nils-herrmann/clean_scirepeval huggingface dataset:
Impact of mucosal healing on long-term outcomes in ulcerative colitis treated with infliximab: a multicenter experience.

Mucosal healing can be achieved with infliximab (IFX).



To assess the impact of mucosal healing on long-term outcomes in patients with ulcerative colitis (UC) when treated with infliximab (IFX) beyond 1 year.



All consecutive adult patients with refractory UC receiving maintenance treatment with IFX in five French referral centres were analysed retrospectively. Only patients who had endoscopic evaluation between 6 and 52 weeks following IFX initiation were included. According to their Mayo endoscopic sub-score, patients were categorised into mucosal healing (sub-score: 0-1) and no mucosal healing (2-3). Outcome measures were colectomy and IFX failure defined by drug withdrawal due to secondary failure among primary responders.



Of the 63 patients (30 women; median age: 38 years), 30 (48%) achieved mucosal healing. The median follow-up duration was 27 (3-79) months. Colectomy-free survival rates at 12, 24 and 36 months were, respectively, 100%, 96% and 96% in patients with mucosal healing. The corresponding figures were, respectively, 80%, 65% and 65% in patients without mucosal healing (P = 0.004). By multivariate analysis, mucosal healing was the only factor associated with colectomy-free survival, with an odds ratio of 18.01 (95%CI: 1.58-204.92). IFX failure-free survival rates at 12, 24 and 36 months were, respectively, 76%, 69% and 64% in patients with mucosal healing, and 44%, 25% and 21% in those without mucosal healing (P = 0.003).



Patients with refractory UC who achieved mucosal healing after IFX initiation had better long-term outcomes, with significantly less colectomy and less IFX failure.
The prognostic significance of admission blood glucose levels in patients with urinary tract infection.

Evaluate the association between admission blood glucose (ABG) and short and long-term outcomes following hospitalization for urinary tract infection (UTI).



Single center, retrospective cohort study of patients admitted to medical wards between January 1, 2011 and December 31, 2013 with a diagnosis of UTI. Patients were classified to those with diabetes mellitus (DM) and those without it. ABG levels were classified to categories: ≤70, 70-110, 111-199, ≥200mg/dl. Primary outcome was all-cause mortality within 30-days and 1-year. Secondary outcomes were hospital readmissions within 30-days and 1-year, and survival rates at end of follow-up.



Cohort included 3405 patients (median age, 78 years; 44% men), 1106 with DM and 2299 without it. Among patients without DM, compared with ABG between 70 and 110mg/dl (n=852, 37%), there was a significant association between ABG and all-cause mortality: hazard ratios (95% CI) with ABG ≤70mg/dl (n=13, 0.6%), 111-199mg/dl (n=1292, 56%), and ≥200mg/dl (n=142, 6%) were: 3.67 (0.89-15.14, p=0.07, 23% mortality (n=3)), 1.85 (1.29-2.64, p<0.001, 7% mortality (n=89)), and 2.94 (1.71-5.07, p<0.0001, 11% mortality (n=15)) at 30-days, and 3.8 (1.87-7.71, 38% mortality (n=5)), 1.35 (1 1.13-1.60, 7% mortality (n=215)), and 2.02 (1.50-2.71, 25% mortality (n=35)) at 1-year (all p<0.001). In patients with DM there was no significant association between ABG and mortality. There was no association between ABG and readmissions in both groups.



There is a significant association between ABG and short and long-term, all-cause mortality in patients without DM, but not in patients with DM, hospitalized for UTI.
Effect of the myeloperoxidase inhibitor AZD3241 on microglia: a PET study in Parkinson's disease.

Impaired mitochondrial function, oxidative stress and formation of excessive levels of reactive oxygen species play a key role in neurodegeneration in Parkinson's disease. Myeloperoxidase is a reactive oxygen generating enzyme and is expressed by microglia. The novel compound AZD3241 is a selective and irreversible inhibitor of myeloperoxidase. The hypothesized mechanism of action of AZD3241 involves reduction of oxidative stress leading to reduction of sustained neuroinflammation. The purpose of this phase 2a randomized placebo controlled multicentre positron emission tomography study was to examine the effect of 8 weeks treatment with AZD3241 on microglia in patients with Parkinson's disease. Parkinson patients received either AZD3241 600 mg orally twice a day or placebo (in 3:1 ratio) for 8 weeks. The binding of (11)C-PBR28 to the microglia marker 18 kDa translocator protein, was examined using positron emission tomography at baseline, 4 weeks and 8 weeks. The outcome measure was the total distribution volume, estimated with the invasive Logan graphical analysis. The primary statistical analysis examined changes in total distribution volume after treatment with AZD3241 compared to baseline. Assessments of safety and tolerability of AZD3241 included records of adverse events, vital signs, electrocardiogram, and laboratory tests. The patients had a mean age of 62 (standard deviation = 6) years; 21 were male, three female and mean Unified Parkinson's Disease Rating Scale III score (motor examination) ranged between 6 and 29. In the AD3241 treatment group (n = 18) the total distribution volume of (11)C-PBR28 binding to translocator protein was significantly reduced compared to baseline both at 4 and 8 weeks (P < 0.05). The distribution volume reduction across nigrostriatal regions at 8 weeks ranged from 13-16%, with an effect size equal to 0.5-0.6. There was no overall change in total distribution volume in the placebo group (n = 6). AZD3241 was safe and well tolerated. The reduction of (11)C-PBR28 binding to translocator protein in the brain of patients with Parkinson's disease after treatment with AZD3241 supports the hypothesis that inhibition of myeloperoxidase has an effect on microglia. The results of the present study provide support for proof of mechanism of AZD3241 and warrant extended studies on the efficacy of AZD3241 in neurodegenerative disorders.
Comparison of CT and CT angiography source images with diffusion-weighted imaging in patients with acute stroke within 6 hours after onset.

Although stroke MRI has advantages over other diagnostic imaging modalities in acute stroke patients, most of these individuals are admitted to emergency units without MRI facilities. There is a need for an accurate diagnostic tool that rapidly and reliably detects hemorrhage, extent of ischemia, and vessel status and potentially estimates tissue at risk. We sought to determine the diagnostic accuracy of the combination of non-contrast-enhanced CT, CT angiography (CTA), and CTA source images (CTA-SI, showing early parenchymal contrast enhancement) in comparison with a multiparametric stroke MRI protocol in patients with acute stroke within 6 hours after onset.



Non-contrast-enhanced CT, CTA, stroke MRI including diffusion-weighted imaging (DWI), and MR angiography (MRA) were performed in patients with symptoms of acute stroke within 6 hours after onset. We analyzed infarct volumes on days 1 and 5 as shown on CTA-SI, DWI, and T2-weighted images (Wilcoxon, Mann-Whitney, Spearman tests), estimated the collateral status, and assessed clinical outcome (modified Rankin Scale, Barthel Index, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale).



We analyzed the data of 20 stroke patients who underwent CT and MRI scanning within 6 hours (mean, 2.83 and 3.38 hours, respectively). Vessel occlusion was present in 16 of 20 patients. CTA-SI volumes did not differ from DWI volumes (P=0.601). Furthermore, the CTA-SI lesion volumes significantly correlated with the initial DWI lesion volumes (P<0.0001, r=0.922) and with outcome lesion volumes (P=0.013 r=0.736). Patients with poor collaterals experienced infarct growth (P=0.0058) and had a significantly worse clinical outcome (all P<0.012); patients with good collaterals did not (P=0.176).



The combination of non-contrast-enhanced CT (exclusion of intracranial hemorrhage), CTA (vessel status), and early contrast-enhanced CTA-SI (demarcation of irreversible infarct) allows diagnostic assessment of acute stroke with a quality comparable to that of stroke MRI. Furthermore, it is possible to distinguish patients at risk of infarct growth from those who are not according to the collateral status, in analogy with the stroke MRI mismatch concept.
Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

The Action to Control Cardiovascular Disease in Diabetes (ACCORD) blood pressure trial is an unmasked, open-label, randomized trial with a sample size of 4,733 participants. This report describes the rationale, design, and methods of the blood pressure interventions in ACCORD. Participants eligible for the blood pressure trial are randomized to 1 of 2 groups with different treatment goals: systolic blood pressure <120 mm Hg for the more intensive goal and systolic blood pressure <140 mm Hg for the less intensive goal. The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease (CVD) event, specifically nonfatal myocardial infarction or stroke, or cardiovascular death during a follow-up period ranging from 4-8 years. The ACCORD blood pressure trial should provide the first definitive clinical trial data on the possible benefit of treating to a more aggressive systolic blood pressure goal in reducing CVD events in patients with diabetes mellitus.
Bilateral antegrade selective cerebral perfusion during surgery on the proximal thoracic aorta

To assess risk factors for hospital death and neurologic outcome after surgery on the proximal thoracic aorta using moderate hypothermic circulatory arrest and bilateral antegrade selective cerebral perfusion.  From October 1995 through June 1999, 163 patients with a mean age of 63 ^ 11 years underwent surgery using bilateral antegrade selective cerebral perfusion. Degenerative aneurysms (55%) and acute type A dissection (28%) were the predominant indications for operation. Forty-six (28%) operations were considered as emergency procedure. Twenty-four (15%) procedures were reoperations.  Mean ASCP time was 48 ^ 20 min. Hospital mortality was 8.6% (n  14; 70% con®dence limit (CL): 6.4±10.8%). Univariate risk factors for hospital mortality were acute type A dissection (P  0:003), central neurologic damage ,24 h before the operation (P  0:000), preoperative hemodynamic instability (P  0:034), and rethoracotomy for any cause (P  0:036). Logistic regression analysis identi®ed central neurologic damage ,24 h (P  0:006, odds ratio 14) as an independent risk factor. Temporary neurologic damage occurred in 3.8% (n  6; 70% CL: 2.3±5.3%) of patients. Logistic regression analysis indicated preoperative hemodynamic instability (P  0:003, odds ratio 13) as an independent risk factor. Perioperative permanent central neurologic damage was reported in another 3.8% (n  6; 70% CL: 2.3±5.3%) patients.  A dissection (P  0:018, odds ratio 8) and the non-use of a midline sternotomy (P  0:049, odds ratio 8) were retained as independent risk factors.  Hospital mortality and perioperative neurologic complications are not signi®cantly in ̄uenced by the duration of antegrade selective cerebral perfusion. Overall complication rate is low. q 2000 Elsevier Science B.V. All rights reserved.
Long term treatment with tienilic acid or thiazides: Comparison of antihypertensive and metabolic effects

A comparison has been made of arterial pressure and major metabolic parameters during long term treatment with tienilic acid and a hydrochlorothiazide-amiloride combination, using a randomized single-blind study without cross-over. A significant fall in systolic and diastolic blood pressure and no change in most biochemical parameters was observed with both drugs. Serum uric acid concentration was decreased during tienilic acid and was slightly increased whilst subjects took the hydrochlorothiazide-amiloride combination; serum potassium was slightly decreased on tienilic acid. No sign of hepatotoxicity was detected.
Apnea-hypopnea indices and snoring in children diagnosed with ADHD: a matched case-control study

To measure apnea-hypopnea indices and snoring in children diagnosed with attention-deficit hyperactivity disorder (ADHD) in a case-control design. Additionally, the study design allowed us to investigate whether or not methylphenidate had any effect on breathing variables. Twenty-eight children (22 boys) aged 6–12 years meeting diagnostic criteria for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV ADHD were studied together with matched controls. Two nights of polysomnography (PSG) were conducted that included recordings of snoring waveforms. A randomly assigned 48-h on-off medication protocol was used for ADHD children. Control children’s recordings were matched for PSG night, but medication was not used. A low apnea-hypopnea index (AHI) threshold of >1event per hour was used to define sleep-disordered breathing (SDB) because of a clinical relevance in ADHD. Categorical analyses for paired binary data showed no significant differences between control and ADHD children for presence of an AHI >1 or snoring. Variables were extracted from a significantly shorter total sleep time (67 min) on the medication night in children with ADHD. Eight (28%) control and 11 (40%) ADHD children snored >60 dB some time during the night. Methylphenidate had no effect on central apneas, AHI, desaturation events, or any snoring data. Our PSG findings show no strong link between ADHD and SDB although our findings could be limited by a small sample size. Findings from PSG studies in the literature argue both for and against an association between ADHD and SDB. Our results suggest medication is not a factor in the debate.
Long-term (4 years) efficacy of lopinavir/ritonavir monotherapy for maintenance of HIV suppression.

Data are scarce on the long-term efficacy of lopinavir/ritonavir monotherapy for the maintenance of HIV suppression. Four years of results of patients randomized to monotherapy in the Only Kaletra (OK) pilot clinical trial are presented.



Twenty-one HIV-infected patients with suppressed HIV replication (<50 copies/mL) for at least 6 months and without previous failure while receiving a protease inhibitor-based regimen started lopinavir/ritonavir monotherapy. Follow-up was performed within the OK pilot clinical trial during the first 2 years and according to routine clinical practice during the 3rd and 4th years.



Fourteen patients (67%) remain on monotherapy and with RNA <50 copies/mL (intention-to-treat analysis, with missing patients scored as failures). Five patients (24%) had virological rebound and all of them were successfully re-suppressed by adding two nucleosides. No major protease inhibitor mutations were found.



Our data support the long-term efficacy and safety of lopinavir/ritonavir monotherapy for the maintenance of HIV suppression, a finding that must be confirmed in larger studies.
A semi-mechanistic integrated pharmacokinetic/pharmacodynamic model of the testosterone effects of the gonadotropin-releasing hormone agonist leuprolide in prostate cancer patients.

Leuprolide is a gonadotropin-releasing hormone (GnRH) agonist, which inhibits gonadotropin secretion by down-regulating pituitary GnRH receptor when administered continuously at therapeutic doses. The objectives of this analysis were to develop a population model that can describe the pharmacokinetics of the 6-month depot formulation of leuprolide acetate in patients with prostate cancer and to characterize the relationship of leuprolide plasma concentrations and serum testosterone concentrations.



The pharmacokinetic and pharmacodynamic analyses were performed using a non-linear mixed-effect modeling approach. Observations were pooled from studies on healthy male volunteers and prostate cancer patients, who were administered a single 1 mg intravenous dose of immediate-release leuprolide acetate and two intramuscular doses of 45 mg of the depot formulation, respectively. The covariates that were screened for the pharmacokinetic model included body weight, creatinine clearance, liver function markers (total bilirubin, blood urea nitrogen, AST, alanine aminotransferase), age, and body mass index.



A two-compartment model with parallel first- and zero-order absorption processes and a delayed first-order process well-characterized the multi-phasic absorption profile of leuprolide acetate depot formulation. Typical population values of the absorption rate constant of the immediate and delayed processes were estimated to be 0.357 and 0.017 day(-1), respectively, with a mean transit time of 9.5 days. No covariates were significant in this analysis. A semi-mechanistic model, which accounts for down-regulation of the GnRH receptor via an inhibitory maximum effect (E max) model and the stimulatory effect of activated receptors on testosterone levels, adequately described serum testosterone profiles following dosing. The equilibrium dissociation constant of leuprolide and the typical leuprolide plasma concentration required to achieve a castration testosterone level of ≤0.5 ng/mL were 0.3 and 0.03 ng/mL, respectively.



Population pharmacokinetics and pharmacodynamics of the leuprolide depot formulation were characterized using an integrated semi-mechanistic model. The developed model adequately describes the leuprolide-testosterone relationship and can potentially be used to facilitate design of clinical studies for new formulations, to aid in the selection of candidate formulations, and for the optimization of doses and dosing schemes.
A randomized trial of hypothesis-driven vs screening neurologic examination.

We hypothesized that trainees would perform better using a hypothesis-driven rather than a traditional screening approach to the neurologic examination.



We randomly assigned 16 medical students to perform screening examinations of all major aspects of neurologic function or hypothesis-driven examinations focused on aspects suggested by the history. Each student examined 4 patients, 2 of whom had focal deficits. Outcomes of interest were the correct identification of patients with focal deficits, number of specific deficits detected, and examination duration. Outcomes were assessed by an investigator blinded to group assignments. The McNemar test was used to compare the sensitivity and specificity of the 2 examination methods.



Sensitivity was higher with hypothesis-driven examinations than with screening examinations (78% vs 56%; p = 0.046), although specificity was lower (71% vs 100%; p = 0.046). The hypothesis-driven group identified 61% of specific examination abnormalities, whereas the screening group identified 53% (p = 0.008). Median examination duration was 1 minute shorter in the hypothesis-driven group (7.0 minutes vs 8.0 minutes; p = 0.13).



In this randomized trial comparing 2 methods of neurologic examination, a hypothesis-driven approach resulted in greater sensitivity and a trend toward faster examinations, at the cost of lower specificity, compared with the traditional screening approach. Our findings suggest that a hypothesis-driven approach may be superior when the history is concerning for an acute focal neurologic process.
A New Type of Direct-Drive Variable-Reluctance Actuators for Industrial Automation

Most advanced manufacturing processes require highspeed and high precision motion control for material transfer, packaging, assembly, and electrical wiring. Examples are surface mounting of electronic components, wire bonding of semiconductor chips, and assembly of watches and hard disks. To achieve precise motion control, most of these high-performance manufacturing machines use rotary d.c. or a.c. motors as the prime motion actuator, and couple their output shafts to mechanical motion translators (e.g. reduction gear, belt, ball screw, etc.). Though this is the most widely used method, it has disadvantages of reduced accuracy, complex mechanical structure, difficult adjustments and alignments, high production cost, and low reliability. In this paper, the author proposes a new direction in high performance machine design, and suggests that future high performance motion systems should be designed through "simplifying the mechanics through specialized directdrive actuators and advanced control methodologies". For this purpose, this paper investigates a class of variable reluctance (VR) direct-drive motion actuators for high performance machines. The paper looks into several specialized motion actuator systems designed by the author, (including limited stroke actuator, gripper, artificial limb, linear motion device, and planar motion device), highlights their features and advantages, and describes the challenges of controlling these devices.
Cost-effectiveness of N-terminal pro-B-type natriuretic-guided therapy in elderly heart failure patients: results from TIME-CHF (Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure).

This study aimed to assess cost-effectiveness of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided versus symptom-guided therapy in heart failure (HF) patients ≥60 years old.



Cost-effectiveness of NT-proBNP guidance in HF patients is unclear. It may create additional costs with uncertain benefits.



In the TIME-CHF (Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure), patients with left ventricular ejection fraction (LVEF) of ≤45% were randomized to receive intensified NT-proBNP-guided therapy or standard, symptom-guided therapy. For cost-effectiveness analysis, 467 (94%) patients (age 76 ± 7 years, 66% male) were eligible. Incremental cost-effectiveness was calculated as incremental costs per gained life-year and quality-adjusted life-year (QALY) within the 18-month trial period, as defined per protocol.



NT-proBNP-guided therapy was dominant (i.e., more effective and less costly) over symptom-guided therapy, saving $2,979 USD (2.5 to 97.5% confidence interval [CI]: $8,758 to $3,265) per patient, with incremental effectiveness of +0.07 life-years and +0.05 QALYs. The probability of NT-proBNP-guided therapy being dominant was 80%, and the probability of saving 1 life-year or QALY at a cost of $50,000 was 97% and 93%, respectively. Exclusion of residence costs resulted in an incremental cost-effectiveness ratio (ICER) of $5,870 per life-year gained. Cost-effectiveness of NT-proBNP-guided therapy was most pronounced in patients <75 years old and in those with <2 significant comorbidities, being dominant in all sensitivity analyses. In the worst-case scenario (excluding residence costs in those with ≥2 comorbidities), the ICER was $11,935 per life-year gained.



NT-proBNP-guided therapy has a high probability of being cost effective in HF patients with reduced LVEF, particularly in patients age 60 to 75 years or with less than 2 comorbidities.