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1.
Infect Dis Ther ; 13(1): 1-19, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38193988

RESUMO

Despite the wide availability of effective vaccines, COVID-19 continues to be an infectious disease of global importance. Remdesivir is a broad-spectrum antiviral and was the first US Food and Drug Administration-approved treatment for COVID-19. In clinical guidelines, remdesivir is currently the only recommended antiviral for use in hospitalized patients with COVID-19, with or without a supplemental oxygen requirement. It is also recommended for nonhospitalized patients with COVID-19 and hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who are at high risk of progression to severe disease. This narrative review explores the evidence for remdesivir across various clinical outcomes and evolution of clinical guidelines through a survey over time of randomized controlled trials, observational studies, and meta-analyses. Remdesivir, compared to standard of care, appears to improve survival and disease progression in a variety of patient populations with COVID-19 across a spectrum of disease severity and SARS-CoV-2 variant periods. Remdesivir also appears to improve time to clinical recovery, increase rate of recovery, and reduce time on supplemental oxygen and readmission rates. More recent large, real-world studies further support the early use of remdesivir in a range of patient populations, including those with immunocompromising conditions.


When people get sick with COVID-19, which is caused by the SARS-CoV-2 virus, treatment with an antiviral may be needed to prevent serious illness. Remdesivir is an antiviral and was the first US Food and Drug Administration-approved treatment for COVID-19. Studies have found that treating COVID-19 with remdesivir can save lives and keep patients from getting sicker. Remdesivir appears to help patients get better faster, need oxygen treatment for less time, and avoid having to go back to the hospital. Newer studies with patients treated in real-world settings, outside of controlled research environments, show that early treatment with remdesivir is likely to help many different groups of patients, including those with health conditions that weaken their body's ability to fight infection. Because of this research, guidelines recommend that remdesivir should be given to some patients with COVID-19 outside of the hospital and to those who need to stay in the hospital for COVID-19. Remdesivir should also be given to those who need to stay in the hospital for other reasons but have COVID-19 and a health condition that puts them at risk of serious illness.

2.
JAMA Netw Open ; 7(5): e2411717, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38787561

RESUMO

Importance: For patients with nonspine bone metastases, short-course radiotherapy (RT) can reduce patient burden without sacrificing clinical benefit. However, there is great variation in uptake of short-course RT across practice settings. Objective: To evaluate whether a set of 3 implementation strategies facilitates increased adoption of a consensus recommendation to treat nonspine bone metastases with short-course RT (ie, ≤5 fractions). Design, Setting, and Participants: This prospective, stepped-wedge, cluster randomized quality improvement study was conducted at 3 community-based cancer centers within an existing academic-community partnership. Rollout was initiated in 3-month increments between October 2021 and May 2022. Participants included treating physicians and patients receiving RT for nonspine bone metastases. Data analysis was performed from October 2022 to May 2023. Exposures: Three implementation strategies-(1) dissemination of published consensus guidelines, (2) personalized audit-and-feedback reports, and (3) an email-based electronic consultation platform (eConsult)-were rolled out to physicians. Main Outcomes and Measures: The primary outcome was adherence to the consensus recommendation of short-course RT for nonspine bone metastases. Mixed-effects logistic regression at the bone metastasis level was used to model associations between the exposure of physicians to the set of strategies (preimplementation vs postimplementation) and short-course RT, while accounting for patient and physician characteristics and calendar time, with a random effect for physician. Physician surveys were administered before implementation and after implementation to assess feasibility, acceptability, and appropriateness of each strategy. Results: Forty-five physicians treated 714 patients (median [IQR] age at treatment start, 67 [59-75] years; 343 women [48%]) with 838 unique nonspine bone metastases during the study period. Implementing the set of strategies was not associated with use of short-course RT (odds ratio, 0.78; 95% CI, 0.45-1.34; P = .40), with unadjusted adherence rates of 53% (444 lesions) preimplementation vs 56% (469 lesions) postimplementation; however, the adjusted odds of adherence increased with calendar time (odds ratio, 1.68; 95% CI, 1.20-2.36; P = .003). All 3 implementation strategies were perceived as being feasible, acceptable, and appropriate; only the perception of audit-and-feedback appropriateness changed before vs after implementation (19 of 29 physicians [66%] vs 27 of 30 physicians [90%]; P = .03, Fisher exact test), with 20 physicians (67%) preferring reports quarterly. Conclusions and Relevance: In this quality improvement study, a multicomponent set of implementation strategies was not associated with increased use of short-course RT within an academic-community partnership. However, practice improved with time, perhaps owing to secular trends or physician awareness of the study. Audit-and-feedback was more appropriate than anticipated. Findings support the need to investigate optimal approaches for promoting evidence-based radiation practice across settings.


Assuntos
Neoplasias Ósseas , Melhoria de Qualidade , Humanos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/radioterapia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Fidelidade a Diretrizes/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos
3.
J Racial Ethn Health Disparities ; 10(6): 2775-2782, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36417149

RESUMO

BACKGROUND: Compared with White patients, Black and Latinx patients have higher infection, hospitalization, and mortality rates from COVID-19; yet, little is known about their perspective before, during, and after a COVID-19 hospitalization. The objective of this study conducted in White, Black, and Latinx patients was to assess perceptions of their COVID-19-related hospitalization from onset of symptoms through the post-discharge period to identify disparities in their perceived care. METHODS: A cross-sectional observational study using an online survey from May 19 to June 23, 2021, was conducted by The Harris Poll in 200 White, 200 Black, and 201 Latinx patients hospitalized for COVID-19 in the US. Main measures obtained included baseline demographic variables, socioeconomic status, and social determinants of health. Survey questions were specific to key aspects of the patient experience before, during, and after a COVID-19-related hospitalization. RESULTS: Compared with White patients, Latinx and Black patients faced unique challenges in their healthcare journey including higher likelihood of delaying their hospitalization (10% Black vs. 4% White patients, respectively, P = 0.025), lower perceived satisfaction with care (82% Latinx vs 91% White patients, P = 0.002), and lower trust in providers following their hospitalization (85% White vs. 65% Latinx [P = 0.027] and 73% Black [P = 0.050] patients). CONCLUSIONS: Patient perceptions of their COVID-19 hospitalization experience revealed disparities in perceived quality of care among minority groups. These findings offer insights that health inequities still exist, and strategies need to be taken to make health care delivery more equitable.


Assuntos
Assistência ao Convalescente , COVID-19 , Humanos , Estudos Transversais , Pacientes Internados , Alta do Paciente , Atenção à Saúde , Hospitais
4.
J Neurointerv Surg ; 11(1): 80-83, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30026256

RESUMO

We report two serial neuroendovascular cases of hydrophilic polymer embolic complications, and highlight a unique case of a routine diagnostic cerebral angiogram that was complicated by delayed intracranial hemorrhage requiring surgical decompression. Histopathology specimens revealed organized intravascular thrombi with foci of non-polarizable, basophilic foreign material. Shavings from the hydrophilic coatings of a standard diagnostic catheter and guidewire share histologic characteristics with this intravascular foreign material, confirming the diagnosis of hydrophilic polymer emboli. While this phenomenon has been described for complex neurointerventional procedures, it is rare with routine diagnostic cerebral angiography. Along with a detailed literature review, these cases provides further evidence that even basic hydrophilic coated catheters and/or wires may contribute to the etiology of iatrogenic emboli in the neurovasculature with the potential for acute and subacute complications, requiring further investigation.


Assuntos
Cateterismo/efeitos adversos , Catéteres/efeitos adversos , Angiografia Cerebral/efeitos adversos , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/etiologia , Polímeros/efeitos adversos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Feminino , Corpos Estranhos , Humanos , Hemorragias Intracranianas/terapia , Masculino , Polímeros/administração & dosagem
6.
Pharmacotherapy ; 26(9): 1241-6, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16945045

RESUMO

STUDY OBJECTIVE: To determine the effect of an ephedra-containing thermogenic herbal compound (TrimSpa) on rate-corrected QT (QTc) interval duration and systolic blood pressure. DESIGN: Randomized, double-blind, placebo-controlled, crossover, intent-to-treat study. SETTING: Student laboratory at a college of pharmacy. SUBJECTS: Thirteen healthy volunteers (eight men, five women). INTERVENTION: Participants were given TrimSpa, which contains more than 30 ingredients including ephedra 15 mg and caffeine 60 mg, or matching placebo 3 times/day for 7 days in a crossover fashion with a 7-day washout period between treatments. MEASUREMENTS AND MAIN RESULTS: Each subject's QTc interval and systolic blood pressure were measured on days 1, 4, and 7. These measurements were performed immediately before study drug ingestion (baseline) and 0.5, 1, and 3 hours after ingestion. No differences in these variables were found between the TrimSpa and placebo groups. In one subject taking TrimSpa, the QTc interval increased 96 msec from baseline, more than double the largest increase in the placebo group. CONCLUSION: Standard doses of TrimSpa did not induce changes in subjects' QTc intervals or systolic blood pressures. However, because the QTc interval dramatically changed in one subject taking TrimSpa, a large study is needed to determine if the effect is an artifact or if the subject represents a subset of people for whom the drug may pose a risk.


Assuntos
Suplementos Nutricionais , Ephedra , Preparações de Plantas/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Cafeína/efeitos adversos , Cafeína/farmacologia , Estudos Cross-Over , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Eletrocardiografia/efeitos dos fármacos , Ephedra/efeitos adversos , Feminino , Humanos , Masculino , Preparações de Plantas/efeitos adversos , Plantas Medicinais/efeitos adversos
7.
Circulation ; 108 Suppl 1: II200-6, 2003 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-12970233

RESUMO

BACKGROUND: The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown. METHODS AND RESULTS: Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2x2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% (P=0.037 and P=0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions, P=0.047 and P=0.040, respectively). CONCLUSIONS: Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.


Assuntos
Amiodarona/uso terapêutico , Fibrilação Atrial/prevenção & controle , Estimulação Cardíaca Artificial , Administração Oral , Idoso , Amiodarona/administração & dosagem , Fibrilação Atrial/economia , Terapia Combinada , Ponte de Artéria Coronária , Determinação de Ponto Final , Feminino , Átrios do Coração , Septos Cardíacos , Implante de Prótese de Valva Cardíaca , Custos Hospitalares , Humanos , Infusões Intravenosas , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Torácicos
8.
Am J Cardiol ; 94(11): 1423-5, 2004 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-15566917

RESUMO

Excessive fluid administration after cardiothoracic surgery has been proposed as a cause of postoperative atrial fibrillation. In this study, we observed that fluid balance and volume administered on postoperative day 2 was greater in patients who developed postoperative AF than in those who did not. We also found that net fluid balance on postoperative day 2 was an independent predictor of postoperative AF among patients not receiving prophylactic therapy.


Assuntos
Fibrilação Atrial/etiologia , Ponte de Artéria Coronária/efeitos adversos , Hidratação/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Complicações Pós-Operatórias/etiologia , Equilíbrio Hidroeletrolítico , Idoso , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
9.
Expert Opin Investig Drugs ; 13(5): 465-77, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15155122

RESUMO

Ximelagatran and bivalirudin are direct thrombin inhibitors that have been studied for the prevention and treatment of thrombosis and have potential advantages over the traditional indirect thrombin inhibitors (i.e., warfarin, unfractionated heparin and low molecular-weight heparin). They are both reversible inhibitors of thrombin and block both circulating and fibrin-bound thrombin. Ximelagatran and bivalirudin possess favourable pharmacokinetic and pharmacodynamic profiles including wider therapeutic indices, faster onsets of action and less interpatient variability compared to indirect thrombin inhibitors. Ximelagatran has shown favourable clinical trial results in venous thromboembolism prophylaxis and atrial fibrillation. Similarly, bivalirudin has shown positive results in patients with acute coronary syndromes, however, further investigation is needed. Ximelagatran and bivalirudin have shown promising results in the management of thrombosis and the results of future studies confirming their use for the aforementioned indications are anticipated.


Assuntos
Antitrombinas/uso terapêutico , Azetidinas/uso terapêutico , Hirudinas/análogos & derivados , Fragmentos de Peptídeos/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Doença Aguda , Administração Oral , Antitrombinas/química , Antitrombinas/farmacologia , Azetidinas/química , Azetidinas/farmacologia , Benzilaminas , Ensaios Clínicos Fase III como Assunto , Doença das Coronárias/tratamento farmacológico , Método Duplo-Cego , Hirudinas/química , Hirudinas/farmacologia , Humanos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Síndrome , Trombose/tratamento farmacológico , Trombose/prevenção & controle
10.
Ann Thorac Surg ; 77(4): 1288-92, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15063253

RESUMO

BACKGROUND: Atrial fibrillation is a common complication of cardiothoracic surgery (coronary artery bypass graft surgery or cardiac valve repair or replacement). Although predictors of postoperative atrial fibrillation have been explored in patients not receiving prophylactic antiarrhythmic therapy, independent predictors of postoperative atrial fibrillation in patients receiving prophylactic amiodarone have not been elucidated. METHODS: This was a substudy of a clinical trial evaluating the efficacy of an amiodarone regimen or an atrial-septal pacing strategy on the occurrence of postoperative atrial fibrillation. The association between the occurrence of postoperative atrial fibrillation and preoperative, intraoperative, and postoperative data from the total study population and the amiodarone and placebo subpopulations were explored using multiple logistic regression analysis. RESULTS: The following clinical factors were independent predictors of postoperative atrial fibrillation in the total population: age (p < 0.001), history of atrial fibrillation (p = 0.021), diabetes mellitus (p = 0.008), and high-dose postoperative nonsteroidal antiinflammatory drug use (p = 0.038). Age (p = 0.016), history of mitral regurgitation (p = 0.029), heart failure (p = 0.010), and postoperative nonsteroidal antiinflammatory drug use (p = 0.038) were independent predictors when amiodarone was used, and age was the only predictor of postoperative atrial fibrillation (p = 0.024) among patients treated with placebo. CONCLUSIONS: This subanalysis demonstrates some novel predictors of postoperative atrial fibrillation, including diabetes mellitus and postoperative nonsteroidal antiinflammatory drug use. We have also demonstrated that predictors of atrial fibrillation differ when prophylactic amiodarone is used.


Assuntos
Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Idoso , Fibrilação Atrial/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cuidados Pré-Operatórios , Fatores de Risco
11.
Pharmacotherapy ; 22(5): 564-8, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12013354

RESUMO

STUDY OBJECTIVE: To evaluate the effects of changing volume status on P-wave duration and dispersion in patients with decompensated heart failure. DESIGN: Prospective analysis. SETTING: Hospital cardiology unit. PATIENTS: Twenty-one patients with symptoms of decompensated heart failure who were treated with diuretics on admission. INTERVENTION: Twelve-lead electrocardiograms were obtained at baseline and after diuresis. Average, minimum, and maximum P-wave duration and P-wave dispersion (minimum minus maximum duration) were determined. MEASUREMENTS AND MAIN RESULTS: P-wave duration was measured manually in all 12 leads by using a 0.5-mm-scale precision ruler and magnifying lens. After 40+/-23 hours of diuresis, 3+/-1 L of fluid was removed. A significant correlation was found between average P-wave duration and amount of fluid removed (r = -0.59, p=0.015). Also, average and maximum P-wave duration were significantly decreased with diuresis (p=0.001 and 0.022, respectively). No other P-wave variables were significantly affected. CONCLUSIONS: Diuresis may attenuate electrophysiologic changes caused by fluid overload.


Assuntos
Diurese/fisiologia , Eletrocardiografia , Insuficiência Cardíaca/fisiopatologia , Idoso , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Eletrofisiologia , Feminino , Furosemida/efeitos adversos , Furosemida/uso terapêutico , Humanos , Masculino , Estudos Prospectivos
12.
Pharmacotherapy ; 23(3): 296-300, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12627926

RESUMO

STUDY OBJECTIVE: To determine the effect of intravenous magnesium sulfate on the QT and QTc intervals in patients receiving ibutilide for immediate chemical cardioversion of atrial flutter or fibrillation. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Hospital cardiology unit. PATIENTS: Twenty patients (mean age 72 +/- 14 yrs) with atrial fibrillation (12 patients) or atrial flutter (8 patients) who were scheduled to receive ibutilide. INTERVENTION: After determining that the patients' baseline QTc intervals were less than 440 msec and baseline serum magnesium levels were within normal limits (mean 2.1 +/- 0.29 mg/dl), the patients were randomly assigned to receive either a 10-minute infusion of magnesium sulfate 2 g in 50 ml of 0.9% sodium chloride or placebo immediately before ibutilide therapy. An additional 2 g of intravenous magnesium sulfate or placebo was given over 1 hour, 10 minutes after the first dose of ibutilide. MEASUREMENTS AND MAIN RESULTS: QT interval duration was measured manually in all 12 leads by using a 0.5-mm-scale precision ruler and magnifying lens. The QT interval increased 29% from baseline at 30 minutes after ibutilide therapy in the placebo group (p=0.007), but no significant change from baseline occurred in the magnesium sulfate group. The 30-minute QTc interval in the placebo group was 18% higher than the baseline value (p=0.01) but did not change significantly in the magnesium sulfate group. QTc changes from baseline were greater in the placebo group than in the magnesium sulfate group at 30 minutes (75 vs 19 msec, respectively, p=0.04). Magnesium sulfate reduced the risk of an ibutilide-induced QTc interval increase of greater than 30 msec or greater than 60 msec and reduced the risk of a QTc interval value of more than 500 msec by 65%, 60%, and 68%, respectively (p=0.07, p=0.175, and p=0.160). CONCLUSIONS: Prophylactic administration of intravenous magnesium sulfate prevents increases in the QT and QTc interval 30 minutes after the last infusion of ibutilide.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Eletrocardiografia/efeitos dos fármacos , Sulfato de Magnésio/farmacologia , Sulfonamidas/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Sulfato de Magnésio/administração & dosagem , Masculino
13.
Pharmacotherapy ; 24(8): 1013-9, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15338850

RESUMO

STUDY OBJECTIVES: To compare the cost-effectiveness of intravenous plus oral amiodarone, atrial septal pacing, and both strategies combined to prevent atrial fibrillation after open heart surgery. Secondary objectives were to compare the cost-effectiveness of amiodarone versus no amiodarone and of pacing versus no pacing, and to compare hospitalization costs of the various strategies. DESIGN: Piggyback cost analysis of a randomized, 2 x 2 factorial trial. SETTING: Urban academic hospital. PATIENTS: One hundred and sixty patients with coronary artery and/or valvular disease. INTERVENTION: Patients were randomized to receive amiodarone or matching placebo and then further randomized to receive atrial septal pacing or no pacing. MEASUREMENTS AND MAIN RESULTS: The economic analysis was conducted from a hospital perspective. Charges were converted to costs using cost:charge ratios. For the cost-effectiveness analysis, a joint distribution of costs and effectiveness was performed using the nonparametric bootstrap method. Amiodarone plus pacing significantly decreased the frequency of atrial fibrillation after open heart surgery, compared with amiodarone alone, pacing alone, and placebo. Total costs (mean+/-SD) were $27,026+/-30,226 for the placebo group, $22,725+/-17,661 for the amiodarone group, $33,868+/-60,309 for the pacing group, and $18,697+/-8174 for the amiodarone plus pacing group (p=0.27). In the joint distribution cost-effectiveness analysis, when compared with placebo, the probability of lower cost but higher effect (superiority) was 67% for amiodarone, 15% for pacing, and 97% for amiodarone plus pacing. In the multivariate analysis, preoperative beta-blockers and amiodarone were negatively associated with hospital costs (p<0.05). CONCLUSIONS: Data suggest that both amiodarone alone and the combination of amiodarone plus pacing are cost-effective compared with placebo. Additional comparative studies of these strategies are warranted to confirm these findings.


Assuntos
Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/prevenção & controle , Análise Custo-Benefício , Hospitalização/economia , Complicações Pós-Operatórias/prevenção & controle , Administração Oral , Amiodarona/economia , Amiodarona/uso terapêutico , Antiarrítmicos/economia , Antiarrítmicos/uso terapêutico , Estimulação Cardíaca Artificial/economia , Procedimentos Cirúrgicos Cardíacos , Feminino , Humanos , Injeções Intravenosas , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade
14.
Am J Health Syst Pharm ; 60(18): 1841-9, 2003 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-14521034

RESUMO

The chemistry and pharmacology, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, dosing and administration, and pharmacoeconomics of bivalirudin are reviewed; clinical trials of bivalirudin's application in percutaneous coronary intervention (PCI) are also discussed. Bivalirudin is a direct thrombin inhibitor approved for use in PCI. It reversibly binds to thrombin's catalytic site and substrate recognition site and blocks both circulating and fibrin-bound thrombin. Peak concentrations occur in less than 5 minutes after bolus-dose administration, and its half-life is approximately 25 minutes. It is primarily eliminated renally, and dosage reduction may be required in patients with severe renal dysfunction. Two clinical trials have demonstrated that bivalirudin is at least as effective as unfractionated heparin (UFH) in preventing ischemic complications in PCI. Other trials have shown that bivalirudin has beneficial ischemic and hemorrhagic outcomes in a more modern PCI setting (i.e., intracoronary stent placement, clopidogrel, and glycoprotein IIb/IIIa-receptor inhibitors). Bivalirudin combined with provisional glycoprotein IIb/IIIa inhibitors was noninferior to UFH with planned glycoprotein IIb/IIIa inhibitors and superior to UFH alone with respect to ischemic and hemorrhagic endopoints in PCI. Major bleeding with bivalirudin has occurred in approximately 3% of patients in clinical trials, and it is not known to have any interactions with the cytochrome P-450 isoenzyme system. The acquisition cost of bivalirudin in one study was less than the combination of UFH and glycoprotein IIb/IIIa inhibitors. Bivalirudin combined with provisional glycoprotein IIb/IIIa inhibitors appears to be an acceptable alternative to the standard of care and is superior to UFH alone in PCI.


Assuntos
Angioplastia Coronária com Balão , Fibrinolíticos/uso terapêutico , Hirudinas/análogos & derivados , Fragmentos de Peptídeos/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Trombina/antagonistas & inibidores , Doença Aguda , Angioplastia Coronária com Balão/efeitos adversos , Ensaios Clínicos como Assunto , Doença das Coronárias/terapia , Interações Medicamentosas , Fibrinolíticos/economia , Fibrinolíticos/farmacocinética , Hirudinas/economia , Hirudinas/farmacocinética , Humanos , Fragmentos de Peptídeos/economia , Fragmentos de Peptídeos/farmacocinética , Proteínas Recombinantes/economia , Proteínas Recombinantes/farmacocinética , Trombose/etiologia , Trombose/prevenção & controle
15.
J Am Coll Cardiol ; 58(9): 915-22, 2011 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-21851879

RESUMO

OBJECTIVES: We sought to describe the United States and the rest of the world (ROW) outcomes from the major ß-blocker heart failure (HF) trials. BACKGROUND: HF trials have demonstrated differences in outcomes by geographic region. METHODS: Randomized, double-blind, placebo-controlled studies that evaluated ß-blockers in HF patients, had a primary endpoint of mortality, and enrolled U.S. patients were included. Relative risk (RR) was calculated for patients enrolled in the United States and ROW. Meta-analysis of the combined mortality rates was performed using the Cochran-Mantel-Haenszel statistic, stratified by study. RESULTS: A total of 8,988 patients were enrolled in the MERIT-HF (Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure), COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival trial), and BEST (ß-Blocker Evaluation of Survival Trial) combined; 4,198 (46.7%) were from the United States. In the U.S. cohort, the RR reduction for each ß-blocker was of smaller magnitude than in the overall cohort and no longer significant, whereas in the ROW subgroup, the mortality benefit for ß-blockade persisted. In the pooled analysis (n = 11,635), the RR of death was reduced by 23% (p < 0.001) with ß-blockade compared with placebo. In contrast, the mortality reduction associated with ß-blockade in the U.S. cohort was small and not statistically significant (RR: 0.92, 95% confidence interval [CI]: 0.82 to 1.02, p = 0.11). The survival benefit persisted in the ROW cohort (RR: 0.64, 95% CI: 0.56 to 0.72, p < 0.001). CONCLUSIONS: Among patients enrolled in the United States, ß-blockade was associated with a lower magnitude of survival benefit, whereas the ROW response was similar to the total study population. This geographic difference in treatment response may be a reflection of population differences, genetics, cultural or social differences in disease management, or low power and statistical chance.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Saúde Global , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
17.
Pacing Clin Electrophysiol ; 28(11): 1147-56, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16359280

RESUMO

OBJECTIVES: To determine the effect of physiologic catecholamine concentrations on the defibrillation threshold (DFT) in patients with implanted cardioverter defibrillators. BACKGROUND: DFT is the minimum energy delivered by an implanted cardioverter defibrillator that successfully converts ventricular fibrillation. DFT testing is performed under conscious sedation. Since activities of daily living enhance sympathetic tone substantially over these nadir levels, it is important to explore the impact of catecholamines on DFT. METHODS: In this double-blind study, we determined DFT by the step-down method. Patients (n = 50) were stratified by beta-blocker use and then randomized to a 7-minute infusion of epinephrine, norepinephrine, or placebo. After study infusion, DFT testing was repeated. Changes in DFT with different study medications were compared. Subgroup analyses of the effects of catecholamines on DFT, based on beta-blocker use, were also performed. RESULTS: Norepinephrine reduced DFT from baseline measurements by 22.6% (P = 0.008). Neither epinephrine nor placebo impacted DFT (P = 0.999, P = 0.317, respectively). In the subgroup analyses, DFT was reduced with norepinephrine regardless of beta-blocker use, while epinephrine reduced DFT among those receiving beta-blockers. No change in DFT was observed in either of the placebo subgroups. CONCLUSIONS: Elevation of plasma norepinephrine concentrations reduces the DFT, while elevations in epinephrine had no effect. Norepinephrine seems to reduce DFT regardless of beta-blocker therapy but epinephrine's effects are beta-blocker dependent.


Assuntos
Desfibriladores Implantáveis , Limiar Diferencial/efeitos dos fármacos , Cardioversão Elétrica/métodos , Epinefrina/administração & dosagem , Sistema de Condução Cardíaco/fisiopatologia , Norepinefrina/administração & dosagem , Taquicardia Ventricular/prevenção & controle , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Catecolaminas/administração & dosagem , Método Duplo-Cego , Cardioversão Elétrica/instrumentação , Feminino , Sistema de Condução Cardíaco/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Ann Pharmacother ; 38(5): 771-5, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15031417

RESUMO

BACKGROUND: Pharmacists' responsibilities in caring for patients with diabetes mellitus are expanding. However, few data are available to support pharmacists optimizing therapy and improving outcomes in these patients. OBJECTIVE: To determine the effect of a clinical pharmacist-directed diabetes management clinic on glycemic control and cardiovascular and renal parameters in patients with type 2 diabetes. METHODS: A nonrandomized, prospective study was conducted in 70 Veterans Affairs patients. Patients met with the pharmacist every 6-8 weeks for approximately 30 minutes for education, medication counseling, monitoring, and management. The primary endpoint was the impact of 9-12 months of participation in the clinic on glycosylated hemoglobin (HbA1C). Secondarily, we evaluated body weight, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure, and level of microalbuminuria. All comparisons were made using a paired t-test at a significance level of p < or = 0.05. RESULTS: HbA1C significantly decreased from 10.3% +/- 2.2% at baseline to 6.9% +/- 1.1% (mean +/- SD) during the 9- to 12-month evaluation period (p < 0.001). The secondary endpoints including systolic (p < 0.001) and diastolic (p < 0.001) blood pressure, total cholesterol (p < 0.001), LDL-C (p < 0.001), triglycerides (p = 0.006), and level of microalbuminuria (p < 0.001) also were reduced at 9-12 months. CONCLUSIONS: This study demonstrated that a clinical pharmacist can effectively care for patients with diabetes referred by their primary care provider because of poor glycemic control.


Assuntos
Albuminúria/diagnóstico , Instituições de Assistência Ambulatorial/organização & administração , Pressão Sanguínea , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas/análise , Assistência Farmacêutica/organização & administração , Idoso , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Lipoproteínas/sangue , Masculino , Educação de Pacientes como Assunto , Estudos Prospectivos , Resultado do Tratamento
19.
Ann Pharmacother ; 36(5): 758-63, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11978148

RESUMO

OBJECTIVE: To determine whether Panax ginseng ingestion can acutely or chronically alter electrocardiographic parameters: PR, QRS, QT, QTc, and RR intervals, and QT and QTc interval dispersion. Effects of P. ginseng on blood pressure and heart rate also were evaluated. METHODS: This is a prospective, randomized, double-blind, placebo-controlled study of healthy adults at the University of Connecticut. Thirty subjects were randomly allocated to receive 28 days of therapy with either P. ginseng extract 200 mg or placebo. Baseline 12-lead electrocardiograms (ECGs) were obtained. Subsequent ECGs were performed following study drug ingestion at 50 minutes, 2 hours, and 5 hours on days 1 and 28. Blood pressure readings were taken with each ECG. RESULTS: P. ginseng ingestion increased the QTc interval by 0.015 seconds on day 1 at 2 hours compared with the placebo group (p = 0.03). It also reduced diastolic blood pressure from 75 +/- 5 mm Hg at baseline to 70 +/- 6 mm Hg at the same time point (p = 0.02). The observed effects are not believed to be clinically significant. No other statistically significant changes were found in electrocardiographic or hemodynamic variables on days 1 or 28. CONCLUSIONS: P. ginseng, at doses of 200 mg of the extract daily, increases the QTc interval and decreases diastolic blood pressure 2 hours after ingestion in healthy adults on the first day of therapy.


Assuntos
Eletrocardiografia/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Panax , Extratos Vegetais/farmacologia , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Extratos Vegetais/uso terapêutico , Estudos Prospectivos , Fatores de Tempo
20.
J Electrocardiol ; 37(2): 127-32, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15127380

RESUMO

Postoperative atrial fibrillation is common after cardiac surgery. Prediction of which patients will develop postoperative atrial fibrillation would be clinically useful. Increased P-wave duration, suggesting atrial conduction delay and measured from preoperative electrocardiograms, predicts postoperative atrial fibrillation. However, postoperative P-wave duration has not been evaluated after cardiac surgery. In this study, we evaluated postoperative P-wave variables (maximum P-wave duration and P-wave dispersion) over 5 days in cardiac surgery patients receiving amiodarone, pacing or no atrial fibrillation prophylaxis. P-wave variables gradually shortened as time passed from surgery. Amiodarone did not shorten P-wave measurements throughout therapy, while pacing shortened P-waves in the immediate postoperative period; however, shortening was not sustained. P-waves did not differ between those who did and did not develop atrial fibrillation with amiodarone or pacing. Our findings suggest that atrial conduction delay resulting from cardiothoracic surgery tends to resolve over time and may not play a critical role in the etiology of postoperative atrial fibrillation.


Assuntos
Fibrilação Atrial/etiologia , Procedimentos Cirúrgicos Cardíacos , Eletrocardiografia , Idoso , Amiodarona/uso terapêutico , Fibrilação Atrial/prevenção & controle , Estimulação Cardíaca Artificial , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias
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