The Tennessee Heart Health Network effectiveness study: A stepped wedge cluster randomized controlled trial to assess the effectiveness of statewide quality improvement cooperative participation on cardiovascular outcomes.

BACKGROUND: Cardiovascular disease (CVD) is the primary cause of premature morbidity and mortality in the United States and Tennessee ranks among the highest in CVD events. While patient-centered outcomes research (PCOR) evidence-based approaches that reach beyond the traditional doctor-patient visit hold promise to improve CVD care and prevent serious complications, most primary care providers lack time, knowledge, and infrastructure to implement these proven approaches. Statewide primary care quality improvement (QI) collaboratives hold potential to help address primary care needs, however, little is known regarding their effectiveness in improving uptake of PCOR evidence-based population health approaches and improving CVD outcomes. This study describes the design and implementation of a stepped-wedge cluster randomized controlled trial to assess the effectiveness of participation in a statewide quality improvement cooperative (The Tennessee Heart Health Network [TN-HHN]) on cardiovascular outcomes. METHODS/DESIGN: The TN-HHN Effectiveness Study randomized 77 practices to 4 waves (i.e., clusters), with each wave beginning three months after the start of the prior wave and lasting for 18 months. All practice clusters received one of three Network interventions, and outcomes are measured for each three months both in the control phase and the intervention phase. Primary outcomes include Center for Medicare and Medicaid Services measures for aspirin use, blood pressure control, cholesterol control, and smoking cessation (ABCS). CONCLUSIONS: This trial, upon its conclusion, will allow us to assess the effect of participation in a statewide quality improvement cooperative on cardiovascular outcomes as well as key contributors to successful practice transformation.

Building Statewide Quality Improvement Capacity to Improve Cardiovascular Care and Health Equity: Lessons from the Tennessee Heart Health Network.

DRIVING FORCES: Many states with high rates of cardiovascular disease (CVD) lack statewide quality improvement (QI) infrastructure (for example, resources, leadership, community) to address relevant health needs of the population. Academic health centers are well positioned to play a central role in addressing this deficiency. This article describes early experience and lessons learned in building statewide QI infrastructure through the Tennessee Heart Health Network (Network). APPROACH: A statewide, multistakeholder network composed of primary care practices (PCPs), health systems, health plans, QI organizations, patients, and academic institutions was led by the University of Tennessee Health Science Center (UTHSC), an academic health center, to improve cardiovascular health by supporting dissemination and implementation of patient-centered outcomes research (PCOR) evidence-based interventions in primary care. PCPs were required to select and implement at least one of three interventions (health coaching, tailored health-related text messaging, and pharmacist-physician collaboration). OUTCOMES AND KEY INSIGHTS: Thirty statewide organizational partners joined the Network in year one, including 18 health systems representing 77 PCPs (30.0% of 257 potentially eligible PCPs identified) with approximately 300,000 patients. The organizational partners share EHRs for the ongoing tracking and reporting of key health metrics, including hypertension control and delivery of tobacco cessation counseling. Of the 77 PCPs, 62 continue participation after year two (80.5% retention). Main barriers to participation and reasons for discontinuing participation included reluctance to share data and changes in leadership at the health system level. These 62 PCPs selected the following interventions to implement: health coaching (41.9%), tailored health-related text messages (48.4%), and pharmacist-physician collaboration (40.3%). CONCLUSION AND WHAT'S NEXT: Academic health centers have broad reach and high acceptability by diverse stakeholders. Tennessee's experience illustrates how academic health centers can serve as platforms for building a statewide infrastructure for disseminating, implementing, and sustaining QI interventions at the practice level. Assessment of Network impact is ongoing.

EMERGENCY ANESTHESIA AND EXPLORATORY LAPAROTOMY IN A COMPROMISED PACIFIC WHITE-SIDED DOLPHIN (LAGENORHYNCHUS OBLIQUIDENS).

Anesthesia and surgery in cetaceans have inherent risks and have rarely been utilized as viable treatment options. This report represents the first known multidisciplinary team approach to emergency laparotomy in a compromised, 22-yr-old, female Pacific white-sided dolphin ( Lagenorhynchus obliquidens ). The inciting clinical signs and ancillary diagnostics were consistent with a mechanical ileus. Although no torsion or obstruction was apparent during surgery, severe enteritis and peritonitis were noted. Postoperatively, the animal was maintained on aggressive medical management with continuous supportive care until succumbing 3 days later with clinical pathology indicative of terminal sepsis and profound inflammation. Postmortem findings included generalized vascular stasis and segmental intestinal volvulus with infarction. To the authors' knowledge, this is one of the most-complex surgical and anesthetic procedures performed in a cetacean. Though the outcome was unsuccessful, this case represents the aquatic veterinary community's collective advances in the ability to treat cetaceans under human care.

Drug therapy problems and medication discrepancies during care transitions in super-utilizers.

OBJECTIVES: First, to investigate the prevalence and types of drug therapy problems and medication discrepancies among super-utilizers, and associated patient characteristics. Second, to examine the outcomes of pharmacist recommendations and estimated cost avoidance through care transitions support focused on medication management. DESIGN: Retrospective analysis of the pharmacist-led interventions as part of the SafeMed Program. SETTING: A large nonprofit health care system serving the major medically underserved areas in Memphis, Tennessee. PARTICIPANTS: Three hundred seventy-four super-utilizing SafeMed participants with multiple chronic conditions and polypharmacy. INTERVENTION: Comprehensive medication review, medication therapy management, enhanced discharge planning, home visits, telephone follow-up, postdischarge medication reconciliation, and care coordination with physicians. MAIN OUTCOME MEASURES: Types of drug therapy problems, outcomes of pharmacist recommendations, estimated cost avoided, medication discrepancies, and self-reported medication adherence. RESULTS: Prevalence of drug therapy problems and postdischarge medication discrepancies was 80.7% and 75.4%, respectively. The most frequently occurring drug therapy problems were enrollee not receiving needed medications (33.4%), underuse of medications (16.9%), and insufficient dose or duration (11.2%). Overall 50.8% of the pharmacist recommendations were accepted by physicians and patients, resulting in an estimated cost avoidance of $293.30 per drug therapy problem identified. Multivariate analysis indicated that participants with a higher number of comorbidities were more likely to have medication discrepancies (odds ratio 1.23 [95% CI 1.05-1.44]). Additional contributors to postdischarge medication discrepancies were difficulty picking up and paying for medications and not being given necessary prescriptions before discharge. CONCLUSION: Drug therapy problems and medication discrepancies are common in super-utilizers with multiple chronic conditions and polypharmacy during transitions of care, and greater levels of comorbidity magnify risk. Pharmacist-led interventions in the SafeMed Program have demonstrated success in resolving enrollees' medication-related issues, resulting in substantial estimated cost savings. Preliminary evidence suggests that the SafeMed model's focus on medication management has great potential to improve outcomes while reducing costs for vulnerable super-utilizing populations nationwide.

SafeMed: Using pharmacy technicians in a novel role as community health workers to improve transitions of care.

OBJECTIVES: To describe the design, implementation, and early experience of the SafeMed program, which uses certified pharmacy technicians in a novel expanded role as community health workers (CPhT-CHWs) to improve transitions of care. SETTING: A large nonprofit health care system serving the major medically underserved areas and geographic hotspots for readmissions in Memphis, TN. PRACTICE INNOVATION: The SafeMed program is a care transitions program with an emphasis on medication management designed to use low-cost health workers to improve transitions of care from hospital to home for superutilizing patients with multiple chronic conditions and polypharmacy. EVALUATION: CPhT-CHWs were given primary responsibility for patient outreach after hospital discharge with the use of home visits and telephone follow-up. SafeMed program CPhT-CHWs served as pharmacist extenders, obtaining medication histories, assisting in medication reconciliation and identification of potential drug therapy problems (DTPs), and reinforcing medication education previously provided by the pharmacist per protocol. RESULTS: CPhT-CHW training included patient communication skills, motivational interviewing, medication history taking, teach-back techniques, drug disposal practices, and basic disease management. Some CPhT-CHWs experienced difficulties adjusting to an expanded scope of practice. Nonetheless, once the Tennessee Board of Pharmacy affirmed that envisioned SafeMed CPhT-CHW roles were consistent with Board rules, additional responsibilities were added for CPhT-CHWs to enhance their effectiveness. Patient outreach teams including CPhT-CHWs achieved increases in home visit and telephone follow-up rates and were successful in helping identify potential DTPs. CONCLUSION: The early experience of the SafeMed program demonstrates that CPhT-CHWs are well suited for novel expanded roles to improve care transitions for superutilizing populations. CPhT-CHWs can identify and report potential DTPs to the pharmacist to help target medication therapy management. Critical success factors include strong CPhT-CHW patient-centered communication skills and strong pharmacist champions. In collaboration with state pharmacy boards and pharmacist associations, the SafeMed CPhT-CHW model can be successfully scaled to serve superutilizing patients throughout the country.

Health information exchange reduces repeated diagnostic imaging for back pain.

STUDY OBJECTIVE: This study seeks to determine whether health information exchange reduces repeated diagnostic imaging and related costs in emergency back pain evaluation. METHODS: This was a longitudinal data analysis of health information exchange patient-visit data. All repeated emergency department (ED) patient visits for back pain with previous ED diagnostic imaging to a Memphis metropolitan area ED between August 1, 2007, and July 31, 2009, were included. Use of a regional health information exchange by ED personnel to access the patient's record during the emergency visit was the primary independent variable. Main outcomes included repeated lumbar or thoracic diagnostic imaging (radiograph, computed tomography [CT], or magnetic resonance imaging [MRI]) and total patient-visit estimated cost. RESULTS: One hundred seventy-nine (22.4%) of the 800 qualifying repeated back pain visits resulted in repeated diagnostic imaging (radiograph 84.9%, CT 6.1%, and MRI 9.5%). Health information exchange use in the study population was low, at 12.5%, and health care providers as opposed to administrative/nursing staff accounted for 80% of the total health information exchange use. Health information exchange use by any ED personnel was associated with reduced repeated diagnostic imaging (odds ratio 0.36; 95% confidence interval 0.18 to 0.71), as was physician or nurse practitioner health information exchange use (odds ratio 0.47; 95% confidence interval 0.23 to 0.96). No cost savings were associated with health information exchange use because of increased CT imaging when health care providers used health information exchange. CONCLUSION: Health information exchange use is associated with 64% lower odds of repeated diagnostic imaging in the emergency evaluation of back pain. Health information exchange effect on estimated costs was negligible. More studies are needed to evaluate specific strategies to increase health information exchange use and further decrease potentially unnecessary diagnostic imaging and associated costs of care.

Does health information exchange reduce unnecessary neuroimaging and improve quality of headache care in the emergency department?

BACKGROUND: Health information exchange (HIE) is advocated as an approach to reduce unnecessary testing and improve quality of emergency department (ED) care, but little evidence supports its use. Headache is a specific condition for which HIE has theoretical benefits. OBJECTIVE: To determine whether health information exchange (HIE) reduces potentially unnecessary neuroimaging, increases adherence with evidence-based guidelines, and decreases costs in the emergency department (ED) evaluation of headache. DESIGN: Longitudinal data analysis SUBJECTS: All repeat patient-visits (N = 2,102) by all 1,252 adults presenting with headache to a Memphis metropolitan area ED two or more times between August 1, 2007 and July 31, 2009. INTERVENTION: Use of a regional HIE connecting the 15 major adult hospitals and two regional clinic systems by authorized ED personnel to access the patient's record during the time period in which the patient was being seen in the ED. MAIN MEASURES: Diagnostic neuroimaging (CT, CT angiography, MRI or MRI angiography), evidence-based guideline adherence, and total patient-visit estimated cost. KEY RESULTS: HIE data were accessed for 21.8 % of ED patient-visits for headache. 69.8 % received neuroimaging. HIE was associated with decreased odds of diagnostic neuroimaging (odds ratio [OR] 0.38, confidence interval [CI] 0.29-0.50) and increased adherence with evidence-based guidelines (OR 1.33, CI 1.02-1.73). Administrative/nursing staff HIE use (OR 0.24, CI 0.17-0.34) was also associated with decreased neuroimaging after adjustment for confounding factors. Overall HIE use was not associated with significant changes in costs. CONCLUSIONS: HIE is associated with decreased diagnostic imaging and increased evidence-based guideline adherence in the emergency evaluation of headache, but was not associated with improvements in overall costs. Controlled trials are needed to test whether specific HIE enhancements to increase HIE use can further reduce potentially unnecessary diagnostic imaging and improve adherence with guidelines while decreasing costs of care.

Macrolide-based transgene control in mammalian cells and mice.

Heterologous mammalian gene regulation systems for adjustable expression of multiple transgenes are necessary for advanced human gene therapy and tissue engineering, and for sophisticated in vivo gene-function analyses, drug discovery, and biopharmaceutical manufacturing. The antibiotic-dependent interaction between the repressor (E) and operator (ETR) derived from an Escherichia coli erythromycin-resistance regulon was used to design repressible (E(OFF)) and inducible (E(ON)) mammalian gene regulation systems (E.REX) responsive to clinically licensed macrolide antibiotics (erythromycin, clarithromycin, and roxithromycin). The E(OFF) system consists of a chimeric erythromycin-dependent transactivator (ET), constructed by fusing the prokaryotic repressor E to a eukaryotic transactivation domain that binds and activates transcription from ETR-containing synthetic eukaryotic promoters (P(ETR)). Addition of macrolide antibiotic results in repression of transgene expression. The E(ON) system is based on E binding to artificial ETR-derived operators cloned adjacent to constitutive promoters, resulting in repression of transgene expression. In the presence of macrolides, gene expression is induced. Control of transgene expression in primary cells, cell lines, and microencapsulated human cells transplanted into mice was demonstrated using the E.REX (E(OFF) and E(ON)) systems. The macrolide-responsive E.REX technology was functionally compatible with the streptogramin (PIP-regulated and tetracycline (TET-regulated expression systems, and therefore may be combined for multiregulated multigene therapeutic interventions in mammalian cells and tissues.

Expressing creatine kinase in transgenic tobacco--a first step towards introducing an energy buffering system in plants.

Creatine kinase a key enzyme in cellular energy homeostasis of vertebrates offers the promise of engineering plants with enhanced stress tolerance. In order to provide plants with such an energy buffering system, tobacco was transformed with a cDNA, encoding the cytosolic brain-type isoform of chicken creatine kinase (BB-CK), the expression of which was under the control of the cauliflower mosaic virus 35S (CaMV 35S) promoter. Transgenic tobacco plants were selected and suspension cultures generated. Both transgenic plants and suspension cultures were shown to stably express enzymatically active BB-CK in vitro and in vivo, and in most cases for three successive generations (T0-T2). Exogenously supplied creatine was shown to enter the plant cells and resulted in only a slight reduction in root growth at concentrations up to 10 mM. Furthermore, the BB-CK expressing tobacco plants and cell suspension cultures were able to convert creatine into phosphocreatine.

Aerosolized salbutamol (albuterol) improves PaO2 in hypoxaemic anaesthetized horses - a prospective clinical trial in 81 horses.

OBJECTIVE: To compare the arterial pH and blood gas values, heart rate and mean arterial blood pressure, in hypoxaemic anaesthetized horses, before and after treatment, with a salbutamol (albuterol) aerosol. ANIMAL POPULATION: Eighty-one client-owned horses weighing between 114 and 925 kg. Fifty-seven underwent emergency abdominal surgery and 24 were anaesthetized for elective procedures. MATERIALS AND METHODS: Pre-anaesthetic medication included xylazine, detomidine, butorphanol and morphine, alone or in various combinations. Induction of anaesthesia was achieved with guaifenesin and ketamine, diazepam and ketamine, or guaifenesin and thiopental. The trachea of all animals was intubated and anaesthesia maintained with either halothane (33 horses) or isoflurane (48 horses) in oxygen. Heart rate and rhythm were monitored continuously. Arterial blood pressure was monitored directly, and arterial blood collected for pH and blood gas analyses. When arterial PaO2 fell below 9.3 kPa (70 mm Hg) and failed to respond to corrective measures including positive pressure ventilation and treatment of hypotension (mean arterial blood pressures <70 mm Hg), a salbutamol aerosol (2 µg kg-1) was delivered via the endotracheal tube. Twenty minutes later, a second arterial blood sample was analysed. RESULTS: There were no significant differences in mean arterial blood pressure, heart rate, arterial pH, base excess and bicarbonate before and after treatment. Arterial O2 tension increased significantly from a mean ± SD of 8.3 ± 1.7 kPa (62.4 ± 13.1 mm Hg) before administration to 15.9 ± 9.8 kPa (119.4 ± 57.7 mm Hg) after treatment. There was a small but significant decrease in PaCO2 from 7.4 ± 1.5 kPa (55.2 ± 11.2 mm Hg) to 7.0 ± 1.3 kPa (52.9 ± 9.8 mm Hg) between sample times. No changes in heart rhythm were observed. A high percentage (approximately 70%) of animals sweated following treatment. CONCLUSIONS: Salbutamol administered at a dose of 2 µg kg-1 via the endotracheal tube of anaesthetized horses with PaO2 values less than 9.3 kPa (70 mm Hg) resulted in an almost two-fold increase in PaO2 values within 20 minutes of treatment. No changes in heart rate or mean arterial blood pressure were associated with the use of salbutamol in this study. The improvement in PaO2 may be a result of bronchodilatation and improved ventilation, increased perfusion secondary to an increase in cardiac output, or a combination of these two factors. Cardiac output and ventilation-perfusion distribution were not measured in this study; therefore, the reason for the increase in PaO2 values cannot be conclusively determined. CLINICAL RELEVANCE: Administration of a salbutamol aerosol is a simple but effective technique that can be used to improve PaO2 values in hypoxaemic horses during inhalant anaesthesia with no apparent detrimental side effects.

Flow effects on the viability and lysis of suspended mammalian cells.

A mouse myeloma cell line growing in suspension was subjected intermittently to flow through a sudden contraction and turbulent flow in a capillary tube. The probability of lysis per pass through the capillary tube increased with average wall shear stress level and with residence time per pass in the tube. Lysis was first observed at a threshold average wall shear stress level of 1800 dyn/cm2. Although the flow caused lysis, it had no effect on cell viability.