Water-based exercise for adults with asthma

BackgroundAsthma is a common condition characterised by airway inflammation and airway narrowing, which can result in intermittent symptoms of wheezing, coughing and chest tightness, possibly limiting activities of daily life. Water-based exercise is believed to offer benefits for people with asthma through pollen-free air, humidity and effects of exercise on physical function.ObjectivesTo evaluate the effectiveness and safety of water-based exercise for adults with asthma.Search methodsWe searched the Cochrane Airways Group Specialised Register of Trials (CAGR), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), PsycINFO, the Latin American and Caribbean Health Science Information Database (LILACS), the Physiotherapy Evidence Database (PEDro), the System for Information on Grey Literature in Europe (SIGLE) and Google Scholar on 13 May 2014. We handsearched ongoing clinical trial registers and meeting abstracts of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the British Thoracic Society (BTS).Selection criteriaWe included all randomised controlled trials (RCTs) of adults with asthma comparing a water-based exercise group versus one or more of the following groups: usual care, land-based exercise, non-exercise.Data collection and analysisTwo review authors (AJG, VS) independently extracted data fromthe primary studies using a standard form developed for this purpose, which includes methods, participants, interventions and outcomes. We contacted trial authors to request additional data. Data were input by one review author and were double-checked by a second review author.Main resultsIn this systematic review, we provide a narrative synthesis of available evidence from three small studies including 136 adult participants. the studies were at high risk of bias. No meta-analysis was possible because of methodological and interventional heterogeneity between included studies. the primary outcomes of quality of life and exacerbations leading to use of steroids were not reported by these studies. for exacerbations leading to health centre/hospital visits, uncertainty was wide because a very small number of events was reported (in a single study). Secondary outcomes symptoms, lung function, changes in medication and adverse effects, where available, described for each included study. the overall quality of the studies was very low, and no clear differences were noted between water-based exercise and comparator treatments. Therefore, we remain very uncertain about the effects of water-based exercise for adults with asthma.Authors' conclusionsThe small number of participants in the three included studies, the clinical and methodological heterogeneity observed and the high risk of bias assessed mean that we are unable to assess the place of water-based exercise in asthma. Randomised controlled trials are needed to assess the efficacy and safety of water-based exercise for adults with asthma. for future research, we suggest greater methodological rigour (participant selection, blinding of outcome assessors, reporting of all outcomes analysed and registering of the study protocol).

JUSTEIS (JISC Usage Surveys: Trends in Electronic Information Services) Strand A: survey of end users of all electronic information services (HE and FE), with Action research report. Final report 2002/2003 Cycle Four.

Urquhart, C. (editor for JUSTEIS team), Spink, S., Thomas, R., Yeoman, A., Durbin, J., Turner, J., Armstrong, A., Lonsdale, R. & Fenton, R. (2003). JUSTEIS (JISC Usage Surveys: Trends in Electronic Information Services) Strand A: survey of end users of all electronic information services (HE and FE), with Action research report. Final report 2002/2003 Cycle Four. Aberystwyth: Department of Information Studies, University of Wales Aberystwyth with Information Automation Ltd (CIQM). Sponsorship: JISC

Automatic 3D Registration of Lung Surfaces in Computed Tomography Scans

We developed an automated system that registers chest CT scans temporally. Our registration method matches corresponding anatomical landmarks to obtain initial registration parameters. The initial point-to-point registration is then generalized to an iterative surface-to-surface registration method. Our "goodness-of-fit" measure is evaluated at each step in the iterative scheme until the registration performance is sufficient. We applied our method to register the 3D lung surfaces of 11 pairs of chest CT scans and report promising registration performance.

Acute eosinophilic pneumonia secondary to daptomycin: a report of three cases.

We describe 3 cases of daptomycin-induced pulmonary toxic effects that are consistent with drug-induced acute eosinophilic pneumonia. Patients presented similarly with dyspnea, cough, hypoxia, and diffuse ground-glass opacities at chest computed tomography. Clinical suspicion for this adverse drug event and cessation of daptomycin until definitive diagnosis can be made is crucial.

Augmentation of cardiac contractility mediated by the human beta(3)-adrenergic receptor overexpressed in the hearts of transgenic mice.

BACKGROUND: Stimulation of beta(1)- and beta(2)-adrenergic receptors (ARs) in the heart results in positive inotropy. In contrast, it has been reported that the beta(3)AR is also expressed in the human heart and that its stimulation leads to negative inotropic effects. METHODS AND RESULTS: To better understand the role of beta(3)ARs in cardiac function, we generated transgenic mice with cardiac-specific overexpression of 330 fmol/mg protein of the human beta(3)AR (TGbeta(3) mice). Hemodynamic characterization was performed by cardiac catheterization in closed-chest anesthetized mice, by pressure-volume-loop analysis, and by echocardiography in conscious mice. After propranolol blockade of endogenous beta(1)- and beta(2)ARs, isoproterenol resulted in an increase in contractility in the TGbeta(3) mice (30%), with no effect in wild-type mice. Similarly, stimulation with the selective human beta(3)AR agonist L-755,507 significantly increased contractility in the TGbeta(3) mice (160%), with no effect in wild-type mice, as determined by hemodynamic measurements and by end-systolic pressure-volume relations. The underlying mechanism of the positive inotropy incurred with L-755,507 in the TGbeta(3) mice was investigated in terms of beta(3)AR-G-protein coupling and adenylyl cyclase activation. Stimulation of cardiac membranes from TGbeta(3) mice with L-755,507 resulted in a pertussis toxin-insensitive 1.33-fold increase in [(35)S]GTPgammaS loading and a 1.6-fold increase in adenylyl cyclase activity. CONCLUSIONS: Cardiac overexpression of human beta(3)ARs results in positive inotropy only on stimulation with a beta(3)AR agonist. Overexpressed beta(3)ARs couple to G(s) and activate adenylyl cyclase on agonist stimulation.

Adaptive stereotactic body radiation therapy planning for lung cancer.

PURPOSE: To investigate the dosimetric effects of adaptive planning on lung stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Forty of 66 consecutive lung SBRT patients were selected for a retrospective adaptive planning study. CBCT images acquired at each fraction were used for treatment planning. Adaptive plans were created using the same planning parameters as the original CT-based plan, with the goal to achieve comparable comformality index (CI). For each patient, 2 cumulative plans, nonadaptive plan (PNON) and adaptive plan (PADP), were generated and compared for the following organs-at-risks (OARs): cord, esophagus, chest wall, and the lungs. Dosimetric comparison was performed between PNON and PADP for all 40 patients. Correlations were evaluated between changes in dosimetric metrics induced by adaptive planning and potential impacting factors, including tumor-to-OAR distances (dT-OAR), initial internal target volume (ITV1), ITV change (ΔITV), and effective ITV diameter change (ΔdITV). RESULTS: 34 (85%) patients showed ITV decrease and 6 (15%) patients showed ITV increase throughout the course of lung SBRT. Percentage ITV change ranged from -59.6% to 13.0%, with a mean (±SD) of -21.0% (±21.4%). On average of all patients, PADP resulted in significantly (P=0 to .045) lower values for all dosimetric metrics. ΔdITV/dT-OAR was found to correlate with changes in dose to 5 cc (ΔD5cc) of esophagus (r=0.61) and dose to 30 cc (ΔD30cc) of chest wall (r=0.81). Stronger correlations between ΔdITV/dT-OAR and ΔD30cc of chest wall were discovered for peripheral (r=0.81) and central (r=0.84) tumors, respectively. CONCLUSIONS: Dosimetric effects of adaptive lung SBRT planning depend upon target volume changes and tumor-to-OAR distances. Adaptive lung SBRT can potentially reduce dose to adjacent OARs if patients present large tumor volume shrinkage during the treatment.

Long- incubation time- interferon-gamma release assays in response to PPD-, ESAT-6- and/or CFP-10 for the diagnosis of Mycobacterium tuberculosis infection in children.

Background:Diagnosis of childhood active tuberculosis (aTB) or latent Mycobacterium tuberculosis (Mtb) infection (LTBI) remains a challenge, and replacement of tuberculin skin tests (TST) by commercialized interferon-gamma release assays (IGRA) is not currently recommended.Methods:266 children between 1 month and 15 years of age, 214 being at risk of recent Mtb infection and 51 being included as controls, were prospectively enrolled. According results of clinical evaluation, TST, chest X-Ray and microbiology, children were classified as non-infected, LTBI or aTB. Long-incubation time PPD-, ESAT-6-, and CFP-10-IGRA were performed and evaluated for their accuracy to correctly classify the children.Results:Whereas both TST and PPD-IGRA were suboptimal to detect aTB, combining CFP-10-IGRA with TST or with PPD-IGRA allowed us to detect all the children with aTB, with 96% specificity for children who were positive for CFP-10-IGRA. Moreover, combination of CFP-10- and PPD-IGRA also detected 96% of children classified as LTBI, but a strong IFN-γ response to CFP-10 (>500 pg/ml) was highly suggestive of aTB at least among children less than 3 years old.Conclusions:Long-incubation time CFP-10- and PPD-IGRA should help the clinicians to identify quickly aTB or LTBI in young children.

Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.

BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann–Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.

Investigation and Development of a Fully 3D Tilt Capable Hybrid SPECT - CT System for Dedicated Breast Imaging

X-ray mammography has been the gold standard for breast imaging for decades, despite the significant limitations posed by the two dimensional (2D) image acquisitions. Difficulty in diagnosing lesions close to the chest wall and axilla, high amount of structural overlap and patient discomfort due to compression are only some of these limitations. To overcome these drawbacks, three dimensional (3D) breast imaging modalities have been developed including dual modality single photon emission computed tomography (SPECT) and computed tomography (CT) systems. This thesis focuses on the development and integration of the next generation of such a device for dedicated breast imaging. The goals of this dissertation work are to: [1] understand and characterize any effects of fully 3-D trajectories on reconstructed image scatter correction, absorbed dose and Hounsifeld Unit accuracy, and [2] design, develop and implement the fully flexible, third generation hybrid SPECT-CT system capable of traversing complex 3D orbits about a pendant breast volume, without interference from the other. Such a system would overcome artifacts resulting from incompletely sampled divergent cone beam imaging schemes and allow imaging closer to the chest wall, which other systems currently under research and development elsewhere cannot achieve.

The dependence of x-ray scatter radiation on object shape, size, material composition and the CT acquisition trajectory, was investigated with a well-established beam stop array (BSA) scatter correction method. While the 2D scatter to primary ratio (SPR) was the main metric used to characterize total system scatter, a new metric called ‘normalized scatter contribution’ was developed to compare the results of scatter correction on 3D reconstructed volumes. Scatter estimation studies were undertaken with a sinusoidal saddle (±15° polar tilt) orbit and a traditional circular (AZOR) orbit. Clinical studies to acquire data for scatter correction were used to evaluate the 2D SPR on a small set of patients scanned with the AZOR orbit. Clinical SPR results showed clear dependence of scatter on breast composition and glandular tissue distribution, otherwise consistent with the overall phantom-based size and density measurements. Additionally, SPR dependence was also observed on the acquisition trajectory where 2D scatter increased with an increase in the polar tilt angle of the system.

The dose delivered by any imaging system is of primary importance from the patient’s point of view, and therefore trajectory related differences in the dose distribution in a target volume were evaluated. Monte Carlo simulations as well as physical measurements using radiochromic film were undertaken using saddle and AZOR orbits. Results illustrated that both orbits deliver comparable dose to the target volume, and only slightly differ in distribution within the volume. Simulations and measurements showed similar results, and all measured dose values were within the standard screening mammography-specific, 6 mGy dose limit, which is used as a benchmark for dose comparisons.

Hounsfield Units (HU) are used clinically in differentiating tissue types in a reconstructed CT image, and therefore the HU accuracy of a system is very important, especially when using non-traditional trajectories. Uniform phantoms filled with various uniform density fluids were used to investigate differences in HU accuracy between saddle and AZOR orbits. Results illustrate the considerably better performance of the saddle orbit, especially close to the chest and nipple region of what would clinically be a pedant breast volume. The AZOR orbit causes shading artifacts near the nipple, due to insufficient sampling, rendering a major portion of the scanned phantom unusable, whereas the saddle orbit performs exceptionally well and provides a tighter distribution of HU values in reconstructed volumes.

Finally, the third generation, fully-suspended SPECT-CT system was designed in and developed in our lab. A novel mechanical method using a linear motor was developed for tilting the CT system. A new x-ray source and a custom made 40 x 30 cm2 detector were integrated on to this system. The SPECT system was nested, in the center of the gantry, orthogonal to the CT source-detector pair. The SPECT system tilts on a goniometer, and the newly developed CT tilting mechanism allows ±15° maximum polar tilting of the CT system. The entire gantry is mounted on a rotation stage, allowing complex arbitrary trajectories for each system, without interference from the other, while having a common field of view. This hybrid system shows potential to be used clinically as a diagnostic tool for dedicated breast imaging.

Comparison of contrast enhanced three dimensional echocardiography with MIBI gated SPECT for the evaluation of left ventricular function

Background. In clinical practice and in clinical trials, echocardiography and scintigraphy are used the most for the evaluation of global left ejection fraction (LVEF) and left ventricular (LV) volumes. Actually, poor quality imaging and geometrical assumptions are the main limitations of LVEF measured by echocardiography. Contrast agents and 3D echocardiography are new methods that may alleviate these potential limitations. Methods. Therefore we sought to examine the accuracy of contrast 3D echocardiography for the evaluation of LV volumes and LVEF relative to MIBI gated SPECT as an independent reference. In 43 patients addressed for chest pain, contrast 3D echocardiography (RT3DE) and MIBI gated SPECT were prospectively performed on the same day. The accuracy and the variability of LV volumes and LVEF measurements were evaluated. Results. Due to good endocardial delineation, LV volumes and LVEF measurements by contrast RT3DE were feasible in 99% of the patients. The mean LV end-diastolic volume (LVEDV) of the group by scintigraphy was 143 65 mL and was underestimated by triplane contrast RT3DE (128 60 mL; p < 0.001) and less by full-volume contrast RT3DE (132 62 mL; p < 0.001). Limits of agreement with scintigraphy were similar for triplane andfull-volume, modalities with the best results for full-volume. Results were similar for calculation of LV end-systolic volume (LVESV). The mean LVEF was 44 16% with scintigraphy and was not significantly different with both triplane contrast RT3DE (45 15%) and full-volume contrast RT3DE (45 15%). There was an excellent correlation between two different observers for LVEDV, LVESV and LVEF measurements and inter observer agreement was also good for both contrast RT3DE techniques. Conclusion. Contrast RT3DE allows an accurate assessment of LVEF compared to the LVEF measured by SPECT, and shows low variability between observers. Although RT3DE triplane provides accurate evaluation of left ventricular function, RT3DE full-volume is superior to triplane modality in patients with suspected coronary artery disease. © 2009 Cosyns et al; licensee BioMed Central Ltd.

Human respiration rate estimation using ultra-wideband distributed cognitive radar system

It has been shown that remote monitoring of pulmonary activity can be achieved using ultra-wideband (UWB) systems, which shows promise in home healthcare, rescue, and security applications. In this paper, we first present a multi-ray propagation model for UWB signal, which is traveling through the human thorax and is reflected on the air/dry-skin/fat/muscle interfaces. A geometry-based statistical channel model is then developed for simulating the reception of UWB signals in the indoor propagation environment. This model enables replication of time-varying multipath profiles due to the displacement of a human chest. Subsequently, a UWB distributed cognitive radar system (UWB-DCRS) is developed for the robust detection of chest cavity motion and the accurate estimation of respiration rate. The analytical framework can serve as a basis in the planning and evaluation of future measurement programs. We also provide a case study on how the antenna beamwidth affects the estimation of respiration rate based on the proposed propagation models and system architecture

Is there an association between angiotensin-converting enzyme gene variants and chronic nonproductive cough?

Background: It is unclear why some patients develop a chronic nonproductive cough. Angiotensin-converting enzyme (ACE) inactivates tussive peptides in the airways such as bradykinin and tachykinins. An insertion/deletion polymorphism in the ACE gene accounts for variation in ACE levels, and patients with the II genotype have lowest serum ACE levels compared with ID and DD genotypes. We hypothesized that the II genotype would be associated with increased risk of developing a chronic cough.

Materials and methods: We recruited 47 patients (33 women), referred for evaluation of cough (median cough duration, 24 months; range, 2 to 240 months). Cough patients were evaluated using a comprehensive diagnostic protocol, and cough reflex sensitivity was measured using a capsaicin inhalation challenge. ACE genotyping was performed on DNA samples from patients using the polymerase chain reaction followed by agarose gel electrophoresis. ACE genotypes in patients with chronic cough were compared with those in 199 healthy control subjects. Serum ACE levels were determined using a colorimetric assay.

Results: Genotype frequencies for the ACE gene were similar between patients and control subjects. There was no correlation between capsaicin sensitivity and ACE genotypes or serum ACE levels.

Conclusion: Susceptibility to develop chronic cough is not associated with ACE genotype.

Multicenter Randomized Controlled Trial of Withdrawal of Inhaled Corticosteroids in Cystic Fibrosis

Rationale: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.

Objectives: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.

Methods: Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age > 6.0 yr, FEV1 ? 40% predicted, and corticosteroid use > 3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.

Measurements and Main Results: Fluticasone group: n = 84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n = 87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23–1.48) fluticasone versus placebo.

Conclusions: In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.