A Multidisciplinary Sepsis Program Enabled by a Two-Stage Clinical Decision Support System: Factors That Influence Patient Outcomes.

Sepsis is an inflammatory response triggered by infection, with risk of in-hospital mortality fueled by disease progression. Early recognition and intervention by multidisciplinary sepsis programs may reverse the inflammatory response among at-risk patient populations, potentially improving outcomes. This retrospective study of a sepsis program enabled by a 2-stage sepsis Clinical Decision Support (CDS) system sought to evaluate the program's impact, identify early indicators that may influence outcomes, and uncover opportunities for quality improvement. Data encompassed 16 527 adult hospitalizations from 2014 and 2015. Of 2108 non-intensive care unit patients screened-in by sepsis CDS, 97% patients were stratified by 177 providers. Risk of adverse outcome improved 30% from baseline to year end, with gains materializing and stabilizing at month 7 after sepsis program go-live. Early indicators likely to influence outcomes include patient age, recent hospitalization, electrolyte abnormalities, hypovolemic shock, hypoxemia, patient location when sepsis CDS activated, and specific alert patterns.

A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study.

OBJECTIVE: To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. DESIGN: Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients' designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. SETTING: Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. PARTICIPANTS: Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. MAIN OUTCOME MEASURE: 'Suspected infection' was the established gold standard to assess clinical decision support clinimetric performance. RESULTS: A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying 'suspected infection' as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. CONCLUSION: A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis.

Cardiac ß-Adrenoceptor Expression Is Reduced in Zucker Diabetic Fatty Rats as Type-2 Diabetes Progresses.

OBJECTIVES: Reduced cardiac ß-adrenoceptor (ß-AR) expression and cardiovascular dysfunction occur in models of hyperglycemia and hypoinsulinemia. Cardiac ß-AR expression in type-2 diabetes models of hyperglycemia and hyperinsulinemia, remain less clear. This study investigates cardiac ß-AR expression in type-2 diabetic Zucker diabetic fatty (ZDF) rats. METHODS: Ex vivo biodistribution experiments with [3H]CGP12177 were performed in Zucker lean (ZL) and ZDF rats at 10 and 16 weeks of age as diabetes develops. Blood glucose, body mass, and diet consumption were measured. Western blotting of ß-AR subtypes was completed in parallel. Echocardiography was performed at 10 and 16 weeks to assess systolic and diastolic function. Fasted plasma insulin, free fatty acids (FFA), leptin and fed-state insulin were also measured. RESULTS: At 10 weeks, myocardial [3H]CGP12177 was normal in hyperglycemic ZDF (17±4.1mM) compared to ZL, but reduced 16-25% at 16 weeks of age as diabetes and hyperglycemia (22±2.4mM) progressed. Reduced ß-AR expression not apparent at 10 weeks also developed by 16 weeks of age in ZDF brown adipose tissue. In the heart, Western blotting at 10 weeks indicated normal ß1-AR (98±9%), reduced ß2-AR (76±10%), and elevated ß3-AR (108±6). At 16 weeks, ß1-AR expression became reduced (69±16%), ß2-AR expression decreased further (68±14%), and ß3-AR remained elevated, similar to 10 weeks (112±9%). While HR was reduced at 10 and 16 weeks in ZDF rats, no significant changes were observed in diastolic or systolic function. CONCLUSIONS: Cardiac ß-AR are reduced over 6 weeks of sustained hyperglycemia in type-2 diabetic ZDF rats. This indicates cardiac [3H]CGP12177 retention and ß1- and ß2-AR expression are inversely correlated with the progression of type-2 diabetes.

Insulin therapy normalizes reduced myocardial ß-adrenoceptors at both the onset and after sustained hyperglycemia in diabetic rats.

AIMS: Reduced cardiac ß-adrenoceptors (ß-AR) and cardiovascular (CV) dysfunction occur in diabetes mellitus (DM) and can be normalized by insulin. It is unclear how the duration of untreated hyperglycemia prior to intervention impacts insulin's effects. This study assesses insulin's effect on reduced myocardial ß-AR and CV function, comparing insulin therapy at the onset of hyperglycemia and after a sustained period of hyperglycemia in streptozotocin (STZ) rats. MAIN METHODS: Ex vivo biodistribution experiments with [(3)H]CGP12177 were performed in high-fat fed STZ rats after 8 weeks of hyperglycemia evaluating cardiac ß-AR expression. Western blotting of ß-AR subtypes was completed in parallel. Serial echocardiography at 0, 6, and 8 weeks post-STZ investigated CV function. Sub-groups of hyperglycemic rats were treated with insulin early, at 1 week post-STZ (InsE) for 7 weeks, or late at 6 weeks post-STZ (InsL) for 2 weeks to observe how the duration of hyperglycemia prior to insulin impacts its effects. KEY FINDINGS: Reduced myocardial [(3)H]CGP12177 binding occurred 8 weeks post-STZ in hyperglycemics, but was normal in both insulin treatments. Western blotting supported reduced ß1-AR in hyperglycemics, but not in either treatment. InsE and InsL treatments improved prolonged mitral valve deceleration (MVD) observed in hyperglycemic animals, but hyperglycemic and InsL still displayed reduced heart rates (HR). SIGNIFICANCE: This work supports that glycemic control with insulin normalizes cardiac ß-AR effectively regardless of prior hyperglycemia but HR may not recover as readily, indirectly supporting the utility of [(11)C]CGP12177 positron emission tomography (PET) in assessing cardiac ß-AR and their modulation with glycemic therapy.

Plasma phospholipids identify antecedent memory impairment in older adults.

Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-ß levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2-3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.

Predictors of coronary artery disease in patients with left bundle branch block who undergo myocardial perfusion imaging.

BACKGROUND: Due to difficulties in diagnosing coronary ischemia in patients with left bundle branch block (LBBB), identifying clinical characteristics that might help to predict coronary artery disease (CAD) is important. Our study aimed to identify clinical predictors of CAD among patients with and without LBBB who undergo myocardial perfusion imaging (MPI). METHODS: All patients with LBBB who underwent MPI (LBBB group) from June 2005 to February 2007 were compared with patients with normal baseline electrocardiography who underwent treadmill MPI (non-LBBB group) during the same period. RESULTS: LBBB patients with CAD were younger and had lower ejection fraction (EF) compared to LBBB patients without CAD. Similarly non-LBBB patients with CAD had lower EF, but did not differ significantly in age compared to non-LBBB patients without CAD. Regression analysis among patients with LBBB showed that EF < 55% was the most significant predictor of CAD, after controlling for other factors. A regression analysis in non-LBBB patients showed that male gender and EF pound 55% were significant predictors of CAD. A regression analysis conducted in the combined data of both LBBB and non-LBBB groups showed male gender, EF pound 55% and LBBB to be the most significant predictors of CAD. CONCLUSIONS: Patients with LBBB have a high probability of CAD based on MPI findings. Patients with LBBB and reduced EF have a much higher likelihood of CAD compared to patients without LBBB and normal EF. Further studies on early invasive approach in patients with LBBB and reduced EF seem warranted.

Physicians' preferences and attitudes about end-of-life care in patients with an implantable cardioverter-defibrillator.

Clinical guidance is deficient regarding deactivation of implantable cardioverter-defibrillators (ICDs) in patients with terminal illnesses. We hypothesized that many physicians are apprehensive about discussing ICD deactivation with their dying patients. Thus, we conducted an anonymous survey of all the physicians in the Department of Medicine at Unity Health System in Rochester, NY. The survey collected information about the knowledge and preferences of these physicians regarding the medical, ethical, and legal issues involved in caring for patients with an ICD and terminal illness. Of the 204 surveys distributed, 87 (43%) were returned. Among the physicians who responded, 64 (74%) reported experience caring for a patient with an ICD and terminal illness. Forty physicians (46%) either thought it was illegal or were not sure if it was legal to deactivate an ICD in these circumstances. However, if reassured about the legality of discontinuing ICD therapy, 79 (91%) of these same respondents said that they would be willing to discuss voluntary ICD deactivation with their dying patients. With increased knowledge about managing the withdrawal of this potentially life-prolonging therapy, physicians are likely to become more skilled at caring for dying patients with an ICD.