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1.
Ann Agric Environ Med ; 27(3): 418-426, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955225

RESUMO

INTRODUCTION AND OBJECTIVE: Burning coal and firewood generates toxic emissions that are associated with respiratory illness, cardiovascular disease, and even death. The aim of the study is to evaluate the association between county-level prevalence of household coal and firewood use and health outcomes, including total, respiratory, and cardiovascular mortality, as well as total and respiratory hospitalization rates. MATERIAL AND METHODS: The ecological study included data on the use of household coal and firewood in 139 counties obtained from the 2015 Chilean National Socio-economic Characterization Survey. Total, respiratory, and cardiovascular mortality, as well as total and respiratory hospitalization rates, were obtained from the Department of Health Statistics. Poisson models with robust error variance, Pearson linear correlation coefficients, and scatterplots were used to explore associations between household coal and firewood use and morbidity-mortality, stratifying by geographic zone. RESULTS: Total, respiratory, and cardiovascular mortality and total and respiratory hospitalization rates were 5.7 per 1,000, 552 per 100,000, 157 per 100,000, 92.5 per 1000, and 8.8 per 1000 inhabitants, respectively. The median prevalence of coal use for residential cooking, heating, or water heating was 3.64%, while the median prevalence of firewood combustion was 12%. In southern counties, age- and gender-adjusted respiratory mortality increased 2.02 (95% CI: 1.17-3.50), 1.5 (95% CI: 1.11-1.89), and 1.76-fold (95% CI: 1.19-2.60) for each percentage increase in household coal and firewood use for heating, cooking and heating water, respectively. CONCLUSIONS: The prevalence of household coal and firewood used for heating and cooking was positively correlated with respiratory mortality and hospitalization in southern zone counties.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Doenças Cardiovasculares/mortalidade , Carvão Mineral/efeitos adversos , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Doenças Respiratórias/mortalidade , Madeira/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Chile/epidemiologia , Culinária , Feminino , Calefação , Humanos , Masculino , Doenças Respiratórias/induzido quimicamente
3.
Rev Med Suisse ; 16(703): 1483-1488, 2020 Aug 26.
Artigo em Francês | MEDLINE | ID: mdl-32852168

RESUMO

The landmark study EMPA-REG OUTCOME firstly demonstrated both a cardiovascular and renal protection with empagliflozin in patients with type 2 diabetes (T2DM) and established cardiovascular disease. Since 2015, two other trials showed a reduction in the hospitalisations for heart failure and the progression of the renal disease, also in patients with multiple risk factors, CANVAS with canagliflozin and DECLARE-TIMI 58 with dapagliflozin. CREDENCE (canagliflozin in T2DM patients with kidney disease) confirmed a renal protection and DAPA-HF (dapagliflozin in patients, with or without T2DM, but reduced ejection fraction) showed a less acute deterioration of heart failure. The positive effect of SGLT2 inhibitors on heart failure predominates, an effect recently confirmed in VERTIS CV with ertugliflozin.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias , Inibidores do Transportador 2 de Sódio-Glicose , Canagliflozina , Doenças Cardiovasculares/induzido quimicamente , Humanos , Hipoglicemiantes , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
5.
Heart Lung Circ ; 29(7): 973-987, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32601020

RESUMO

Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.


Assuntos
Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Administração dos Cuidados ao Paciente/métodos , Pneumonia Viral , Algoritmos , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/classificação , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia
6.
PLoS One ; 15(7): e0235418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614859

RESUMO

BACKGROUND: Little is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs. METHODS: KTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections. RESULTS: A total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3-14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups. CONCLUSIONS: TAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.


Assuntos
Imunossupressão/efeitos adversos , Imunossupressores , Transplante de Rim/reabilitação , Tacrolimo , Adulto , Doenças Cardiovasculares/induzido quimicamente , Estudos de Coortes , Infecções por Citomegalovirus/induzido quimicamente , Feminino , Rejeição de Enxerto/induzido quimicamente , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/induzido quimicamente , Infecções por Polyomavirus/induzido quimicamente , Insuficiência Renal/induzido quimicamente , República da Coreia , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/sangue
7.
Artigo em Inglês | MEDLINE | ID: mdl-32586013

RESUMO

Exposure to surrounding greenness is associated with reduced mortality in Caucasian populations. Little is known however about the relationship between green vegetation and the risk of death in Asian populations. Therefore, we opted to evaluate the association of greenness with mortality in Taiwan. Death information was retrieved from the Taiwan Death Certificate database between 2006 to 2014 (3287 days). Exposure to green vegetation was based on the normalized difference vegetation index (NDVI) collected by the Moderate Resolution Imagine Spectroradiometer (MODIS). A generalized additive mixed model was utilized to assess the association between NDVI exposure and mortality. A total of 1,173,773 deaths were identified from 2006 to 2014. We found one unit increment on NDVI was associated with a reduced mortality due to all-cause (risk ratio [RR] = 0.901; 95% confidence interval = 0.862-0.941), cardiovascular diseases (RR = 0.892; 95% CI = 0.817-0.975), respiratory diseases (RR = 0.721; 95% CI = 0.632-0.824), and lung cancer (RR = 0.871; 95% CI = 0.735-1.032). Using the green land cover as the alternative green index showed the protective relationship on all-cause mortality. Exposure to surrounding greenness was negatively associated with mortality in Taiwan. Further research is needed to uncover the underlying mechanism.


Assuntos
Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/mortalidade , Meio Ambiente , Material Particulado/efeitos adversos , Características de Residência/estatística & dados numéricos , Adolescente , Adulto , Doenças Cardiovasculares/induzido quimicamente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mortalidade , População Rural , Taiwan/epidemiologia , População Urbana , Adulto Jovem
8.
Ecotoxicol Environ Saf ; 201: 110827, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32535366

RESUMO

Numerous experimental and epidemiological studies have demonstrated that exposure to PM2.5 may result in pathogenesis of several major cardiovascular diseases (CVDs), which can be attributed to the combined adverse effects induced by the complicated components of PM2.5. Organic materials, which are major components of PM2.5, contain thousands of chemicals, and most of them are environmental hazards. However, the contamination profile and contribution to overall toxicity of PM2.5-bound organic components (OCs) have not been thoroughly evaluated yet. Herein, we aim to provide an overview of the literature on PM2.5-bound hydrophobic OCs, with an emphasis on the chemical identity and reported impairments on the cardiovascular system, including the potential exposure routes and mechanisms. We first provide an update on the worldwide mass concentration and composition data of PM2.5, and then, review the contamination profile of PM2.5-bound hydrophobic OCs, including constitution, concentration, distribution, formation, source, and identification. In particular, the link between exposure to PM2.5-bound hydrophobic OCs and CVDs and its possible underlying mechanisms are discussed to evaluate the possible risks of PM2.5-bound hydrophobic OCs on the cardiovascular system and to provide suggestions for future studies.


Assuntos
Poluentes Atmosféricos/toxicidade , Doenças Cardiovasculares/induzido quimicamente , Sistema Cardiovascular/efeitos dos fármacos , Monitoramento Ambiental/métodos , Compostos Orgânicos/toxicidade , Material Particulado/toxicidade , Poluentes Atmosféricos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Compostos Orgânicos/química , Material Particulado/química
9.
Lancet Diabetes Endocrinol ; 8(7): 606-615, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32559476

RESUMO

BACKGROUND: Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. METHODS: In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. FINDINGS: Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12·2), 170 335 (44·1%) of 386 248 were women, and 111 933 (30·1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61-0·77; p<0·0001), all-cause death (0·59, 0·52-0·67; p<0·0001), and the composite of hospitalisation for heart failure or all-cause death (0·64, 0·57-0·72; p<0·0001). Risks of myocardial infarction (HR 0·88, 0·80-0·98; p=0·020) and stroke (0·85 0·77-0·93; p=0·0004) were significantly but modestly lower with SGLT2 inhibitors versus DPP-4 inhibitors. INTERPRETATION: In this large, international, observational study, initiation of SGLT2 inhibitors versus DPP-4 inhibitors was associated with lower risks of heart failure, death, myocardial infarction, and stroke, providing further support for the cardiovascular benefits associated with use of SGLT2 inhibitors in patients with type 2 diabetes. FUNDING: AstraZeneca.


Assuntos
Biomarcadores/análise , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Glicemia/análise , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Feminino , Seguimentos , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida
10.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188383, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32535158

RESUMO

Androgen deprivation therapy (ADT) is the primary systemic therapy for treating locally advanced or metastatic prostate cancer (PCa). Despite its positive effect on PCa patient survival, ADT causes various adverse effects, including increased cardiovascular risk factors and cardiotoxicity. Lifespans extension, early use of ADT, and second-line treatment with next-generation androgen receptor pathway inhibitors would further extend the duration of ADT and possibly increase the risk of ADT-induced cardiotoxicity. Meanwhile, information on the molecular mechanisms underlying ADT-induced cardiotoxicity and measures to prevent it is limited, mainly due to the lack of specifically designed preclinical studies and clinical trials. This review article compiles up-to-date evidence obtained from observational studies and clinical trials, in order to gain new insights for deciphering the association between ADT use and cardiotoxicity. In addition, potential cardioprotective strategies involving GnRH receptors and second messenger cGMP are discussed.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/administração & dosagem , Androgênios/metabolismo , Antineoplásicos Hormonais/administração & dosagem , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , GMP Cíclico/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Longevidade/fisiologia , Masculino , Estudos Observacionais como Assunto , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Receptores LHRH/agonistas , Receptores LHRH/antagonistas & inibidores , Receptores LHRH/metabolismo , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento
11.
Am J Physiol Heart Circ Physiol ; 319(2): H282-H305, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32559138

RESUMO

Ambient air, occupational settings, and the use and distribution of consumer products all serve as conduits for toxicant exposure through inhalation. While the pulmonary system remains a primary target following inhalation exposure, cardiovascular implications are exceptionally culpable for increased morbidity and mortality. The epidemiological evidence for cardiovascular dysfunction resulting from acute or chronic inhalation exposure to particulate matter has been well documented, but the mechanisms driving the resulting disturbances remain elusive. In the current review, we aim to summarize the cellular and molecular mechanisms that are directly linked to cardiovascular health following exposure to a variety of inhaled toxicants. The purpose of this review is to provide a comprehensive overview of the biochemical changes in the cardiovascular system following particle inhalation exposure and to highlight potential biomarkers that exist across multiple exposure paradigms. We attempt to integrate these molecular signatures in an effort to provide direction for future investigations. This review also characterizes how molecular responses are modified in at-risk populations, specifically the impact of environmental exposure during critical windows of development. Maternal exposure to particulate matter during gestation can lead to fetal epigenetic reprogramming, resulting in long-term deficits to the cardiovascular system. In both direct and indirect (gestational) exposures, connecting the biochemical mechanisms with functional deficits outlines pathways that can be targeted for future therapeutic intervention. Ultimately, future investigations integrating "omics"-based approaches will better elucidate the mechanisms that are altered by xenobiotic inhalation exposure, identify biomarkers, and guide in clinical decision making.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Sistema Cardiovascular/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Material Particulado/efeitos adversos , Adaptação Fisiológica , Adolescente , Adulto , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Reprogramação Celular , Epigênese Genética , Feminino , Humanos , Masculino , Exposição Materna/efeitos adversos , Camundongos , Pessoa de Meia-Idade , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Medição de Risco , Fatores de Risco , Adulto Jovem
13.
Medicina (B Aires) ; 80(3): 271-274, 2020.
Artigo em Espanhol | MEDLINE | ID: covidwho-344356

RESUMO

Due to the coronavirus disease 2019 (COVID-19) pandemic, a wide number of compounds are under scrutiny regarding their antiviral activity, one of them being hydroxychloroquine. Cardiac aspects of the use of chloroquine and hydroxychloroquine are reviewed in this manuscript. A non-systematic review of the medical literature was performed. Information about their safety and efficacy as antimalarials, antivirals, as well as in the long-term treatment of rheumatic diseases was collected. We found an anti-inflammatory effect with reduction of longterm cardiovascular events, a very infrequent heart disease due to a lysosomal effect of the drug, and at the hemodynamic level hypotension, tachycardia, and QT interval prolongation, exacerbated when combined with azithromycin. However, the rate of adverse cardiac events of hydroxychloroquine (and chloroquine) was low.


Assuntos
Antivirais/efeitos adversos , Betacoronavirus , Doenças Cardiovasculares/induzido quimicamente , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Antirreumáticos/efeitos adversos , Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Pandemias , Fatores de Risco
16.
Life Sci ; 255: 117843, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32464123

RESUMO

Metabolic diseases, such as obesity and type 2 diabetes, are known risk factors for cardiovascular (CV) diseases. Thus, patients with those comorbidities could be at increased risk of experiencing cardiotoxicity related to treatment with Anthracyclines and the other new generation targeted anticancer drugs. However, investigations addressing the mechanisms underlying the development of CV complications and poor outcome in such cohort of patients are still few and controversial. Given the importance of a personalized approach against chemotherapy-induced cardiomyopathy, this review summarizes our current knowledge on the pathophysiology of chemotherapy-induced cardiomyopathy and its association with obesity and type 2 diabetes. Along with clinical evidences, future perspectives of preclinical research around this field and its role in addressing important open questions, including the development of more proactive strategies for prevention, and treatment of cardiotoxicity during and after chemotherapy in the presence of metabolic diseases, is also presented.


Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Doenças Metabólicas/complicações , Animais , Antineoplásicos/administração & dosagem , Cardiotoxicidade/fisiopatologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Humanos , Neoplasias/tratamento farmacológico , Obesidade/complicações , Fatores de Risco
17.
Medicine (Baltimore) ; 99(18): e19976, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358371

RESUMO

OBJECTIVE: The aim of this systematic review and meta-analysis is to assess the cardiovascular (CV) risk of celecoxib on knee osteoarthritis (KOA) patients compared with the risk in those prescribed other non-selective non-steroidal anti-inflammatory drugs (NSAIDs), no intervention or placebo-controlled patients. METHODS: The following databases will be searched: MEDLINE, EMBASE, the Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese Nation Knowledge Infrastructure, Wanfang Database, and the Chongqing VIP from inception to April 1, 2020. All randomized controlled trials (RCTs) of celecoxib that presented data on serious cardiovascular events among KOA patients will be included. Study selection, data extraction, quality assessment, and assessment of risk bias will be performed by 2 reviewers independently. Odds ratios and correlative 95% confidence intervals will be calculated to present the association between the celecoxib and CV risk using Review Manager version 5.3 when there is sufficient available data. ETHICS AND DISSEMINATION: This review does not require ethical approval. The results of this review may be published in a peer-reviewed journal or disseminated at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020166721.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Celecoxib/efeitos adversos , Osteoartrite do Joelho/tratamento farmacológico , Humanos , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Fatores de Risco
18.
Arch Cardiovasc Dis ; 113(6-7): 420-432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32418884

RESUMO

BACKGROUND: The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized. AIM: To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting. METHODS: We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data. RESULTS: MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58-7.07), peripheral oedema (OR 2.87 95% CI 1.93-4.27) and syncope (OR 6.71, 95% CI 3.00-14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03-10.09), peripheral oedema (arOR 1.39, 95% CI 1.17-1.66), syncope (arOR 1.56, 95% CI 1.22-1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04-7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21-1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach. CONCLUSIONS: In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors.


Assuntos
Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Fibrossarcoma/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Bases de Dados Factuais , Feminino , Fibrossarcoma/enzimologia , Fibrossarcoma/epidemiologia , Fibrossarcoma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Segurança do Paciente , Farmacovigilância , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento
19.
Cardiovasc Pathol ; 48: 107219, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32473412

RESUMO

In this review, we summarize previously reported case reports (n=66) in which the presence of ochronotic pigment was found in one or more cardiovascular structures either at necropsy or after operative excision of a cardiac valve or portions of arteries or both. As illustration, we describe black pigment in operatively excised aortic valves and aorta in 2 patients, both probably examples of secondary ochronosis. Ochronosis appears to have fascinated a number of prominent historical figures in medicine, and this review also summarizes their important contributions to this topic.


Assuntos
Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Ácido Homogentísico/metabolismo , Ocronose , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/patologia , Sistema Cardiovascular/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/efeitos adversos , Fatores de Risco
20.
Encephale ; 46(3S): S14-S34, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32376004

RESUMO

The 2019-20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage - in case of minimal infectious signs and in a situation, which does not allow rapid control - should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Transtornos Mentais/tratamento farmacológico , Pandemias , Pneumonia Viral , Psicotrópicos/uso terapêutico , Fatores Etários , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Biotransformação , Doenças Cardiovasculares/induzido quimicamente , Comorbidade , Continuidade da Assistência ao Paciente , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Citocromo P-450 CYP1A2/metabolismo , Interações Medicamentosas , Febre/induzido quimicamente , França/epidemiologia , Gastroenteropatias/induzido quimicamente , Humanos , Transtornos Mentais/induzido quimicamente , Transtornos Mentais/epidemiologia , Preparações Farmacêuticas/provisão & distribução , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Psicotrópicos/administração & dosagem , Psicotrópicos/efeitos adversos , Psicotrópicos/farmacocinética , Transtornos Respiratórios/induzido quimicamente , Medição de Risco , Abandono do Hábito de Fumar , Avaliação de Sintomas
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