nils-herrmann/clean_scirepeval huggingface dataset:
A cost-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis.

Recently, new treatment options for rheumatoid arthritis (RA) patients with an inadequate response to methotrexate (MTX) have become available. Given the wide variability in efficacy and costs among these different treatment options, we sought to determine their cost-effectiveness (CE) in order to guide policy in different cost-constrained settings.



We performed a CE analysis comparing 6 treatment options for patients with MTX-resistant RA: 1) etanercept + MTX, 2) etanercept monotherapy, 3) cyclosporine + MTX, 4) triple therapy (hydroxychloroquine, sulfasalazine, and MTX), 5) continuation of MTX monotherapy, and 6) no second-line agent. A decision model was used with a time horizon of 6 months. We used 2 measures of effectiveness based on published clinical trial data: the American College of Rheumatology 20% response criteria (ACR 20); and a weighted average of proportions of patients achieving responses of ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response [ACR 70WR]). Incremental CE ratios were calculated as the additional cost per patient achieving either outcome, compared with the next least expensive option. To help interpret CE relative to these RA-specific outcomes, we conducted a separate, "reference" CE analysis of MTX use in MTX-naive RA patients, using the same outcomes.



In our reference analysis, MTX therapy for MTX-naive RA cost $1,100 per ACR 20 outcome and $1,500 per ACR 70WR, compared with no second-line agent. In our base-case analysis with either outcome, MTX continuation, cyclosporine + MTX, and etanercept monotherapy cost more, but either were not more efficacious or had a higher incremental CE ratio than the next most expensive option (i.e., they were dominated). Therefore, these options were not cost-effective. The least expensive option, triple therapy, cost 1.3 times more per patient with ACR 20 outcome ($1,500/ACR 20) and 2.1 times more per ACR 70WR ($3,100/ACR 70WR) than MTX therapy for MTX-naive RA. The most efficacious option, the combination of etanercept and MTX, cost 38 times more per patient with ACR 20 outcome ($4,600/ACR 20) and 23 times more per ACR 70WR ($34,800/ACR 70WR) than MTX therapy for MTX-naive RA. Overall, the results of extensive sensitivity analyses did not substantially affect these results.



Our analysis indicates that if 15 mg/week MTX is cost-effective for achieving ACR 20 or ACR 70WR in MTX-naive RA over a 6-month period, then most likely so is triple therapy in MTX-resistant RA. Whether etanercept + MTX is cost-effective depends on whether $34,800/ACR 70WR (or $42,600/ACR 20) over a 6-month period is considered acceptable.
Study on the clinical significance and related factors of thirst and xerostomia in maintenance hemodialysis patients.

To analyse the clinical significance and related factors of thirst and xerostomia and to find methods to alleviate thirst and xerostomia in maintenance hemodialysis (MHD) patients.



Forty-two MHD patients were included for observational study and eleven patients were enrolled for crossover trial. Thirst was assessed by 100-mm visual analog scales (VAS) and dialysis thirst inventory (DTI). Meanwhile, xerostomia was assessed by VAS and xerostomia inventory (XI). Depression, kidney disease quality of life (KDQOL), salivary flow rates and inter dialytic weight gain (IDWG) were measured. Data were analyzed by ANOVA and correlation coefficient was used to assess the correlations between continuous variables. The results of crossover trial were investigated by two-sample T-tests.



Strong positive correlations among DTI, VAS thirst score, XI and VAS xerostomia score were found (P=0.000). Daily IDWG was positively correlated with VAS thirst score (r=0.315, P=0.042) and DTI(r=0.391, P=0.010). UWS (unstimulated whole saliva) was negatively correlated with VAS xerostomia score (r=-0.308, P=0.048). Residual urine output was negatively correlated with DTI (r=-0.402, P=0.008), VAS xerostomia score (r=-0.461, P=0.002) and XI (r=-0.403, P=0.008). In the crossover trial, DTI, XI, IDWG2d, IDWG3d, VAS thirst and xerostomia score were significantly reduced by the use of chewing gum (P=0.000, 0.001, 0.009, 0.017, 0.038, 0.001). The VAS thirst score, DTI and IDWG3d were significantly reduced by receiveing straw (P=0.016, 0.003, 0.049).



Thirst and xerostomia might affect the quality of life in MHD patients. Both chewing gum and straw could decrease thirst and IDWG.
Improved survival with MEK inhibition in BRAF-mutated melanoma.

Activating mutations in serine-threonine protein kinase B-RAF (BRAF) are found in 50% of patients with advanced melanoma. Selective BRAF-inhibitor therapy improves survival, as compared with chemotherapy, but responses are often short-lived. In previous trials, MEK inhibition appeared to be promising in this population.



In this phase 3 open-label trial, we randomly assigned 322 patients who had metastatic melanoma with a V600E or V600K BRAF mutation to receive either trametinib, an oral selective MEK inhibitor, or chemotherapy in a 2:1 ratio. Patients received trametinib (2 mg orally) once daily or intravenous dacarbazine (1000 mg per square meter of body-surface area) or paclitaxel (175 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to receive trametinib. Progression-free survival was the primary end point, and overall survival was a secondary end point.



Median progression-free survival was 4.8 months in the trametinib group and 1.5 months in the chemotherapy group (hazard ratio for disease progression or death in the trametinib group, 0.45; 95% confidence interval [CI], 0.33 to 0.63; P<0.001). At 6 months, the rate of overall survival was 81% in the trametinib group and 67% in the chemotherapy group despite crossover (hazard ratio for death, 0.54; 95% CI, 0.32 to 0.92; P=0.01). Rash, diarrhea, and peripheral edema were the most common toxic effects in the trametinib group and were managed with dose interruption and dose reduction; asymptomatic and reversible reduction in the cardiac ejection fraction and ocular toxic effects occurred infrequently. Secondary skin neoplasms were not observed.



Trametinib, as compared with chemotherapy, improved rates of progression-free and overall survival among patients who had metastatic melanoma with a BRAF V600E or V600K mutation.
Measuring the use and career histories of drug users in treatment: reliability of the Lifetime Drug Use History (LDUH) and its data yield relative to clinical case notes.

There is no generally accepted clinical or research instrument available for recording the longitudinal course of a drug-using 'career'. This paper reports on an initial examination of the properties of the Lifetime Drug Use History Questionnaire (LDUH), built around monthly mapping of drug use patterns in relation to other life events.



Forty heroin and cocaine users completed structured interviews at two treatment sites. Twenty subjects were interviewed on two occasions separated by a 3-day interval, using either the same interviewer (n = 10) or two different interviewers (n = 10) as assessments of inter-rater and test - retest reliability.



Very good inter-rater agreements were observed, demonstrated by Cronbach's alpha and intraclass correlation coefficients generally higher than 0.8 and 0.7, respectively. Additionally, concordance with clinical notes was assessed for four drug use history variables, resulting in poorer rates of agreement. An exact matching with clinical records was obtained for the variable 'age of first use of heroin' in 47.2% (n = 17) of the heroin users, while a good agreement (only 1 or 2 years' difference) was found in 36.1% of cases (n = 5).



The LDUH method resulted in high reliability for heroin and cocaine and suggests an effective, clinically applicable method for history-taking. The paucity and inconsistency of similar information in the clinical notes would further justify the use of a standardised method for recording drug histories.
Benchmarking a set of exam questions for introductory programming

This paper reports on the combining of two related but hitherto distinct themes in programming education research. The first is the recognition that students in programming courses tend to perform far more poorly than their teachers would like, and further, more poorly than their teachers would expect without a careful analysis of their results. The second is the proposal of a number of different styles of examination question, sometimes coupled with analysis of student performance on those questions, typically at single institutions. This work combines these themes by including a common set of short questions in the final examinations of introductory programming courses at six institutions in Australia and New Zealand, and analysing the student performance across all six institutions. The analysis results in a set of four simple questions that can be used to benchmark student performance in introductory programming courses at a wide range of institutions.
Prevention of hypotension during spinal anesthesia for cesarean delivery: an effective technique using combination phenylephrine infusion and crystalloid cohydration.

Many methods for preventing hypotension during spinal anesthesia for cesarean delivery have been investigated, but no single technique has proven to be effective and reliable. This randomized study studied the efficacy of combining simultaneous rapid crystalloid infusion (cohydration) with a high-dose phenylephrine infusion.



Nonlaboring patients scheduled to undergo elective cesarean delivery received an intravenous infusion of 100 mug/min phenylephrine that was started immediately after spinal injection and titrated to maintain systolic blood pressure near baseline values until uterine incision. In addition, patients received infusion of lactated Ringer's solution that was given either rapidly (group 1, n = 57) or at a minimal maintenance rate (group 0, n = 55). Maternal hemodynamic changes and neonatal condition were compared.



Six patients were excluded from analysis. Only 1 of 53 patients (1.9% [95% confidence interval, 0.3-9.9%]) in group 1 experienced hypotension versus 15 of 53 patients (28.3% [95% confidence interval, 18.0-41.6%]) in group 0 (P = 0.0001). Compared with group 0, patients in group 1 had greater values for the following: serial measurements of systolic blood pressure (P = 0.02), minimum recorded systolic blood pressure (P = 0.0002), and minimum recorded heart rate (P = 0.013). Total phenylephrine consumption was smaller in group 1 compared with group 0 (P = 0.008). Neonatal outcome and maternal side effects were similar between groups.



Combination of a high-dose phenylephrine infusion and rapid crystalloid cohydration is the first technique to be described that is effective for preventing hypotension during spinal anesthesia for cesarean delivery.
Exercise training improves conduit vessel function in patients with coronary artery disease.

It is well established that endothelial dysfunction is present in coronary artery disease (CAD), although few studies have determined the effect of training on peripheral conduit vessel function in patients with CAD. A randomized, crossover design determined the effect of 8 wk of predominantly lower limb, combined aerobic and resistance training, in 10 patients with treated CAD. Endothelium-dependent dilation of the brachial artery was determined, by using high-resolution vascular ultrasonography, from flow-mediated vasodilation (FMD) after ischemia. Endothelium-independent vasodilation was measured after administration of glyceryl trinitrate (GTN). Baseline function was compared with that of 10 control subjects. Compared with matched healthy control subjects, FMD and GTN responses were significantly impaired in the untrained CAD patients [3.0 +/- 0.8 (SE) vs. 5.8 +/- 0.8% and 14.5 +/- 1.9 vs. 20.4 +/- 1.5%, respectively; both P < 0.05]. Training significantly improved FMD in the CAD patients (from 3.0 +/- 0.8 to 5.7 +/- 1.1%; P < 0.05) but not responsiveness to GTN (14.5 +/- 1.9 vs. 12.1 +/- 1.4%; P = not significant). Exercise training improves endothelium-dependent conduit vessel dilation in subjects with CAD, and the effect, evident in the brachial artery, appears to be generalized rather than limited to vessels of exercising muscle beds. These results provide evidence for the benefit of exercise training, as an adjunct to routine therapy, in patients with a history of CAD.
Cardiovascular status after Kawasaki disease in the UK

Kawasaki disease (KD) is an acute vasculitis that causes coronary artery aneurysms (CAA) in young children. Previous studies have emphasised poor long-term outcomes for those with severe CAA. Little is known about the fate of those without CAA or patients with regressed CAA. We aimed to study long-term cardiovascular status after KD by examining the relationship between coronary artery (CA) status, endothelial injury, systemic inflammatory markers, cardiovascular risk factors (CRF), pulse-wave velocity (PWV) and carotid intima media thickness (cIMT) after KD.



Circulating endothelial cells (CECs), endothelial microparticles (EMPs), soluble cell-adhesion molecules cytokines, CRF, PWV and cIMT were compared between patients with KD and healthy controls (HC). CA status of the patients with KD was classified as CAA present (CAA+) or absent (CAA-) according to their worst-ever CA status. Data are median (range).



Ninety-two KD subjects were studied, aged 11.9 years (4.3-32.2), 8.3 years (1.0-30.7) from KD diagnosis. 54 (59%) were CAA-, and 38 (41%) were CAA+. There were 51 demographically similar HC. Patients with KD had higher CECs than HC (p=0.00003), most evident in the CAA+ group (p=0.00009), but also higher in the CAA- group than HC (p=0.0010). Patients with persistent CAA had the highest CECs, but even those with regressed CAA had higher CECs than HC (p=0.011). CD105 EMPs were also higher in the KD group versus HC (p=0.04), particularly in the CAA+ group (p=0.02), with similar findings for soluble vascular cell adhesion molecule 1 and soluble intercellular adhesion molecule 1. There was no difference in PWV, cIMT, CRF or in markers of systemic inflammation in the patients with KD (CAA+ or CAA-) compared with HC.



Markers of endothelial injury persist for years after KD, including in a subset of patients without CAA.
Respiratory response to carbon dioxide stimulation during low flow supplemental oxygen therapy in chronic obstructive pulmonary disease.

Oxygen supplementation is the treatment most commonly used to relieve dyspnea in chronic obstructive pulmonary disease (COPD). There is a lack of data, however, on the response of the respiratory drive to low flow oxygen in severe stable COPD. The purpose of this investigation was to evaluate the magnitude of chemoresponsiveness to low flow supplemental oxygen in patients with COPD of variable severity in terms of mouth occlusion pressure at 100 msec (P0.1), P0.1 and minute ventilation (MV) response to CO2 stimulation, and blood gas tension.



Twenty-six patients with stable COPD of variable severity were divided into two groups: those with mild airway obstruction and normocapnia (n = 14) and those with hyperinflation and hypercapnia (n = 12).



Arterial oxygen tension, oxygen saturation, and arterial CO2 tension were significantly increased after oxygen therapy in COPD patients with or without hypercapnia (all p < 0.01). COPD patients with hypercapnia had a significantly higher P0.1 (0.7 +/- 0.07 kPa) than those with normocapnia (0.3 +/- 0.03 kPa, p < 0.01). Oxygen significantly decreased the P0.1 adjusted by end tidal CO2 pressure (delta P0.1/PETCO2) only in patients with hyperinflation and hypercapnia, from 0.2 +/- 0.05 to 0.1 +/- 0.03 kPa (p < 0.05). There was a weak correlation between P0.1/PETCO2 and forced vital capacity (FVC; r = 0.41, p < 0.05) or forced expiratory volume in 1 second (FEV1; r = 0.45, p < 0.05). In addition, the arterial CO2 tension (PaCO2) was inversely related to P0.1/PETCO2 (r = -0.57, p < 0.01). The MV with 6% CO2 (MVCO2) was also significantly decreased in the hypercapnic group from 17.9 +/- 3.7 to 14.8 +/- 4.9 L after oxygen therapy (p < 0.01). The maximum inspiratory pressure did not change after oxygen usage in either group.



We conclude that short-term oxygen therapy may blunt respiratory response to CO2 in COPD with chronic hypercapnia. Cautious observation of respiratory response is needed during oxygen therapy in COPD patients with a higher magnitude of air-trapping and hypercapnia.
Taking simvastatin in the morning compared with in the evening: randomised controlled trial.

Statins are widely prescribed for the primary and secondary prevention of coronary artery disease. They act by inhibiting the enzyme HMG CoA reductase, which controls synthesis of cholesterol in the liver. Most manufacturers of statins recommend that they are taken at night, on the basis of physiological studies which show that most cholesterol is synthesised when dietary intake is at its lowest. One small clinical trial found that taking smaller doses of simvastatin than are used in treatment, in the morning, was less efficient. However, a trial using atorvastatin found no significant difference in cholesterol concentrations between patients taking the statin in the morning and those taking it in the evening. Doubt has been cast on whether statins need to be taken at night, particularly as many patients also receive treatment with other cardioprotective drugs and compliance may be compromised by multiple dosing. We determined whether taking simvastatin in the morning had significantly different efficiency from taking it in the evening, by measuring cholesterol concentrations in fasting patients’ serum.
Exercise training increases interleukin-10 after an acute myocardial infarction: a randomised clinical trial.

The present study assessed the effects of exercise training on biomarkers of inflammation in postinfarction patients. This single-centre prospective randomized controlled trial encompassed 42 patients after the first myocardial infarction divided into exercise-training (n=22) or usual care (n=20) groups. Complete randomization was performed by choosing one of 2 sealed envelopes. The exercise-training group participated in an 8-week programme comprising 3 aerobic exercise sessions per week. The control group received usual care. The main measures were changes in circulating levels of C-reactive protein, interleukin (IL)-6 and -10, soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1), anthropometrics, dietary intake, daily physical activity, and cardiorespiratory fitness. 4 patients terminated the study prematurely, leaving 38 for the statistical analysis (exercise-training, n=20; control group, n=18). In comparison to control group, exercise-training group improved IL-10 levels [1.7(7.0) vs.  - 0.3(2.4) pg/mL, P<0.05], daily moderate-intensity physical activity (12.9±21.3 vs.  - 0.7±13.4 min, P<0.05), and cardiorespiratory fitness (3.0±3.5 vs. 0.3±4.1 ml/min/kg, P<0.05). Additionally, the change in VCAM-1 and ICAM-1 levels was significantly higher in the control group (respectively, 26.6±112.1 vs. 94.1±90.0 ng/mL and 7.3±41.0 vs. 35.0±39 ng/mL, P<0.05). In conclusion, exercise training improved the inflammatory profile in post myocardial infarction patients by enhancing the anti-inflammatory cytokine IL-10.
Effects of recombinant human IGF-I/IGF-binding protein-3 complex on glucose and glycerol metabolism in type 1 diabetes.

Recombinant human IGF-I (rhIGF-I) complexed with its natural binding protein IGF-binding protein (IGFBP)-3 (rhIGF-I/IGFBP-3) is a novel formulation that has been shown to improve insulin sensitivity in type 1 diabetes, yet the mechanisms are not clear. We used stable isotopes to investigate the effects of rhIGF-I/IGFBP-3 on glucose and glycerol metabolism in type 1 diabetes. Fifteen subjects (age 13-24 years; 10 males) were studied on three occasions in random order. Each study period lasted for two days, and an injection of either placebo or rhIGF-I/IGFBP-3 (0.1-0.8 mg x kg(-1) x day (-1)) was given subcutaneously at 6:00 p.m. on days 1 and 2. Following the second injection, the subjects were kept euglycemic overnight by a variable rate insulin infusion, followed by a 4-h, two-step (insulin 0.6 and 1.5 mU x kg(-1) x min (-1)) hyperinsulinemic-euglycemic clamp. During the overnight basal steady state, rhIGF-I/IGFBP-3 dose-dependently reduced endogenous glucose production rate (R(a)) (P = 0.004), while peripheral glucose uptake (R(d)) was not different from placebo. The increase in glucose R(d) during hyperinsulinemic clamp was greater following rhIGF-I/IGFBP-3 than placebo, both during the first (P = 0.008) and second step (P = 0.008) of the clamp. No significant differences were found in glycerol R(a), a measure of lipolysis, between rhIGF-I/IGFBP-3 and placebo. In conclusion, rhIGF-I/IGFBP-3 enhances glucose metabolism by controlling both endogenous glucose output and peripheral glucose uptake.
Exocarp Properties and Transcriptomic Analysis of Cucumber (Cucumis sativus) Fruit Expressing Age-Related Resistance to Phytophthora capsici

Very young cucumber (Cucumis sativus) fruit are highly susceptible to infection by the oomycete pathogen, Phytophthora capsici. As the fruit complete exponential growth, at approximately 10-12 days post pollination (dpp), they transition to resistance. The development of age-related resistance (ARR) is increasingly recognized as an important defense against pathogens, however, underlying mechanisms are largely unknown. Peel sections from cucumber fruit harvested at 8 dpp (susceptible) and 16 dpp (resistant) showed equivalent responses to inoculation as did whole fruit, indicating that the fruit surface plays an important role in defense against P. capsici. Exocarp from 16 dpp fruit had thicker cuticles, and methanolic extracts of peel tissue inhibited growth of P. capsici in vitro, suggesting physical or chemical components to the ARR. Transcripts specifically expressed in the peel vs. pericarp showed functional differentiation. Transcripts predominantly expressed in the peel were consistent with fruit surface associated functions including photosynthesis, cuticle production, response to the environment, and defense. Peel-specific transcripts that exhibited increased expression in 16 dpp fruit relative to 8 dpp fruit, were highly enriched (P<0.0001) for response to stress, signal transduction, and extracellular and transport functions. Specific transcripts included genes associated with potential physical barriers (i.e., cuticle), chemical defenses (flavonoid biosynthesis), oxidative stress, penetration defense, and molecular pattern (MAMP)-triggered or effector-triggered (R-gene mediated) pathways. The developmentally regulated changes in gene expression between peels from susceptible- and resistant- age fruits suggest programming for increased defense as the organ reaches full size.