RESUMO
The COVID-19 pandemic has brought concerns to managers, healthcare professionals, and the general population related to the potential mechanical ventilators' shortage for severely ill patients. In Brazil, there are several initiatives aimed at producing alternative ventilators to cover this gap. To assist the teams that work in these initiatives, we provide a discussion of some basic concepts on physiology and respiratory mechanics, commonly used mechanical ventilation terms, the differences between triggering and cycling, the basic ventilation modes and other relevant aspects, such as mechanisms of ventilator-induced lung injury, respiratory drive, airway heating and humidification, cross-contamination risks, and aerosol dissemination. After the prototype development phase, preclinical bench-tests and animal model trials are needed to determine the safety and performance of the ventilator, following the minimum technical requirements. Next, it is mandatory going through the regulatory procedures as required by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA). The manufacturing company should be appropriately registered by ANVISA, which also must be notified about the conduction of clinical trials, following the research protocol approval by the Research Ethics Committee. The registration requisition of the ventilator with ANVISA should include a dossier containing the information described in this paper, which is not intended to cover all related matters but to provide guidance on the required procedures.
A pandemia por COVID-19 tem deixado os gestores, os profissionais de saúde e a população preocupados com a potencial escassez de ventiladores pulmonares para suporte de pacientes graves. No Brasil, há diversas iniciativas com o intuito de produzir ventiladores alternativos para ajudar a suprir essa demanda. Para auxiliar as equipes que atuam nessas iniciativas, são expostos alguns conceitos básicos sobre fisiologia e mecânica respiratória, os termos comumente utilizados no contexto da ventilação mecânica, as fases do ciclo ventilatório, as diferenças entre disparo e ciclagem, os modos ventilatórios básicos e outros aspectos relevantes, como mecanismos de lesão pulmonar induzida pela ventilação mecânica, pacientes com drive respiratório, necessidade de umidificação de vias aéreas, risco de contaminação cruzada e disseminação de aerossóis. Após a fase de desenvolvimento de protótipo, são necessários testes pré-clínicos de bancada e em modelos animais, a fim de determinar a segurança e o desempenho dos equipamentos, seguindo requisitos técnicos mínimos exigidos. Então, é imprescindível passar pelo processo regulatório exigido pela Agência Nacional de Vigilância Sanitária (ANVISA). A empresa responsável pela fabricação do equipamento deve estar regularizada junto à ANVISA, que também deve ser notificada da condução dos testes clínicos em humanos, seguindo protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. O registro do ventilador junto à ANVISA deve ser acompanhado de um dossiê, composto por documentos e informações detalhadas neste artigo, que não tem o propósito de esgotar o assunto, mas de nortear os procedimentos necessários.
Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Respiração Artificial/instrumentação , Ventiladores Mecânicos , Animais , Brasil/epidemiologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Desenho de Equipamento , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Mecânica Respiratória , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controleRESUMO
RESUMO A pandemia por COVID-19 tem deixado os gestores, os profissionais de saúde e a população preocupados com a potencial escassez de ventiladores pulmonares para suporte de pacientes graves. No Brasil, há diversas iniciativas com o intuito de produzir ventiladores alternativos para ajudar a suprir essa demanda. Para auxiliar as equipes que atuam nessas iniciativas, são expostos alguns conceitos básicos sobre fisiologia e mecânica respiratória, os termos comumente utilizados no contexto da ventilação mecânica, as fases do ciclo ventilatório, as diferenças entre disparo e ciclagem, os modos ventilatórios básicos e outros aspectos relevantes, como mecanismos de lesão pulmonar induzida pela ventilação mecânica, pacientes com drive respiratório, necessidade de umidificação de vias aéreas, risco de contaminação cruzada e disseminação de aerossóis. Após a fase de desenvolvimento de protótipo, são necessários testes pré-clínicos de bancada e em modelos animais, a fim de determinar a segurança e o desempenho dos equipamentos, seguindo requisitos técnicos mínimos exigidos. Então, é imprescindível passar pelo processo regulatório exigido pela Agência Nacional de Vigilância Sanitária (ANVISA). A empresa responsável pela fabricação do equipamento deve estar regularizada junto à ANVISA, que também deve ser notificada da condução dos testes clínicos em humanos, seguindo protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. O registro do ventilador junto à ANVISA deve ser acompanhado de um dossiê, composto por documentos e informações detalhadas neste artigo, que não tem o propósito de esgotar o assunto, mas de nortear os procedimentos necessários.
ABSTRACT The COVID-19 pandemic has brought concerns to managers, healthcare professionals, and the general population related to the potential mechanical ventilators' shortage for severely ill patients. In Brazil, there are several initiatives aimed at producing alternative ventilators to cover this gap. To assist the teams that work in these initiatives, we provide a discussion of some basic concepts on physiology and respiratory mechanics, commonly used mechanical ventilation terms, the differences between triggering and cycling, the basic ventilation modes and other relevant aspects, such as mechanisms of ventilator-induced lung injury, respiratory drive, airway heating and humidification, cross-contamination risks, and aerosol dissemination. After the prototype development phase, preclinical bench-tests and animal model trials are needed to determine the safety and performance of the ventilator, following the minimum technical requirements. Next, it is mandatory going through the regulatory procedures as required by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA). The manufacturing company should be appropriately registered by ANVISA, which also must be notified about the conduction of clinical trials, following the research protocol approval by the Research Ethics Committee. The registration requisition of the ventilator with ANVISA should include a dossier containing the information described in this paper, which is not intended to cover all related matters but to provide guidance on the required procedures.
Assuntos
Humanos , Animais , Pneumonia Viral/terapia , Respiração Artificial/instrumentação , Ventiladores Mecânicos , Infecções por Coronavirus/terapia , Pneumonia Viral/epidemiologia , Brasil/epidemiologia , Mecânica Respiratória , Infecções por Coronavirus/epidemiologia , Desenho de Equipamento , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Pandemias , COVID-19RESUMO
BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).
Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/uso terapêutico , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Feminino , Próteses Valvulares Cardíacas , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos , Rivaroxabana/efeitos adversos , Tromboembolia/mortalidadeRESUMO
BACKGROUND: It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels <150 mmHg in this population is currently based on experts' opinion. To clarify this issue, we systematically reviewed and quantified available evidence on the impact of achieving different SBP levels <150 mmHg on various adverse outcomes in subjects aged ≥60 years old receiving antihypertensive drug treatment. METHODS: We searched 8 databases to identify randomized controlled trials (RCTs) and post-hoc analyses or subanalyses of RCTs reporting the effects of attaining different SBP levels <150 mmHg on the risk of stroke, acute myocardial infarction, heart failure, cardiovascular mortality and all-cause mortality in participants aged ≥60 years. We performed random-effects meta-analyses stratified by study design. RESULTS: Eleven studies (> 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg. CONCLUSIONS: Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/fisiopatologia , Idoso , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento de Redução do RiscoRESUMO
Consumption of food products enriched with plant sterols and the use of ezetimibe reduce cholesterol absorption in the intestine and effectively reduce low-density lipoprotein (LDL) plasma levels. We evaluated the therapeutic effect of the ezetimibe+plant sterol association in patients with coronary artery disease still not reaching recommended lipid levels despite the use of statins. We performed a prospective open-label study with 41 patients with stable coronary disease and LDL >70 mg/dL. Patients were randomized into four groups for a 6-week treatment: the control (CT) group remained on the same statin therapy, the ezetimibe (EZ) group received 10 mg/day of ezetimibe, the plant sterol (PS) group received spread enriched with 2 g of plant sterols, and the ezetimibe+PS (EZ+PS) group received 10 mg/day EZ +2 g PS. Initial mean LDL level was 97.4 ± 31.1 mg/dL in control group, 105.1 ± 23.1 mg/dL in EZ group, 95.4 ± 27.7 mg/dL in PS group, and 97.0 ± 8.3 mg/dL in EZ+PS group (P > .05). After 6 weeks of treatment, LDL of patients slightly increased in the control group (+8.9%; P > .05) and dropped in EZ group (-19.1%; P = .06), PS group (-16.6%; P = .01), and EZ+PS group (-27.3%; P < .01). Mean LDL levels after treatment were 70.5 ± 17.9 mg/dL in EZ+PS group, lower than the other groups (control was 106.1 ± 34.9 mg/dL, EZ group was 85.0 ± 35.6 mg/dL, and PS was 79.6 ± 29.7 mg/dL) (P = .05 variance analysis factor [ANOVA]). Body weight, body-mass index, and glucose plasma levels did not change significantly after intervention. The combination of PS+ezetimibe was associated with lower LDL levels and suggests beneficial therapeutic effect against major cardiovascular events.
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteínas LDL/sangue , Fitosteróis/administração & dosagem , Adulto , Idoso , Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana/sangue , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic complications and premature valve failure. DESIGN: GALILEO is an international, randomized, open-label, event-driven, phase III trial in more than 1,520 patients without an indication for oral anticoagulation who underwent a successful TAVR (ClinicalTrials.govNCT02556203). Patients are randomized (1:1 ratio), 1 to 7days after a successful TAVR, to either a rivaroxaban-based strategy or an antiplatelet-based strategy. In the experimental arm, subjects receive rivaroxaban (10mg once daily [OD]) plus acetylsalicylic acid (ASA, 75-100mg OD) for 90days followed by rivaroxaban alone. In the control arm, subjects receive clopidogrel (75mg OD) plus ASA (as above) for 90days followed by ASA alone. In case new-onset atrial fibrillation occurs after randomization, full oral anticoagulation will be implemented with maintenance of the original treatment assignment. The primary efficacy end point is the composite of all-cause death, stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, and systemic embolism. The primary safety end point is the composite of life-threatening, disabling, and major bleeding, according to the Valve Academic Research Consortium definitions. CONCLUSIONS: GALILEO will test the hypothesis that a rivaroxaban-based antithrombotic strategy reduces the risk of thromboembolic complications post-TAVR with an acceptable risk of bleeding compared with the currently recommended antiplatelet therapy-based strategy in subjects without need of chronic oral anticoagulation.
Assuntos
Estenose da Valva Aórtica/cirurgia , Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/uso terapêutico , Substituição da Valva Aórtica Transcateter , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Clopidogrel , Quimioterapia Combinada , Embolia/epidemiologia , Embolia/prevenção & controle , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/prevenção & controle , Humanos , Mortalidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Cuidados Pós-Operatórios/métodos , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Trombose/epidemiologia , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controleRESUMO
BACKGROUND: Early termination of clinical trials due to low recruitment represents an understudied challenge for clinical research. We aimed to describe characteristics of cardiovascular trials terminated because of low recruitment and identify the major predictors of such early termination. METHODS: We reviewed all cardiovascular clinical trials (7,042 studies) registered in ClinicalTrials.gov from February 29, 2000, to January 17, 2013, and assessed information about trials that were completed and those that were terminated early. Logistic regression models were developed to identify independent predictors of early termination due to low recruitment. RESULTS: Our search strategy identified 6,279 cardiovascular clinical trials, of which 684 (10.9%) were terminated prematurely. Of these halted trials, the main reason for termination was lower than expected recruitment (278 trials; 53.6%). When comparing trials that terminated early because of low recruitment with those that were completed, we found that studies funded by the National Institutes of Health or other US federal agencies (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.14-0.89), studies of behavior/diet intervention (OR 0.35, 95% CI 0.19-0.65), and single-arm design studies (OR 0.57, 95% CI 0.42-0.78) were associated with a lower risk of early termination. University/hospital-funded (OR 1.52, 95% CI 1.10-2.10) and mixed-source-funded studies (OR 2.14, 95% CI 1.52-3.01) were associated with a higher likelihood of early termination due to lower than expected recruitment rates. CONCLUSIONS: Low recruitment represents the main cause of early termination of cardiovascular clinical trials. Funding source, type of intervention, and study design are factors associated with early termination due to low recruitment and might be good targets for improving enrollment into cardiovascular clinical trials.
Assuntos
Doenças Cardiovasculares , Ensaios Clínicos como Assunto , Término Precoce de Ensaios Clínicos/estatística & dados numéricos , Seleção de Pacientes , Adulto , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , National Library of Medicine (U.S.) , Prevalência , Sistema de Registros/estatística & dados numéricos , Viés de Seleção , Estados UnidosRESUMO
Tight control of blood glucose reduces cardiovascular events and total mortality is conflicting. To summarize clinical effects of tight versus conventional glucose control in patients with type 2 diabetes. We systematically searched MEDLINE, EMBASE, Cochrane Library, and ISI Web of Knowledge with no limits of language and time. Further trials were searched from the reference lists of identified studies. We included randomized controlled comparing different levels of blood glucose control intensity in type 2 diabetic patients. Two independent reviewers extracted data of eligible studies using standard case report forms. We investigated total mortality, cardiovascular and microvascular events, and hypoglycemia in patients with type 2 diabetes. We used random-effects models to obtain relative risks (RR) with 95% confidence intervals (CI). We included 6 trials involving 27,654 patients. There was no significant effect of tight blood glucose control on all-cause mortality (RR 1.03; 95% CI 0.90-1.17) or cardiovascular mortality (RR 1.04; 95% CI 0.83-1.29). Tight glucose control reduced the risk for nonfatal MI (RR 0.85; 95% CI 0.76-0.95), although had no effect on the incidence of nonfatal stroke (RR 1.02; 95% CI 0.88-1.17). For microvascular events, tight glucose control reduced the risk progression of retinopathy (RR 0.80; 95% CI 0.71-0.91), incidence of peripheral neuropathy (RR 0.94; 95% CI 0.89-0.99), and progression of nephropathy (RR 0.55; 95% CI 0.37-0.80), but had not significant effect on the incidence of nephropathy (RR 0.69; 95% CI 0.42-1.14). The risk of severe hypoglycemia increased with tight glucose control (RR 2.39; 95% CI 1.79-3.18). Tight blood glucose control reduces the risk for some macrovascular and microvascular events, without effect on all-cause mortality and cardiovascular mortality. Tight glucose control increases the risk of severe hypoglycemia.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/terapia , Idoso , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
CONTEXT: Studies have found that patients with acute coronary syndromes (ACS) often do not receive evidence-based therapies in community practice. This is particularly true in low- and middle-income countries. OBJECTIVE: To evaluate whether a multifaceted quality improvement (QI) intervention can improve the use of evidence-based therapies and reduce the incidence of major cardiovascular events among patients with ACS in a middle-income country. DESIGN, SETTING, AND PARTICIPANTS: The BRIDGE-ACS (Brazilian Intervention to Increase Evidence Usage in Acute Coronary Syndromes) trial, a cluster-randomized (concealed allocation) trial conducted among 34 clusters (public hospitals) in Brazil and enrolling a total of 1150 patients with ACS from March 15, 2011, through November 2, 2011, with follow-up through January 27, 2012. INTERVENTION: Multifaceted QI intervention including educational materials for clinicians, reminders, algorithms, and case manager training, vs routine practice (control). MAIN OUTCOME MEASURES: Primary end point was the percentage of eligible patients who received all evidence-based therapies (aspirin, clopidogrel, anticoagulants, and statins) during the first 24 hours in patients without contraindications. RESULTS: Mean age of the patients enrolled was 62 (SD, 13) years; 68.6% were men, and 40% presented with ST-segment elevation myocardial infarction, 35.6% with non-ST-segment elevation myocardial infarction, and 23.6% with unstable angina. The randomized clusters included 79.5% teaching hospitals, all from major urban areas and 41.2% with 24-hour percutaneous coronary intervention capabilities. Among eligible patients (923/1150 [80.3%]), 67.9% in the intervention vs 49.5% in the control group received all eligible acute therapies (population average odds ratio [OR(PA)], 2.64 [95% CI, 1.28-5.45]). Similarly, among eligible patients (801/1150 [69.7%]), those in the intervention group were more likely to receive all eligible acute and discharge medications (50.9% vs 31.9%; OR(PA),, 2.49 [95% CI, 1.08-5.74]). Overall composite adherence scores were higher in the intervention clusters (89% vs 81.4%; mean difference, 8.6% [95% CI, 2.2%-15.0%]). In-hospital cardiovascular event rates were 5.5% in the intervention group vs 7.0% in the control group (OR(PA), 0.72 [95% CI, 0.36-1.43]); 30-day all-cause mortality was 7.0% vs 8.4% (ORPA, 0.79 [95% CI, 0.46-1.34]). CONCLUSION: Among patients with ACS treated in Brazil, a multifaceted educational intervention resulted in significant improvement in the use of evidence-based therapies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00958958.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Administração de Caso , Prática Clínica Baseada em Evidências/estatística & dados numéricos , Melhoria de Qualidade , Síndrome Coronariana Aguda/mortalidade , Idoso , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Brasil , Lista de Checagem , Clopidogrel , Países em Desenvolvimento , Educação Médica Continuada , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária , Sistemas de Alerta , Método Simples-Cego , Ticlopidina/análogos & derivados , População UrbanaRESUMO
Translating evidence into clinical practice in the management of acute coronary syndromes (ACS) is challenging. Few ACS quality improvement interventions have been rigorously evaluated to determine their impact on patient care and clinical outcomes. We designed a pragmatic, 2-arm, cluster-randomized trial involving 34 clusters (Brazilian public hospitals). Clusters were randomized to receive a multifaceted quality improvement intervention (experimental group) or routine practice (control group). The 6-month educational intervention included reminders, care algorithms, a case manager, and distribution of educational materials to health care providers. The primary end point was a composite of evidence-based post-ACS therapies within 24 hours of admission, with the secondary measure of major cardiovascular clinical events (death, nonfatal myocardial infarction, nonfatal cardiac arrest, and nonfatal stroke). Prescription of evidence-based therapies at hospital discharge were also evaluated as part of the secondary outcomes. All analyses were performed by the intention-to-treat principle and took the cluster design into account using individual-level regression modeling (generalized estimating equations). If proven effective, this multifaceted intervention would have wide use as a means of promoting optimal use of evidence-based interventions for the management of ACS.
Assuntos
Síndrome Coronariana Aguda/terapia , Gerenciamento Clínico , Medicina Baseada em Evidências/métodos , Hospitais Públicos/estatística & dados numéricos , Melhoria de Qualidade/organização & administração , Brasil , Método Duplo-Cego , HumanosRESUMO
BACKGROUND: Leukocytes total count is an independent risk marker for cardiovascular events. The ratio between neutrophils and lymphocytes (N/L) count has been investigated as a new predictor for cardiovascular risk, although its diagnostic role when assessing patients suspected of an acute coronary syndrome (ACS) condition is not yet known. OBJECTIVE: To evaluate the diagnostic power of N/L ratio in patients who have been admitted at a Chest Pain Unit (CPU) with the suspicion of ACS. METHODS: Evaluation was conducted in 178 patients admitted with chest pain. Diagnostic flowchart including clinical, electrocardiographic, and laboratory data. Diagnosis obtained was: acute myocardial infarction (AMI) with (AMI-STE) and with no segment T elevation (AMI-NSTE), unstable angina (UA ) and non-cardiac pain (NC). Total and differential leukocyte count was conducted in peripheral blood sample collected at admission. RESULTS: Patients diagnosed with non-cardiac pain reported the lowest N/L ratio (n=45; 3.0 +/- 1.6), followed by UA (n=65; 3.6 +/- 2.9), AMI-NSTE (n=33; 4.8 +/- 3.7) and AMI-STE (n=35; 6.9 +/- 5.7); p < 0.0001. N/L ratio above 5.7 (highest quartile) reported 91.1% specificity, 4.51 odds ratio (CI 95% 1.51 to 13.45) for the final diagnosis of ACS when compared to the groups at lower quartiles. CONCLUSION: The N/L ratio presents correlation with final diagnosis of patients with suspicion of ACS at admission. Considering this is a low cost, good reproductibility test, new studies should ellucidate whether the ratio may be of relevance for diagnosis flowcharts currently in use.
Assuntos
Síndrome Coronariana Aguda/sangue , Angina Instável/sangue , Dor no Peito/sangue , Linfócitos/patologia , Infarto do Miocárdio/sangue , Neutrófilos/patologia , Síndrome Coronariana Aguda/diagnóstico , Biomarcadores/sangue , Métodos Epidemiológicos , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-IdadeRESUMO
FUNDAMENTO: A contagem total de leucócitos é um marcador de risco independente para eventos cardiovasculares. A relação entre a contagem de neutrófilos e linfócitos (N/L) tem sido explorada como novo preditor de risco cardiovascular, mas seu papel diagnóstico na avaliação de pacientes com suspeita de síndrome coronariana aguda (SCA) é desconhecido. OBJETIVO: Avaliar o valor diagnóstico da relação N/L em pacientes admitidos com suspeita de SCA em uma Unidade de Dor Torácica (UDT). MÉTODOS: Foram avaliados 178 pacientes admitidos com dor torácica, seguindo fluxograma diagnóstico conforme aspectos clínicos, eletrocardiográficos e laboratoriais. Os diagnósticos estabelecidos foram: infarto agudo do miocárdio com (IAMEST) e sem elevação de segmento ST (IAMSEST), angina instável (AI) e dor não-cardíaca (NC). Contagens total e diferencial de leucócitos foram realizadas em amostra de sangue periférico coletada na admissão. RESULTADOS: Pacientes com dor diagnosticada como não-cardíaca apresentaram a menor relação N/L (n = 45; 3,0 ± 1,6), seguidos por AI (n = 65; 3,6 + 2,9), IAMSEST (n = 33; 4,8 ± 3,7) e IAMEST (n = 35; 6,9 ± 5,7) (p < 0,0001). A relação N/L acima de 5,7 (quartil mais elevado) teve especificidade de 91,1 por cento, com odds ratio de 4,51 (intervalo de confiança de 95 por cento [IC 95 por cento], 1,51 a 13,45) para um diagnóstico final de SCA, em comparação com os grupos em quartis menores. CONCLUSÃO: A relação N/L apresenta correlação com o diagnóstico final de pacientes admitidos com suspeita de SCA. Por ser um exame de baixo custo e com boa reprodutibilidade, novos estudos deverão elucidar se a relação poderá ter importância nos fluxogramas diagnósticos atualmente empregados.
BACKGROUND: Leukocytes total count is an independent risk marker for cardiovascular events. The ratio between neutrophils and lymphocytes (N/L) count has been investigated as a new predictor for cardiovascular risk, although its diagnostic role when assessing patients suspected of an acute coronary syndrome (ACS) condition is not yet known. OBJECTIVE: To evaluate the diagnostic power of N/L ratio in patients who have been admitted at a Chest Pain Unit (CPU) with the suspicion of ACS. METHODS: Evaluation was conducted in 178 patients admitted with chest pain. Diagnostic flowchart including clinical, electrocardiographic, and laboratory data. Diagnosis obtained was: acute myocardial infarction (AMI) with (AMI-STE) and with no segment T elevation (AMI-NSTE), unstable angina (UA ) and non-cardiac pain (NC). Total and differential leukocyte count was conducted in peripheral blood sample collected at admission. RESULTS: Patients diagnosed with non-cardiac pain reported the lowest N/L ratio (n=45; 3.0 ± 1.6), followed by UA (n=65; 3.6 ± 2.9), AMI-NSTE (n=33; 4.8 ± 3.7) and AMI-STE (n=35; 6.9 ± 5.7); p < 0.0001. N/L ratio above 5.7 (highest quartile) reported 91.1 percent specificity, 4.51 odds ratio (CI 95 percent 1.51 to 13.45) for the final diagnosis of ACS when compared to the groups at lower quartiles. CONCLUSION: The N/L ratio presents correlation with final diagnosis of patients with suspicion of ACS at admission. Considering this is a low cost, good reproductibility test, new studies should ellucidate whether the ratio may be of relevance for diagnosis flowcharts currently in use.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Coronariana Aguda/sangue , Angina Instável/sangue , Dor no Peito/sangue , Linfócitos/patologia , Infarto do Miocárdio/sangue , Neutrófilos/patologia , Síndrome Coronariana Aguda/diagnóstico , Biomarcadores/sangue , Métodos Epidemiológicos , Contagem de LinfócitosRESUMO
PURPOSE: To evaluate the role of Losartan in skin healing repair. METHODS: One hundred and eleven male Wistar rats were distributed into four groups, at random. Group I (n=31) underwent a laparotomy to induce hypertension by stenosis of the left renal artery, and 48 hours later it received Losartan (10 mg/Kg) daily. Group II (n=30) went through the same procedure and received isotonic saline solution. Group III (n=30) underwent a simulated laparotomy. Group IV (n=20) to confirm the induced hypertension method. Ketamine and Xylazin anesthesia was used in every painful/stressful procedure. After 15 days, skin healing repair was studied by a dorsal midline skin incision and second layer-skin incision in groups I, II and III, that was sutured in one layer with 4-0 nylon suture. Samples of the dorsal wall scar were taken 4, 7 and 14 days after the last procedure, and sent to strength and displacement analysis and histological preparation. RESULTS: By the 4th and 7th days of the analysis, group II scars showed to be less resistant than group III scars (p<0,05). The total amount of collagen was higher in group III on the three studied periods. The percentage occupied by total collagen in the wound area, on the 14th day, was lower in group I, due to its lower percentage of type I collagen CONCLUSION: Scars treated with Losartan were initially less resistant and had a lower collagen deposition.
Assuntos
Anti-Hipertensivos/farmacologia , Colágeno/análise , Hipertensão/tratamento farmacológico , Losartan/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Anti-Hipertensivos/uso terapêutico , Colágeno/metabolismo , Humanos , Losartan/uso terapêutico , Masculino , Ratos , Ratos WistarRESUMO
OBJETIVO: Avaliar a influência do Losartan na reparação de feridas da pele. MÉTODOS: Cento e onze ratos Wistar, machos, foram distribuídos aleatoriamente em quatro grupos. Grupo I (n=31), submetidos à laparotomia com indução de hipertensão pela estenose da artéria renal esquerda e que após 48 horas receberam Losartan (10 mg/Kg) diariamente. Grupo II (n=30) submetidos ao mesmo procedimento e que receberam solução salina isotônica. Grupo III (n=30) submetidos à laparotomia sem indução de hipertensão. Grupo IV (n=20) animais que serviram para a confirmação do método de indução da hipertensão. Anestesia com quetamina e xilazina foi utilizada para todos os procedimentos com dor ou estresse. Após 15 dias, a cicatrização da pele foi estudada fazendo-se uma incisão medial, no dorso, seguida de síntese com sutura de náilon 4.0, nos animais dos grupos I, II e III. As avaliações foram realizadas após 4, 7 e 14 dias verificando-se a resistência e analizando-se as preparações histológicas. RESULTADOS: No 4.º e no 7.º dia as cicatrizes dos animais do grupo I eram menos resistentes do que as do grupo III (p<0,05). A densidade de colágeno era maior nos cortes histológicos do grupo III nos três períodos estudados. A percentagem de colágeno nos campos histológicos analisados, no 14.º dia, era menor no grupo I, devida a baixa densidade de colágeno tipo I. CONCLUSÃO: Feridas tratadas com Losartan são inicialmente menos resistentes e apresentam menor densidade de colágeno.
Assuntos
Animais , Humanos , Masculino , Ratos , Anti-Hipertensivos/farmacologia , Colágeno/análise , Hipertensão/tratamento farmacológico , Losartan/farmacologia , Cicatrização/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Colágeno/metabolismo , Losartan/uso terapêutico , Ratos WistarRESUMO
BACKGROUND: Local invasion is the hallmark of malignant glioma dissemination. Leptomeningeal dissemination, a serious complication of malignant gliomas, has been increasingly observed. To correlate the physiopathologic mechanisms and the magnetic resonance imaging patterns of neuroaxis dissemination, a classification of malignant glioma dissemination is proposed (Instituto de Neurologia de Curitiba Classification). METHODS: This classification includes the following patterns of dissemination: leptomeningeal (type I), nodular (type Ia), diffuse (type Ib); subependymal (type II); satellite (type IIIa, IIIb); and mixed (type IV), combination of 2 or more previous types. Of 138 patients with histologically confirmed gliomas treated between 2000 and 2004, 10 presented neuroaxis dissemination and were evaluated. RESULTS: The distribution of dissemination patterns was as follows: subependymal, 4 of 10; diffuse leptomeningeal, 1 of 10; nodular leptomeningeal, 1 of 10; and satellite, 4 of 10. Mean interval between primary tumor and dissemination was 4 months. The most frequent glioma dissemination risk factor was entering the ventricular system during surgery. CONCLUSIONS: Improvements in our diagnostic imaging capabilities have contributed to a better understanding of the patterns of malignant glioma dissemination. Using this information, we present a useful classification scheme, applicable to patients with neuroaxis dissemination, which will help standardize future discussions aimed at understanding these patterns of tumor spread.
Assuntos
Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , Glioma/classificação , Glioma/secundário , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Feminino , Glioma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Fatores de Risco , Análise de SobrevidaRESUMO
PURPOSE: The aging of the population has led to an increased number of interventions in elderly patients, with hypothyroidism, even at the subclinical level, being a common situation among these patients. The objective of the present study was to determine the influence of hypothyroidism on the healing process of colon anastomoses in aged rats. METHODS: 96 male Wistar rats were used, 48 of them young and 48 old. Half the young animals and half the old ones were euthyroid and half were hypothyroid. Hypothyroidism was obtained by total thyroidectomy. Thirty days after surgery the animals were submitted to median laparotomy followed by transverse colotomy of the left colon with end-to-end anastomosis and laparorrhaphy. Six animals from each group were submitted to euthanasia by drawing lots on the 3rd, 7th and 14th postoperative day and submitted to macroscopic, resistance, and histopathological analysis of the anastomoses. RESULTS: No dehiscence was observed and the gain of resistance and the general histological evolution in terms of epithelialization and inflammatory reaction was similar in all groups. Analysis of total collagen content revealed that the anastomoses of young and old animals showed the same behavior on the 3rd day, although less collagen was observed in hypothyroid animals (YN x YH p = 0.0000; ON x OH p = 0.0000). This behavior persisted on the 7th and 14 day. Less collagen I was present in the anastomoses of hypothyroid animals on the 3 (YN x YH p = 0.0015; ON x OH p = 0.0000), 7th (YN x YH p = 0.0006; ON x OH p = 0.0001) and 14th day (YN x YH p = 0.0181; ON x OH p = 0.0057), the same occurring for collagen III on the 3rd (x YH p = 0.0007; ON x OH p = 0.0260), 7th (YN x YH p = 0.0160; ON x OH p = 0.2670) and 14th day (YN x YH p = 0.0000; ON x OH p = 0.0030). CONCLUSION: Analysis of the results permitted us to conclude that lower collagen concentration du to low synthesis and delayed scar maturation in the anastomoses occurred and was much more due to hypothyroidism than to aging.
Assuntos
Envelhecimento/fisiologia , Colo/cirurgia , Hipotireoidismo/fisiopatologia , Cicatrização/fisiologia , Fatores Etários , Anastomose Cirúrgica , Animais , Biomarcadores/análise , Cicatriz/patologia , Colágeno/análise , Colágeno/biossíntese , Modelos Animais de Doenças , Hipotireoidismo/complicações , Masculino , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Deiscência da Ferida Operatória/fisiopatologia , Resistência à Tração , Fatores de TempoRESUMO
OBJETIVO: O envelhecimento da população tem feito crescer o número de intervenções em pacientes idosos, sendo o hipotireoidismo, ainda que sub-clínico, é uma situação bastante comum nestes doentes. O presente estudo busca conhecer a influência do hipotireoidismo no processo de cicatrização de anastomoses colônicas em ratos idosos. MÉTODO: Utilizaram-se 96 ratos Wistar, machos; 48 deles jovens e 48 velhos. Metade dos animais jovens e metade dos velhos eram eutireoideanos e metade eram hipotireoideanos. Conseguiu-se o hipotireoidismo por meio de tireoidectomia total. Após 30 dias, fez-se uma laparotomia mediana seguida de colotomia transversa de cólon esquerdo com anastomose término-terminal e laparorrafia. No 3.°, 7.° e 14.° dias de pós-operatório, sorteados, 6 animais de cada grupo, que foram submetidos à eutanásia. Fez-se a análise macroscópica das anastomoses, da resistência e estudo histopatológico. RESULTADOS: Não se detectaram deiscências e o ganho de resistência e a evolução histológica geral, considerando epitelização e reação inflamatória foi semelhante em todos os grupos. A análise do conteúdo total de colágeno revelou, no 3.° dia, que as anastomoses de jovens e velhos tinham o mesmo comportamento, porém via-se menos colágeno nas anastomoses dos animais com hipotireoidismo (JN x JH p=0,0000; VN x VH p=0,0000). Este comportamento se manteve no 7.° e no 14.° dia. A presença de colágeno I era menor nas anastomoses dos animais hipotireoideanos no 3.° dia (JN x JH p=0,0015; VN x VH p=0,0000), no 7.° dia (JN x JH p=0,0006; VN x VH p=0,0001) e no 14.° dia (JN x JH p=0,0181; VN x VH p=0,0057) o mesmo acontecendo com o colágeno III, no 3.° dia (x JH p=0,0007; VN x VH p=0,0260), no 7.° dia (JN x JH p=0,0160; VN x VH p=0,2670) e no 14.° dia (JN x JH p=0,0000; VN x VH p=0,0030). CONCLUSÃO: A análise dos resultados permite concluir que existe diminuição da concentração de colágeno decorrente da baixa da síntese e retardo de maturação das cicatrizes das anastomoses muito mais às custas do hipotireoidismo do que do envelhecimento.