Non-cardiac chest pain patients in the emergency department: Do physicians have a plan how to diagnose and treat them? A retrospective study

BACKGROUND Non-cardiac chest pain is common and there is no formal recommendation on what diagnostic tests to use to identify underlying diseases after an acute coronary syndrome has been ruled out. OBJECTIVE To evaluate the diagnostic tests, treatment recommendations and initiated treatments in patients presenting with non-cardiac chest pain to the emergency department (ED). METHODS Single-center, retrospective medical chart review of patients presenting to the ED. Included were all medical records of patients aged 18 years and older presenting to the ED with chest pain and a non-cardiac discharge diagnosis between January 1, 2009 and December 31, 2011. Information on the diagnosis, diagnostic tests performed, treatment initiated and recommendation for further diagnostic testing or treatment were extracted. The primary outcomes of interest were the final diagnosis, diagnostic tests, and treatment recommendations. A formal ACS rule out testing was defined as serial three troponin testing. RESULTS In total, 1341 ED admissions for non-cardiac chest pain (4.2% of all ED admissions) were analyzed. Non-specific chest pain remained the discharge diagnosis in 44.7% (n = 599). Identified underlying diseases included musculoskeletal chest pain (n = 602, 44.9%), pulmonary (n = 30, 2.2%), GI-tract (n = 35, 2.6%), or psychiatric diseases (n = 75, 5.6%). In 81.4% at least one troponin test and in 89% one ECG were performed. A formal ACS rule out troponin testing was performed in 9.2% (GI-tract disease 14.3%, non-specific chest pain 14.0%, pulmonary disease 10.0%, musculoskeletal chest pain 4.7%, and psychiatric disease 4.0%). Most frequently analgesics were prescribed (51%). A diagnostic test with proton pump inhibitor (PPI) was prescribed in 20% (mainly in gastrointestinal diseases). At discharge, over 72 different recommendations were given, ranging from no further measures to extensive cardiac evaluation. CONCLUSION In this retrospective study, a formal work-up to rule out ACS was found in a minority of patients presenting to the ED with chest pain of non-cardiac origin. A wide variation in diagnostic processes and treatment recommendations reflect the uncertainty of clinicians on how to approach patients after a cardiac cause was considered unlikely. Panic and anxiety disorders were rarely considered and a useful PPI treatment trial to diagnose gastroesophageal reflux disease was infrequently recommended

Riboswitch-mediated Attenuation of Transgene Cytotoxicity Increases Adeno-associated Virus Vector Yields in HEK-293 Cells

Cytotoxicity of transgenes carried by adeno-associated virus (AAV) vectors might be desired, for instance, in oncolytic virotherapy or occur unexpectedly in exploratory research when studying sparsely characterized genes. To date, most AAV-based studies use constitutively active promoters (e.g., the CMV promoter) to drive transgene expression, which often hampers efficient AAV production due to cytotoxic, antiproliferative, or unknown transgene effects interfering with producer cell performance. Therefore, we explored artificial riboswitches as novel tools to control transgene expression during AAV production in mammalian cells. Our results demonstrate that the guanine-responsive GuaM8HDV aptazyme efficiently attenuates transgene expression and associated detrimental effects, thereby boosting AAV vector yields up to 23-fold after a single addition of guanine. Importantly, riboswitch-harboring vectors preserved their ability to express functional transgene at high levels in the absence of ligand, as demonstrated in a mouse model of AAV-TGFβ1-induced pulmonary fibrosis. Thus, our study provides the first application-ready biotechnological system-based on aptazymes, which should enable high viral vector yields largely independent of the transgene used. Moreover, the RNA-intrinsic, small-molecule regulatable mode of action of riboswitches provides key advantages over conventional transcription factor-based regulatory systems. Therefore, such riboswitch vectors might be ultimately applied to temporally control therapeutic transgene expression in vivo.publishe

Impact of the introduction of high-sensitive troponin assay in the emergency department: a retrospective study.

BACKGROUND Compared to troponin T/I test, the introduction of a high-sensitive (hs) troponin test may result in a higher proportion of positive test results in patients with chest pain and over testing in patients without acute coronary syndrome. We assessed the impact of the introduction of the hs-troponin assay on the discharge diagnoses and the number of diagnostic tests in patients presenting with chest pain in a real-life setting in an ED. METHODS Retrospective chart review of patients presenting with chest pain to one of the largest hospitals in Switzerland. We compared the standard troponin period (12/2009 to 11/2010) to the hs-troponin period (12/2010 to 12/2011). RESULTS Data from 1,274 patients (standard 597 (46.9%), hs-troponin 677 (53.1%)) were analyzed. The proportion of patients with NSTEMI increased (hs-troponin 14.9% compared to 9.7%); the proportion in unstable angina (1.5% to 4.0%) and other cardiac illnesses (8.1% to 11.7%) decreased. Although the proportion of non-cardiac chest pain illnesses (67%) remained unchanged, the proportion of positive hs-troponin was higher (6.1% vs. 2.0%). The average number of additional tests/person decreased in troponin positive patients (2.0 to 1.7 test per patient; p=0.02) and troponin negative patients (3.1 to 2.8 tests; p<0.0001). CONCLUSION Although the introduction of the hs-troponin test resulted in a higher proportion of positive hs-troponin tests in patients with non-cardiac chest pain, the average number of diagnostic tests decreased in patients with chest pain presenting to an ED indicating an increased confidence of clinicians in their diagnosis

Datasets describing the introduction of the high-sensitive troponin in the emergency department.

Chest pain is a common clinical condition in the emergency department. A high sensitive (hs) troponin test assay may help to identify patients with acute coronary syndrome earlier compared to conventional tests but also entails the risk of a high proportion of positive test results in patients without cardiac disease. We assessed the impact of the introduction of the hs-troponin test in clinical practice in an emergency department. We compared December 1, 2009 until November 30, 2010 (standard test period) to December 1, 2010 - the date of the introduction of the hs-troponin assay - until December 31, 2011 (hs troponin test period) of patients presenting with chest pain to one of the ten largest hospitals in Switzerland. We identified electronic health records using the following ICD-10 codes: R06.4 (hyperventilation), R07.1 (chest pain when breathing), R07.2 (precordial pain), R07.3 (other chest pain), and R07.4 (chest pain not specified), I20 (angina pectoris), I21 (acute MI), I22 (recurrent MI), I23 (complications after acute MI), and I24 (other acute ischemic heart disease). Included were all medical records of adult patients (≥18 years) presenting to the ED with chest pain and with ≥1 troponin test. Excluded were records without troponin test, pregnancy, trauma patients/life-threatening conditions, malignant disease, current fracture, renal replacement therapy/severe kidney failure (creatinine clearance 3 months due to chest pain were defined as a new index visit of a second episode. The extraction form with predefined variables was pilot-tested in 20 records. Additional diagnostic tests were ECG, treadmill test, coronary angiography, MIBI scintigraphy, echocardiography, chest X-ray, computer tomography (CT) of the chest or abdomen, sonography of the abdomen or pleura, gastroscopy, and lung function tests. We compared the number of non-invasive / invasive cardiac diagnostic tests in troponin positive and negative patients and the number of diagnostic tests after the exclusion of patients with STEMI diagnosis. Non-invasive / invasive cardiac tests included treadmill test, coronary angiography, MIBI scintigraphy, and echocardiography. We calculated average monthly tests per patient and compared mean tests per patient between groups. We used a t-test to quantify the evidence for differential number of diagnostic tests per patient in each period. Between-group differences were estimated with 95% confidence intervals. All analyses were performed with the statistical software R for windows [1]. Interpretation of this data can be found in a research article titled Impact of the introduction of high-sensitive troponin assay on the evaluation of chest pain patients in the emergency department: a retrospective study [2])

Non-cardiac chest pain patients in the emergency department: Do physicians have a plan how to diagnose and treat them? A retrospective study.

BACKGROUND Non-cardiac chest pain is common and there is no formal recommendation on what diagnostic tests to use to identify underlying diseases after an acute coronary syndrome has been ruled out. OBJECTIVE To evaluate the diagnostic tests, treatment recommendations and initiated treatments in patients presenting with non-cardiac chest pain to the emergency department (ED). METHODS Single-center, retrospective medical chart review of patients presenting to the ED. Included were all medical records of patients aged 18 years and older presenting to the ED with chest pain and a non-cardiac discharge diagnosis between January 1, 2009 and December 31, 2011. Information on the diagnosis, diagnostic tests performed, treatment initiated and recommendation for further diagnostic testing or treatment were extracted. The primary outcomes of interest were the final diagnosis, diagnostic tests, and treatment recommendations. A formal ACS rule out testing was defined as serial three troponin testing. RESULTS In total, 1341 ED admissions for non-cardiac chest pain (4.2% of all ED admissions) were analyzed. Non-specific chest pain remained the discharge diagnosis in 44.7% (n = 599). Identified underlying diseases included musculoskeletal chest pain (n = 602, 44.9%), pulmonary (n = 30, 2.2%), GI-tract (n = 35, 2.6%), or psychiatric diseases (n = 75, 5.6%). In 81.4% at least one troponin test and in 89% one ECG were performed. A formal ACS rule out troponin testing was performed in 9.2% (GI-tract disease 14.3%, non-specific chest pain 14.0%, pulmonary disease 10.0%, musculoskeletal chest pain 4.7%, and psychiatric disease 4.0%). Most frequently analgesics were prescribed (51%). A diagnostic test with proton pump inhibitor (PPI) was prescribed in 20% (mainly in gastrointestinal diseases). At discharge, over 72 different recommendations were given, ranging from no further measures to extensive cardiac evaluation. CONCLUSION In this retrospective study, a formal work-up to rule out ACS was found in a minority of patients presenting to the ED with chest pain of non-cardiac origin. A wide variation in diagnostic processes and treatment recommendations reflect the uncertainty of clinicians on how to approach patients after a cardiac cause was considered unlikely. Panic and anxiety disorders were rarely considered and a useful PPI treatment trial to diagnose gastroesophageal reflux disease was infrequently recommended

EAES recommendations for the management of gastroesophageal reflux disease

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most frequent benign disorders of the upper gastrointestinal tract. Management of GERD has always been controversial since modern medical therapy is very effective, but laparoscopic fundoplication is one of the few procedures that were quickly adapted to the minimal access technique. The purpose of this project was to analyze the current knowledge on GERD in regard to its pathophysiology, diagnostic assessment, medical therapy, and surgical therapy, and special circumstances such as GERD in children, Barrett's esophagus, and enteroesophageal and duodenogastroesophageal reflux. METHODS: The European Association of Endoscopic Surgery (EAES) has tasked a group of experts, based on their clinical and scientific expertise in the field of GERD, to establish current guidelines in a consensus development conference. The expert panel was constituted in May 2012 and met in September 2012 and January 2013, followed by a Delphi process. Critical appraisal of the literature was accomplished. All articles were reviewed and classified according to the hierarchy of level of evidence and summarized in statements and recommendations, which were presented to the scientific community during the EAES yearly conference in a plenary session in Vienna 2013. A second Delphi process followed discussion in the plenary session. RESULTS: Recommendations for pathophysiologic and epidemiologic considerations, symptom evaluation, diagnostic workup, medical therapy, and surgical therapy are presented. Diagnostic evaluation and adequate selection of patients are the most important features for success of the current management of GERD. Laparoscopic fundoplication is the most important therapeutic technique for the success of surgical therapy of GERD. CONCLUSIONS: Since the background of GERD is multifactorial, the management of this disease requires a complex approach in diagnostic workup as well as for medical and surgical treatment. Laparoscopic fundoplication in well-selected patients is a successful therapeutic option