nils-herrmann/clean_scirepeval huggingface dataset:
Phase I trial of a new schedule of romidepsin in patients with advanced cancers.

Romidepsin is a potent histone deacetylase inhibitor (HDI) with activity in T-cell lymphoma. Given preclinical data showing greater induction of gene expression with longer exposures to HDIs, a phase I study of a day 1, 3, and 5 romidepsin schedule was evaluated. A secondary objective was to assess the effect of romidepsin on radioactive iodine (RAI) uptake in thyroid cancers.



Open-label, single-arm, phase I, 3 + 3 dose escalation study. Romidepsin was administered as a 4-hour infusion on days 1, 3, and 5 of a 21-day cycle. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed, including histone acetylation in peripheral blood mononuclear cells (PBMC), RAI uptake in refractory thyroid cancer, and HDI-related ECG changes.



Twenty-eight patients with solid tumors, including 11 patients with thyroid cancer were enrolled. Six dose levels were explored, and 7 mg/m(2) on days 1, 3, and 5 was identified as tolerable. No Response Evaluation Criteria In Solid Tumors-defined objective responses were recorded although 9 patients had stable disease a median 30 weeks (range, 21-112) including 6 with thyroid cancer a median of 33 weeks. PD studies detected acetylated histones in PBMCs and ECG changes beginning at low dose levels. Follow-up RAI scans in patients with RAI refractory thyroid cancer did not detect meaningful increases.



A romidepsin dose of 7 mg/m(2) administered on days 1, 3, and 5 was found tolerable and resulted in histone acetylation in PBMCs. Although there were no objective responses with romidepsin alone, this schedule may be useful for developing combination studies in solid tumors.
A Factorization Method for 3 D Multi-body Motion Estimation and Segmentation ∗

We study the problem of estimating the motion of independently moving objects observed by a moving perspective camera. We show that infinitesimal image measurements corresponding to independent motions lie on orthogonal six-dimensional subspaces of a higher-dimensional linear space. We propose a factorization algorithm that estimates the number of independent motions, the segmentation of the image points and the motion of each object relative to the camera from a set of image points and their optical flows in multiple frames. We evaluate the proposed algorithm on synthetic and real image sequences.
Efficacy and safety of ABT-335 (fenofibric acid) in combination with atorvastatin in patients with mixed dyslipidemia.

In patients with mixed dyslipidemia characterized by increased triglycerides (TG), decreased high-density lipoprotein (HDL) cholesterol, and increased low-density lipoprotein (LDL) cholesterol, monotherapy with lipid-altering drugs often fails to achieve all lipid targets. This multicenter, double-blind, active-controlled study evaluated ABT-335 (fenofibric acid) in combination with 2 doses of atorvastatin in patients with mixed dyslipidemia. A total of 613 patients with LDL cholesterol > or =130 mg/dl, TG > or =150 mg/dl, and HDL cholesterol <40 mg/dl for men and <50 mg/dl for women were randomly assigned to ABT-335 (135 mg), atorvastatin (20, 40, or 80 mg), or combination therapy (ABT-335 + atorvastatin 20 or 40 mg) and treated for 12 weeks. Combination therapy with ABT-335 + atorvastatin 20 mg resulted in significantly greater improvements in TG (-45.6% vs -16.5%) and HDL cholesterol (14.0% vs 6.3%) compared with atorvastatin 20 mg and LDL cholesterol (-33.7% vs -3.4%) compared with ABT-335. Similarly, significantly greater improvements were observed with ABT-335 + atorvastatin 40 mg in TG (-42.1% vs -23.2%) and HDL cholesterol (12.6% vs 5.3%) compared with atorvastatin 40 mg and LDL cholesterol (-35.4% vs -3.4%) compared with ABT-335 monotherapy. Combination therapy also improved multiple secondary variables. Combination therapy was generally well tolerated with a safety profile consistent with those of ABT-335 and atorvastatin monotherapies. No rhabdomyolysis was reported. In conclusion, ABT-335 + atorvastatin combination therapy resulted in more effective control of multiple lipid parameters than either monotherapy and may be an appropriate therapy for patients with mixed dyslipidemia.
Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men.

The aim of the present study was to analyse the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone.



Randomized, double-blind, placebo-controlled study.



Forty-eight men over 60 years old with decreased testosterone levels (< or =320 ng/dL) comprised the study. Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months; the remaining 23 participants formed the control group. All participants had measurements of bone mineral density (BMD) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-beta estradiol levels.



Testosterone treated group exhibited a significant (p < 0.05) increment (from 1.198 +/- 0.153 to 1.240 +/- 0.141 g/cm(2)) in lumbar BMD in parallel with a significant (p < 0.001) increment (from 301 +/- 32 to 471 +/- 107 ng/dL) in testosterone concentrations, whereas no significant change occurred in femoral neck BMD.



Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels.
Behavioral treatment of social phobia in youth: does parent education training improve the outcome?

Social phobia is one of the most common anxiety disorders in children and adolescents, and it runs a fairly chronic course if left untreated. The goals of the present study were to evaluate if a parent education course would improve the outcome for children with a primary diagnosis of social phobia and if comorbidity at the start of treatment would impair the outcome of the social phobia. A total of 55 children, 8-14 years old, were randomly assigned to one of three conditions: 1) Child is treated, 2) Child is treated and parent participates in the course, or 3) A wait-list for 12 weeks. The treatment consisted of individual exposure and group social skills training based on the Beidel, Turner, and Morris (2000) SET-C. Children and parents were assessed pre-, post-, and at one year follow-up with independent assessor ratings and self-report measures. Results showed that there was no significant difference between the two active treatments and both were better than the wait-list. The treatment effects were maintained or furthered at the follow-up. Comorbidity did not lead to worse outcome of social phobia. Comorbid disorders improved significantly from pre-to post-treatment and from post-to follow-up assessment without being targeted in therapy.
Asthma control cost-utility randomized trial evaluation (ACCURATE): the goals of asthma treatment

Despite the availability of effective therapies, asthma remains a source of significant morbidity and use of health care resources. The central research question of the ACCURATE trial is whether maximal doses of (combination) therapy should be used for long periods in an attempt to achieve complete control of all features of asthma. An additional question is whether patients and society value the potential incremental benefit, if any, sufficiently to concur with such a treatment approach. We assessed patient preferences and cost-effectiveness of three treatment strategies aimed at achieving different levels of clinical control:1. sufficiently controlled asthma2. strictly controlled asthma3. strictly controlled asthma based on exhaled nitric oxide as an additional disease marker



720 Patients with mild to moderate persistent asthma from general practices with a practice nurse, age 18-50 yr, daily treatment with inhaled corticosteroids (more then 3 months usage of inhaled corticosteroids in the previous year), will be identified via patient registries of general practices in the Leiden, Nijmegen, and Amsterdam areas in The Netherlands. The design is a 12-month cluster-randomised parallel trial with 40 general practices in each of the three arms. The patients will visit the general practice at baseline, 3, 6, 9, and 12 months. At each planned and unplanned visit to the general practice treatment will be adjusted with support of an internet-based asthma monitoring system supervised by a central coordinating specialist nurse. Patient preferences and utilities will be assessed by questionnaire and interview. Data on asthma control, treatment step, adherence to treatment, utilities and costs will be obtained every 3 months and at each unplanned visit. Differences in societal costs (medication, other (health) care and productivity) will be compared to differences in the number of limited activity days and in quality adjusted life years (Dutch EQ5D, SF6D, e-TTO, VAS). This is the first study to assess patient preferences and cost-effectiveness of asthma treatment strategies driven by different target levels of asthma control.
Improving the management of family psychosocial problems at low-income children's well-child care visits: the WE CARE Project.

Our goal was to evaluate the feasibility and impact of an intervention on the management of family psychosocial topics at well-child care visits at a medical home for low-income children.



A randomized, controlled trial of a 10-item self-report psychosocial screening instrument was conducted at an urban hospital-based pediatric clinic. Pediatric residents and parents were randomly assigned to either the intervention or control group. During a 12-week period, parents of children aged 2 months to 10 years presenting for a well-child care visit were enrolled. The intervention components included provider training, administration of the family psychosocial screening tool to parents before the visit, and provider access to a resource book that contained community resources. Parent outcomes were obtained from postvisit and 1-month interviews, and from medical chart review. Provider outcomes were obtained from a self-administered questionnaire collected after the study.



Two hundred parents and 45 residents were enrolled. Compared with the control group, parents in the intervention group discussed a significantly greater number of family psychosocial topics (2.9 vs 1.8) with their resident provider and had fewer unmet desires for discussion (0.46 vs 1.41). More parents in the intervention group received at least 1 referral (51.0% vs 11.6%), most often for employment (21.9%), graduate equivalent degree programs (15.3%), and smoking-cessation classes (14.6%). After controlling for child age, Medicaid status, race, educational status, and food stamps, intervention parents at 1 month had greater odds of having contacted a community resource. The majority of residents in the intervention group reported that the survey instrument did not slow the visit; 54% reported that it added <2 minutes to the visit.



Brief family psychosocial screening is feasible in pediatric practice. Screening and provider training may lead to greater discussion of topics and contact of community family support resources by parents.
Comparison of outcome and interventional complication rate in patients with acute stroke treated with mechanical thrombectomy with and without bridging thrombolysis.

No randomized trial has investigated the effect of mechanical thrombectomy (MT) alone in patients with acute stroke. There are conflicting results as to whether prior intravenous thrombolysis (IVT) facilitates subsequent MT, and data in patients treated with MT alone owing to contraindications to IVT are limited.



To compare consecutive patients treated with MT alone or with preceding IVT in a large tertiary neurointerventional center, with special emphasis on contraindications to IVT.



Retrospective analysis of 283 consecutive patients with acute ischemic stroke treated with MT in a tertiary neurovascular center over 14 months. Data on characteristics of periprocedural times, recanalization rate, complications, and long-term functional outcome were collected prospectively.



Information on prior IVT and functional outcome was available in 250 patients. Mean (SD) follow-up period was 5.7 (5.1) months and 105 (42%) patients received both IVT and MT. No significant differences were found in successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) 2b/3, 73.8% vs 73.1, p=0.952), complication rates, and long-term favorable outcome (modified Rankin Scale 0-2, 35.2% vs 40%, p=0.444) between patients receiving MT plus IVT and those receiving MT alone. A favorable outcome in patients directly treated with MT alone who were eligible for IVT was achieved in 48.2%. Thrombectomy was safe and resulted in a favorable outcome in 32% of patients with absolute contraindications to IVT.



Preceding use of IVT was not an independent predictor of favorable outcome in patients with acute stroke treated with MT and complication rates did not differ whether or not IVT was used. MT is safe and achieved a favorable outcome in one-third of patients with stroke ineligible for IVT.
Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial

Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5-10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24-45 years.



Women aged 24-45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. 
1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83.1% (50.6-95.8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22.6% (-2.9 to 41.9, 90/1886 cases vs 115/1883 cases), since infection and disease were present at baseline. We recorded no vaccine-related serious adverse events.



The quadrivalent HPV vaccine is efficacious in women aged 24-45 years not infected with the relevant HPV types at enrolment.



Merck (USA).
Paclitaxel-coated balloon angioplasty vs. plain balloon dilation for the treatment of failing dialysis access: 6-month interim results from a prospective randomized controlled trial.

To report the 6-month results of a prospective randomized trial investigating angioplasty with paclitaxel-coated balloons (PCB) vs. plain balloon angioplasty (BA) for the treatment of failing native arteriovenous fistulae (AVF) or prosthetic arteriovenous grafts (AVG).



The enrollment criteria for this non-inferiority hypothesis trial included clinical signs of failing dialysis access with angiographic documentation of a significant venous stenotic lesion in patients with AVF or AVG circuits. From March to December 2010, 40 patients (29 men; mean age 64.1 ± 14.3 years) were randomized to undergo either PCB dilation (n = 20) or standard BA (n = 20) of a stenosed venous outflow lesion. Regular angiographic follow-up was scheduled bimonthly. Study outcome measures included device success (<30% residual stenosis without postdilation), procedural success (<30% residual stenosis), and primary patency of the treated lesion (<50% angiographic restenosis and no need for any interim repeat procedures).



Baseline and procedural variables were comparably distributed between both groups. Device success was 9/20 (45%) for the PCB device vs. 20/20 (100%) for standard control BA (p<0.001). Procedural success was 100% in both groups after further high-pressure post-dilation as necessary. There were no major or minor complications in either group. At 6 months, cumulative target lesion primary patency was significantly higher after PCB application (70% in PCB group vs. 25% in BA group, p<0.001; HR 0.30, 95% CI 0.12 to 0.71, p<0.006).



PCB angioplasty improves patency after angioplasty of venous stenoses of failing vascular access used for dialysis.
Composite versus conventional coronary artery bypass grafting strategy for the anterolateral territory: study protocol for a randomized controlled trial

In severe coronary artery disease, coronary artery bypass grafting (CABG) surgery is indicated to re-establish an adequate blood supply to the ischemic myocardium. Effectiveness of CABG surgery for symptom relief and mortality decrease should therefore depend on bypass graft patency. As bypass using a left internal mammary artery (LIMA)-to-left anterior descending coronary artery (LAD) anastomosis allows the best results in terms of graft patency, we designed a new surgical technique using a saphenous vein graft as a venous bridge to distribute the LIMA flow to the cardiac anterolateral territory. This novel strategy could extend the patency benefits associated to the LIMA. Other potential benefits of this technique include easier surgical technique, possibility to use saphenous vein grafts as vein patch angioplasty, shorter saphenous vein grafts requirement and reduced or eliminated manipulations of the ascendant aorta (and associated stroke risk).



Between July 2012 and 2016, 200 patients undergoing a primary isolated CABG surgery using cardiopulmonary bypass with a LAD bypass graft and at least another target on the anterolateral territory will be randomized (1:1) according to 1) the new composite strategy and 2) the conventional strategy with a LIMA-to-LAD anastomosis and revascularization of the other anterolateral target(s) with a separated aorto-coronary saphenous vein graft. The primary objective of the trial is to assess whether the composite strategy allows non-inferior anterolateral graft patency index (proportion of non-occluded CABGs out of the total number of CABGs) compared to the conventional technique. The primary outcome is the anterolateral graft patency index, evaluated at one year by 256-slice computed tomography angiography. Ten years of clinical follow-up is planned to assess clinical outcomes including death, myocardial infarction and need for revascularization.



This non-inferiority trial has the potential to advance the adult cardiac surgery field, given the potential benefits associated with the composite grafting strategy.
Criterion-Related Validity of a Diarrhea Questionnaire in HIV-Infected Patients

Clinical trials evaluating HIV-related diarrhea have used varied unidimensional end points to assess diarrhea severity. We hypothesized that a self-reported measure of diarrhea that assesses stool form, stool frequency, and diarrhea morbidity would accurately portray the severity of HIV-related diarrhea. During a clinical trial for HIV-related diarrhea, we evaluated the instrument among 17 patients, comparing survey results with objective measures of diarrhea morbidity recorded concurrently. The survey scores demonstrated consistently high Spearman correlations with nursing assessment of stool form (0.6693), observed stool frequency (0.7023), and cumulative stool weight (0.8216), all recorded over six days of intensive inpatient observation (P < 0.01 for each). Of the three components of the survey, only the stool form assessment, which uses pictorial representations of stool consistency, correlated significantly across all three objective measures (0.8069–0.8792). In demonstrating the concurrent, criterion-related validity of this survey, we found it helpful for evaluating HIV-related diarrhea and suggest its utility for HIV-seronegative subjects as well.
Abbreviated infusion of eptifibatide after successful coronary intervention The BRIEF-PCI (Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention) randomized trial.

The purpose of this study was to assess whether the early discontinuation of eptifibatide infusion in nonemergent percutaneous coronary intervention (PCI) is associated with a higher frequency of periprocedural ischemic myonecrosis.



The recommended regimen for eptifibatide is a double bolus followed by an infusion for 18 h. It is not known whether the infusion can be shortened if the PCI is uncomplicated.



We enrolled 624 patients with stable angina, acute coronary syndrome, or recent ST-segment elevation myocardial infarction (>48 h) who underwent successful coronary stenting and received eptifibatide. Patients were randomly assigned to receive either an 18-h infusion or an abbreviated infusion of <2 h. The primary end point was the incidence of periprocedural myonecrosis defined as troponin-I elevation >0.26 microg/l. Secondary end points included death, myocardial infarction, urgent target vessel revascularization at 30 days, and in-hospital major bleeding using the REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events) trial criteria.



The incidence of periprocedural myonecrosis was 30.1% in the <2-h group versus 28.3% in the 18-h group (mean difference: 1.8%; upper bound of 95% confidence interval: 7.8%; p < 0.012 for noninferiority). The 30-day incidence of myocardial infarction, death, and target vessel revascularization was similar in both groups (p = NS). Major bleeding was less frequent in the <2-h group (1.0% vs. 4.2%, p = 0.02).



After uncomplicated PCI, eptifibatide infusion can be abbreviated safely to <2 h. It is not inferior to the standard 18-h infusion in preventing ischemic outcome, and it may be associated with less major bleeding. (Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention [BRIEF PCI]; NCT00111566).