Health status in the TORCH study of COPD: treatment efficacy and other determinants of change

BACKGROUND: Little is known about factors that determine health status decline in clinical trials of COPD. OBJECTIVES: To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo. METHODS: St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months. MEASUREMENTS AND MAIN RESULTS: Data from 4951 patients in 28 countries were available. SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains. SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001). There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women. Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1. The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change. CONCLUSIONS: In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors. Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation

Challenges of achieving good environmental status in the Northeast Atlantic

The sustainable exploitation of marine ecosystem services is dependent on achieving and maintaining an adequate ecosystem state to prevent undue deterioration. Within the European Union, the Marine Strategy Framework Directive (MSFD) requires member states to achieve Good Environmental Status (GEnS), specified in terms of 11 descriptors. We analyzed the complexity of social-ecological factors to identify common critical issues that are likely to influence the achievement of GEnS in the Northeast Atlantic (NEA) more broadly, using three case studies. A conceptual model developed using a soft systems approach highlights the complexity of social and ecological phenomena that influence, and are likely to continue to influence, the state of ecosystems in the NEA. The development of the conceptual model raised four issues that complicate the implementation of the MSFD, the majority of which arose in the Pressures and State sections of the model: variability in the system, cumulative effects, ecosystem resilience, and conflicting policy targets. The achievement of GEnS targets for the marine environment requires the recognition and negotiation of trade-offs across a broad policy landscape involving a wide variety of stakeholders in the public and private sectors. Furthermore, potential cumulative effects may introduce uncertainty, particularly in selecting appropriate management measures. There also are endogenous pressures that society cannot control. This uncertainty is even more obvious when variability within the system, e.g., climate change, is accounted for. Also, questions related to the resilience of the affected ecosystem to specific pressures must be raised, despite a lack of current knowledge. Achieving good management and reaching GEnS require multidisciplinary assessments. The soft systems approach provides one mechanism for bringing multidisciplinary information together to look at the problems in a different light

Effect of exacerbations on health status in subjects with chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Acute exacerbations may cause deteriorations in the health status of subjects with chronic obstructive pulmonary disease (COPD). The present study prospectively evaluated the effects of such exacerbations on the health status and pulmonary function of subjects with COPD over a 6-month period, and examined whether those subjects showed a steeper decline in their health status versus those subjects without exacerbations.</p> <p>Methods</p> <p>A total of 156 subjects with COPD (mean age 71.4 ± 6.3 years) were included in the analysis. At baseline and after 6 months, their pulmonary function and health status were evaluated using the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ). An acute exacerbation was defined as a worsening of respiratory symptoms requiring the administration of systemic corticosteroids or antibiotics, or both.</p> <p>Results</p> <p>Forty-eight subjects experienced one or more exacerbations during the 6-month study period, and showed a statistically and clinically significant decline in Symptom scores on the SGRQ, whereas subjects without exacerbations did not show a clinically significant decline. Logistic multiple regression analyses confirmed that the exacerbations significantly influenced the Fatigue and Mastery domains of the CRQ, and the Symptoms in the SGRQ. Twelve subjects with frequent exacerbations demonstrated a more apparent decline in health status.</p> <p>Conclusion</p> <p>Although pulmonary function did not significantly decline during the 6-month period, acute exacerbations were responsible for a decline in health status. To minimize deteriorations in health status, one must prevent recurrent acute exacerbations and reduce the exacerbation frequencies in COPD subjects.</p

Coulomb implosion mechanism of negative ion acceleration in laser plasmas

Coulomb implosion mechanism of the negatively charged ion acceleration in laser plasmas is proposed. When a cluster target is irradiated by an intense laser pulse and the Coulomb explosion of positively charged ions occurs, the negative ions are accelerated inward. The maximum energy of negative ions is several times lower than that of positive ions. The theoretical description and Particle-in-Cell simulation of the Coulomb implosion mechanism and the evidence of the negative ion acceleration in the experiments on the high intensity laser pulse interaction with the cluster targets are presented.Comment: 4 page

Manufacturing Process Control with VLSI-Compatible Sensors

Pressure sensor elements compatible with NMOS and CMOS VLSI fabrication processes, and suitable for on-line process control, are being devEnoped. The techniques employed offer either single Enements or flexible conformable arrays of capacitive or piezoresistive units. By using standard integrated circuit processing, the sensors themsEnves are naturally compatible with further Enectronic processing both on and off chip. Solid state sensors also offer cost effective batch fabrication processes and the ability to have signal conditioning and processing right on the substrate, without bulky interconnects and multiple packages

Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

MRI for assessment of anal fistula

Magnetic resonance imaging (MRI) is the best imaging modality for preoperative assessment of patients with anal fistula. MRI helps to accurately demonstrate disease extension and predict prognosis. This in turn helps make therapy decisions and monitor therapy. The pertinent anatomy, fistula classification and MRI findings will be discussed

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

An Explicit Strategy Prevails When the Cerebellum Fails to Compute Movement Errors

In sensorimotor adaptation, explicit cognitive strategies are thought to be unnecessary because the motor system implicitly corrects performance throughout training. This seemingly automatic process involves computing an error between the planned movement and actual feedback of the movement. When explicitly provided with an effective strategy to overcome an experimentally induced visual perturbation, people are immediately successful and regain good task performance. However, as training continues, their accuracy gets worse over time. This counterintuitive result has been attributed to the independence of implicit motor processes and explicit cognitive strategies. The cerebellum has been hypothesized to be critical for the computation of the motor error signals that are necessary for implicit adaptation. We explored this hypothesis by testing patients with cerebellar degeneration on a motor learning task that puts the explicit and implicit systems in conflict. Given this, we predicted that the patients would be better than controls in maintaining an effective strategy assuming strategic and adaptive processes are functionally and neurally independent. Consistent with this prediction, the patients were easily able to implement an explicit cognitive strategy and showed minimal interference from undesirable motor adaptation throughout training. These results further reveal the critical role of the cerebellum in an implicit adaptive process based on movement errors and suggest an asymmetrical interaction of implicit and explicit processes