Energy utilization associated with regular activity breaks and continuous physical activity: A randomized crossover trial

Aims

To quantify and compare energy utilization associated with prolonged sitting alone, or interrupted with regular activity breaks and/or an additional bout of continuous physical activity.

Spirometry can be done in family physicians' offices and alters clinical decisions in management of asthma and COPD

BACKGROUND: Spirometry is recommended for diagnosis and management of obstructive lung disease. While many patients with asthma and COPD are cared for by primary care practices, limited data are available on the use and results associated with spirometry in primary care. OBJECT: To assess the technical adequacy, accuracy of interpretation, and impact of office spirometry. DESIGN: A before-and-after quasiexperimental design. SETTING: Three hundred eighty-two patients from 12 family medicine practices across the United States. PARTICIPANTS: Patients with asthma and COPD, and staff from the 12 practices. MEASUREMENTS: Technical adequacy of spirometry results, concordance between family physician and pulmonary expert interpretations of spirometry test results, and changes in asthma and COPD management following spirometry testing. RESULTS: Of the 368 tests completed over the 6 months, 71% were technically adequate for interpretation. Family physician and pulmonary expert interpretations were concordant in 76% of completed tests. Spirometry was followed by changes in management in 48% of subjects with completed tests, including 107 medication changes (>85% concordant with guideline recommendations) and 102 nonpharmacologic changes. Concordance between family physician and expert interpretations of spirometry results was higher in those patients with asthma compared to those with COPD. DISCUSSION AND CONCLUSIONS: US family physicians can perform and interpret spirometry for asthma and COPD patients at rates comparable to those published in the literature for international primary care studies, and the spirometry results modify care.     

Airway tissue mast cells in persistent asthma: predictor of treatment failure when patients discontinue inhaled corticosteroids

STUDY OBJECTIVES: To determine if persistent airway tissue mast cells are associated with treatment failure when patients discontinue inhaled corticosteroids (ICS). DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Multicenter, tertiary referral centers. Patients or participants: Forty-five subjects with asthma recruited from six medical centers in the United States. INTERVENTIONS: The Asthma Clinical Research Network undertook a 28-week, randomized, multicenter, double-blind, placebo-controlled trial of 164 subjects with clinically stable, persistent asthma. A subset of subjects (n = 45) underwent bronchoscopy with endobronchial biopsy and BAL at the end of a 6-week run-in period, during which all subjects received triamcinolone acetonide (TAA), 400 microg bid. Airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells were quantified morphometrically along with determination of BAL tryptase. At the end of the run-in period, subjects were then randomized to receive salmeterol (42 micro g bid), placebo, or continue TAA for 16 weeks followed by a second bronchoscopy. Measurements and results: Outcome variables included airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells that were quantified morphometrically and BAL tryptase. Thirty-five subjects completed the treatment phase; an additional 10 subjects, who were randomized to either salmeterol or placebo after the run-in, had treatment failure. When the bronchoscopy results performed at the end of the run-in, prior to randomization, were analyzed, the treatment failure group demonstrated significantly more tissue mast cells as compared to the nontreatment failure group despite 6 weeks of therapy with TAA (p = 0.04). BAL tryptase was also significantly higher in the treatment failure group (p < 0.0001). Of those subjects who completed the study, tissue mast cells and BAL tryptase did not change significantly within any of the treatment groups during the treatment phase (p > 0.05). CONCLUSIONS: Persistent elevations in airway tissue mast cells and BAL tryptase after treatment with TAA predict treatment failure in patients for whom discontinuation of ICS is being considered.     

A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma

Asthma is an inflammatory disorder caused by airway exposures to allergens and chemical irritants. Studies focusing on immune, smooth muscle, and airway epithelial function revealed many aspects of the disease mechanism of asthma. However, the limited efficacies of immune-directed therapies suggest the involvement of additional mechanisms in asthmatic airway inflammation. TRPA1 is an irritant-sensing ion channel expressed in airway chemosensory nerves. TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma. Here, we examined the role of TRPA1 in allergic asthma in the murine ovalbumin model. Strikingly, genetic ablation of TRPA1 inhibited allergen-induced leukocyte infiltration in the airways, reduced cytokine and mucus production, and almost completely abolished airway hyperreactivity to contractile stimuli. This phenotype is recapitulated by treatment of wild-type mice with HC-030031, a TRPA1 antagonist. HC-030031, when administered during airway allergen challenge, inhibited eosinophil infiltration and prevented the development of airway hyperreactivity. Trpa1^−/− mice displayed deficiencies in chemically and allergen-induced neuropeptide release in the airways, providing a potential explanation for the impaired inflammatory response. Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge. TRPA1 may represent a promising pharmacological target for the treatment of asthma and other allergic inflammatory conditions.     

Elevation in serum thyroglobulin during prolonged Antarctic residence: effect of thyroxine supplement in the polar 3,5,3'-triiodothyronine syndrome

Extended Antarctic residence (AR) is associated with an increase in serum TSH, a decrease in free T(4), and an increase in T(3) production and clearance. It is not clear whether these adaptations reflect changes in clearance alone or whether intrinsic thyroidal synthetic activity also changes. Thyroglobulin (Tg) secretion is an independent marker of intrinsic thyroid activity whose kinetics are independent of those of T(3) and T(4). In this study we examined changes in Tg levels in healthy subjects before and during AR and their responses to thyroid supplementation to help determine whether alterations in thyroid activity, and not just kinetics of clearance, underlie the changes seen with the polar T(3) syndrome. In cohort 1, we compared measurements of TSH and Tg in 12 subjects before deployment and monthly for 11 months during AR. In cohort 2, we compared the same measurements in 12 subjects monthly for 11 months of AR. Subjects were randomized to receive either placebo or levothyroxine in cohort 1 for 7 months and in cohort 2 for 11 months. Tg increased over baseline during the first 4 months of AR by 17.0 +/- 4.6% and after 7 more months by 31.7 +/- 4.3% over baseline in the placebo group of both cohorts (P < 0.0002). When L-T(4) was taken, Tg returned to a value not different from baseline (4.5 +/- 3.9%). The percent changes from baseline in serum TSH and Tg during AR were highly correlated (P < 0.00003) in the placebo group for both cohorts. The rise in Tg with TSH and the reduction in Tg with L-T(4) provide evidence of target tissue response to TSH and further confirm the TSH rise as physiologically significant. The results also suggest that the adaptive changes in thyroid hormone economy with AR reflect TSH-dependent changes in thyroid synthetic activity, which may help explain a portion of the increases in T(3) production found with AR.     

Idiopathic pulmonary fibrosis: new insights into pathogenesis

The combination of the unique pathologic features of usual interstitial pneumonia (UIP) on biopsy, the progressive clinical course, and resistance to anti-inflammatory therapy constitutes the cardinal manifestations of what is termed idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia, and it has led to recent suggestions that new therapies should be directed at regulating fibroblast functions rather than targeting the inflammatory response. The observation that "early" UIP looks like "late" UIP but there is less of it has been largely responsible for re-evaluation of the paradigm that IPF is the result of uncontrolled lung inflammation. This article highlights aspects of current thoughts on pathogenesis of IFP and expands on recent reviews.     

An Electronic Protocol for Translation of Research Results to Clinical Practice: A Preliminary Report

Introduction

We evaluated the feasibility of using an electronic protocol developed for research use (Research-eProtocol-insulin) for blood glucose management in usual intensive care unit clinical practice.

Methods

We implemented the rules of Research-eProtocol-insulin in the electronic medical record of the Intermountain Healthcare hospital system (Clinical-eProtocol-insulin) for use in usual clinical practice. We evaluated the performance of Clinical-eProtocol-insulin rules in the intensive care units of seven Intermountain Healthcare hospitals and compared this performance with the performance of Research-eProtocol-insulin at the LDS Hospital Shock/Trauma/Respiratory Intensive Care Unit.

Results

Clinician (nurse or physician) compliance with computerized protocol recommendations was 95% (of 21,325 recommendations) with Research-eProtocol-insulin and 92% (of 109,458 recommendations) with Clinical-eProtocol-insulin. The blood glucose distribution in clinical practice (Clinical-eProtocol-insulin) was similar to the research use distribution (Research-eProtocol-insulin); however, the mean values (119 mg/dl vs 113 mg/dl) were statistically different (P = 0.0001). Hypoglycemia rates in the research and practice settings did not differ: the percentage of measurements ≤40 mg/dl (0.11% vs 0.1%, P = 0.65) and the percentage of patients with at least one blood glucose ≤40 mg/dl (4.2% vs 3%, P = 0.23) were not statistically significantly different.

Conclusion

Our electronic blood glucose protocol enabled translation of a research decision-support tool (Research-eProtocol-insulin) to usual clinical practice (Clinical-eProtocol-insulin).     

Benchmarking the nurse consultant role in rheumatology

This article demonstrates how the four core standards for the nurse consultant role have been developed and applied in the field of rheumatology. The authors suggest that the standards: expert practice, leadership and service redesign, research and education, are relevant for consultant nurses in all specialties. The standards can be used by other nurse consultants to benchmark their practice.     

Time-dependence of appropriate implantable defibrillator therapy in patients with ischemic cardiomyopathy

Introduction: Little is known about the risk of appropriate implantable cardioverter-defibrillator (ICD) therapy outside the context of controlled clinical trials where routine practice patients are followed for longer durations and questions of device replacement frequently arise. We assessed the incidence and time-dependence of appropriate ICD therapy in a routine clinical practice primary prevention population with prior myocardial infarction (MI) and reduced left ventricular ejection fraction (LVEF).
Methods and Results: Patients with prior MI and LVEF ≤35%, who received an ICD at our institution (1995–2005) for primary prevention, were identified. Incidence and time-dependence of first appropriate ICD therapy for ventricular arrhythmia (VA) and rapid VA (cycle length ≤260 ms) were determined. Of 525 ICD recipients for primary prevention, 115 (22%) had appropriate ICD therapy. Incidence of first appropriate ICD therapy was highest in the first year postimplant (20%), decreased to 12% in year 2, and remained at 6–11% yearly thereafter. A similar trend was observed with rapid VA, a higher risk in the first year (6%), and a lower but persistent risk thereafter (3.8% in year 7).
Conclusion: In a routine clinical practice primary prevention population with prior MI and LVEF ≤35%, the incidence of first ICD therapy for VA, including potentially life-threatening VA, is highest in the first year postimplant, and persists for up to seven years thereafter. Risk of first appropriate ICD therapy persists over time, and thus replacement of ICDs appears to be indicated for all patients.     

Is Peri-Operative Isolated Systolic Hypertension (ISH) a Cardiac Risk Factor?

We are presenting a review of Isolated Systolic Hypertension (ISH) as a cardiovascular risk factor with emphasis on the perioperative period.Isolated systolic hypertension is associated with aging and is the most frequent subtype (65%) among patients with uncontrolled hypertension. ISH is strongly associated with increased risks of cardiac and cerebrovascular events exceeding those in comparably aged individuals with diastolic hypertension. Patients with ISH show an increase in left ventricular (LV) mass and an increase in the prevalence of left ventricular hypertrophy (LVH). These LV changes increase cardiovascular events and frequently lead to diastolic dysfunction (DD). Treatment to reduce elevated systolic blood pressure has been shown to reduce the risk of cardiovascular events.In the perioperative setting, essential hypertension has not been found to be a significant risk factor for cardiac complications. Most of the studies were based on the definition of essential hypertension and underpowered in sample size. The significance of perioperative ISH, however, is not well studied, partly due to its recognition only fairly recently as a cardiovascular risk factor in the non-surgical setting, and partly due to the evolving definition of ISH.Perioperative cardiac complications remain a significant problem to the healthcare system and to the patient. Although the incidence of perioperative cardiac complications is prominent in high-risk patients as defined by the Revised Cardiac Risk Index (RCRI), the bulk of the cardiac complications actually occur in low-risk group. Currently, little understanding exists on the occurrence of perioperative cardiac complications in low- risk patients. A factor such as ISH, with its known pathophysiological changes, is a potential perioperative risk factor.We believe ISH is an under-recognized perioperative risk factor and deserves further studying. Our research group has recently been funded by the Heart Stroke Foundation (HSF) to examine ISH as a perioperative risk factor (PROMISE Study).Key Words: Isolated systolic hypertension, cardiovascular risk factors, perioperative.