Haemodynamic compensations for exercise tissue oxygenation in early stages of COPD: an integrated cardiorespiratory assessment study.

BACKGROUND: Cardiovascular comorbidities are increasingly being recognised in early stages of chronic obstructive pulmonary disease (COPD) yet complete cardiorespiratory functional assessments of individuals with mild COPD or presenting with COPD risk factors are lacking. This paper reports on the effectiveness of the cardiocirculatory-limb muscles oxygen delivery and utilisation axis in smokers exhibiting no, or mild to moderate degrees of airflow obstruction using standardised cardiopulmonary exercise testing (CPET). METHODS: Post-bronchodilator spirometry was used to classify participants as 'ever smokers without' (n=88), with 'mild' (n=63) or 'mild-moderate' COPD (n=56). All underwent CPET with continuous concurrent monitoring of oxygen uptake (V'O2) and of bioimpedance cardiac output (Qc) enabling computation of arteriovenous differences (a-vO2). Mean values of Qc and a-vO2 were mapped across set ranges of V'O2 and Qc isolines to allow for meaningful group comparisons, at same metabolic and circulatory requirements. RESULTS: Peak exercise capacity was significantly reduced in the 'mild-moderate COPD' as compared with the two other groups who showed similar pulmonary function and exercise capacity. Self-reported cardiovascular and skeletal muscle comorbidities were not different between groups, yet disease impact and exercise intolerance scores were three times higher in the 'mild-moderate COPD' compared with the other groups. Mapping of exercise Qc and a-vO2 also showed a leftward shift of values in this group, indicative of a deficit in peripheral O2 extraction even for submaximal exercise demands. Concurrent with lung hyperinflation, a distinctive blunting of exercise stroke volume expansion was also observed in this group. CONCLUSION: Contrary to the traditional view that cardiovascular complications were the hallmark of advanced disease, this study of early COPD spectrum showed a reduced exercise O2 delivery and utilisation in individuals meeting spirometry criteria for stage II COPD. These findings reinforce the preventive clinical management approach to preserve peripheral muscle circulatory and oxidative capacities.

Multidimensional breathlessness assessment during cardiopulmonary exercise testing in healthy adults.

PURPOSE: This study explored if healthy adults could discriminate between different breathlessness dimensions when rated immediately one after another (successively) during symptom-limited incremental cardiopulmonary cycle exercise testing (CPET) using multiple single-item rating scales. METHODS: Fifteen apparently healthy adults (60% male) aged 22 ± 2 years performed six incremental cycle CPETs separated by ≥ 48 h. During each CPET (at rest, every 2-min and at end exercise), participants rated different breathlessness sensations using the 0-10 modified Borg scale using one of six assessment protocols, randomized for order: (1) 'BREATHLESSALL' = breathlessness sensory intensity (SI), breathlessness unpleasantness (UN), work/effort of breathing (SQW/E), and unsatisfied inspiration (SQUI) assessed; (2) SI and UN assessed; and (3-6) SI, UN, SQW/E, and SQUI each assessed alone. Physiological responses to CPET were also evaluated. RESULTS: Physiological and breathlessness responses to CPET were comparable across the six protocols, with the exception of SI rated lower at the highest submaximal power output (220 ± 56 watts) during the BREATHLESSALL protocol (0-10 Borg units 4.2 ± 1.7) compared to SI + UN (5.2 ± 2.1, p = 0.03) and SI alone (5.1 ± 1.9, p = 0.04) protocols. Ratings of SI and SQW/E were not significantly different when assessed in the same protocol, and were significantly higher than UN and SQUI, which were comparable. CONCLUSION: In healthy younger adults, use of two separate single-item rating scales to assess breathlessness during CPET is feasible and enables the distinct sensory intensity and affective dimensions of exertional breathlessness to be assessed.

Mobile Gait Analysis using Personalised Hidden Markov Models for Hereditary Spastic Paraplegia Patients.

Gait analysis provides a quantitative method to assess disease progression or intervention effect on gait disorders. While mobile gait analysis enables continuous monitoring in free living conditions, state of the art gait analysis for diseases such as hereditary spastic paraplegia (HSP) is currently limited to motion capture systems which are large and expensive. The challenge with HSP is its heterogeneous nature and rarity, leading to a wide range of ages, severity and gait patterns as well as small patient numbers. We propose a sensor-based mobile solution, based on a personalised hierarchical hidden Markov Model (hHMM) to extract spatio-temporal gait parameters. This personalised hHMM achieves a mean absolute error of 0.04 s ± 0.03 s for stride time estimation with respect to a GAITRite® reference system. We use the successful extraction of initial ground contact to explore the limits of the double integration method for such heterogeneous diseases. While our personalised model compensates for the heterogeneity of the disease, it would require a new model per patient. We observed that the general model was sufficient for some of the less severely affected patients.

Lower GI bleeding: epidemiology and management.

Gastrointestinal (GI) bleeding from the colon is a common reason for hospitalization and is becoming more common in the elderly. While most cases will cease spontaneously, patients with ongoing bleeding or major stigmata of hemorrhage require urgent diagnosis and intervention to achieve definitive hemostasis. Colonoscopy is the primary modality for establishing a diagnosis, risk stratification, and treating some of the most common causes of colonic bleeding, including diverticular hemorrhage which is the etiology in 30% of cases. Other interventions, including angiography and surgery, are usually reserved for instances of bleeding that cannot be stabilized or allow for adequate bowel preparation for colonoscopy. We discuss the colonoscopic diagnosis, risk stratification, and definitive treatment of colonic hemorrhage in patients presenting with severe hematochezia.

Cost effectiveness of high-dose intravenous esomeprazole for peptic ulcer bleeding.

Peptic ulcer bleeding (PUB) is a serious and sometimes fatal condition. The outcome of PUB strongly depends on the risk of rebleeding. A recent multinational placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT00251979) showed that high-dose intravenous (IV) esomeprazole, when administered after successful endoscopic haemostasis in patients with PUB, is effective in preventing rebleeding. From a policy perspective it is important to assess the cost efficacy of this benefit so as to enable clinicians and payers to make an informed decision regarding the management of PUB. Using a decision-tree model, we compared the cost efficacy of high-dose IV esomeprazole versus an approach of no-IV proton pump inhibitor for prevention of rebleeding in patients with PUB. The model adopted a 30-day time horizon and the perspective of third-party payers in the USA and Europe. The main efficacy variable was the number of averted rebleedings. Healthcare resource utilization costs (physician fees, hospitalizations, surgeries, pharmacotherapies) relevant for the management of PUB were also determined. Data for unit costs (prices) were primarily taken from official governmental sources, and data for other model assumptions were retrieved from the original clinical trial and the literature. After successful endoscopic haemostasis, patients received either high-dose IV esomeprazole (80 mg infusion over 30 min, then 8 mg/hour for 71.5 hours) or no-IV esomeprazole treatment, with both groups receiving oral esomeprazole 40 mg once daily from days 4 to 30. Rebleed rates at 30 days were 7.7% and 13.6%, respectively, for the high-dose IV esomeprazole and no-IV esomeprazole treatment groups (equating to a number needed to treat of 17 in order to prevent one additional patient from rebleeding). In the US setting, the average cost per patient for the high-dose IV esomeprazole strategy was $US14 290 compared with $US14 239 for the no-IV esomeprazole strategy (year 2007 values). For the European setting, Sweden and Spain were used as examples. In the Swedish setting the corresponding respective figures were Swedish kronor (SEK)67 862 ($US9220 at average 2006 interbank exchange rates) and SEK67 807 ($US9212) [year 2006 values]. Incremental cost-effectiveness ratios were $US866 and SEK938 ($US127), respectively, per averted rebleed when using IV esomeprazole. For the Spanish setting, the high-dose IV esomeprazole strategy was dominant (more effective and less costly than the no-IV esomeprazole strategy) [year 2008 values]. All results appeared robust to univariate/threshold sensitivity analysis, with high-dose IV esomeprazole becoming dominant with small variations in assumptions in the US and Swedish settings, while remaining a dominant approach in the Spanish scenario across a broad range of values. Sensitivity variables with prespecified ranges included lengths of stay and per diem assumptions, rebleeding rates and, in some cases, professional fees. In patients with PUB, high-dose IV esomeprazole after successful endoscopic haemostasis appears to improve outcomes at a modest increase in costs relative to a no-IV esomeprazole strategy from the US and Swedish third-party payer perspective. Whereas, in the Spanish setting, the high-dose IV esomeprazole strategy appeared dominant, being more effective and less costly.