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1.
Circ Heart Fail ; 12(7): e005931, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31288565

RESUMO

BACKGROUND: Identifying low-risk acute heart failure patients safe for discharge from the emergency department is a major unmet need. METHODS AND RESULTS: A prospective, observational, multicenter pilot study targeting lower risk acute heart failure patients to determine whether hsTnT (high-sensitivity troponin T) identifies emergency department acute heart failure patients at low risk for rehospitalization and mortality. hsTnT was drawn at baseline and 3 hours. Phone follow-up occurred at 30 and 90 days. The primary end point composite of all-cause mortality, rehospitalization, and emergency department visits at 90 days (changed from 30 days because of lack of mortality events), analyzed using logistic regression. Secondary end points: 30- and 90-day all-cause mortality. hsTnT values less than the 99th percentile were defined as low hsTnT. Out of 527 enrolled patients, 499 comprised the initial analysis set. Of these, 332 had both 0- and 3-hour hsTnT drawn, of whom 319 completed 30 day follow-up. The average age was 62, 60% male, and 57% black. Median hsTnT was 26.4 ng/L (interquartile range, 15.1-44.3). There were 99 (21%) 30-day composite events, 13 (2.7%) deaths at 30 days, and 25 deaths (8.2%) at 90 days. Serial hsTnT values below the 99th percentile were not associated with a lower risk for the 90-day primary composite end point (odds ratio, 0.79; 95% CI, 0.42-1.50; P=0.4736). However, no deaths occurred in the low hsTnT group at 30 days with 1 death at 90 days. CONCLUSIONS: hsTnT did not identify patients at low risk for the primary outcome of rehospitalization, emergency department visits, and mortality at 90 days. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02592135.

2.
Sci Rep ; 9(1): 9776, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278310

RESUMO

Prostate cancer is the most commonly diagnosed cancer in men with African American men disproportionally suffering from the burden of this disease. Biomarkers that could discriminate indolent from aggressive and drug resistance disease are lacking. MicroRNAs are small non-coding RNAs that affect numerous physiological and pathological processes, including cancer development and have been suggested as biomarkers and therapeutic targets. In the present study, we investigated the role of miR-214 on prostate cancer cell survival/migration/invasion, cell cycle regulation, and apoptosis. miR-214 was differentially expressed between Caucasian and African American prostate cancer cells. Importantly, miR-214 overexpression in prostate cancer cells induced apoptosis, inhibiting cell proliferation and colony forming ability. miR-214 expression in prostate cancer cells also inhibited cell migration and 3D spheroid invasion. Mechanistically, miR-214 inhibited prostate cancer cell proliferation by targeting protein tyrosine kinase 6 (PTK6). Restoration of PTK6 expression attenuated the inhibitory effect of miR-214 on cell proliferation. Moreover, simultaneous inhibition of PTK6 by ibrutinib and miR-214 significantly reduced cell proliferation/survival. Our data indicates that miR-214 could act as a tumor suppressor in prostate cancer and could potentially be utilized as a biomarker and therapeutic target.

3.
Clin Exp Emerg Med ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31295990

RESUMO

Objective: Bedside consultation by cardiologists may facilitate safe discharge of selected patients from the emergency department (ED) even when admission is recommended by the History, Electrocardiogram, Age, Risk factors, Troponin (HEART) pathway. If bedside evaluation is unavailable, phone consultation between emergency physicians and cardiologists would be most impactful if the resultant disposition is discordant with the HEART pathway. We therefore evaluate discordance between actual disposition and that suggested by the HEART pathway in patients presenting to the ED with chest pain for whom cardiology consultation occurred exclusively by phone and to assess the impact of phone-consultation on disposition. Methods: We performed a single-center, retrospective study of adults presenting to the ED with chest pain whose emergency physician had a phone consultation with a cardiologist. Actual disposition was abstracted from the medical record. HEART pathway category (low-risk, discharge; high-risk, admit) was derived from ED documentation. For discharged patients, major adverse cardiac events were assessed at 30 days by chart review and phone follow-up. Results: For the 170 patients that had cardiologist phone consultation, discordance between actual disposition and the HEART pathway was 17%. The HEART pathway recommended admission for nearly 80% of discharged patients. Following cardiologist phone-consultation, 10% of high-risk patients were discharged, with the majority having undergone a functional study recommended by the cardiologist. At 30 days, discharged patients had experienced no episodes of major adverse cardiac events or rehospitalization for cardiac reasons. Conclusion: For patients presenting to the ED with chest pain, cardiology phone-consultation has the potential to safely impact disposition, primarily by facilitating functional testing in high-risk individuals.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31276777

RESUMO

PURPOSE: Understanding prostate-specific antigen (PSA) kinetics after radiation therapy plays a large role in the management of patients with prostate cancer (PCa). This is particularly true in establishing expectations regarding PSA nadir (nPSA) and PSA bounces, which can be disconcerting. As increasingly more patients are being treated with stereotactic body radiation therapy (SBRT) for low- and intermediate-risk PCa, it is imperative to understand the PSA response to SBRT. METHODS AND MATERIALS: PSA data from 5 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2004 to 2016. Patients received 35 to 40 Gy in 5 fractions, per institutional standards. Patients who had less than 12 months of PSA data or received androgen deprivation therapy were excluded from this study. Linear and logistic multivariable analysis were performed to identify predictors of nPSA, bounce, and biochemical recurrence, and joint latent class models were developed to identify significant predictors of time to biochemical failure. RESULTS: A total of 1062 patients were included in this study. Median follow-up was 66 months (interquartile range [IQR], 36.4-89.9 months). Biochemical failure per the Phoenix criteria occurred in 4% of patients. Median nPSA was 0.2 ng/mL, median time to nPSA was 40 months, 84% of patients had an nPSA ≤0.5 ng/mL, and 54% of patients had an nPSA ≤0.2 ng/mL. On multivariable analysis, nPSA was a significant predictor of biochemical failure. Benign PSA bounce was noted in 26% of patients. The median magnitude of PSA bounce was 0.52 ng/mL (IQR, 0.3-1.0 ng/mL). Median time to PSA bounce was 18.1 months (IQR, 12.0-31.1 months). On multivariable analysis, age and radiation dose were significantly associated with a lower incidence of bounce. Joint latent class models modeling found that nPSA and radiation dose were significantly associated with longer time to biochemical failure. CONCLUSIONS: In this multi-institutional cohort of patients with long-term follow-up, we found that SBRT led to low nPSAs. In turn, lower nPSAs are associated with reduced incidence of, and longer time to, biochemical failure. Benign PSA bounces occurred in a quarter of patients, as late as several years after treatment. Further studies are needed to directly compare the PSA response of patients who receive SBRT versus other treatment modalities.

5.
J Am Coll Cardiol ; 73(17): 2195-2205, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31047008

RESUMO

BACKGROUND: Circulating biomarkers can facilitate diagnosis and risk stratification for complex conditions such as heart failure (HF). Newer molecular platforms can accelerate biomarker discovery, but they require significant resources for data and sample acquisition. OBJECTIVES: The purpose of this study was to test a pragmatic biomarker discovery strategy integrating automated clinical biobanking with proteomics. METHODS: Using the electronic health record, the authors identified patients with and without HF, retrieved their discarded plasma samples, and screened these specimens using a DNA aptamer-based proteomic platform (1,129 proteins). Candidate biomarkers were validated in 3 different prospective cohorts. RESULTS: In an automated manner, plasma samples from 1,315 patients (31% with HF) were collected. Proteomic analysis of a 96-patient subset identified 9 candidate biomarkers (p < 4.42 × 10-5). Two proteins, angiopoietin-2 and thrombospondin-2, were associated with HF in 3 separate validation cohorts. In an emergency department-based registry of 852 dyspneic patients, the 2 biomarkers improved discrimination of acute HF compared with a clinical score (p < 0.0001) or clinical score plus B-type natriuretic peptide (p = 0.02). In a community-based cohort (n = 768), both biomarkers predicted incident HF independent of traditional risk factors and N-terminal pro-B-type natriuretic peptide (hazard ratio per SD increment: 1.35 [95% confidence interval: 1.14 to 1.61; p = 0.0007] for angiopoietin-2, and 1.37 [95% confidence interval: 1.06 to 1.79; p = 0.02] for thrombospondin-2). Among 30 advanced HF patients, concentrations of both biomarkers declined (80% to 84%) following cardiac transplant (p < 0.001 for both). CONCLUSIONS: A novel strategy integrating electronic health records, discarded clinical specimens, and proteomics identified 2 biomarkers that robustly predict HF across diverse clinical settings. This approach could accelerate biomarker discovery for many diseases.

6.
JACC Heart Fail ; 7(5): 383-391, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31047017

RESUMO

OBJECTIVES: This study sought to describe sodium excretion in acute decompensated heart failure (ADHF) clearly and to evaluate the prognostic ability of urinary sodium and fluid-based metrics. BACKGROUND: Sodium retention drives volume overload, with fluid retention largely a passive, secondary phenomenon. However, parameters (urine output, body weight) used to monitor therapy in ADHF measure fluid rather than sodium balance. Thus, the accuracy of fluid-based metrics hinges on the contested assumption that urinary sodium content is consistent. METHODS: Patients enrolled in the ROSE-AHF (Renal Optimization Strategies Evaluation-Acute Heart Failure) trial with 24-h sodium excretion available were studied (n = 316). Patients received protocol-driven high-dose loop diuretic therapy. RESULTS: Sodium excretion through the first 24 h was highly variable (range 0.12 to 19.8 g; median 3.63 g, interquartile range: 1.85 to 6.02 g) and was not correlated with diuretic agent dose (r = 0.06; p = 0.27). Greater sodium excretion was associated with reduced mortality in a univariate model (hazard ratio: 0.80 per doubling of sodium excretion; 95% confidence interval: 0.66 to 0.95; p = 0.01), whereas gross urine output (p = 0.43), net fluid balance (p = 0.87), and weight change (p = 0.11) were not. Sodium excretion of less than the prescribed dietary sodium intake (2 g), even in the setting of a negative net fluid balance, portended a worse prognosis (hazard ratio: 2.02; 95% confidence interval: 1.17 to 3.46; p = 0.01). CONCLUSIONS: In patients hospitalized with ADHF who were receiving high-dose loop diuretic agents, sodium concentration and excretion were highly variable. Sodium excretion was strongly associated with 6-month mortality, whereas traditional fluid-based metrics were not. Poor sodium excretion, even in the context of fluid loss, portends a worse prognosis.

7.
Int J Radiat Oncol Biol Phys ; 105(1): 149-154, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31108142

RESUMO

PURPOSE: The impact of higher scatter doses per fraction on testicular function and quality of life after prostate stereotactic body radiation therapy (SBRT) is poorly studied. METHODS AND MATERIALS: Six hundred thirty-six patients treated with SBRT for low- to intermediate-risk prostate cancer from 2009 to 2014 were included. Changes in testosterone and in sexual and hormonal domain scores on the Expanded Prostate Cancer Index Composite-26 (EPIC) questionnaire over a 24-month period were evaluated via a 1-sided t test. EPIC score changes were evaluated in comparison with a distribution-based minimal clinically important difference threshold, wherein changes of greater than one half or greater than one third of the standard deviation in each domain were considered as medium-sized or small-sized effects, respectively. RESULTS: Median and mean percent changes in testosterone at the 3- to 6-month, 7- to 12-month, 13- to 18-month, and 19- to 24-month time periods were -13.41% and -4.49% (P = .02); -12.23% and -2.77% (P = .13); -11.20% and -0.29% (P = .47); -5.00% and + 1.20% (P = .65). When analyzed after dividing the cohort into 3 groups based on baseline testosterone values using tertiles, testosterone tended to increase in patients in the first group and decrease in patients in the third group. Overall, the decline in EPIC hormonal domain scores never exceeded the threshold for a small-sized effect, though the decline in EPIC sexual domain scores did pass this threshold at the 19- to 24-month time period (mean 10.90 point decline). This decline was not present when groups were examined individually. CONCLUSIONS: In this large cohort of prospectively followed patients, there was a transient decline in testosterone shortly after SBRT that normalized by 24 months posttreatment. There was no significant change in EPIC hormonal domain scores. A significant decline in EPIC sexual domain scores, consistent with a small-sized clinically detectable difference, manifested between 19 and 24 months of follow-up. These results are consistent with testosterone decline patterns and sexual function changes seen after other forms of photon-based radiation therapy.

8.
Curr Heart Fail Rep ; 16(1): 12-20, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30828762

RESUMO

PURPOSE OF REVIEW: Acute heart failure accounts for over one million hospital discharges annually. Current guidelines suggest treatments for AHF should begin "without delay" but this time interval has not been clearly defined. RECENT FINDINGS: Data suggest that certain treatments such as earlier treatment with diuretics and vasodilators may improve patient symptom relief, morbidity, and mortality. Secondary analyses of clinical trials of novel treatments under development have not shown similar results. The data are equivocal regarding the impact of early treatment in AHF on in-hospital and long-term morbidity and mortality. Improved clinical trial designs will help answer when and if "early" treatment should begin and whether it impacts short- and long-term outcomes in AHF.

9.
Circulation ; 139(9): 1157-1161, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30857401
10.
Am J Ther ; 26(2): e234-e247, 2019 Mar/Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30839372

RESUMO

BACKGROUND: Cardiogenic shock (CS) is a life-threatening state of tissue hypoperfusion, associated with a very high risk of mortality, despite intensive monitoring and modern treatment modalities. The present review aimed at describing the therapeutic advances in the management of CS. AREAS OF UNCERTAINTY: Many uncertainties about CS management remain in clinical practice, and these relate to the intensity of invasive monitoring, the type and timing of vasoactive therapies, the risk-benefit ratio of mechanical circulatory support (MCS) therapy, and optimal ventilation mode. Furthermore, most of the data are obtained from CS in the setting of acute myocardial infarction (AMI), although for non-AMI-CS patients, there are very few evidences for etiological or MCS therapies. DATA SOURCES: The prospective multicentric acute heart failure registries that specifically presented characteristics of patients with CS, distinct to other phenotypes, were included in the present review. Relevant clinical trials investigating therapeutic strategies in post-AMI-CS patients were added as source information. Several trials investigating vasoactive medications and meta-analysis providing information about benefits and risks of MCS devices were reviewed in this study. THERAPEUTIC ADVANCES: Early revascularization remains the most important intervention for CS in settings of AMI, and in patients with multivessel disease, recent trial data recommend revascularization on a "culprit-lesion-only" strategy. Although diverse types of MCS devices improve hemodynamics and organ perfusion in patients with CS, results from almost all randomized trials incorporating clinical end points were inconclusive. However, development of new algorithms for utilization of MCS devices and progresses in technology showed benefit in selected patients. A major advance in the management of CS is development of concept of regional CS centers based on the level of facilities and expertise. The modern systems of care with CS centers used as hubs integrated with emergency medical systems and other referee hospitals have the potential to improve patient outcomes. CONCLUSIONS: Additional research is needed to establish new triage algorithms and to clarify intensity and timing of pharmacological and mechanical therapies.


Assuntos
Administração dos Cuidados ao Paciente , Choque Cardiogênico/terapia , Humanos , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/organização & administração , Triagem
11.
Am J Ther ; 26(2): e222-e233, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30839371

RESUMO

BACKGROUND: Acute decompensated heart failure (ADHF) is the most common presenting phenotype of acute heart failure (AHF). The main goal of this article was to review the contemporary management strategies in these patients and to describe how future clinical trials may address unmet clinical needs. AREAS OF UNCERTAINTY: The current pathophysiologic understanding of AHF is incomplete. The guideline recommendations for the management of ADHF are based only on algorithms provided by expert consensus guided by blood pressure and/or clinical signs of congestion or hypoperfusion. The lack of adequately conducted trials to address the unmet need for evidence therapy in AHF has not yet been surpassed, and at this time, there is no evidence-based strategy for targeted decongestive therapy to improve outcomes. The precise time point for initiation of guideline-directed medical therapies (GDMTs), as respect to moment of decompensation, is also unknown. DATA SOURCES: The available data informing current management of patients with ADHF are based on randomized controlled trials, observational studies, and administrative databases. THERAPEUTIC ADVANCES: A major step-forward in the management of ADHF patients is recognizing congestion, either clinical or hemodynamic, as a major trigger for heart failure (HF) hospitalization and most important target for therapy. However, a strategy based exclusively on congestion is not sufficient, and at present, comprehensive assessment during hospitalization of cardiac and noncardiovascular substrate with identification of potential therapeutic targets represents "the corner-stone" of ADHF management. In the last years, substantial data have emerged to support the continuation of GDMTs during hospitalization for HF decompensation. Recently, several clinical trials raised hypothesis of "moving to the left" concept that argues for very early implementation of GDMTs as potential strategy to improve outcomes. CONCLUSIONS: The management of ADHF is still based on expert consensus documents. Further research is required to identify novel therapeutic targets, to establish the precise time point to initiate GDMTs, and to identify patients at risk of recurrent hospitalization.


Assuntos
Gerenciamento Clínico , Insuficiência Cardíaca , Doença Aguda , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos
12.
JAMA Netw Open ; 2(2): e188006, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30735235

RESUMO

Importance: Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective: To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants: This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures: The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results: A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance: In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

13.
ACS Appl Mater Interfaces ; 11(3): 3181-3188, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30590927

RESUMO

Cationic frameworks are an emerging class of exceptional solid adsorbents capable of encapsulating highly toxic and persistent anionic pollutants. The controlled generation of cationic frameworks, however, lags behind the abundant design strategies devised to control the structures and topologies of neutral frameworks. In this regard, we report a rational approach that allows the conversion of the synthetic approach toward constructing a neutral framework into one allowing for the synthesis of a cationic one without incurring any changes to the overall topology or the selected metal ion. We demonstrate that the replacement of a functional group on an organic linker that promotes a similar coordination mode, but bearing one less negative charge, can yield the systematic generation of cationic frameworks. Moreover, we confirm the cationic nature of the metal-organic frameworks through preliminary anion-exchange experiments and propose a method to retain permanent porosity in cationic frameworks through the use of strongly binding anions. Altogether, these results show great promise for the construction of tunable nanoporous frameworks capable of carrying out anion-exchange processes.

14.
Heart Lung ; 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30448355

RESUMO

BACKGROUND: Medical treatment for acute heart failure (AHF) has not changed substantially over the last four decades. Emergency department (ED)-based evidence for treatment is limited. Outcomes remain poor, with a 25% mortality or re-admission rate within 30 days post discharge. Targeting pulmonary congestion, which can be objectively assessed using lung ultrasound (LUS), may be associated with improved outcomes. METHODS: BLUSHED-AHF is a multicenter, randomized, pilot trial designed to test whether a strategy of care that utilizes a LUS-driven treatment protocol outperforms usual care for reducing pulmonary congestion in the ED. We will randomize 130 ED patients with AHF across five sites to, a) a structured treatment strategy guided by LUS vs. b) a structured treatment strategy guided by usual care. LUS-guided care will continue until there are ≤15 B-lines on LUS or 6h post enrollment. The primary outcome is the proportion of patients with B-lines ≤ 15 at the conclusion of 6 h of management. Patients will continue to undergo serial LUS exams during hospitalization, to better understand the time course of pulmonary congestion. Follow up will occur through 90 days, exploring days-alive-and-out-of-hospital between the two arms. The study is registered on ClinicalTrials.gov (NCT03136198). CONCLUSION: If successful, this pilot study will inform future, larger trial design on LUS driven therapy aimed at guiding treatment and improving outcomes in patients with AHF.

15.
World Neurosurg ; 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30476672

RESUMO

BACKGROUND: Prostate Cancer is the most common cancer among American men, with an incidence of approximately 233,000 cases per year.Intracranial metastases are rare and specifically, metastasis to the pineal gland has only been reported in 2 post mortem cases in the literature. CASE DESCRIPTION: We present the first documented case of confirmed prostate cancer metastasis to the pineal gland in a living patient. The patient underwent an endoscopic third ventriculostomy and pineal lesion biopsy with complete resolution of his hydrocephalus and presenting symptoms. His biopsy results confirmed the prostate origin of the metastasis, and he subsequently underwent stereotactic radiosurgery for treatment of this lesion. CONCLUSION: This is the first report of the clinical management of metastatic prostate cancer to the pineal region and description of the clinical outcome. Although prostate cancer is the most common cancer in American men, metastasis to the pineal has only been reported twice from autopsy examinations. Overall, pineal tumors in the geriatric population are exceedingly rare, and the age and co-morbidities in this patient made management quite unique.

16.
ESC Heart Fail ; 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30295437

RESUMO

AIMS: We conducted a prospective study of emergency department (ED) patients with acute heart failure (AHF) to determine if worsening HF (WHF) could be predicted based on urinary electrolytes during the first 1-2 h of ED care. Loop diuretics are standard therapy for AHF patients. A subset of patients hospitalized for AHF will develop a blunted natriuretic response to loop diuretics, termed diuretic resistance, which often leads to WHF. Early detection of diuretic resistance could facilitate escalation of therapy and prevention of WHF. METHODS AND RESULTS: Patients were eligible if they had an ED AHF diagnosis, had not yet received intravenous diuretics, had a systolic blood pressure > 90 mmHg, and were not on dialysis. Urine electrolytes and urine output were collected at 1, 2, 4, and 6 h after diuretic administration. Worsening HF was defined as clinically persistent or WHF requiring escalation of diuretics or administration of intravenous vasoactives after the ED stay. Of the 61 patients who qualified in this pilot study, there were 10 (16.3%) patients who fulfilled our definition of WHF. At 1 h after diuretic administration, patients who developed WHF were more likely to have low urinary sodium (9.5 vs. 43.0 mmol; P < 0.001) and decreased urine sodium concentration (48 vs. 80 mmol/L; P = 0.004) than patients without WHF. All patients with WHF had a total urine sodium of <35.4 mmol at 1 h (100% sensitivity and 60% specificity). CONCLUSIONS: One hour after diuretic administration, a urine sodium excretion of <35.4 mmol was highly suggestive of the development of WHF. These relationships require further testing to determine if early intervention with alternative agents can prevent WHF.

17.
Front Oncol ; 8: 373, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30254985

RESUMO

Purpose/Objective: High-grade glioma is the most common primary malignant tumor of the CNS, with death often resulting from uncontrollable intracranial disease. Radiation dose may be limited by the tolerance of critical structures, such as the brainstem and optic apparatus. In this report, long-term outcomes in patients treated with conventionally fractionated stereotactic boost for tumors in close proximity to critical structures are presented. Materials/Methods: Patients eligible for inclusion in this single institution retrospective review had a pathologically confirmed high-grade glioma status post-surgical resection. Inclusion criteria required tumor location within one centimeter of a critical structure, including the optic chiasm, optic nerve, and brainstem. Radiation therapy consisted of external beam radiation followed by a conventionally fractionated stereotactic boost. Oncologic outcomes and toxicity were assessed. Results: Thirty patients eligible for study inclusion underwent resection of a high-grade glioma. The median initial adjuvant EBRT dose was 50 Gy with a median conventionally fractionated stereotactic boost of 10 Gy. All stereotactic treatments were given in 2 Gy daily fractions. Median follow-up time for the entire cohort was 38 months with a median overall survival of 45 months and 5-year overall survival of 32.5%. The median freedom from local progression was 45 months, and the 5-year freedom from local progression was 29.7%. Two cases of radiation retinopathy were identified following treatment. No patient experienced toxicity attributable to the optic chiasm, optic nerve, or brainstem and no grade 3+ radionecrosis was observed. Conclusions: Oncologic and toxicity outcomes in high-grade glioma patients with tumors in unfavorable locations treated with conventionally fractionated stereotactic boost are comparable to those reported in the literature. This treatment strategy is appropriate for those patients with resected high-grade glioma in close proximity to critical structures.

18.
Contemp Clin Trials ; 72: 137-145, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30125731

RESUMO

Nearly 85% of acute heart failure (AHF) patients who present to the emergency department (ED) with acute heart failure are hospitalized. Once hospitalized, within 30 days post-discharge, 27% of patients are re-hospitalized or die. Attempts to improve outcomes with novel therapies have all failed. The evidence for existing AHF therapies are poor: No currently used AHF treatment is known to improve long-term outcomes. ED treatment is largely the same today as 40 years ago. Admitting patients who could have avoided hospitalization may contribute to adverse outcomes. Hospitalization is not benign; patients enter a vulnerable phase post-discharge, at increased risk for morbidity and mortality. When hospitalization is able to be shortened or avoid completely, certain risks can be mitigated, including risk of medication errors, in-hospital falls, delirium, nosocomial infections, and other iatrogenic complications. Additionally, patients would prefer to be home, not hospitalized. Furthermore, hospitalization and re-hospitalization for AHF predominantly affects patients of lower socioeconomic status (SES). Avoiding hospitalization in patients who do not require admission may improve outcomes and quality of life, while reducing costs. Short stay unit (SSU: <24 h, also referred to as an 'observation unit') management of AHF may be effective for lower risk patients. However, to date there have only been small studies or retrospective analyses on the SSU management for AHF patients. In addition, SSU management has been considered 'cheating' for hospitals trying to avoid 30-day readmission penalties, as SSUs or observation units do not count as an admission. However, more recent analyses demonstrate differential use of observation status has not led to decreases in re-admission, suggesting this concern may be misplaced. Thus, we propose a robust clinical effectiveness trial to demonstrate the effectiveness of this patient-centered strategy.

19.
Artigo em Inglês | MEDLINE | ID: mdl-30099132

RESUMO

BACKGROUND: Prostate cancer survivors who receive androgen deprivation therapy (ADT) are at increased risk of cardiovascular disease. They require coordinated care between cancer specialist and primary care physicians (PCPs) to monitor for cancer control and manage cardiovascular risk factors. METHODS: We prospectively enrolled 103 men receiving ADT with radiotherapy from 7 institutions to assess cardiovascular risk factors and survivorship care. Medical records, fasting labs, and patient-reported outcomes using a validated instrument were assessed at baseline (pre-treatment) and 1 year post-RT. RESULTS: Cardiovascular disease (39%) and risk factors (diabetes 22%, hypertension 63%, hyperlipidemia 31%) were prevalent at baseline. During the first year after RT completion, 63% received cardiovascular monitoring concordant with American Heart Association guidelines. Fasting labs at 1 year showed 24% with inadequately controlled blood sugar, and 22% elevated cholesterol. Patient perceptions about care coordination were relatively low. At 1 year, 57% reported that their PCP "always know about the care I receive at other places," 67% reported that their cancer physician "communicated with other providers I see," and 65% reported the cancer physician "knows the results of my visits with other doctors." CONCLUSIONS: Prostate cancer patients who receive ADT and RT are a vulnerable population with prevalent baseline cardiovascular disease and risk factors, and suboptimal survivorship care specifically related to coordinated care and cardiovascular monitoring. Clinical trials examining ways to improve the care and outcomes of these survivors are needed.

20.
Int J Cardiol ; 269: 207-212, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30041982

RESUMO

BACKGROUND: We sought to examine whether factors impacting the time to emergency department (ED) administration of intravenous (IV) furosemide were associated with the duration of hospital admission for patients with acute heart failure (AHF). METHODS AND RESULTS: We conducted a single-center, retrospective analysis of patients presenting to the ED and admitted between January 1, 2007 and December 31, 2014 who received a dose of IV furosemide. A Cox proportional hazards model was used to examine the likelihood that a patient would be discharged home alive, adjusting for patient demographics, AHF severity (low, moderate, high), laboratory result timing, and known AHF confounders. We identified 695 patients who met study criteria with 430 (61.9%) in the low-severity group. In the overall model, every 60-minute delay in IV furosemide administration was associated with an 8% lower chance of successful discharge home relative to someone who received early furosemide (aHR 0.93, 95%CI 0.87, 0.98, P = 0.012). Subgroup analysis suggests this association was most impactful in low-acuity patients. Our adjusted analysis suggests delaying furosemide administration until after serum creatinine results resulted in a 41% lower chance of successful discharge home relative to someone who had furosemide administered prior to creatinine results (aHR 1.41, 95%CI 1.07, 1,84). CONCLUSIONS: AHF patients, particularly those with lower severity, may benefit from rapid administration of IV furosemide in the ED. This suggests that a key determinant of hospital visit duration in this low-risk cohort is decongestion, which occurs sooner when IV therapy is begun early in the ED stay regardless of serum creatinine.

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