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1.
J Cardiovasc Pharmacol ; 78(3): 403-406, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34173810

RESUMO

BACKGROUND: Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction (HFrEF). Little is known about outcomes of HFrEF patients transitioned from sodium nitroprusside (SNP) to sacubitril-valsartan during an admission for acute decompensated heart failure. We sought to describe characteristics of patients initiated on sacubitril-valsartan while receiving SNP and, in particular, those patients who did and did not experience hypotension requiring interruption or discontinuation of sacubitril-valsartan. METHODS: We performed a retrospective case series of adult patients (>18 years) with HFrEF (left ventricular ejection fraction ≤40%) admitted to the University of Michigan cardiac intensive care unit between July 2018 to September 2020 who received sacubitril-valsartan while on SNP. RESULTS: A total of 15 patients with acute decompensated heart failure were initiated on sacubitril-valsartan while on SNP. The mean age was 57 ± 15.9 years. Seven (46.7%) patients experienced hypotension. The patients in the cohort who experienced hypotension were numerically older (60 ± 17 vs. 55 ± 15.5), and the majority were white (86%). Patients with hypotension had a numerically lower left ventricular ejection fraction (13 ± 4.2 vs. 18 ± 8.2) and higher serum creatinine (1.4 ± 0.54 vs. 0.88 ± 0.25). Seven (100%) patients received a diuretic on the day of sacubitril-valsartan initiation in those who experienced hypotension compared with 2 (25%) in those who did not experience hypotension. CONCLUSIONS: In almost half of patients admitted to the cardiac intensive care unit with acutely decompensated HFrEF, significant hypotension was seen when initiating sacubitril-valsartan while on SNP. Future studies should evaluate appropriate patients for this transition and delineate appropriate titration parameters.


Assuntos
Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Hipotensão/induzido quimicamente , Nitroprussiato/efeitos adversos , Inibidores de Proteases/efeitos adversos , Valsartana/efeitos adversos , Vasodilatadores/efeitos adversos , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Unidades de Cuidados Coronarianos , Diuréticos/efeitos adversos , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotensão/diagnóstico , Hipotensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neprilisina/antagonistas & inibidores , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
2.
Curr Opin Cardiol ; 32(6): 755-760, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28759470

RESUMO

PURPOSE OF REVIEW: This review aims to summarize recent reports on percutaneous coronary intervention (PCI) strategies for patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). RECENT FINDINGS: Recent randomized clinical trials and meta-analyses have suggested that patients with STEMI and multivessel CAD may benefit more from multivessel PCI (either multivessel primary PCI or staged PCI before hospital discharge) than culprit vessel-only primary PCI. These reports have changed clinical practice guideline recommendations that now conclude that multivessel PCI may be considered in selected hemodynamically stable patients with significant noninfarct artery stenoses based on anatomic criteria alone. Fractional flow reserve measurement can document functional significance in nonculprit stenoses, but fractional flow reserve-guided PCI has not been shown to impact mortality or myocardial infarction rates. Additionally, nonculprit artery chronic total occlusion PCI was not effective in improving left ventricular function in one randomized trial. SUMMARY: Multivessel primary PCI or staged PCI is effective and safe in selected patients with STEMI and multivessel coronary disease. Future randomized controlled trials are needed to define the optimal timing of multivessel PCI, as well as the appropriate use of PCI in nonculprit stenoses.


Assuntos
Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Doença da Artéria Coronariana/complicações , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Fatores de Tempo
3.
Catheter Cardiovasc Interv ; 89(4): 728-734, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28239949

RESUMO

OBJECTIVES: The aim is to examine trends in procedural indication, arterial beds treated, and device usage in peripheral arterial interventions (PVIs). BACKGROUND: There is little data on indication, vascular beds treated and devices utilized for peripheral arterial interventions. METHODS: We used data from 43 hospitals participating in the BMC2 VIC registry. PVIs were separated by year and divided by arterial segment. Lower extremity PVIs were subclassified as having been performed for claudication or critical limb ischemia (CLI). Yearly device usage was also included. A repeated measure ANOVA was used to determine trends. RESULTS: 44,650 PVIs were performed from 2006 to 2013. Renal interventions decreased from 18% of interventions in 2006 to 5.6% in 2013 (P < 0.001) and femoral-popliteal increased from 54.9% in 2006 to 64.5% in 2013 (P < 0.001). No significant trend was seen for aorta-iliac or below-the-knee interventions. 58.6% of PVIs were performed for claudication in 2006 and this decreased to 44.6% in 2013 (P = 0.025). Indications for CLI were 24.1% in 2006 and 47.5% in 2013 (P < 0.001). There were significant increases in the use of balloon angioplasty (P = 0.029) and cutting/scoring balloons (P < 0.001) while cryoballoon usage decreased (P < 0.001). No significant changes were found with stenting, atherectomy, and laser. CONCLUSIONS: There is a significant increase in patients presenting with CLI. Renal artery intervention rates are decreasing while femoral-popliteal interventions are increasing. Additionally, balloon angioplasty and cutting/scoring balloon usage is increasing. © 2017 Wiley Periodicals, Inc.


Assuntos
Planos de Seguro Blue Cross Blue Shield , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Sistema de Registros , Medição de Risco/métodos , Instrumentos Cirúrgicos/estatística & dados numéricos , Procedimentos Cirúrgicos Vasculares/instrumentação , Idoso , Feminino , Humanos , Masculino , Michigan/epidemiologia , Morbidade/tendências , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Procedimentos Cirúrgicos Vasculares/tendências
4.
Nature ; 458(7239): 732-6, 2009 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-19360080

RESUMO

The clinical development of an inhibitor of cellular proteasome function suggests that compounds targeting other components of the ubiquitin-proteasome system might prove useful for the treatment of human malignancies. NEDD8-activating enzyme (NAE) is an essential component of the NEDD8 conjugation pathway that controls the activity of the cullin-RING subtype of ubiquitin ligases, thereby regulating the turnover of a subset of proteins upstream of the proteasome. Substrates of cullin-RING ligases have important roles in cellular processes associated with cancer cell growth and survival pathways. Here we describe MLN4924, a potent and selective inhibitor of NAE. MLN4924 disrupts cullin-RING ligase-mediated protein turnover leading to apoptotic death in human tumour cells by a new mechanism of action, the deregulation of S-phase DNA synthesis. MLN4924 suppressed the growth of human tumour xenografts in mice at compound exposures that were well tolerated. Our data suggest that NAE inhibitors may hold promise for the treatment of cancer.


Assuntos
Antineoplásicos/farmacologia , Ciclopentanos/farmacologia , Inibidores Enzimáticos/farmacologia , Neoplasias/tratamento farmacológico , Pirimidinas/farmacologia , Enzimas Ativadoras de Ubiquitina/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Proteínas Culina/metabolismo , Feminino , Humanos , Camundongos , Proteína NEDD8 , Inibidores de Proteassoma , Transplante Heterólogo , Ubiquitinas/metabolismo
5.
Clin Microbiol Infect ; 30(4): 499-506, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38163481

RESUMO

OBJECTIVES: Diagnostic error in the use of respiratory cultures for ventilator-associated pneumonia (VAP) fuels misdiagnosis and antibiotic overuse within intensive care units. In this prospective quasi-experimental study (NCT05176353), we aimed to evaluate the safety, feasibility, and efficacy of a novel VAP-specific bundled diagnostic stewardship intervention (VAP-DSI) to mitigate VAP over-diagnosis/overtreatment. METHODS: We developed and implemented a VAP-DSI using an interruptive clinical decision support tool and modifications to clinical laboratory workflows. Interventions included gatekeeping access to respiratory culture ordering, preferential use of non-bronchoscopic bronchoalveolar lavage for culture collection, and suppression of culture results for samples with minimal alveolar neutrophilia. Rates of adverse safety outcomes, positive respiratory cultures, and antimicrobial utilization were compared between mechanically ventilated patients (MVPs) in the 1-year post-intervention study cohort (2022-2023) and 5-year pre-intervention MVP controls (2017-2022). RESULTS: VAP-DSI implementation did not associate with increases in adverse safety outcomes but did associate with a 20% rate reduction in positive respiratory cultures per 1000 MVP days (pre-intervention rate 127 [95% CI: 122-131], post-intervention rate 102 [95% CI: 92-112], p < 0.01). Significant reductions in broad-spectrum antibiotic days of therapy per 1000 MVP days were noted after VAP-DSI implementation (pre-intervention rate 1199 [95% CI: 1177-1205], post-intervention rate 1149 [95% CI: 1116-1184], p 0.03). DISCUSSION: Implementation of a VAP-DSI was safe and associated with significant reductions in rates of positive respiratory cultures and broad-spectrum antimicrobial use. This innovative trial of a VAP-DSI represents a novel avenue for intensive care unit antimicrobial stewardship. Multicentre trials of VAP-DSIs are warranted.


Assuntos
Pneumonia Associada à Ventilação Mecânica , Humanos , Antibacterianos/uso terapêutico , Unidades de Terapia Intensiva , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Estudos Prospectivos , Estudos de Viabilidade
6.
Am Heart J Plus ; 382024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38434252

RESUMO

Objective: Patients who survive critical illness endure complex physical and mental health conditions, referred to as post-intensive care syndrome (PICS). The University of Michigan's post-intensive cardiac care outpatient long-term outreach (PICCOLO) clinic is designed for patients recently admitted to the coronary care unit (CCU). The long-term goal of this clinic is to understand post-CCU patients' needs and design targeted interventions to reduce their morbidity and mortality post-discharge. As a first step toward this goal, we aimed to define the post-discharge needs of CCU survivors. Design setting particpants: We retrospectively reviewed case-mix data (including rates of depression, PTSD, disability, and cognitive abnormalities) and health outcomes for patients referred to the PICCOLO clinic from July 1, 2018, through June 30, 2021 at Michigan Medicine. Results: Of the 134 referred patients meeting inclusion criteria, 74 (55 %) patients were seen in the PICCOLO clinic within 30 days of discharge. Patients seen in the clinic frequently screened positive for depression (PHQ-2 score ≥3, 21.4 %) and cognitive impairment (MOCA <26, 38.8 %). Further, patients also reported high rates of physical difficulty (mean WHODAS 2.0 score 28.4 %, consistent with moderate physical difficulty). Consistent with medical intensive care unit (ICU) patients, CCU survivors experience PICS. Conclusion: This work highlights the feasibility of an outpatient care model and the need to leverage information gathered from this care model to develop treatment strategies and pathways to address symptoms of PICS in CCU survivors, including depression, cognitive impairment, and physical disability.

7.
Blood ; 116(9): 1515-23, 2010 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-20525923

RESUMO

MLN4924 is a potent and selective small molecule NEDD8-activating enzyme (NAE) inhibitor. In most cancer cells tested, inhibition of NAE leads to induction of DNA rereplication, resulting in DNA damage and cell death. However, in preclinical models of activated B cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), we show that MLN4924 induces an alternative mechanism of action. Treatment of ABC DLBCL cells with MLN4924 resulted in rapid accumulation of pIkappaBalpha, decrease in nuclear p65 content, reduction of nuclear factor-kappaB (NF-kappaB) transcriptional activity, and G(1) arrest, ultimately resulting in apoptosis induction, events consistent with potent NF-kappaB pathway inhibition. Treatment of germinal-center B cell-like (GCB) DLBCL cells resulted in an increase in cellular Cdt-1 and accumulation of cells in S-phase, consistent with cells undergoing DNA rereplication. In vivo administration of MLN4924 to mice bearing human xenograft tumors of ABC- and GCB-DLBCL blocked NAE pathway biomarkers and resulted in complete tumor growth inhibition. In primary human tumor models of ABC-DLBCL, MLN4924 treatment resulted in NF-kappaB pathway inhibition accompanied by tumor regressions. This work describes a novel mechanism of targeted NF-kappaB pathway modulation in DLBCL and provides strong rationale for clinical development of MLN4924 against NF-kappaB-dependent lymphomas.


Assuntos
Ciclopentanos/farmacologia , Centro Germinativo/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , NF-kappa B/metabolismo , Pirimidinas/farmacologia , Ubiquitinas/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Feminino , Citometria de Fluxo , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteína NEDD8 , NF-kappa B/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ubiquitinas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
J Thromb Thrombolysis ; 34(1): 114-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22323092

RESUMO

Our objective was to determine the association of activated partial thromboplastin time (aPTT) with recurrent ischemic events and non-coronary artery bypass surgery-related thrombolysis in myocardial infarction major bleeding. We studied 4,985 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) participating in SYNERGY, a prospective, randomized, international trial designed to emulate contemporary practice wherein unfractionated heparin (UFH) is given intravenously and titrated according to a weight-adjusted dosing nomogram to a target aPTT of 1.5-2 times the upper limit of normal (approximately 50-70 s). Aspirin was administered to 95% of patients, clopidogrel to 63%, and glycoprotein IIb/IIIa receptor inhibitors to 58%. More than 90% of patients underwent early coronary angiography, and 69% were revascularized. Used as a time-dependent covariate, aPTT was evaluated as a predictor of time to ischemic or major hemorrhagic events in proportional hazards regression models. Using discrete variable analysis, aPTT was categorized as persistently below a lower threshold of anticoagulation (<50 vs. ≥50 s) for recurrent ischemic events and above an upper threshold (>70 vs. ≤70 s) for major hemorrhagic events. UFH treatment lasted a median of 42 (30, 78) h. At >6-12 (n = 3,021), >12-24 (n = 3,406), and >24-48 (n = 2,497) h, 34, 41, and 46% of patients achieved the target aPTT range, respectively. Both before and after adjusting for baseline predictors of anticoagulant response and risk score (age, hypertension, diabetes, smoking, ST depression, and renal function), no significant relationship between aPTT values and recurrent ischemic events or major bleeding was found. No relationship was observed between clinical outcomes and aPTT values persistently above or below the designated thresholds. Measurements of aPTT were not associated with clinical outcomes among patients with NSTE ACS treated with UFH. The required intensity of anticoagulation for benefit may be relatively modest when UFH is administered concomitantly with dual or triple platelet-directed therapy, particularly in patients undergoing early coronary revascularization.


Assuntos
Síndrome Coronariana Aguda/sangue , Tempo de Tromboplastina Parcial , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão , Feminino , Fibrinolíticos/administração & dosagem , Hemorragia/sangue , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
9.
Crit Care Nurse ; 42(2): 56-61, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35362078

RESUMO

BACKGROUND: In patients receiving mechanical ventilation, spontaneous awakening trials reduce morbidity and mortality when paired with spontaneous breathing trials. However, spontaneous awakening trials are not performed every day they are indicated and little is known about spontaneous awakening trial protocol use in cardiac intensive care units. LOCAL PROBLEM: Spontaneous awakening trial completion rate at the study institution was low and no trial protocol was regularly used. METHODS: A preintervention-postintervention retrospective cohort study was performed in adult patients with at least 24 hours of invasive mechanical ventilation in Michigan Medicine's cardiac intensive care unit. Patients with SARS-CoV-2 infection were excluded. Data included demographics, sedation, mechanical ventilation duration, and in-hospital mortality. A nurse-driven spontaneous awakening trial protocol modified for the cardiac intensive care unit was implemented in October 2020. RESULTS: Compared with the preintervention cohort (n = 29, May through July 2020), the postintervention cohort (n = 27, October 2020 through February 2021) had a higher ratio of number of trials performed to number of days eligible for trial (0.91 vs 0.52; P < .01). Median continuous sedative infusion duration was shorter after intervention (2.3 vs 3.6 days; P = .02). Median mechanical ventilation duration (3.8 vs 4.7 days; P = .18) and mortality (41% vs 41%; P = .95) were similar between groups. CONCLUSIONS: Spontaneous awakening trial protocol implementation led to a higher trial completion rate and a shorter duration of continuous sedative infusion. Larger studies are needed to assess the impact of protocolized spontaneous awakening trials on cardiac intensive care unit patient outcomes.


Assuntos
COVID-19 , Adulto , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , SARS-CoV-2 , Desmame do Respirador
10.
Acad Emerg Med ; 29(2): 217-227, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34416069

RESUMO

BACKGROUND: Exception from informed consent (EFIC) enables the enrollment of research subjects with emergent conditions to clinical trials without prior consent. EFIC study approval requires community consultation and public disclosure. We hypothesized that the integration of social media with targeted emails and in-person outreach is an effective community consultation strategy. METHODS: We utilized social media with targeted emails and in-person outreach for the community consultation of the ACCESS cardiac arrest trial. Study advertisements were disseminated using Facebook and Instagram, and targeted emails were sent to emergency medicine, prehospital, and cardiology providers. We also interviewed at-risk individuals with cardiac conditions, their caretakers, and patient advocacy groups. Participants were asked to complete a survey about their opinions about the study. RESULTS: We collected 559 surveys over an 8-week period, and 70.5% of the surveys were obtained using social media. The median (IQR) age of survey respondents was 44 (33-57) years; 89.9% were White and 60.1% were women. A total of 91.3% believed ACCESS was an important study. Compared to the in-person group, more from social media (81.8% vs. 63.3%, p < 0.05) and targeted email (77.4% vs. 63.3%, p < 0.05) groups said they would include their loved ones in the study. More from the in-person group believed that their opinion would be considered seriously compared to the social media (75.9% vs. 62.6%, p < 0.05) and targeted email (75.9% vs. 54.5%, p < 0.05) groups. The incorporation of social media and targeted emails for community consultation reduced the cost per survey by fourfold compared to an in-person-only strategy. CONCLUSIONS: The integration of social media with targeted emails and in-person outreach was a feasible and cost-saving approach for EFIC community consultation. Future work is necessary to determine the perception and best utilization of social media for community consultation.


Assuntos
Correio Eletrônico , Consentimento Livre e Esclarecido , Encaminhamento e Consulta , Mídias Sociais , Adulto , Revelação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Heart Lung ; 52: 48-51, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34872013

RESUMO

BACKGROUND: The complex needs of cardiac patients shortly after discharge from a cardiac intensive care unit (CICU) provides a unique opportunity for a pharmacist to help optimize medication management and guideline-directed medical therapy (GDMT). OBJECTIVE: This study describes the impact of a pharmacist in a multidisciplinary post-CICU clinic. METHODS: We performed a retrospective cohort study of patients ≥18 years of age who completed a visit in the University of Michigan Post Intensive Cardiac Care Outpatient Long-Term Outreach (PICCOLO) Clinic from July 2018 to May 2020. RESULTS: One hundred and six CICU survivors were referred. Of these 12 chose to follow-up with long term care providers. A total of 70 of the remaining 94 (74%) completed a visit. The median age was 65 (54-72) years, 71.4% were male, and 85.7% were Caucasian. The median number of pharmacist interventions at each visit was 4 (3-5), all patients had at least 1 intervention. Interventions included medication dose adjustment (n = 46); GDMT optimization (n = 42); medication change (n = 18); medication addition (n = 23) and cessation (n = 21); lab monitoring (n = 97); refill assistance (n = 16); pillbox provision (n = 8); and medication cost assistance (n = 8). CONCLUSIONS: Pharmacist led interventions in a post CICU clinic resulted in medication changes to optimize therapy, increased laboratory monitoring, medication cost savings for patients, and interventions to facilitate GDMT adherence.


Assuntos
Unidades de Terapia Intensiva , Farmacêuticos , Idoso , Cuidados Críticos , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Estudos Retrospectivos
12.
Am J Cardiol ; 163: 117-123, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34794647

RESUMO

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.


Assuntos
Antipsicóticos/efeitos adversos , Unidades de Cuidados Coronarianos , Delírio/tratamento farmacológico , Hipotensão/induzido quimicamente , Síndrome do QT Longo/induzido quimicamente , Olanzapina/efeitos adversos , Fumarato de Quetiapina/efeitos adversos , Taquicardia Ventricular/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/terapia , Delírio/complicações , Endocardite/complicações , Endocardite/terapia , Feminino , Parada Cardíaca/complicações , Parada Cardíaca/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/complicações , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Choque Cardiogênico/complicações , Choque Cardiogênico/terapia
13.
Eur Heart J Acute Cardiovasc Care ; 10(4): 422-426, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33620428

RESUMO

AIMS: Dexmedetomidine is one of the sedative agents recommended by the Society of Critical Care Medicine as a preferred option over benzodiazepines in critically ill, mechanically ventilated patients. Little data exists describing sedation in the cardiac intensive care unit (CICU). The purpose of this study was to determine the prevalence of adverse events in CICU patients treated with dexmedetomidine. METHODS AND RESULTS: This was a retrospective cohort analysis of patients >18 years old admitted to the University of Michigan CICU from June 2014 to October 2019 who received dexmedetomidine therapy. The primary outcome was the composite of adverse events including bradycardia, hypotension, increasing vasopressor/inotrope requirements, and asystole. Secondary outcomes included individual components of the primary outcome. Patients that experienced adverse events were compared to those that did not experience adverse events to identify risk factors for adverse events. A total of 197 patients were included. There were 116 adverse events in 106 patients. Hypotension was the most common adverse event, making up 60.3% of adverse events reported. Increased vasopressor requirement and bradycardia both occurred in 22 patients (18.9%). Asystole occurred in two patients. B-type natriuretic peptide (BNP) levels were significantly higher in those experiencing an adverse event (848 pg/mL vs. 431 pg/mL; P = 0.03). CONCLUSIONS: Patients admitted to the CICU experienced a high rate of adverse events with dexmedetomidine use. Those experiencing adverse events were more likely to have a higher BNP. Future studies should explore the safety of alternative sedative agents to ascertain safe pharmacological options for patients admitted to the CICU.


Assuntos
Dexmedetomidina , Adolescente , Estado Terminal , Dexmedetomidina/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Unidades de Terapia Intensiva , Estudos Retrospectivos
14.
Am J Cardiol ; 124(9): 1478-1483, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31500818

RESUMO

Cardiac rehabilitation (CR) is associated with decreased mortality and rehospitalization rates for patients with a variety of cardiac conditions. Although CR referral rates for STEMI patients have improved, rates for heart failure have remained low. Many of these patients are admitted to the cardiac intensive care unit (CICU). However, it is unknown how often CICU survivors qualify for cardiac rehabilitation, how often they are referred, and why eligible patients are not referred. This is a retrospective single-center study of 417 consecutive patients admitted to CICU for >48 hours from March 30, 2016 to March 30, 2017. We excluded patients with in-hospital mortality or those discharged AMA, to hospice or transferred. Chart abstraction was used to determine CR indications based on known American College of Cardiology/American Heart Association guidelines. If CR was indicated, medical records through September 2017 were reviewed to determine both referral and participation rates. In the absence of a referral, medical records were reviewed for potential barriers. A total of 296 CICU survivors were identified upon discharge with 185 (63%) having guideline-directed indications for CR referral. The most common indications were heart failure with reduced ejection fraction (HFrEF, 38%), cardiothoracic surgery (26%), and STEMI (23%). Upon discharge, only 30% of patients were referred to CR. The referral rate increased by 33% to 63% by 18 months postdischarge. CR referrals were most frequently placed following STEMI (91%), NSTEMI (80%), and postpercutaneous coronary intervention (80%). Only 35% of HFrEF discharges were referred to CR. Of patients not referred to CR, no explanation for a lack of referral was documented 87% of the time. In conclusion, nearly 2 of 3 patients discharged from the CICU had CR indications, most commonly HFrEF. CR referrals are frequently not placed and reason for nonreferral is rarely documented. CICU admission may provide a defined event to prompt referral.


Assuntos
Reabilitação Cardíaca/estatística & dados numéricos , Unidades de Cuidados Coronarianos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Isquemia Miocárdica/reabilitação , Sobreviventes/estatística & dados numéricos , Idoso , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Incidência , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências
15.
Cancer Res ; 66(4): 2367-75, 2006 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16489043

RESUMO

Two major pathways for apoptosis have been identified, involving either mitochondria (intrinsic) or tumor necrosis factor (TNF)-family death receptors (extrinsic) as initiators of caspase protease activation and cell death. Because tumor resistance to TNF-family death receptor ligands is a common problem, helping malignant cells evade host immune defenses, we sought to identify compounds that selectively sensitize resistant tumor cells to death receptor ligands. We screened a 50,000-compound library for agents that enhanced anti-FAS antibody-mediated killing of FAS-resistant PPC-1 prostate cancer cell, then did additional analysis of the resulting hits to arrive at eight compounds that selectively sensitized PPC-1 cells to anti-FAS antibody (extrinsic pathway agonist) without altering sensitivity to staurosporine and etoposide (VP-16; intrinsic pathway agonists). These eight compounds did not increase Fas surface levels and also sensitized PPC-1 cells to apoptosis induced by TNF-family member TNF-related apoptosis-inducing ligand, consistent with a post-receptor mechanism. Of these, two reduced expression of c-FLIP, an intracellular antagonist of the extrinsic pathway. Characterization of the effects of the eight compounds on a panel of 10 solid tumor cell lines revealed two structurally distinct compounds that frequently sensitize to extrinsic pathway agonists. Structure-activity relation studies of one of these compounds revealed a pharmacophore from which it should be possible to generate analogues with improved potency. Altogether, these findings show the feasibility of identifying compounds that selectively enhance apoptosis via the extrinsic pathway, thus providing research tools for uncovering resistance mechanisms and a starting point for novel therapeutics aimed at restoring sensitivity of tumor cells to immune effector mechanisms.


Assuntos
Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Receptores do Fator de Necrose Tumoral/fisiologia , Anticorpos/imunologia , Anticorpos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Etoposídeo/farmacologia , Humanos , Ligantes , Masculino , Glicoproteínas de Membrana/farmacologia , Neoplasias da Próstata/imunologia , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Receptores do Fator de Necrose Tumoral/metabolismo , Estaurosporina/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF , Fator de Necrose Tumoral alfa/farmacologia , Receptor fas/imunologia
16.
Trends Cardiovasc Med ; 27(2): 95-102, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27450063
18.
Can J Cardiol ; 31(4): 548.e1-3, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25745881

RESUMO

Cor triatriatum sinister is a congenital heart disorder that can lead to progressive dyspnea, pulmonary hypertension, and ultimately right ventricular (RV) failure. We report a case in which symptoms of progressive pulmonary hypertension were initially attributed to asthma, leading to a delayed diagnosis that resulted in suprasystemic pulmonary pressures and RV dysfunction. Rapid symptomatic and hemodynamic improvement was observed after surgical repair, with normalization of pulmonary artery pressures and RV function.


Assuntos
Coração Triatriado/complicações , Hipertensão Pulmonar/etiologia , Pressão Propulsora Pulmonar/fisiologia , Recuperação de Função Fisiológica , Adulto , Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos/métodos , Coração Triatriado/diagnóstico , Coração Triatriado/cirurgia , Progressão da Doença , Ecocardiografia , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Imagem Cinética por Ressonância Magnética , Função Ventricular Direita/fisiologia
20.
PLoS One ; 10(9): e0138251, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26379053

RESUMO

BACKGROUND: Substantial geographic variation exists in percutaneous coronary intervention (PCI) use across the United States. It is unclear the extent to which high PCI utilization can be explained by PCI for inappropriate indications. The objective of this study was to examine the relationship between PCI rates across regional healthcare markets utilizing hospital referral regions (HRRs) and PCI appropriateness. METHODS: The number of PCI procedures in each HRR was obtained from the 2010 100% Medicare limited data set. HRRs were divided into quintiles of PCI utilization with increasing rates of utilization progressing to quintile 5. NCDR CathPCI Registry® data were used to evaluate patient characteristics, appropriate use criteria (AUC), and outcomes across the HRR quintiles defined by PCI utilization with the study population restricted to HRRs where ≥ 80% of the PCIs were performed at institutions participating in the registry. PCI appropriateness was defined using 2012 AUC by the American College of Cardiology (ACC)/American Heart Association (AHA)/The Society for Cardiovascular Angiography and Interventions (SCAI). RESULTS: Our study cohort comprised of 380,981 patients treated at 178 HRRs. Mean PCI rates per 1,000 increased from 4.6 in Quintile 1 to 10.8 in Quintile 5. The proportion of non-acute PCIs was 27.7% in Quintile 1 increasing to 30.7% in Quintile 5. Significant variation (p < 0.001) existed across the quintiles in the categorization of appropriateness across HRRs of utilization with more appropriate PCI in lower utilization areas (Appropriate: Q1, 76.53%, Q2, 75.326%, Q3, 75.23%, Q4, 73.95%, Q5, 72.768%; Inappropriate: Q1 3.92%, Q2 4.23%, Q3 4.32%, Q4 4.35%, Q5 4.05%; Uncertain: Q1 8.29%, Q2 8.84%, Q3 8.08%, Q4 9.01%, Q5 8.93%; Not Mappable: Q1 11.26%, Q2 11.67%, Q3 12.37%, Q4 12.69%, Q5 14.34%). There was no difference in risk-adjusted mortality across quintiles of PCI utilization. CONCLUSIONS: Geographic regions with lower PCI rates have a higher proportion of PCIs performed for appropriate indications. Areas that perform more PCIs also appear to perform more elective PCI and many could not be mapped by the AUC.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Intervenção Coronária Percutânea/estatística & dados numéricos , American Heart Association , Angioplastia Coronária com Balão/estatística & dados numéricos , Estudos de Coortes , Atenção à Saúde/estatística & dados numéricos , Feminino , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Sistema de Registros/estatística & dados numéricos , Estados Unidos
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