nils-herrmann/clean_scirepeval huggingface dataset:
Esophagogastric Junction Morphology Predicts Susceptibility to Exercise-Induced Reflux

Although strenuous exercise has been reported to increase gastroesophageal reflux, there are few data exploring the mechanism behind this relationship. The aim of this study was to use vigorous exercise as a provocation for strain-induced reflux and examine the correlation between endoscopically assessed EGJ integrity and exercise-induced reflux.Ten controls and 10 GERD patients were studied for a 2-day period using the wireless Bravo™ pH monitoring system. The subjects were randomly assigned to perform 60 min of exercise on day 1 or 2 consuming the same diet on both days. Exercise consisted of 30 min of running and 30 min of 5 resistance exercises. Subjects underwent endoscopy to grade the EGJ “flap valve” and manometry to measure basal LES pressure.Nineteen subjects completed the 2-day study with 100% data capture during exercise. Median acid exposure was increased more than threefold for both controls and GERD patients during exercise when compared to nonexercise periods. In addition, a strong correlation existed between EGJ grade and % time pH < 4 during exercise while there was not a significant correlation between LES pressure and EGJ grade. These findings were present even after exclusion of hiatus hernia patients (flap valve grade 4).CONCLUSIONS:Exercise caused a threefold increase in esophageal acid exposure in both controls and GERD patients. The degree of exercise-induced reflux is strongly correlated with EGJ morphology and this supports the hypothesis that anatomical integrity of the EGJ is of cardinal importance in preventing strain-induced reflux.
Influence of dietary lipid composition on cardiac pathology in farmed Atlantic salmon, Salmo salar L.

The present study investigated the short-term (5 months) effect of replacing dietary marine oils with vegetable oils on the development of arteriosclerotic changes in the heart of Atlantic salmon, Salmo salar. The experiment was performed as a randomized observer-blinded and controlled trial. Farmed Atlantic salmon were randomly sampled from a study population containing 900 individuals. The salmon were divided into three groups and given diets with either 100% fish oil (Diet 1), a 50/50% mixture of fish oil and rapeseed oil (Diet 2) or 100% rapeseed oil (Diet 3). Ten sexually immature salmon from each dietary group were sampled in March and August 2002. Additionally, 47 sexually mature wild salmon were randomly collected in mid-September 2001. Serial histological sections were taken from the bulbus arteriosus and ventricle wall for histopathological evaluation of the coronary arteries and myocardium. No significant differences in mean coronary changes recorded by the main variable 'mean range lesion' (MRL) were detected between the groups in March or August. MRL increased significantly between March and August with Diet 2 (P < 0.01), was nearly significant with Diet 3 (P = 0.06) and was unchanged with Diet 1. This pattern coincided with the Diet 2 group having the highest increase in heart weight. MHC class II immunoreactive cells in the coronary changes were detected in sections from one individual in each group. Heart weight was the most dominant variable in the data set and explained linearly 15.5% of the variation in MRL. Body weight, fish length and heart weight were all significantly, positively and linearly correlated to MRL. The Diet 2 group had the highest growth rate and also exhibited a significant increase in MRL. The possible influence of diet composition on weight gain and MRL needs to be further elucidated. Increase in heart weight seems to be the dominating predictor of the appearance of MRL in Atlantic salmon. However, the present results cannot exclude the possibility that differences in fatty acid composition of fish feed can influence the development of arteriosclerotic changes in Atlantic salmon.
Ensuring valid measurements for a disabled population: an insulin pen pilot study.

Williams, Ph.D., R.N., C.D.E., Frances Payne Bolton School of Nursing, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106; email address ann.s.williams@case.edu Health promotion and self-management for persons with disabilities have been severely underemphasized in health care research. As researchers seek to fill these gaps in knowledge, it is essential that they validate their methods through use of pilot studies. The following pilot study illustrates how such exploration can lead to unexpected and necessary modification of methods.
Pilot study to assess the safety of local lidocaine injections during endoscopic submucosal dissection for early gastric cancer

In Japan, endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is performed by endoscopists on patients under sedation. There is an increased risk of anesthesia-related complications due to the higher sedative doses required during lengthier ESDs, so we sought to determine whether a local pain control method could safely reduce such doses. Twenty EGC patients enrolled in this study received local lidocaine injections during ESDs at our hospital (lidocaine group; LG). Electrocardiography, heart rate, oxygen saturation, and blood pressure were monitored during and after the ESDs, along with the doses of midazolam and pentazocine. Pain assessments were recorded for LG patients on the day of their ESDs and the following day. The mean volume of lidocaine injection solution was 55.4 ml and the mean dose of lidocaine was 236 mg (range, 100–300 mg). The mean size of the resected specimens was 39.3 mm and mean procedure time was 66.0 min. There were no lidocaine-related complications, and electrocardiography, heart rate, oxygen saturation and blood pressure measurements were normal. In comparison to 157 consecutive patients (control group; CG), who had similar characteristics and had undergone ESDs previously with submucosal injections of conventional normal saline solution, the mean ± SD pentazocine dose of 15.8 ± 10.3 mg in the LG was significantly lower (P < 0.01) than the dose of 23.1 ± 9.5 mg in the CG, and none of the LG patients complained of abdominal pain on the day of their ESDs, whereas such pain was reported by 17% (27/157) of the CG. Local lidocaine injections into the submucosal layer were safe when administered during ESDs performed on EGC patients under sedation.
Capecitabine plus paclitaxel versus epirubicin plus paclitaxel as first-line treatment for metastatic breast cancer: efficacy and safety results of a randomized, phase III trial by the AGO Breast Cancer Study Group

Capecitabine/taxane combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, noninferiority trial comparing capecitabine plus paclitaxel (XP) with epirubicin plus paclitaxel (EP) as first-line therapy for MBC, regarding progression-free survival (PFS) as primary efficacy endpoint. Females who had received no prior chemotherapy for MBC were randomized to six 3-weekly cycles of XP (capecitabine 1000 mg/m2 b.i.d., days 1–14; paclitaxel 175 mg/m2 3-h infusion, day 1) or EP (epirubicin 60 mg/m2 1-h infusion, day 1; paclitaxel as above). Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Each arm included 170 patients, most of whom received all six cycles as planned. The difference in means of (logarithmic) PFS times (−0.205) did not meet the pre-defined level for noninferiority (−0.186). However, PFS was similar in the two arms [HR: XP vs. EP: 1.012 (95 % CI 0.785–1.304); median 10.4 months XP vs. 9.2 months EP]. Overall survival was also similar [HR 1.027 (95 % CI 0.740–1.424); median 22.0 vs. 26.1 months], and response rate was 47 % versus 42 %. Both regimens were tolerable: there were more grade 3/4 diarrhea and grade 3 hand–foot syndromes with XP and more grade 3/4 hematologic toxicities with EP. There were no major differences in QoL. Although, noninferiority of XP to EP was formally not proven, first-line XP was active and feasible. XP is a valid first-line alternative to anthracycline/taxane regimens, especially in patients previously treated with adjuvant anthracyclines.
Randomised controlled trial comparing hospital at home care with inpatient hospital care. I: three month follow up of health outcomes.

To compare hospital at home care with inpatient hospital care in terms of patient outcomes.



Randomised controlled trial with three month follow up.



District general hospital and catchment area of neighbouring community trust.



Patients recovering from hip replacement (n=86), knee replacement (n=86), and hysterectomy (n=238); elderly medical patients (n=96); and patients with chronic obstructive airways disease (n=32).



Hospital at home care or inpatient hospital care.



Dartmouth COOP chart to measure patients' general health status; SF-36 to measure possible limitations in physical functioning of patients with hysterectomy; disease specific measures-chronic respiratory disease questionnaire, Barthel index for elderly medical patients, Oxford hip score, and Bristol knee score; hospital readmission and mortality data; carer strain index to measure burden on carers; patients' and carers' preferred form of care.



At follow up, there were no major differences in outcome between hospital at home care and hospital care for any of the patient groups except that those recovering from hip replacement reported a significantly greater improvement in quality of life with hospital at home care (difference in change from baseline value 0.50, 95% confidence interval 0.13 to 0.88). Hospital at home did not seem suitable for patients recovering from a knee replacement, as 14 (30%) of patients allocated to hospital at home remained in hospital. Patients in all groups preferred hospital at home care except those with chronic obstructive airways disease. No differences were detected for carer burden. Carers of patients recovering from knee replacement preferred hospital at home care, while carers of patients recovering from a hysterectomy preferred hospital care.



Few differences in outcome were detected. Thus, the cost of hospital at home compared with hospital care becomes a primary concern.
Low 25-hydroxyvitamin D, but not the bioavailable fraction of 25-hydroxyvitamin D, is a risk factor for multiple sclerosis.

Low 25-hydroxyvitamin D [25(OH)D] levels correlate with higher disease activity in patients with multiple sclerosis (MS). However, it is not clear whether low 25(OH)D levels directly contribute to increased disease activity or merely represent a consequence of reduced endogenous vitamin D synthesis in more disabled MS patients. Furthermore, recent data suggest that bioavailable vitamin D, which also integrates the levels of vitamin D binding proteins and albumin, could be a biologically more relevant parameter than 25(OH)D.



Measured de-seasonalized 25(OH)D3 and vitamin D binding protein and calculated bioavailable and free vitamin D were compared in the baseline serum samples of 76 patients with clinically isolated syndrome enrolled in a longitudinal observational study and in 76 age- and sex-matched healthy controls (HC).



25(OH)D3 levels were lower in patients with clinically isolated syndrome (P = 0.002) than in HC, and more patients (8/76, 10.5%) than HC (1/76, 1.3%) had 25(OH)D3 levels <25 nmol/l (P = 0.03). In contrast, levels of 25(OH)D2, vitamin D binding protein and calculated levels of free and bioavailable vitamin D did not differ between the two groups.



Lower 25(OH)D3 levels already in the earliest phase of disease and in clinically hardly affected patients suggest that low 25(OH)D3 levels are rather a risk factor for than a consequence of MS. Nevertheless, because bioavailable vitamin D levels did not differ between the two groups, the mechanism underlying the association of 25(OH)D3 and MS does not appear to be related to reduced bioavailability of vitamin D.
Activation of EGFR and ERBB2 by Helicobacter pylori results in survival of gastric epithelial cells with DNA damage.

The gastric cancer-causing pathogen Helicobacter pylori up-regulates spermine oxidase (SMOX) in gastric epithelial cells, causing oxidative stress-induced apoptosis and DNA damage. A subpopulation of SMOX(high) cells are resistant to apoptosis, despite their high levels of DNA damage. Because epidermal growth factor receptor (EGFR) activation can regulate apoptosis, we determined its role in SMOX-mediated effects.



SMOX, apoptosis, and DNA damage were measured in gastric epithelial cells from H. pylori-infected Egfr(wa5) mice (which have attenuated EGFR activity), Egfr wild-type mice, or in infected cells incubated with EGFR inhibitors or deficient in EGFR. A phosphoproteomic analysis was performed. Two independent tissue microarrays containing each stage of disease, from gastritis to carcinoma, and gastric biopsy specimens from Colombian and Honduran cohorts were analyzed by immunohistochemistry.



SMOX expression and DNA damage were decreased, and apoptosis increased in H. pylori-infected Egfr(wa5) mice. H. pylori-infected cells with deletion or inhibition of EGFR had reduced levels of SMOX, DNA damage, and DNA damage(high) apoptosis(low) cells. Phosphoproteomic analysis showed increased EGFR and erythroblastic leukemia-associated viral oncogene B (ERBB)2 signaling. Immunoblot analysis showed the presence of a phosphorylated (p)EGFR-ERBB2 heterodimer and pERBB2; knockdown of ErbB2 facilitated apoptosis of DNA damage(high) apoptosis(low) cells. SMOX was increased in all stages of gastric disease, peaking in tissues with intestinal metaplasia, whereas pEGFR, pEGFR-ERBB2, and pERBB2 were increased predominantly in tissues showing gastritis or atrophic gastritis. Principal component analysis separated gastritis tissues from patients with cancer vs those without cancer. pEGFR, pEGFR-ERBB2, pERBB2, and SMOX were increased in gastric samples from patients whose disease progressed to intestinal metaplasia or dysplasia, compared with patients whose disease did not progress.



In an analysis of gastric tissues from mice and patients, we identified a molecular signature (based on levels of pEGFR, pERBB2, and SMOX) for the initiation of gastric carcinogenesis.
Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis.

Interleukin-1 increases nitrooxidative stress. We investigated the effects of a human recombinant interleukin-1a receptor antagonist (anakinra) on nitrooxidative stress and vascular and left ventricular function.



In an acute, double-blind trial, 23 patients with rheumatoid arthritis were randomized to receive a single injection of anakinra (150 mg s.c.) or placebo and, after 48 hours, the alternative treatment. At baseline and 3 hours after the injection, we assessed (1) coronary flow reserve, aortic distensibility, systolic and diastolic (Em) velocity of the mitral annulus, and E to Em ratio (E/Em) using echocardiography; (2) flow-mediated, endothelium-dependent dilation of the brachial artery; and (3) malondialdehyde, nitrotyrosine, interleukin-6, endothelin-1, and C-reactive protein. In a chronic, nonrandomized trial, 23 patients received anakinra and 19 received prednisolone for 30 days, after which all indices were reassessed. Compared with baseline, there was a greater reduction in malondialdehyde, nitrotyrosine, interleukin-6, and endothelin-1 and a greater increase in flow-mediated dilation, coronary flow reserve, aortic distensibility, systolic velocity of mitral annulus, and E/Em after anakinra than after placebo (malondialdehyde -25% versus 9%; nitrotyrosine -38% versus -11%; interleukin-6 -29% versus 0.9%; endothelin-1 -36% versus -11%; flow-mediated dilation 45% versus -9%; coronary flow reserve 29% versus 4%; and aortic distensibility 45% versus 2%; P<0.05 for all comparisons). After 30 days of treatment, the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group (P<0.05).



Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin.
Cost-effectiveness analysis of a rural telemedicine collaborative care intervention for depression.

Collaborative care interventions for depression in primary care settings are clinically beneficial and cost-effective. Most prior studies were conducted in urban settings.



To examine the cost-effectiveness of a rural telemedicine-based collaborative care depression intervention.



Randomized controlled trial of intervention vs usual care.



Seven small (serving 1000 to 5000 veterans) Veterans Health Administration community-based outpatient clinics serving rural catchment areas in 3 mid-South states. Each site had interactive televideo dedicated to mental health but no psychiatrist or psychologist on site.  395 met eligibility criteria and were enrolled from April 2003 to September 2004. Of those enrolled, 360 (91.1%) completed a 6-month follow-up and 335 (84.8%) completed a 12-month follow-up.  A stepped-care model for depression treatment was used by an off-site depression care team to make treatment recommendations via electronic medical record. The team included a nurse depression care manager, clinical pharmacist, and psychiatrist. The depression care manager communicated with patients via telephone and was supported by computerized decision support software.



The base case cost analysis included outpatient, pharmacy, and intervention expenditures. The effectiveness outcomes were depression-free days and quality-adjusted life years (QALYs) calculated using the 12-Item Short Form Health Survey standard gamble conversion formula.



The incremental depression-free days outcome was not significant (P = .10); therefore, further cost-effectiveness analyses were not done. The incremental QALY outcome was significant (P = .04) and the mean base case incremental cost-effectiveness ratio was $85 634/QALY. Results adding inpatient costs were $111 999/QALY to $132 175/QALY.



In rural settings, a telemedicine-based collaborative care intervention for depression is effective and expensive. The mean base case result was $85 634/QALY, which is greater than cost per QALY ratios reported for other, mostly urban, depression collaborative care interventions.
A phase I study of high-dose rosuvastatin with standard dose erlotinib in patients with advanced solid malignancies

Synergistic cytotoxicity with high-dose statins and erlotinib has been demonstrated in preclinical models across a number of tumour types. In this phase I study, we evaluated the safety and potential anti-tumour activity of escalating doses of rosuvastatin in combination with the standard clinical dose of erlotinib in heavily pretreated patients with advanced solid tumours. This was a single-center, phase I open-label study to determine the safety and recommended phase two dose (RPTD) of rosuvastatin in combination with 150 mg/day standard dose of erlotinib. Using a 3 + 3 study design and 28-day cycle, escalating doses of rosuvastatin from 1 to 8 mg/kg/day ×2 weeks (cycle 1) and 3 weeks (subsequent cycles) given concurrently with erlotinib were evaluated. In order to expand the experience and to gain additional safety and pharmacokinetic data, two expansions cohorts using concurrent or alternating weekly dosing regimens at the RPTD were also evaluated. All 24 patients enrolled were evaluable for toxicity, and 22 for response. The dose-limiting toxicity (DLT) of reversible muscle toxicity was seen at the 2 mg/kg/day dose level. Maximal tolerated dose (MTD) was determined to be 1 mg/kg/day. Thirty-three percent of patients developed at least 1≥ grade 2 muscle toxicity (rhabdomyolysis: 1/24, myalgia: 7/24) resulting in one study-related death. Durable stable disease for more than 170 days was seen in 25 % of patients that received concurrent treatment and were evaluable for response (n = 16). Plasma erlotinib levels on study were unaffected by the addition of rosuvastatin. The observed disease stabilization rate of 25 % with combination therapy in this heavily pretreated population is encouraging, however, the high levels of muscle toxicities observed limited this combination strategy.
Primary screening of blood donors by nat testing for HCV-RNA: development of an "in-house" method and results.

An "in-house" RT-PCR method was developed that allows the simultaneous detection of the RNA of the Hepatitis C Virus (HCV) and an artificial RNA employed as an external control. Samples were analyzed in pools of 6-12 donations, each donation included in two pools, one horizontal and one vertical, permitting the immediate identification of a reactive donation, obviating the need for pool dismembering. The whole process took 6-8 hours per day and results were issued in parallel to serology. The method was shown to detect all six HCV genotypes and a sensitivity of 500 IU/mL was achieved (95% hit rate). Until July 2005, 139,678 donations were tested and 315 (0.23%) were found reactive for HCV-RNA. Except for five false-positives, all 310 presented the corresponding antibody as well, so the yield of NAT-only donations was zero, presenting a specificity of 99.83%. Detection of a window period donation, in the population studied, will probably demand testing of a larger number of donations. International experience is showing a rate of 1:200,000 - 1:500,000 of isolated HCV-RNA reactive donations.
The development of the pediatric cardiac quality of life inventory: a quality of life measure for children and adolescents with heart disease

Mortality after surgery for congenital heart disease (CHD) has decreased. Quality of life (QOL) assessment in survivors has become increasingly important. The purpose of this project was to create the Pediatric Cardiac Quality of Life Inventory (PCQLI). Items were generated through nominal groups of patients, parents, and providers. The pilot PCQLI was completed by children (age 8–12), adolescents (age 13–18), and their parents at three cardiology clinics. Item reduction was performed through analysis of items, principal components, internal consistency (IC), and patterns of correlation. A total of 655 patient–parent pairs completed the pilot PCQLI. Principal components identified included: impact of disease (ID); psychosocial impact (PI); and emotional environment (EE). After item reduction ID and PI had excellent IC (ID = 0.88–0.91; PI = 0.78–0.85) and correlated highly with each other (0.81–0.90) and with the total score (TS) (ID = 0.95–0.96; PI = 0.87–0.93). EE was not correlated with ID, PI, or TS and was removed from the final forms. Two-ventricle CHD patients had a higher TS than single-ventricle CHD patients across all forms (P < 0.001). The PCQLI has patient and parent-proxy forms, has wide age range, and discriminates between CHD subgroups. The ID and PI subscales of the PCQLI have excellent IC and correlate well with each other and the TS.
Role ofhistamine released in hypertonic saline induced bronchoconstriction

The lengthy and balanced editorial on treatment duration in small cell lung cancer (January 1990;45:1-2) makes no mention of the first large scale randomised trial specifically addressing this question to be published world wide. In 1986 we reported a randomised trial with over 300 patients, which resulted from collaboration amongst chest physicians, radiotherapists, and medical oncologists in Nottingham and elsewhere in the Midlands.' Unlike most subsequent trials we chose not to randomise patients who had clearly demonstrable signs of residual disease after an initial period of induction chemotherapy (that is, partial remissions or failures) as we felt intuitively that these patients (whose tumours were thus not very sensitive to chemotherapy) were very unlikely to benefit from more of the same. The results of the later trials have confirmed that our suspicions were correct. In the Midlands trial limited and extensive stage patients who had responded very well to induction treatment were randomised separately. There were inadequate numbers of limited stage cases for worthwhile conclusions. In extensive disease, however, there