Incretins as a novel therapeutic strategy in patients with diabetes and heart failure.

Heart failure (HF) and diabetes mellitus (DM) commonly co-exist, with a prevalence of DM of up to 40 % in HF patients. Treatment of DM in patients with HF is challenging since many of the contemporary therapies used for the treatment of DM are either contraindicated in HF or are limited in their use due to the high prevalence of co-morbidities such as significant renal dysfunction. This article presents an overview of the physiology of the incretin system and how it can be targeted therapeutically, highlighting implications for the management of patients with DM and HF. Receptors for the incretin glucagon-like peptide-1 (GLP-1) are expressed throughout the cardiovascular system and the myocardium and are up-regulated in HF. GLP-1 therapy improves cardiac function in animal models of HF through augmented glucose uptake in the myocardium mediated through a p38 MAP kinase pathway. Small clinical studies have shown that GLP-1 improves ejection fraction, reduces BNP levels and enhances functional capacity in patients with chronic HF. A number of randomized controlled trials are currently underway to define the utility of targeting the incretin system in HF patients with DM. Incretin-based therapy may represent a novel therapeutic strategy in the treatment of HF patients with diabetes, in particular for their cardioprotective effects independent of those attributable to tight glycemic control.

eHealth technology use and eHealth literacy after percutaneous coronary intervention.

AIMS: Electronic health (eHealth) sources have great potential to improve patients' access to health information for self-management of secondary prevention after percutaneous coronary intervention (PCI). It remains unclear, however, whether patients are health-related digitally active and whether they have sufficient eHealth literacy. This study aimed to determine the extent to which patients after PCI are health-related digitally active at baseline, 2 and 6 months after PCI, and to determine the association between patients' eHealth literacy and their health-related digital activity. METHODS AND RESULTS: This multicentre cohort study included patients at three large referral PCI centres in Norway (n = 1970). Data were collected from medical records, national registries, and patients' self-reports. The eHealth Literacy Scale (eHEALS) assessed patients' eHealth literacy. At baseline, 67% had used the internet to find health information. The mean eHEALS score was 25.71 (standard deviation 6.22), illustrating a lower level of eHealth literacy. There were substantial associations between eHealth literacy and use of the internet to find health information [coefficient 10.90, 95% confidence interval (CI) 8.05-14.57]. At the 2-month follow-up, there were substantial associations between baseline eHealth literacy and use of the internet to find information about health, prevention, illness, or treatment [odds ratio (OR) 1.19, 95% CI 1.14-1.24] and use of health applications (OR 1.15, 95% CI 1.08-1.22). CONCLUSION: This study provides evidence that patients' level of eHealth literacy after PCI is associated to how patients use, and can make use of, eHealth technology for health information. REGISTRATION: ClinicalTrials.gov (NCT03810612).

Organic dust exposure increases mast cell tryptase in bronchoalveolar lavage fluid and airway epithelium of heaves horses.

BACKGROUND: Mast cell degranulation is believed to act as a key event in initiating and maintaining airway response to allergen challenge in human asthma. It is hypothesized that the mast cell may play a similar role in equine heaves, which shares many similarities with occupational dust-induced asthma. OBJECTIVE: The aim of this study was to quantify the mast cell proteinase tryptase in bronchoalveolar lavage fluid (BALF) from control and heaves-susceptible horses and to investigate tryptase mRNA and protein expression in pulmonary mast cells. METHODS: Equine BALF tryptase concentrations were determined by ELISA from control and heaves-susceptible horses pre and post 24 h hay/straw challenge (HSC). Tryptase mRNA and protein expression were investigated by quantitative PCR and immunohistochemistry in bronchial and bronchiolar tissue samples of control and heaves-susceptible horses. RESULTS: Both control and heaves-susceptible horses had significantly increased BALF tryptase concentrations following HSC (P=0.003 and 0.034, respectively). Increased numbers of tryptase-expressing intra-epithelial mast cells were demonstrated in heaves horses, but not controls, following challenge (P=0.02). Bronchiolar tissue from heaves horses removed from challenge contained significantly lower tryptase transcripts than that from control horses (P=0.02). CONCLUSION: Mast cell degranulation and tryptase release into the airways occur following HSC of control and heaves-susceptible horses. The greater number of mast cells available in the bronchiolar epithelium of heaves horses may be clinically significant in the pulmonary inflammatory response of heaves.

Comparison of the antioxidant status in tracheal and bronchoalveolar epithelial lining fluids in recurrent airway obstruction.

REASONS FOR PERFORMING STUDY: Following a period of airway inflammation the clearance of inflammatory cells along the mucociliary escalator may impose a considerable oxidant load on the trachea. OBJECTIVES: To determine the degree of oxidative stress in tracheal epithelial lining fluid (ELF) in comparison to that present in peripheral airways after an acute exposure to organic dust. METHODS: Tracheal wash fluid and bronchoalveolar lavage fluid (BALF) were collected for cytology and antioxidant analyses from 6 recurrent airway obstruction (RAO)-affected horses and 6 healthy control horses before and after stabling on straw bedding for 24 h. RESULTS: In RAO-affected horses, organic dust exposure resulted in a significant decrease in ascorbic acid concentration in tracheal ELF (P<0.0001), which was greater than the decrease in bronchoalveolar ELF (P = 0.0003). The percentage decrease in tracheal ELF ascorbic acid correlated with the percentage decrease in bronchoalveolar ELF ascorbic acid (r = 0.76; P = 0.004) following exposure. CONCLUSIONS: Acute organic dust exposure results in significant antioxidant depletion in the trachea, which may reflect inflammation and oxidative processes in peripheral airways. POTENTIAL RELEVANCE: Further work is required to evaluate the role of ascorbic acid depletion in the pathogenesis of RAO.

Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone.

REASONS FOR PERFORMING STUDY: Inhaled ozone can induce oxidative injury and airway inflammation. Horses affected by recurrent airway obstruction (RAO) have a decreased pulmonary antioxidant capacity, which may render them more susceptible to oxidative challenge. It is currently unknown whether RAO-affected horses are more susceptible to oxidative stress than those unaffected by RAO. OBJECTIVES: To determine whether ozone exposure induces greater oxidative stress and airway inflammation in RAO-affected horses in remission than in healthy horses. METHODS: Seven healthy control horses and 7 RAO-affected horses were exposed to 0.8 ppm ozone for 2 h at rest. RESULTS: At baseline, bronchoalveolar lavage fluid (BALF) ascorbic acid concentrations were lower in RAO-affected horses than healthy controls. Ozone appeared to preferentially oxidise glutathione rather than ascorbic acid 6 h after exposure. Individual healthy and RAO-affected horses demonstrated oxidation of BALF glutathione after ozone exposure. Overall, RAO-affected horses did not demonstrate increased oxidative stress following ozone exposure, compared with healthy horses. Ozone did not induce significant airway inflammation in either group. CONCLUSIONS: RAO-affected horses in remission are not more sensitive to ozone despite a decreased pulmonary antioxidant capacity. Sensitivity to ozone appears to be independent of initial pulmonary antioxidant status. POTENTIAL RELEVANCE: Horses with high susceptibility to oxidative stress may benefit from antioxidant supplementation.

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.

Environmental enrichment decreases intravenous self-administration of amphetamine in female and male rats.

RATIONALE: Previous work has shown that environmental enrichment alters amphetamine-induced locomotor activity and conditioned place preference. OBJECTIVE: The present study examined the effect of environmental enrichment on amphetamine self-administration. METHODS: Female and male rats were raised from 21 days of age in one of three different conditions: an enriched condition (EC) containing novel objects and social partners, a social condition (SC) containing social partners only, or an isolated conditioned (IC) without objects or social partners. Beginning at 51 days of age, rats were then tested for operant responding for a sucrose reinforcer using an incremental fixed ratio (FR) requirement across four sessions. Rats were then implanted with a chronic indwelling intravenous catheter and were allowed to self-administer amphetamine (0.03 or 0.1 mg/kg per infusion) for five FR1 sessions, followed by a progressive ratio (PR) session. RESULTS: EC rats initially showed an increase in sucrose-reinforced responding relative to IC rats and this environment-induced difference was greater in females than in males. However, in both sexes, the environment-induced difference in sucrose-reinforced responding dissipated completely across repeated sessions. With amphetamine self-administration, both EC and SC rats earned fewer infusions than IC rats across repeated FRI sessions using the low dose of amphetamine (0.03 mg/kg per infusion), but not using the higher dose of amphetamine (0.1 mg/kg per infusion). EC rats also earned fewer self-infusions of the low amphetamine dose on the PR session relative to IC rats. The effects of environmental enrichment on amphetamine self-administration were similar in both females and males. CONCLUSION: These results suggest that environmental enrichment may serve as a protective factor for reducing amphetamine self-administration.

The effect of primary care gatekeepers on the management of patients with chest pain.

OBJECTIVE: To determine whether patients with chest pain referred to a cardiologist from a gatekeeper managed care organization differ from those referred from an open-access managed care organization. STUDY DESIGN: Retrospective study using clinical and claims data from a cardiac network database. PATIENTS AND METHODS: We reviewed data from 1414 patients with chest pain or angina who were referred to a cardiologist between January 1, 1995, and June 30, 1996. We examined baseline clinical characteristics and subsequent physician practice patterns for these patients, who were referred from either a primary care gatekeeper model (n = 490) or an open-access model (n = 924). RESULTS: Although twice as many open-access patients were referred to a cardiologist, there were no differences in patient demographics or clinical characteristics at the time of referral. Cardiologists ordered similar diagnostic tests for patients from both types of managed care plans, and gatekeeper patients did not have a higher rate of abnormal tests. Rates of cardiac catheterization, coronary angioplasty, myocardial infarction, and hospitalization were similar in both groups. A significantly higher percentage of gatekeeper patients received a cardiac catheterization on the day of referral (7% versus 1%; P = .05). Open-access patients were significantly more likely to continue to be seen by a cardiologist (44% versus 28%; P < .01). Cardiology professional charges per patient were lower among gatekeeper patients ($972 +/- 1398 versus $1187 +/- 1897; P = .06), and total cardiology professional charges were significantly lower for the gatekeeper group because of the smaller number of patients seen. CONCLUSIONS: The type of cardiology services provided to patients with chest pain was not affected by the primary care administrative structure of the managed care organization, but the higher volume of patient referrals from the open-access plan may be an important consideration for cardiology practices participating in capitated contracts. The lower volume of referrals and coordination of care suggest potential cost advantages for the gatekeeper model.

Predictors and outcomes associated with early extubation in older adults undergoing coronary artery bypass surgery.

BACKGROUND: Older age has been associated with prolonged mechanical ventilation after coronary artery bypass surgery. Prolonged mechanical ventilation contributes to increased morbidity and mortality and to use of limited financial resources among older adults. OBJECTIVES: To examine selected physiological and pathophysiological variables ofpresurgicalpatients to predict duration of mechanical ventilation in older adults after coronary artery bypass surgery. METHODS: Nonrandomized study of a clinical database of 919 patients (> or =65 years old) who had coronary artery bypass surgery between October 1996 and December 1997. RESULTS: Median elapsed time after coronary artery bypass surgery until extubation was used to sort patients into 2 groups: group 1, 6 hours or fewer (n = 464); and group 2, more than 6 hours (n = 455). With stepwise logistic regression, the physiological model included age (odds ratio, 1.05; P<.001) and female sex (odds ratio, 1.48; P = .005) with weak discrimination by group (concordance statistic = 0.5880). The pathophysiological model, which included renal insufficiency (odds ratio, 3.28; P = .01), previous peripheral vascular surgery (odds ratio, 2.87; P = .03), nonelective preoperative clinical status (odds ratio, 2.8; P = .006), congestive heartfailure (odds ratio, 2.6; P<.001), and reoperation (odds ratio, 2.34; P = .007), showed moderate discrimination bygroup (concordance statistic =0.6755). CONCLUSION: Many older adults were easily extubated and had good outcomes. The variables comorbid conditions and severity of illness provided better discrimination between extubation groups than a physiological model provided. Both predictive models allowed limited discrimination between groups.

Asymptomatic laryngocele: incidence and association with laryngeal cancer.

Since laryngoceles are usually asymptomatic, their incidence is probably higher than the literature suggests. With the advent of computed tomography, the incidence and significance of the asymptomatic laryngocele in a general head and neck practice can be addressed. To this end, 304 consecutive patients with a variety of otolaryngic diagnoses were studied prospectively by computed tomography of the neck from January 1983 to February 1985. Thirty-eight (12.5%) of the patients had asymptomatic laryngoceles, defined as air-containing structures in the supraglottic region extending more than 5 mm above the superior border of the thyroid cartilage during normal breathing. The incidence of laryngoceles associated with laryngeal cancer (29%) was higher than that for laryngoceles associated with other diseases (9%). No patient with an asymptomatic laryngocele not associated with laryngeal cancer showed evidence of a subsequent laryngeal neoplasm during close follow-up of 10 to 36 months.

A collaborative program for cardiovascular patient follow-up.

Transitions from one health care system to another are common, but they can affect coordination of care and measurement of patient outcomes. In this project, a community hospital and a tertiary center collaborated to obtain follow-up information on patients 30 days after they underwent cardiac catheterization and revascularization. Results show that patients experienced similar physical and emotional concerns regardless of diagnosis or procedure. Although the intent was to gather information, nurses also provided education and arranged services for patients. This project has implications for the development of collaborative interventions to improve care for patients after undergoing coronary procedures.

The effect of inspired gas density on pulmonary artery transmural pressure and exercise induced pulmonary haemorrhage.

REASONS FOR PERFORMING STUDY: Pulmonary capillary stress failure, largely as a result of high pulmonary vascular pressures, has been implicated in the aetiology of EIPH. However, the role of the respiratory system in determining the magnitude of EIPH has received little attention. HYPOTHESIS: Horses breathing a gas of greater density than air will exhibit greater transmural pulmonary arterial pressures (TPAP) and more severe EIPH, and horses breathing a gas of lower density than air will exhibit lower TPAP and less severe EIPH, both compared with horses breathing air. METHODS: Following a warm-up, 8 Thoroughbred horses were exercised for 1 min at 10, 11 and 12 m/sec (5 degrees incline) breathing air or 21% oxygen/79% helium or 21% oxygen/79% argon in a randomised order. Heart rate, respiratory rate, pulmonary arterial pressure and oesophageal pressure were measured during exercise. Bronchoalveolar lavage fluid (BALF) was collected from the dorsocaudal regions of the left and right lungs 40 min post exercise and red blood cell (RBC) counts were performed. RESULTS: The exercise tests induced mild EIPH. Maximum changes in oesophageal pressure were lower on helium-oxygen compared to argon-oxygen (P<0.001). TPAP and median RBC counts did not differ between gas mixtures. BALF RBC counts from the left lung correlated with counts from the right lung (P<0.0001). However BALF RBC counts from the left lung were higher than those from the right lung (P = 0.004). CONCLUSION: As alterations in pulmonary arterial and oesophageal pressure caused by changes in inspired gas density were of similar magnitude, TPAP remained unchanged and there was no significant effect on EIPH severity. POTENTIAL RELEVANCE: Manipulations that decrease swings in intrapleural pressure may only decrease the degree of EIPH in horses severely affected by the condition.

Changes in selected physiological and laboratory measurements in elite horses competing in a 160 km endurance ride.

REASON FOR PERFORMING STUDY: Limited information exists about the physiological changes and clinical problems that occur in elite horses competing in high-speed 160 km endurance races. OBJECTIVES: To provide initial data describing changes in physiological and laboratory measurements in horses competing in a high-speed, 160 km endurance race under temperate conditions and to compare data between horses that successfully completed the race and those that failed to finish. METHODS: Body mass (BM) was measured, blood samples were collected, and veterinary examinations performed on horses before, during, and at the finish of a CEI*** 160 km endurance race. RESULTS: Of 36 horses participating in the study, 22 (61%) completed the race. Twelve horses were eliminated for lameness and 2 for persistent heart rate elevation. Mean speed of finishers was 15.2 km/h. Mean +/- s.d. BM loss of finishers at the end of the race (5.7 +/- 2.6%) was not different (P = 0.58) from BM loss of nonfinishers at elimination (6.7 +/- 34%). Similarly, there were no significant differences in heart rate or veterinary assessment of hydration at the race end for finishers as compared to the elimination point for nonfinishers. PCV increased while sodium, chloride and potassium concentrations decreased with exercise but differences between finishers and nonfinishers were not detected. In contrast, both total and ionised calcium concentrations decreased in successful horses but remained unchanged in nonfinishers. CONCLUSIONS: Elite endurance horses are more likely to be eliminated from competition for lameness than metabolic problems; however, it remains unclear whether these conditions are entirely distinct. The magnitude of the decrease in sodium concentration in both finishers and nonfinishers was greater than in previous reports of 160 km rides. POTENTIAL RELEVANCE: These data should be of use for both organisers and participants in elite 160 km endurance races. The tendency toward hyponatraemia as well as the difference in calcium concentrations between finishers and nonfinishers warrant further study.

Retrospective study of predictive variables for maximal heart rate (HRmax) in horses undergoing strenuous treadmill exercise.

REASONS FOR PERFORMING STUDY: Heart rate is one of the most commonly measured variables in equine exercise physiology and relative exercise intensity commonly expressed as % of maximal heart rate. A number of influences affect maximal heart rate (HRmax), including age of the horse but other factors have not been described. OBJECTIVES: To determine if fitness, health status, gender, breed, athletic use, body mass, in addition to age, are predictive of HRmax in the horse. METHODS: Maximal heart rate data from 328 horses which underwent treadmill exercise tests at 5 different laboratories were obtained retrospectively. Univariable linear regression analyses were performed on individual variables. Multiple linear regression analysis using a backward elimination modelling procedure was then used to relate the observed HRmax values simultaneously with different predictive variables. Variables were retained in the final regression model if they or any of their categories were significantly predictive of HRmax at P<0.05 and if there was a significant collective contribution to the model from inclusion of each variable, also at P<0.05. RESULTS: Age, fitness status, laboratory, gender and breed/use (combined category) were all statistically significantly predictive of HRmax. Together these variables accounted for 41% of the variance in HRmax. Age alone accounted for only approximately 13% of the variation between horses in HRmax. Neither body mass nor health status were significantly predictive. CONCLUSIONS: HRmax in the horse declines with age but is also influenced by other factors. As the factors investigated accounted for only 41% of the variation between horses, other unidentified variables with a strong influence on HRmax remain to be identified. POTENTIAL RELEVANCE: Factors such as fitness, age, gender, breed and use need to be considered when interpreting estimates or measurements of HRmax.

Outcomes measurement. Multidisciplinary approaches and patient outcomes after stroke.

Synergism is an apt description for the powerful results that can occur when multidisciplinary approaches are used. Studies have documented that multidisciplinary teams produce improved patient outcomes in selected patient groups, including recent studies of patients with strokes. Multidisciplinary teams in patient care are still far from being the normative model of care delivery. In the interest of better patient care and outcomes, it is time for health care professionals to actively engage in multidisciplinary approaches, because the sum of our collaborative efforts is greater than our individual disciplinary parts.

Outcomes measurement and evidence-based nursing practice.

Outcome measurement and evidence-based practice are complementary and iterative efforts; both contribute to quality health care. In this article, hemodynamic monitoring is utilized as an example to discuss outcome measurement and evidence-based practice. The use of technology, medications, and other interventions ideally would be based on sound scientific evidence of efficacy and effectiveness in clinical practice. Outcome measurement can contribute to the evidence and strengthen the process of appropriate technology use and evidence-based practice.

Outcomes measurement.

Patient outcomes have been referred to as the "ultimate definition of effectiveness and efficiency," and there is an increasing emphasis on identifying and measuring the results of interventions and practice. This new department will focus on issues surrounding patient outcomes such as definitions, measurement, sources of data, nurse-sensitive versus multidisciplinary outcomes, and determining the evidence on which to base practice. The goal of the department is to stimulate questions and encourage discussion that will contribute to the necessary knowledge for defining, measuring, and ultimately improving cardiovascular patient outcomes.

Outcome measurement: self-management in heart failure.

Improvement in heart failure outcomes depend on patients' abilities to care for themselves and manage aspects of their condition, and patient self-management has itself become an outcome to be measured. Some behaviors, such as diet and fluid restriction, are prescribed, and self-management is often equated with adherence to the treatment regimen. Self-management has also been defined as cognitive decision making in response to symptoms and conceptualized as a process with stages from novice to expert. Greater understanding and measurement of patient decision making and self-management expertise facilitates the development of effective interventions to improve patient outcomes.