Dis ; 14(6): e0008277, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32569275

RESUMO

BACKGROUND: Better knowledge of the efficacy and safety of single-dose 40 mg/kg oral praziquantel in preschool-age children is required, should preventive chemotherapy programs for schistosomiasis be expanded to include this age group. METHODOLOGY: We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged <6 years) and 2,010 school-age children (aged 6-14 years). Children had a documented Schistosoma mansoni or S. haematobium infection, were treated with single 40 mg/kg oral praziquantel, and assessed between 21 and 60 days post-treatment. Efficacy was expressed as arithmetic mean and individual egg reduction rate (ERR) and meta-analyzed using general linear models and mixed models. Safety was summarized using reported adverse events (AEs). PRINCIPAL FINDINGS: Preschool-age children had significantly lower baseline Schistosoma egg counts and more losses to follow-up compared to school-age children. No difference in efficacy was found between preschool- and school-age children using a general linear model of individual-participant ERR with baseline log-transformed egg count as covariate and study, age, and sex as fixed variables, and a mixed model with a random effect on the study. Safety was reported in only four studies (n = 1,128 individuals); few AEs were reported in preschool-age children 4 and 24 hours post-treatment as well as at follow-up. Three severe but not serious AEs were recorded in school-age children during follow-up. CONCLUSIONS/SIGNIFICANCE: There is no indication that single-dose 40 mg/kg oral praziquantel would be less efficacious and less safe in preschool-age children compared to school-age children, with the caveat that only few randomized comparisons exist between the two age groups. Preventive chemotherapy might therefore be extended to preschool-age children, with proper monitoring of its efficacy and safety.


Assuntos
Anti-Helmínticos/administração & dosagem , Quimioprevenção/métodos , Praziquantel/administração & dosagem , Esquistossomose Urinária/prevenção & controle , Esquistossomose mansoni/prevenção & controle , Administração Oral , Adolescente , Animais , Anti-Helmínticos/efeitos adversos , Criança , Pré-Escolar , Fezes/parasitologia , Feminino , Humanos , Modelos Lineares , Masculino , Contagem de Ovos de Parasitas , Praziquantel/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Schistosoma haematobium , Schistosoma mansoni , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose mansoni/tratamento farmacológico , Resultado do Tratamento
20.
Ann Hematol ; 99(7): 1429-1440, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32514626

RESUMO

With the advent of new targeted drugs in hematology and oncology patient prognosis is improved. Combination with antifungal prophylaxis challenges clinicians due to pharmacological profiles prone to drug-drug interactions (DDI). Midostaurin is a novel agent for FLT3-TKD/-ITDmut-acute myeloid leukemia (AML) and metabolized via cytochrome P450 3A4 (CYP3A4). Posaconazole is a standard of care antifungal agent used for prophylaxis during induction treatment of AML and a strong CYP3A4 inhibitor. Concomitant administration of both drugs leads to elevated midostaurin exposure. Both drugs improve overall survival at low numbers needed to treat. The impact of CYP3A4-related DDI remains to be determined. Severe adverse events have been observed; however, it remains unclear if they can be directly linked to DDI. The lack of prospective clinical studies assessing incidence of invasive fungal infections and clinical impact of DDI contributes to neglecting live-saving antifungal prophylaxis. Management strategies to combine both drugs have been proposed, but evidence on which approach to use is scarce. In this review, we discuss several approaches in the specific clinical setting of concomitant administration of midostaurin and posaconazole and give examples from everyday clinical practice. Therapeutic drug monitoring will become increasingly important to individualize and personalize antineoplastic concomitant and antifungal treatment in the context of DDI. Pharmaceutical companies addressing the issue in clinical trials may take a pioneer role in this field. Other recently developed and approved drugs for the treatment of AML likely inhere potential of DDI marking a foreseeable issue in future treatment of this life-threatening disease.


Assuntos
Antifúngicos/uso terapêutico , Quimioprevenção/tendências , Infecções Fúngicas Invasivas/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Estaurosporina/análogos & derivados , Triazóis/uso terapêutico , Antifúngicos/classificação , Quimioprevenção/métodos , Interações Medicamentosas , Drogas em Investigação/uso terapêutico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/microbiologia , Leucemia Mieloide Aguda/mortalidade , Prognóstico , Estaurosporina/uso terapêutico
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