A Comparison of Esomeprazole and Lansoprazole for Control of Intragastric pH in Patients With Symptoms of Gastro-Oesophageal Reflux Disease

Background: Intragastric acid suppression is the most direct measure of the pharmacodynamic efficacy of proton pump inhibitors, which are the most effective drugs for acid-related diseases. Aim: To compare the effectiveness of once and twice daily dosing of lansoprazole and esomeprazole in controlling intragastric acidity ( target gastric pH \u3e 4.0) over a 24-hour period. Methods: In an open-label, two-way crossover study, 45 Helicobacter pylori-negative patients with gastro-oesophageal reflux disease were randomized to receive one of two regimens: 30 mg lansoprazole or esomeprazole 40 mg once daily. Intragastric pH was assessed by 24-hour pH monitoring on day 5 of each regimen. Dosing was increased to twice daily and pH was re-assessed on day 10. Following a 14-day washout, patients were crossed over to the other medication and the dosage regimens and pH assessments were repeated. Results: Data were analysed from 35 patients who completed all scheduled assessments and had 24-hour monitoring for each end-point. Mean time pH \u3e 4.0 and mean 24-hour pH were highest for esomeprazole 40 mg twice daily, followed by lansoprazole 30 mg twice daily, esomeprazole 40 mg once daily and lansoprazole 30 mg once daily. Esomeprazole 40 mg twice daily provided superior control of intragastric pH compared with either once or twice daily dosing of lansoprazole and once daily dosing of esomeprazole (P \u3c 0.01). Esomeprazole 40 mg once daily was comparable with lansoprazole 30 mg twice daily and both were superior to lansoprazole 30 mg once daily (P \u3c 0.01). Conclusions: Response to acid suppression treatment depends on the treatment selected. Esomeprazole 40 mg twice daily provided better control of intragastric pH than all other regimens evaluated. Esomeprazole 40 mg daily, however, was comparable with lansoprazole 30 mg twice daily and superior to lansoprazole 30 mg once daily

Ecosystem-scale measurements of biomass water using cosmic ray neutrons

Accurate estimates of biomass are imperative for understanding the global carbon cycle. However, measurements of biomass and water in the biomass are difficult to obtain at a scale consistent with measurements of mass and energy transfer, ~1 km, leading to substantial uncertainty in dynamic global vegetation models. Here we use a novel cosmic ray neutron method to estimate a stoichiometric predictor of ecosystem-scale biomass and biomass water equivalent over tens of hectares. We present two experimental studies, one in a ponderosa pine forest and the other in a maize field, where neutron-derived estimates of biomass water equivalent are compared and found consistent with direct observations. Given the new hectometer scale of nondestructive observation and potential for continuous measurements, we anticipate this technique to be useful to many scientific disciplines

Radiometric sensitivity to soil moisture at 1.4 GHz through a corn crop at maximum biomass

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95107/1/wrcr9929.pd

Toward Identifying the Next Generation of Superfund and Hazardous Waste Site Contaminants

Reproduced with permission from Environmental Health Perspectives."This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants." doi:10.1289/ehp.1002497Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Superfund-relevant CECs can be characterized by specific attributes: they are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites.Support for the workshop, from which this article evolved, was provided by the National Institute of Environmental Health Sciences Superfund Research Program (P42-ES04940)

Toward Identifying the Next Generation of Superfund and Hazardous Waste Site Contaminants

Reproduced with permission from Environmental Health Perspectives."This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants." doi:10.1289/ehp.1002497Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Superfund-relevant CECs can be characterized by specific attributes: they are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites.Support for the workshop, from which this article evolved, was provided by the National Institute of Environmental Health Sciences Superfund Research Program (P42-ES04940)

A randomised clinical trial on cardiotocography plus fetal blood sampling versus cardiotocography plus ST-analysis of the fetal electrocardiogram (STAN®) for intrapartum monitoring

<p>Abstract</p> <p>Background</p> <p>Cardiotocography (CTG) is worldwide the method for fetal surveillance during labour. However, CTG alone shows many false positive test results and without fetal blood sampling (FBS), it results in an increase in operative deliveries without improvement of fetal outcome. FBS requires additional expertise, is invasive and has often to be repeated during labour. Two clinical trials have shown that a combination of CTG and ST-analysis of the fetal electrocardiogram (ECG) reduces the rates of metabolic acidosis and instrumental delivery. However, in both trials FBS was still performed in the ST-analysis arm, and it is therefore still unknown if the observed results were indeed due to the ST-analysis or to the use of FBS in combination with ST-analysis.</p> <p>Methods/Design</p> <p>We aim to evaluate the effectiveness of non-invasive monitoring (CTG + ST-analysis) as compared to normal care (CTG + FBS), in a multicentre randomised clinical trial setting. Secondary aims are: 1) to judge whether ST-analysis of fetal electrocardiogram can significantly decrease frequency of performance of FBS or even replace it; 2) perform a cost analysis to establish the economic impact of the two treatment options.</p> <p>Women in labour with a gestational age ≥ 36 weeks and an indication for CTG-monitoring can be included in the trial.</p> <p>Eligible women will be randomised for fetal surveillance with CTG and, if necessary, FBS or CTG combined with ST-analysis of the fetal ECG.</p> <p>The primary outcome of the study is the incidence of serious metabolic acidosis (defined as pH < 7.05 and Bd_ecf> 12 mmol/L in the umbilical cord artery). Secondary outcome measures are: instrumental delivery, neonatal outcome (Apgar score, admission to a neonatal ward), incidence of performance of FBS in both arms and cost-effectiveness of both monitoring strategies across hospitals.</p> <p>The analysis will follow the intention to treat principle. The incidence of metabolic acidosis will be compared across both groups. Assuming a reduction of metabolic acidosis from 3.5% to 2.1 %, using a two-sided test with an alpha of 0.05 and a power of 0.80, in favour of CTG plus ST-analysis, about 5100 women have to be randomised. Furthermore, the cost-effectiveness of CTG and ST-analysis as compared to CTG and FBS will be studied.</p> <p>Discussion</p> <p>This study will provide data about the use of intrapartum ST-analysis with a strict protocol for performance of FBS to limit its incidence. We aim to clarify to what extent intrapartum ST-analysis can be used without the performance of FBS and in which cases FBS is still needed.</p> <p>Trial Registration Number</p> <p>ISRCTN95732366</p

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival. METHODS: New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m2 administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m2 administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m2 repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m2 administered intravenously over 2 h and oral capecitabine 1000 mg/m2 twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m2 intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m2 every 2 weeks with regimen one and three or a loading dose of 400 mg/m2 followed by a weekly infusion of 250 mg/m2 with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-to-treat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367. FINDINGS: Between Feb 26, 2007, and Oct 12, 2012, 257 eligible patients were randomly assigned to chemotherapy with cetuximab (n=129) or without cetuximab (n=128). This analysis was carried out 5 years after the last patient was recruited, as defined in the protocol, at a median follow-up of 66·7 months (IQR 58·0-77·5). Median progression-free survival was 22·2 months (95% CI 18·3-26·8) in the chemotherapy alone group and 15·5 months (13·8-19·0) in the chemotherapy plus cetuximab group (hazard ratio [HR] 1·17, 95% CI 0·87-1·56; p=0·304). Median overall survival was 81·0 months (59·6 to not reached) in the chemotherapy alone group and 55·4 months (43·5-71·5) in the chemotherapy plus cetuximab group (HR 1·45, 1·02-2·05; p=0·036). There was no significant difference in the secondary outcomes of preoperative response or pathological resection status between groups. Five deaths might have been treatment-related (one in the chemotherapy alone group and four in the chemotherapy plus cetuximab group). The most common grade 3-4 adverse events reported were: neutrophil count decreased (26 [19%] of 134 in the chemotherapy alone group vs 21 [15%] of 137 in the chemotherapy plus cetuximab group), diarrhoea (13 [10%] vs 14 [10%]), skin rash (one [1%] vs 22 [16%]), thromboembolic events (ten [7%] vs 11 [8%]), lethargy (ten [7%] vs nine [7%]), oral mucositis (three [2%] vs 14 [10%]), vomiting (seven [5%] vs seven [5%]), peripheral neuropathy (eight [6%] vs five [4%]), and pain (six [4%] vs six [4%]). INTERPRETATION: Although the addition of cetuximab to chemotherapy improves the overall survival in some studies in patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting. FUNDING: Cancer Research UK