Determining predictors of underlying etiology and clinical deterioration in patients with physiologic instability in the emergency department

Thesis (M.A.)--Boston UniversityShock is a critical state defined by inadequate oxygen delivery to tissues. It is well known in the critical care community that early diagnosis and treatment of shock are crucial to improving patient outcomes. However, in many cases, when a state of circulatory shock has been reached, irreversible damage already occurred. In the present study, we broadened our patient cohort from those with shock to those with physiologic instability with the intent of finding predictive factors that allow us to recognize when a patient is at risk for deterioration or when it is already occurring. These patients included patients with pre-shock, shock, and other forms of dysfunction. The purpose of this study was to determine the predictors of underlying etiology of physiologic instability as well as the likelihood of clinical deterioration in these various states, using elements from the physical exam, history, laboratory values, and vital sign measurements. This study was a prospective observational study of patients, from November 15, 2012 to March 1, 2013, found to have physiologic instability in the emergency department at an urban, academic tertiary-care hospital with 55,000 annual visits. Physiologic instability was defined as any one of the following abnormalities: heart rate (HR) > 130, respiratory rate (RR>24), shock index (SI) > 1, systolic blood pressure (SBP) 4.0 mmol/L, for a time period of more than five minutes. We identified 540 patients, 74.8% of which were included. Data describing epidemiology, and elements from the patient history and physical exam were abstracted from physician charts and the final etiology of physiologic instability, defined as septic, cardiogenic, hypovolemic, hemorrhagic, or other, was adjudicated by a physician. Blood samples from a subset of our patient group were collected from the hospital hematology laboratory and sent to the Wyss Institute to be analyzed using a novel bacterial detection assay. All of the covariates that data was collected for were analyzed to determine their diagnostic and prognostic value. [TRUNCATED

Prohormones in the early diagnosis of cardiac syncope

Background--The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional-pro-A-type natriuretic peptide (MRproANP), C-terminal proendothelin 1, copeptin, and midregionalproadrenomedullin. Methods and Results--We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1-year follow-up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes (P < 0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76-0.84), 0.69 (95% CI, 0.64-0.74), 0.58 (95% CI, 0.52-0.63), and 0.68 (95% CI, 0.63-0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82-0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87-0.93), which was significantly higher than for the ED probability alone (P=0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of < 77 pmol/L and an ED probability of < 20% had a sensitivity and a negative predictive value of 99%. Conclusions--The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope

Can Bedside Ultrasound Inferior Vena Cava Measurements Accurately Diagnose Congestive Heart Failure in the Emergency Department? A Clin-IQ

Congestive heart failure (CHF) is a major cause of morbidity and mortality. Early diagnosis of CHF in patients presenting to the emergency department with undifferentiated dyspnea would allow clinicians to begin appropriate treatment more promptly. Current guidelines recommend B-type natriuretic peptide (BNP) levels for more accurate diagnosis of CHF in dyspneic patients. Although BNP levels are relatively inexpensive, the test is not usually performed at bedside and results may take up to an hour or more. BNP also may have a “gray zone” in which the values can neither confirm nor rule out CHF. BNP has a reported sensitivity of 87% and specificity of 74% at a cutoff of 400 pg/ml. Studies investigating bedside ultrasound inferior vena cava (IVC) measurements for identifying CHF report a specificity of 84% to 96% and sensitivity values ranging from 37% to 93%, depending on the study. Given that ultrasound IVC measurements are performed at bedside and results are available rapidly, it is reasonable to evaluate whether ultrasound IVC measurements obtained by appropriately trained emergency department clinicians, alone or in combination with BNP, may increase diagnostic accuracy of CHF

Research Advances: January 2014

The VA has a comprehensive research agenda to help the newest generation of Veterans -- those returning from operations Enduring Freedom, Iraqi Freedom, and New Dawn. In addition to exploring new treatments for traumatic brain injury and other complex blast-related injuries, VA researchers are examining ways to improve the delivery of health care services for these Veterans and promote their reintegration back into their families, communities, and workplaces.This publication reviews recent advances in research about Veterans' health and well-being

The role of b-type natriuretic peptide in heart failure management

Summary. Heart failure is a complex clinical syndrome that manifests itself with signs and symptoms which are neither sensitive nor specific for the diagnosis of heart failure. Natriuretic peptides and in particular b-type natriuretic peptide (and nt-proBNP) are widely used in clinical practice around the world as a maker of heart failure. BNP is primarly released from the left ventricle in response to pressure and volume overload. The strongest evidence for the use of BNP is to rule in or rule out heart failure as cause of breathlessness in people who present to the emergency room. There is enthusiasm for use of BNP as a market of heart failure severity as well as a predictor of outcomes in people with heart failure and trials are ongoing. Nesiritide, a recombinant form of BNP is currently being tested as a possible treatment in people with acutely decompensated heart failure

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels

Clinical applications of MRI in the diagnosis of pulmonary embolism

Pulmonary embolism (PE) is a potentially serious medical condition and is the third most common cause of death among cardiovascular diseases. The diagnosis of PE is made with imaging due to its nonspecific clinical signs and symptoms. Historically, pulmonary angiography has been the gold standard until the emergence of computed tomography pulmonary angiography (CTPA), which has now become the go-to modality due to its fast imaging, availability, and high diagnostic accuracy. However, as with pulmonary angiography, CTPA has its drawbacks, such as ionizing radiation and iodinated contrast agents. It is estimated that approximately 20% of patients with suspected PE have a contraindication to this method. The overall aim of this doctoral thesis can be divided into three parts: 1. To evaluate the diagnostic accuracy of our in-house developed MRI protocol for diagnosing acute PE. 2. To explore other areas where this method could be of benefit since it allows for multiple examinations without any risk to the patients. 3. To understand the emergency doctor's decisions regarding imaging requests for suspected PE. Studies 1–3 are based on a native standard SSFP sequence under free breathing and without respiratory or cardiac gating, repeated five times at each anatomical position. This is done to catch/image the vessels at different breathing and cardiac cycles. Study 4 is a retrospective analysis of the protocol used by physicians to order CTPA in the clinical setting. In Study 1, we looked at the one-year outcome of patients who underwent our MRI protocol as the only diagnostic method for suspected PE due to contraindication to CTPA. This study used clinical outcome instead of an imaging modality as the reference. Our results showed that out of 45 patients with a negative MRI result for PE, only one was diagnosed with DVT within three months. In Study 2, we looked at the feasibility of the MRI method for looking at the natural history of acute PE. We examined 18 patients within 36 hours of PE diagnosis with CTPA and then at one week, one, three, and six months. Our results showed that most of the resolution happens within the first few weeks of the treatment. In Study 3, we evaluated the diagnostic accuracy of our in-house developed MRI protocol in reference to CTPA. A total of 243 cases were included, and two radiologists read the MRI exams. Our results showed a sensitivity of 87% and 89% for Readers 1 and 2, specificity of 100% for both, and a kappa value of 0.88. In Study 4, we looked at PE from a clinician's perspective. Therefore, we retrospectively calculated the clinical decision support system (CDSS) points by extracting data from the Electronic Medical Records (EMR) to examine whether the radiology requests were based on a clinical hunch or the available and recommended clinical decision support systems. Our results showed that clinician bypass these CDSS, which unfortunately leads to lower yield. To conclude, this doctoral thesis has shown that our MRI method is a viable option for diagnosing PE in patients with contraindication to CTPA and can also be used in treatment follow-up of these patients. However, insights from study number 4 inthis thesis showed that the diagnosis of PE is complicated, and more research is needed to improve the diagnostic accuracy for these patients

Addressing the heart failure epidemic: from mechanical circulatory support to stem cell therapy

At an annual cost of over thirty billion dollars annually, the diagnosis and management of heart failure is one of the most significant public health concerns of the twenty first century, as nearly twenty percent of Americans will develop some form of heart failure in their lifetime. The incidence of newly diagnosed heart failure has remained stable over the last several years at approximately 650,000 diagnoses per year; however, due to several contributing factors the prevalence has continued to rise despite substantial advancements in interventional therapies. The three most significant contributing factors to the rising heart failure prevalence have been identified as 1) significant advancements in technology and medical intervention have dramatically improved the survival rate of those experiencing acute coronary events. This has resulted in a greater number of patients who then progress to chronic heart failure. 2) The management of those with chronic heart failure has been dramatically improved which has allowed those with the disease to live longer and 3) heart failure is in large part a disease associated with advancing age. As the population in the United States and other developed countries continue to grow, such a strong association will inevitably result in a rapidly increasing prevalence. Current clinically therapies for managing heart failure can be categorized into three major groups: pharmaceutical therapy, mechanical circulatory support, or cell-based therapy. Pharmaceutical therapies are used in the earlier stages of disease progression or to manage symptoms and comorbidities of later stage heart failure. Mechanical circulatory support is often implemented when the disease progresses to a more severe state, where volume and / or pressure overload of the ventricles is present. Many modalities of mechanical circulatory support serve as a bridge to transplant, as the only long-term treatment of advanced decompensated heart failure is cardiac transplantation. The third category of treatments for HF is cell-based or stem cell therapies. These therapies are still in their infancies but hold significant potential of cardiac regeneration and reversal of the pathologic remodeling associated with heart failure. While the management of the early stages of heart failure have improves, addressing end-stage failure remains a significant obstacle in resolving the U.S. of the heart failure epidemic. The use of ventricular assist devices (VADs) has improved the management of end-stage failure over the last few decades, but VADs serve mostly as a bridge to transplant, so eventually a donor organ and cardiac transplantation is required. As the population continues to grow, the number of patients in need of a donor heart will increase, leading to an even larger discrepancy between the number of donor organs available and those in severe need. While advancements in VAD technology have reduced potential complications and increased the duration and effectiveness of the mechanical circulatory support, a long-term permanent treatment is still very much in need. Cell-based cardiac therapy or cardiac stem cell therapy holds the greatest potential to solving this age-old problem. The ability to not only regenerate dead or damaged tissue in the heart but also reverse pathologic remodeling due to heart failure could cure millions of patients of heart failure, returning them to a healthy, fully functioning state. The last decade has shed much light on the potential of stem cell therapies, but also has illuminated significant barriers to creating a clinically acceptable treatment. While these barriers seem tall, it is crucial that much time and resources be invested into stem cell therapies for cardiac applications as they hold the greatest potential to being able to effectively treat, rather than manage, those with heart failure. In addition to regenerating dead of damaged myocardium, stem cell technology has the potential to grow an entire organ that is patient specific in its origin, and would fully alleviate having to wait for an available donor organ. The ability to grow an entire organ in the lab, which can later be transplanted, would forever change the way medicine is practiced, while saving millions if not billions of lives worldwide