A symptom-limited incremental step test determines maximum physiological responses in patients with chronic obstructive pulmonary disease

Background: Step tests have been used to evaluate exercise tolerance and effort-related hypoxemia in different diseases. A symptom-limited incremental step test (IST) has never been tested in COPD patients.Aim: To compare maximal physiological responses between an IST and cardiopulmonary exercise testing (CPET), to test the reproducibility of the IST on different days, and to provide a predict equation to estimate VO2 from the IST in patients with COPD.Material and methods: At the same day, thirty-four patients (VEF1 46 +/- 14% of pred) underwent a CPET on cycle ergometer and the first 151 (IST-1) (1 h apart). After 2-5 days, patients repeated the IST (IST-2). Pulmonary gas exchange was measured during all tests.Results: Peak VO2 was significantly higher in IST-1 and IST-2 than in CEPT (Mean +/- SD: 1.19 +/- 0.39 L, 1.20 +/- 0.40 L, 1.07 +/- 0.35 L) with no difference for ventilation (VE), heart rate (HR), and perception of effort. ISTs were highly reproducible, with significant intraclass correlation coefficient (CCI [95% confidence interval]) for number of steps (0.98[0.95-0.99]), VO2 (0.99 [0.98-0.99]), VE (0.97[0.93-0.99]), HR (0.92[0.81-0.97]), and SpO(2) (0.96[0.90-0.98]). Desaturation was significantly higher for IST-1 and IST-2 compared with cycling (Mean +/- SD: -6 +/- 5%, -6 +/- 4%, - 3 +/- 3%). Number of steps and patient weight explained 81% of the variance in peak VO2 (p < 0.001).Conclusion: A symptom-limited incremental step test, externally paced, elicits maximal cardiopulmonary and metabolic responses, and is well tolerated and reproducible in patients with COPD. (C) 2013 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Nove Julho UNINOVE, Postgrad Program Rehabil Sci, BR-01504001 São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Med, Div Resp Dis, São Paulo, BrazilUniv Fed Juiz de Fora, Human Physiol Dept, Juiz de Fora, MG, BrazilFed Univ São Paulo UNIFESP, Dept Med, Div Resp Dis, São Paulo, BrazilFAPESP: 2010/09732-6Web of Scienc

Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial

BACKGROUND: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer. METHODS: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m(2) gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m(2) oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434. FINDINGS: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5-31·5) compared with 25·5 months (22·7-27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68-0·98], p=0·032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group. INTERPRETATION: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma

Preoperative predictive factors for intensive care unit admission after pulmonary resection

Objective: To determine whether the use of a set of preoperative variables can predict the need for postoperative ICU admission. Methods: This was a prospective observational cohort study of 120 patients undergoing elective pulmonary resection between July of 2009 and April of 2012. Prediction of ICU admission was based on the presence of one or more of the following preoperative characteristics: predicted pneumonectomy; severe/very severe COPD; severe restrictive lung disease; FEV1 or DLCO predicted to be < 40% postoperatively; SpO2 on room air at rest < 90%; need for cardiac monitoring as a precautionary measure; or American Society of Anesthesiologists physical status &#8805; 3. The gold standard for mandatory admission to the ICU was based on the presence of one or more of the following postoperative characteristics: maintenance of mechanical ventilation or reintubation; acute respiratory failure or need for noninvasive ventilation; hemodynamic instability or shock; intraoperative or immediate postoperative complications (clinical or surgical); or a recommendation by the anesthesiologist or surgeon to continue treatment in the ICU. Results: Among the 120 patients evaluated, 24 (20.0%) were predicted to require ICU admission, and ICU admission was considered mandatory in 16 (66.6%) of those 24. In contrast, among the 96 patients for whom ICU admission was not predicted, it was required in 14 (14.5%). The use of the criteria for predicting ICU admission showed good accuracy (81.6%), sensitivity of 53.3%, specificity of 91%, positive predictive value of 66.6%, and negative predictive value of 85.4%. Conclusions: The use of preoperative criteria for predicting the need for ICU admission after elective pulmonary resection is feasible and can reduce the number of patients staying in the ICU only for monitoring

Hydrological Connectivity Between Headwater Streams and Downstream Waters: How Science Can Inform Policy

In January 2001, the U.S. Supreme Court ruled that the U.S. Army Corps of Engineers exceeded its statutory authority by asserting Clean Water Act (CWA) jurisdiction over non-navigable, isolated, intrastate waters based solely on their use by migratory birds. The Supreme Court’s majority opinion addressed broader issues of CWA jurisdiction by implying that the CWA intended some “connection” to navigability and that isolated waters need a “significant nexus” to navigable waters to be jurisdictional. Subsequent to this decision (SWANCC), there have been many lawsuits challenging CWA jurisdiction, many of which are focused on headwater, intermittent, and ephemeral streams. To inform the legal and policy debate surrounding this issue, we present information on the geographic distribution of headwater streams and intermittent and ephemeral streams throughout the U.S., summarize major findings from the scientific literature in considering hydrological connectivity between headwater streams and downstream waters, and relate the scientific information presented to policy issues surrounding the scope of waters protected under the CWA. Headwater streams comprise approximately 53% (2,900,000 km) of the total stream length in the U.S., excluding Alaska, and intermittent and ephemeral streams comprise approximately 59% (3,200,000 km) of the total stream length and approximately 50% (1,460,000 km) of the headwater stream length in the U.S., excluding Alaska. Hillslopes, headwater streams, and downstream waters are best described as individual elements of integrated hydrological systems. Hydrological connectivity allows for the exchange of mass, momentum, energy, and organisms longitudinally, laterally, vertically, and temporally between headwater streams and downstream waters. Via hydrological connectivity, headwater, intermittent and ephemeral streams cumulatively contribute to the functional integrity of downstream waters; hydrologically and ecologically, they are a part of the tributary system. As this debate continues, scientific input from multiple fields will be important for policymaking at the federal, state, and local levels and to inform water resource management regardless of the level at which those decisions are being made. Strengthening the interface between science, policy, and public participation is critical if we are going to achieve effective water resource management