nils-herrmann/clean_scirepeval huggingface dataset:
Recombinant human activated protein C attenuates cardiovascular and microcirculatory dysfunction in acute lung injury and septic shock

This prospective, randomized, controlled, experimental animal study looks at the effects of recombinant human activated protein C (rhAPC) on global hemodynamics and microcirculation in ovine acute lung injury (ALI) and septic shock, resulting from smoke inhalation injury.



Twenty-one sheep (37 ± 2 kg) were operatively prepared for chronic study and randomly allocated to either the sham, control, or rhAPC group (n = 7 each). The control and rhAPC groups were subjected to insufflation of four sets of 12 breaths of cotton smoke followed by instillation of live Pseudomonas aeruginosa into both lung lobes, according to an established protocol. Healthy sham animals were not subjected to the injury and received only four sets of 12 breaths of room air and instillation of the vehicle (normal saline). rhAPC (24 μg/kg/hour) was intravenously administered from 1 hour post injury until the end of the 24-hour experiment. Regional microvascular blood flow was analyzed using colored microspheres. All sheep were mechanically ventilated with 100% oxygen, and fluid resuscitated with lactated Ringer's solution to maintain hematocrit at baseline levels.



The rhAPC-associated reduction in heart malondialdehyde (MDA) and heart 3-nitrotyrosine (a reliable indicator of tissue injury) levels occurred parallel to a significant increase in mean arterial pressure and to a significant reduction in heart rate and cardiac output compared with untreated controls that showed a typical hypotensive, hyperdynamic response to the injury (P < 0.05). In addition, rhAPC significantly attenuated the changes in microvascular blood flow to the trachea, kidney, and spleen compared with untreated controls (P < 0.05 each). Blood flow to the ileum and pancreas, however, remained similar between groups. The cerebral blood flow as measured in cerebral cortex, cerebellum, thalamus, pons, and hypothalamus, was significantly increased in untreated controls, due to a loss of cerebral autoregulation in septic shock. rhAPC stabilized cerebral blood flow at baseline levels, as in the sham group.



We conclude that rhAPC stabilized cardiovascular functions and attenuated the changes in visceral and cerebral microcirculation in sheep suffering from ALI and septic shock by reduction of cardiac MDA and 3-nitrotyrosine.
Creatinine clearance following cimetidine for estimation of glomerular filtration rate

Simultaneous inulin (C in) and creatinine clearance (C Cr) studies were performed on 53 pediatric renal patients using a cimetidine protocol. Since cimetidine blocks the tubular secretion of creatinine, it was hypothesized that C Cr measured following cimetidine would closely approximate the C in. C in was compared with C Cr with the latter calculated from: (1) a 24-h urine collection, (2) plasma creatinine, height, and a proportionality constant, (3) the same plasma and urine specimens used for calculating C in, and (4) from the plasma and urine specimens of the four 30-min clearance periods treated as a single 2-h clearance. The C in was very closely approximated by the C Cr calculated from the same specimens used for the C in and by the 2-h clearance. The cimetidine protocol, with C Cr derived from a 2-h urine collection obtained under supervision in the office or clinic, provides a convenient and inexpensive procedure for estimation of glomerular filtration rate in a clinical setting.
Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training.

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potentiation characteristics of recently paralyzed soleus muscle. Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue potentiation during a repetitive soleus activation protocol that induced low-frequency fatigue. Ten subjects with acute paralysis (<6 mo) demonstrated no torque potentiation in response to repetitive stimulation. Seven of these acute subjects completed 2 yr of home-based isometric soleus electrical stimulation training of one limb (compliance = 83%; 8,300 contractions/wk). With the early implementation of electrically stimulated training, potentiation characteristics of trained soleus muscles were preserved as in the acute postinjury state. In contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after spinal cord injury (SCI). A single acute SCI subject who was followed longitudinally developed potentiation characteristics very similar to the untrained limbs of the training subjects. The results of the present investigation support that postfatigue potentiation is a characteristic of fast-fatigable muscle and can be prevented by timely neuromuscular electrical stimulation training. Potentiation is an important consideration in the design of functional electrical stimulation control systems for people with SCI.
Body composition and survival in dialysis patients: results from an international cohort study.

High body mass index appears protective in hemodialysis patients, but uncertainty prevails regarding which components of body composition, fat or lean body mass, are primarily associated with survival.



Data between April 2006 and December 2012 were extracted from the Fresenius Medical Care Europe subset of the international MONitoring Dialysis Outcomes initiative. Fresenius Medical Care Europe archives a unique repository of predialysis body composition measurements determined by multifrequency bioimpedance (BCM Body Composition Monitor). The BCM Body Composition Monitor reports lean tissue indices (LTIs) and fat tissue indices (FTIs), which are the respective tissue masses normalized to height squared, relative to an age- and sex-matched healthy population. The relationship between LTI and FTI and all-cause mortality was studied by Kaplan-Meier analysis, multivariate Cox regression, and smoothing spline ANOVA logistic regression.



In 37,345 hemodialysis patients, median (25th-75th percentile) LTI and FTI were 12.2 (10.3-14.5) and 9.8 (6.6-12.4) kg/m(2), respectively. Median (25th-75th percentile) follow-up time was 266 (132-379) days; 3458 (9.2%) patients died during follow-up. Mortality was lowest with both LTI and FTI in the 10th-90th percentile (reference group) and significantly higher at the lower LTI and FTI extreme (hazard ratio [HR], 3.37; 95% confidence interval [95% CI], 2.94 to 3.87; P<0.001). Survival was best with LTI between 15 and 20 kg/m(2) and FTI between 4 and 15 kg/m(2) (probability of death during follow-up: <5%). When taking the relation between both compartments into account, the interaction was significant (P=0.01). Higher FTI appeared protective in patients with low LTI (HR, 3.37; 95% CI, 2.94 to 3.87; P<0.001 at low LTI-low FTI, decreasing to HR, 1.79; 95% CI, 1.47 to 2.17; P<0.001 at low LTI-high FTI).



This large international study indicates best survival in patients with both LTI and FTI in the 10th-90th percentiles of a healthy population. In analyses of body composition, both lean tissue and fat tissue compartments and also their relationship should be considered.
Relaxation, reduction in angry articulated thoughts, and improvements in borderline hypertension and heart rate

An intensive 7-week relaxation therapy was evaluated in a sample of unmedicated borderline hypertensive men. All subjects were provided state-of-the-art medical information regarding changes known to affect hypertension favorably, e.g., lower salt intake and regular exercise. In addition, relaxation subjects were trained in muscle relaxation that entailed audiotaped home practice. As predicted, relaxation combined with hygiene lowered blood pressure more than did hygiene alone. Neither treatment favorably affected a paper-and-pencil measure of anger but relaxation did lower anger-hostility on a new cognitive assessment procedure, Articulated Thoughts in Simulated Situations (ATSS). Moreover, ATSS anger-hostility reduction was correlated with blood pressure or heart rate reductions, for all subjects and especially for those in the Relaxation condition. This represents the first clinically demonstrated link between change in a cognitive variable and change in cardiovascular activity. Finally, results were especially strong in subjects high in norepinephrine, suggesting its importance in essential hypertension.
Normal presenting levels of high-sensitivity troponin and myocardial infarction.

To analyse whether levels of high-sensitivity cardiac troponin (hs-cTn) below their respective 99th percentile can be used as a single parameter to rule out acute myocardial infarction (AMI) at presentation.



Prospective, multicentre study.



We measured hs-cTn using four different methods (hs-cTnT Roche, hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting to the emergency department with acute chest pain. Two independent cardiologists adjudicated the final diagnosis. Patients were followed for death or AMI during a mean period of 24 months.



Among 2072 consecutive patients with hs-cTnT measurements available, 21.4% had an adjudicated diagnosis of AMI (sensitivity 89.6%, 95% CI 86.4% to 92.3%, negative predictive value (NPV): 96.5%, 95% CI 95.4% to 97.4%). Among 1180 consecutive patients with hs-cTnI Siemens measurements available, 20.0% had AMI (sensitivity 94.1%, 95% CI 90.3% to 96.7%, NPV: 98.0%, 95% CI: 96.6% to 98.9%). Among 1151 consecutive patients with hs-cTnI Beckman Coulter measurements available, 19.7% had AMI (sensitivity 92.1%, 95% CI 87.8% to 95.2%, NPV: 97.5%, 95% CI 96.0% to 98.5%). Among 1567 consecutive patients with hs-cTnI Abbott measurements available, 20.0% had AMI (sensitivity 77.2%, 95% CI 72.1% to 81.7%, NPV: 94.3%, 95% CI 92.8% to 95.5%).



Normal hs-cTn levels at presentation should not be used as a single parameter to rule out AMI as 6%-23% of adjudicated AMI cases had normal levels of hs-cTn levels at presentation. Our data highlight the lack of standardisation among hs-cTnI assays resulting in substantial differences in sensitivity and NPV at the 99th percentile.
Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study.

To investigate the efficacy and safety of certolizumab pegol (CZP) in a broad population of patients with active RA.



In this 12-week, double-blind period of the phase IIIb trial, RA patients with inadequate response to at least one DMARD were randomized 4:1 to CZP (400 mg at weeks 0, 2 and 4, followed by 200 mg every 2 weeks) or placebo (every 2 weeks) plus current therapy stratified by previous TNF inhibitor use, concomitant methotrexate use and disease duration (<2 vs ≥2 years). The primary outcome was ACR20 response rate at week 12.



Of 1063 patients (CZP = 851; placebo = 212), 37.6% had previous TNF inhibitor use. Baseline mean HAQ Disability Index (HAQ-DI) and DAS 28-joint assessment-ESR [DAS28(ESR)] values were 1.5 and 6.4 in the CZP group, and 1.6 and 6.4 in the placebo group, respectively. The primary endpoint was significant (week 12 ACR20, CZP vs placebo: 51.1 vs 25.9%; P < 0.001); differences were noted at week 2 (31.8 vs 8.5%; P < 0.001). HAQ-DI and DAS28(ESR) change from baseline and ACR50 were significant from week 2. Week 12 ACR20 responses were similar across CZP patient subgroups regardless of concomitant DMARD use at baseline. Adverse and serious adverse events were comparable between CZP and placebo, with no new safety signals.



CZP was associated with rapid and consistent clinical responses and improved physical function in a diverse group of RA patients, irrespective of concomitant or previous therapy.
Effect of Helicobacter pylori eradication on treatment of gastro-oesophageal reflux disease: a double blind, placebo controlled, randomised trial.

The role of Helicobacter pylori eradication in the management of gastro-oesophageal reflux disease (GORD) is controversial. We hypothesised that H pylori eradication leads to worsened control of reflux disease.



Consecutive patients with weekly reflux symptoms were prospectively recruited for endoscopy and symptom evaluation. Patients were enrolled if they had H pylori infection and required long term acid suppressants. Eligible patients were randomly assigned to omeprazole triple therapy (HpE group) or omeprazole with placebo antibiotics (Hp+ group) for one week. Omeprazole 20 mg daily was given for eight weeks for healing of oesophagitis and symptom relief. This was followed by a maintenance dose of 10 mg daily for up to 12 months. The primary study end point was the probability of treatment failure within 12 months, which was defined as either incomplete resolution of symptoms or oesophagitis at the initial treatment phase, or relapse of symptoms and oesophagitis during the maintenance phase. Predictors of treatment failure were determined by Cox's proportional hazards model.



A total of 236 GORD patients were screened and 113 (47.9%) were positive for H pylori; 104 (92%) patients were included in the intention to treat analysis (53 in the HpE group and 51 in the Hp+ group). Thirty one patients (30%) had erosive oesophagitis at baseline. H pylori was eradicated in 98% of the HpE group and in 3.9% of the Hp+ group. Overall, 15 patients (28.3%) in the HpE group and eight patients (15.7%) in the Hp+ group had treatment failure. The 12 month probability of treatment failure was 43.2% (95% confidence interval (CI) 29.9-56.5%) in the HpE group and 21.1% (95% CI 9.9-32.3%) in the Hp+ group (log rank test, p = 0.043). In the Cox proportional hazards model, after adjustment for the covariates age, sex, erosive oesophagitis, hiatus hernia, degree of gastritis, and severity of symptoms at baseline, H pylori eradication was the only predictor of treatment failure (adjusted hazard ratio 2.47 (95% CI 1.05-5.85)).



H pylori eradication leads to more resilient GORD.
Financial Incentives for Home-Based Health Monitoring: A Randomized Controlled Trial

Home wireless device monitoring could play an important role in improving the health of patients with poorly controlled chronic diseases, but daily engagement rates among these patients may be low. To test the effectiveness of two different magnitudes of financial incentives for improving adherence to remote-monitoring regimens among patients with poorly controlled diabetes. Randomized, controlled trial.  Seventy-five patients with a hemoglobin A1c greater than or equal to 7.5 % recruited from a Primary Care Medical Home practice at the University of Pennsylvania Health System. Twelve weeks of daily home-monitoring of blood glucose, blood pressure, and weight (control group; n = 28); a lottery incentive with expected daily value of $2.80 (n = 26) for daily monitoring; and a lottery incentive with expected daily value of $1.40 (n = 21) for daily monitoring. Daily use of three home-monitoring devices during the three-month intervention (primary outcome) and during the three-month follow-up period and change in A1c over the intervention period (secondary outcomes). Incentive arm participants used devices on a higher proportion of days relative to control (81 % low incentive vs. 58 %, P = 0.007; 77 % high incentive vs. 58 %, P = 0.02) during the three-month intervention period. There was no difference in adherence between the two incentive arms (P = 0.58). When incentives were removed, adherence in the high incentive arm declined while remaining relatively high in the low incentive arm. In month 6, the low incentive arm had an adherence rate of 62 % compared to 35 % in the high incentive arm (P = 0.015) and 27 % in the control group (P = 0.002). A daily lottery incentive worth $1.40 per day improved monitoring rates relative to control and had significantly better efficacy once incentives were removed than a higher incentive.
Rectal salmon calcitonin for the treatment of postmenopausal osteoporosis

In a 2-year study, we examined bone mass and calcium metabolism in 36 elderly women with moderate osteoporosis. The study period comprised 1 year of observation, during which the women received no treatment affecting calcium metabolism, and 1 year of treatment, during which all participants received daily salmon calcitonin (sCT) 100 IU rectally and calcium 500 mg. During the observational period a significant bone loss of 1.5% was seen in the forearm (P<0.01), whereas the spinal bone mass was virtually unchanged. After institution of treatment, the bone loss was arrested in the forearm and a significant increase of about 2% was seen in the spine (P<0.01). The net effect of treatment revealed a positive outcome in both bone compartments (1.9% and 2.9%, P<0.05−0.01). Correspondingly, the parameters of bone turnover (serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxyproline/creatinine) did not change during the observational period, but significantly declined, 10–30%, during sCT treatment (P<0.01−0.001). Tolerance was generally good, although in one woman, anoscopy revealed irritative changes in the rectal mucosa. We conclude that, given rectally, sCT is well absorbed and well tolerated and that it has a beneficial effect on calcium metabolism in moderately osteoporotic women.
Self-reported frailty is associated with low calcaneal bone mineral density in a multiracial population of community-dwelling elderly

Low bone mineral density (BMD) is associated with frailty assessed using performance-based measures. However, the latter can be cumbersome and difficult to standardize. We examined whether an easily obtained self-reported frailty measure also predicted low BMD. In 230 elderly (82% female, 58% African–American), calcaneal BMD was measured by DXA and frailty evaluated using the VES-13 questionnaire. In addition to the original scoring, we developed a modified scoring system which provided a broader assessment of frailty and excluded age, which is a known independent predictor of BMD. A telephone interview conducted 6 years later ascertained interval fragility fractures and survival status. A higher modified frailty score was associated with lower BMD (p = 0.002), even after adjusting for age, weight, sex, and race and was more predictive of death at 6 years (p = 0.009) than the original score (p = 0.08). Based on our model, a subject with the highest frailty score differed from an otherwise similar subject with the lowest score by a calcaneal BMD of 1.4 T-score units, corresponding to 2–3 times higher fracture risk. Self-reported frailty is associated with low calcaneal BMD and can be used to identify subjects with a greater risk of osteoporosis than expected from traditional risk factors.
Automated test plan generator for database applications systems

As database applications become larger and more complex, the development of suitable test plans to assure robust and reliable software becomes essential. The testing procedure must establish the applications reliability from the human expectation viewpoint as well as its correctness and robustness.The predetermined goals of this testing procedure are to assure high reliability of the application and ascertain that the software performed according to specifications, while remaining within the project's time and budgetary constraints. Errors identified during development can be corrected with minimal cost when compared to errors uncovered by users after the software release. By overlapping testing with development, and automating the production of a standardized set of test plans, the incremental production time can be minimized. By generating an application specific test plan, syntactic and semantic specifications of the actual system applications can be tested. A side effect of this specific, interleaved correctness testing is the uncovering of user interface inconsistencies and their refinement before exposure of the application to the real end user.Analysis of the results of our experimental testing showed the keystone to be the test plan. Since the completeness and veracity of this document is a prime determining factor in the validity of the testing, we have developed program using C++ on a Sun workstation to automatically generate test plans from the design schema.This paper presents an automated/manual testing scheme suitable for assuring the validity of large database applications. The initial premises, design execution and consequences of the test procedure is detailed followed by a description of the automation of strategic components.
Biventricular pacing improves the blunted force-frequency relation present during univentricular pacing in patients with heart failure and conduction delay.

In patients with chronic heart failure (CHF) and conduction delay, biventricular (BiV) and left ventricular (LV) pacing similarly improve systolic function at resting heart rates. We hypothesized that BiV and univentricular pacing differentially affect contractile function at increasing heart rates.



Twenty-two patients (aged 66+/-2 years, QRS 179+/-8 ms, LV ejection fraction 23+/-1%) underwent cardiac catheterization before device implantation to measure LV hemodynamics at baseline (rate 68+/-2 bpm; sinus rhythm n=18; atrial fibrillation n=4) and during BiV, LV, and right ventricular (RV) stimulation at 80, 100, 120, and 140 bpm. BiV and LV pacing at 80 bpm equally augmented dP/dtmax as compared with baseline and RV pacing (P<0.001). Stimulation rate significantly interacted with the effect of BiV, LV, and RV pacing on LV end-diastolic pressure (LVEDP), systolic pressure (LVSP), and dP/dtmax. Increasing the rate from 80 to 140 bpm enhanced dP/dtmax from 913+/-28 to 1119+/-50 mm Hg/s during BiV stimulation (P<0.001) but had no significant effect on contractility during single-site LV (951+/-47 versus 1002+/-54 mm Hg/s) or RV (800+/-46 versus 881+/-49 mm Hg/s) pacing. At 140 bpm, LVEDP was lower and LVSP higher during BiV pacing than during RV and LV pacing (LVEDP 12+/-1 versus 17+/-1 and 16+/-1 mm Hg, P<0.001; LVSP 112+/-5 versus 106+/-5 and 108+/-6 mm Hg, P<0.01 and P=0.09; BiV versus RV and LV pacing, respectively).



Different modes of ventricular stimulation alter the in vivo force-frequency relation of CHF patients. In contrast to single-site LV and RV pacing, contractile function improves with increasing heart rates during BiV stimulation. This effect may contribute to the enhanced exercise capacity during BiV pacing and could provide a functional benefit over LV-only pacing in patients for whom resynchronization therapy is indicated.