nils-herrmann/clean_scirepeval huggingface dataset:
Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function.

Intervention for cystic fibrosis lung disease early in its course has the potential to delay or prevent progressive changes that lead to irreversible airflow obstruction. Denufosol is a novel ion channel regulator designed to correct the ion transport defect and increase the overall mucociliary clearance in cystic fibrosis lung disease by increasing chloride secretion, inhibiting sodium absorption, and increasing ciliary beat frequency in the airway epithelium independently of cystic fibrosis transmembrane conductance regulator genotype.



To evaluate the efficacy and safety of denufosol in patients with cystic fibrosis who had normal to mildly impaired lung function characteristic of early cystic fibrosis.



A total of 352 patients greater than or equal to 5 years old with cystic fibrosis who had FEV(1) greater than or equal to 75% of predicted normal were randomized to receive inhaled denufosol, 60 mg, or placebo three times daily in a Phase 3, randomized, double-blind, placebo-controlled, 24-week trial.



Main outcome measures included change in FEV(1) from baseline to Week 24 endpoint and adverse events. Mean change from baseline to Week 24 endpoint in FEV(1) (primary efficacy endpoint) was 0.048 L for denufosol (n = 178) and 0.003 L for placebo (n = 174; P = 0.047). No significant differences between groups were observed for secondary endpoints including exacerbation rate and other measures of lung function. Denufosol was well tolerated with adverse event and growth profiles similar to placebo.



Denufosol improved lung function relative to placebo in cystic fibrosis patients with normal to mildly impaired lung function.
Vascular endothelial growth factor-trap overcomes defects in dendritic cell differentiation but does not improve antigen-specific immune responses.

Induction of antitumor immune responses requires adequate function of dendritic cells. Dendritic cell defects in cancer patients have been implicated in tumor escape and the limited efficacy of cancer vaccines. Previous studies have shown that vascular endothelial growth factor (VEGF) plays a major role in abnormal dendritic cell differentiation and function in cancer. It has been proposed that inhibition of VEGF may result in improved immune responses. The goal of this study was to test this hypothesis.



Fifteen patients with refractory solid tumors were enrolled into a phase I clinical trial of VEGF-Trap. Phenotype and function of different subsets of mononuclear cells were measured before and at different time points after the start of treatment.



VEGF-Trap treatment did not affect the total population of dendritic cells, their myeloid or plasmacytoid subsets, myeloid-derived suppressor cells (MDSC), or regulatory T cells. It significantly increased the proportion of mature dendritic cells. However, that improvement was not associated with an overall increase in immune responses to various antigens and mitogens. A subset analysis revealed significant improvement in immune responses in patients who had no increase in the proportion of MDSC. An improvement in immune responses was absent in patients with an increase in the proportion of MDSC.



Inhibition of VEGF signaling may improve differentiation of dendritic cells in cancer patients. However, it was not sufficient to improve immune responses. This shows multifaceted nature of immune deficiency and points out to the need for complex approach to modulation of immune reactivity in cancer.
Cervical epidural injections in chronic discogenic neck pain without disc herniation or radiculitis: preliminary results of a randomized, double-blind, controlled trial.

Chronic neck pain is a common problem in the adult population with a typical 12-month prevalence of 30% to 50%. However, there is a lack of consensus regarding the causes and treatments of chronic neck pain. Despite limited evidence, cervical epidural injections are one of the commonly performed non-surgical interventions in the management of chronic neck pain.



A randomized, double-blind, active control trial.



An interventional pain management practice, a specialty referral center, a private practice setting in the United States.



To evaluate the effectiveness of cervical interlaminar epidural injections with local anesthetic with or without steroids in the management of chronic neck pain with or without upper extremity pain in patients without disc herniation or radiculitis or facet joint pain.



Patients without disc herniation or radiculitis and negative for facet joint pain by means of controlled diagnostic medial branch blocks were randomly assigned to one of 2 groups: injection of local anesthetic only or local anesthetic mixed with non-particulate betamethasone. Seventy patients were included in this analysis. Randomization was performed by computer-generated random allocation sequence by simple randomization.



Multiple outcome measures were utilized including the Numeric Rating Scale (NRS), the Neck Disability Index (NDI), employment status, and opioid intake with assessment at 3, 6, and 12 months post-treatment. Significant pain relief or functional status was defined as a 50% or more reduction.



Significant pain relief (> or = 50%) was demonstrated in 80% of patients in both groups and functional status improvement (> or = 50%) in 69% of Group I and 80% of Group II. The overall average procedures per year were 3.9 +/- 1.01 in Group I and 3.9 +/- 0.8 in Group II with an average total relief per year of 40.3 +/- 14.1 weeks in Group I and 42.1 +/- 9.9 weeks in Group II over a period of 52 weeks in the successful group.



The results of this study are limited by the lack of a placebo group and a preliminary report of 70 patients, with 35 patients in each group.



Cervical interlaminar epidural injections with local anesthetic with or without steroids may be effective in patients with chronic function-limiting discogenic.
Effect of coordination training with and without stochastic resonance stimulation on dynamic postural stability of subjects with functional ankle instability and subjects with stable ankles.

To examine the effects of coordination training with and without stochastic resonance (SR) stimulation on dynamic postural stability.



Experimental with repeated measures.



Research Laboratory.



Thirty subjects with functional ankle instability (FAI) and 30 healthy subjects.



Subjects were assigned to a conventional coordination training group, SR stimulation coordination training group, or control group. Training groups performed coordination exercises for 6 weeks. Single leg jump-landing tests were performed before training began (pretest), and then once every 2 weeks. Jump-landing tests required subjects to land on a single leg on a force plate and stabilize quickly.



Anterior/posterior (A/P) and medial/lateral (M/L) time-to-stabilization (TTS).



The FAI group improved their A/P TTS over their pretest by 16% (test 2), 22% (test 3), and 22% (posttest). They also improved their M/L TTS over their pretest by 16% (test 3) and 22% (posttest). Control groups did not improve their TTS (P>0.05). SR stimulation did not statistically influence TTS (P>0.05). Effect sizes (ES), however, for our 3-way interaction analyses for A/P TTS (ES=0.40) and M/L TTS (ES=0.30) suggested that SR stimulation improved the FAI group's M/L TTS after 2 weeks of training, and improved their A/P TTS and M/L TTS to a greater degree after 4 weeks than coordination training alone.



Coordination training can improve dynamic postural instabilities associated with FAI. SR stimulation might be an alternative therapy for FAI, as this stimulation might improve dynamic postural stability more quickly and to a greater extent than coordination training without SR stimulation.
Impact of Catheter Ablation for Paroxysmal Atrial Fibrillation in Patients With Sick Sinus Syndrome　- Important Role of Non-Pulmonary Vein Foci.

The clinical efficacy of catheter ablation (CA) for paroxysmal atrial fibrillation (PAF) in patients with sick sinus syndrome (SSS) and the mechanism and predictors of recurrence are not yet completely elucidated.



Of 963 consecutive patients who underwent PAF ablation during the study period, a total of 108 patients with SSS (SSS group) and 108 matched controls without SSS (non-SSS group) were followed up. During the follow-up period (mean, 32.8±17.5 months), the SSS group had significantly higher AF recurrence rate since the last procedure than the non-SSS group (26.9% vs. 12.0%; P=0.02). The SSS group had significantly higher prevalence of non-pulmonary vein (non-PV) foci than the non-SSS group (25.9% vs. 13.9%; P=0.027). On multivariate analysis congestive heart failure (HR, 13.7; 95% CI: 1.57-119; P=0.02) and non-PV foci (HR, 5.75; 95% CI: 1.69-19.6; P=0.005) were independent predictors of recurrence following CA in the SSS group. In the SSS group, 88 patients had bradycardia-tachycardia syndrome without prior permanent pacemaker implantation. Of these, 6 required pacemaker implantation because of AF and sinus pause recurrence.



Patients with SSS are at higher risk of AF recurrence after CA. Non-PV foci are associated with AF recurrence following PAF with SSS.
Use of sodium thiosulphate in a multi-interventional setting for the treatment of calciphylaxis in dialysis patients.

Calciphylaxis is a life-threatening complication in patients with end-stage renal disease (ESRD). No established therapy exists so far. The aim of the present study was to determine the therapeutic response to a multi-interventional treatment regimen with consistent use of sodium thiosulphate (STS) in an Austrian cohort of calciphylaxis patients.



We retrospectively collected demographic, clinical and laboratory data on 27 calciphylaxis patients treated with STS at seven Austrian dialysis centres between June 2004 and November 2010.



Twenty-seven dialysis patients (68 ± 12 years) were treated with STS for a median (25th, 75th percentile) of 96 (54, 133) days. Seven patients (26%) suffered from proximal-type, and 20 patients (74%) from distal-type calciphylaxis. Fourteen patients (52%) showed a complete remission, five patients (19%) a partial remission and eight patients (30%) progression that resulted in amputation in four patients. During a median follow-up of 101 (79, 273) days, 14 patients died (52%). Non-survivors were older (P = 0.04), showed higher CRP values (P = 0.04), presented more frequently with proximal-type calciphylaxis (P = 0.03), had a higher disease severity score at diagnosis (P = 0.01), were treated more often with antibiotics (P = 0.01) and cinacalcet (P = 0.03) and had a lower remission rate during treatment (P = 0.004) than did survivors. The use of antibiotics and cinacalcet, disease severity at diagnosis and remission rates were found to be significant survival predictors in logistic regression analysis.



Calciphylaxis remains a serious complication with high mortality. Early and consistent therapy including STS may help to improve the disease outcome.
A population approach to study the influence of nevirapine administration on lopinavir pharmacokinetics in HIV-1 infected patients

The influence of nevirapine (NVP) on lopinavir (LPV) pharmacokinetics was investigated by a population analysis based on a non-linear mixed-effect modelling method. In this analysis, 95 HIV-1 infected patients were studied [52 treated with LPV/ritonavir (400/100 mg twice a day) plus nucleoside reverse transcriptase inhibitors (group A), 22 patients treated with LPV/ritonavir (533.3/133.3 mg twice a day) plus NVP (group B) and 21 patients treated with LPV/ritonavir (400/100 mg twice a day) plus NVP (group C)]. The apparent clearance of LPV [mean±SD: 4.56±3.94 l h−1 (group A) versus 7.14±1.77 l h−1 (group B) versus 7.74±1.45 l h−1 (group C)] was significantly (P <0.001) increased by the presence of NVP in the antiretroviral regimen and the mean trough plasma concentration of LPV was reduced in group C relative to group A [mean±SD: 2.23±1.35 mg/l versus 5.29±2.19 mg/l (P < 0.001)]. These results suggest an induction of LPV metabolism by NVP.
Voluntary decrease in breathing frequency in exercising asthmatic subjects.

Exercise rehabilitation programmes are increasingly recommended in young asthmatics, but it is unclear whether or not training should incorporate instructions on breathing pattern. In this study, we examined the effects of voluntarily decreasing breathing frequency on their ventilatory equivalents for oxygen and carbon dioxide (minute ventilation (V'E)/oxygen consumption (V'O2) and V'E/CO2 production (V'CO2), respectively), noninvasively determined physiological dead space/tidal volume (VD/VT) and dyspnoea. Fifteen young asthmatic subjects were assigned to two groups: low frequency breathing (LFB) and controls. They first underwent an exercise test at a cardiac frequency of 150 beats x min(-1). They were trained at this level for nine sessions. LFB subjects were instructed to decrease respiratory frequency by 40% during exercise. Control subjects received no instructions. A second test was then performed in the same conditions. LFB subjects decreased V'E/V'O2, V'E/V'CO2 and VD/VT by 22, 19 and 12%, respectively. Arterial oxygen saturation (Sa,O2) fell to 89+/-4% and end-tidal carbon dioxide tension (PET,CO2) rose to 6.5+/-0.7 kPa (49+/-5 mmHg). In controls, these variables were identical in the two tests. Dyspnoea was lower in the second test in all subjects. In conclusion, breathing pattern may be profoundly altered during exercise without concomitant increase in dyspnoea. However, directing breathing patterns for exercise rehabilitation requires an individual assessment of the desired pattern in order to prevent hypercapnia or hypoxia.
Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection.

It is unclear whether therapy for human immunodeficiency virus type 1 (HIV-1) should be initiated with a four-drug or two sequential three-drug regimens.



In this multicenter trial we compared initial therapy involving four-drug regimens containing efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine and lamivudine with therapy involving two consecutive three-drug regimens the first of which contained either efavirenz or nelfinavir.



A total of 980 subjects were followed for a median of 2.3 years. There was no significant difference in the occurrence of regimen failures between the group that received the four-drug regimen containing didanosine, stavudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with didanosine, stavudine, and nelfinavir (hazard ratio for regimen failure, 1.24) or didanosine, stavudine, and efavirenz (hazard ratio, 1.01). There was no significant difference between the group that received the four-drug regimen containing zidovudine, lamivudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with zidovudine, lamivudine, and nelfinavir (hazard ratio, 1.06) or zidovudine, lamivudine, and efavirenz (hazard ratio, 1.45). A four-drug regimen was associated with a longer time to the first regimen failure than the three-drug regimens containing didanosine, stavudine, and nelfinavir (hazard ratio for a first regimen failure, 0.55); didanosine, stavudine, and efavirenz (hazard ratio, 0.63); or zidovudine, lamivudine, and nelfinavir (hazard ratio, 0.49), but not the three-drug regimen containing zidovudine, lamivudine, and efavirenz (hazard ratio, 1.21).



There was no significant difference in the duration of successful HIV-1 treatment between a single four-drug regimen and two consecutive three-drug regimens. Among these treatment strategies, initiating therapy with the three-drug regimen of zidovudine, lamivudine, and efavirenz is the optimal choice.
Value of the "TAVI2-SCORe" versus surgical risk scores for prediction of one year mortality in 511 patients who underwent transcatheter aortic valve implantation.

A bedside-available transcatheter aortic valve implantation (TAVI)-dedicated prognostic risk score is an unmet clinical need. We aimed to develop such a risk score predicting 1-year mortality post-TAVI and to compare it with the performance of the logistic EuroSCORE (LES) I and LES-II and the Society of Thoracic Surgeons' (STS) score. Baseline variables of 511 consecutive patients who underwent TAVI that were independently associated with 1-year mortality post-TAVI were included in the "TAVI2-SCORe." Discrimination and calibration abilities of the novel score were assessed and compared with surgical risk scores. One-year mortality was 17.0% (n = 80 of 471). Porcelain thoracic aorta (hazard ratio [HR] 2.56), anemia (HR 2.03), left ventricular dysfunction (HR 1.98), recent myocardial infarction (HR 3.78), male sex (HR 1.81), critical aortic valve stenosis (HR 2.46), old age (HR 1.68), and renal dysfunction (HR 1.76) formed the TAVI2-SCORe (all p <0.05). According to the number of points assigned (1 for each variable and 2 for infarction), patients were stratified into 5 risk categories: 0, 1 (HR 2.6), 2 (HR 3.6), 3 (HR 10.5), and ≥4 (HR 17.6). TAVI2-SCORe showed better discrimination ability (Harrells' C statistic 0.715) compared with LES-I, LES-II, and STS score (0.609, 0.633, and 0.50, respectively). Cumulative 1-year survival rate was 54% versus 88% for patients with TAVI2-SCORE ≥3 versus <3 points, respectively (p <0.001). Contrary to surgical risk scores, there was no significant difference between observed and expected 1-year mortality for all TAVI2-SCORe risk strata (all p >0.05, Hosmer-Lemeshow statistic 0.304), suggesting superior calibration performance. In conclusion, the TAVI2-SCORe is an accurate, simple, and bedside-available score predicting 1-year mortality post-TAVI, outperforming conventional surgical risk scores for this end point.
Docosahexaenoic acid supplementation improved lipocentric but not glucocentric markers of insulin sensitivity in hypertriglyceridemic men.

Increase in obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from human intervention studies have varied. Results from some human and animal studies suggest that docosahexaenoic acid (22:6n-3; DHA) may be more effective than eicosapentaenoic acid (20:5n-3; EPA) in the prevention of IR.



By using a placebo-controlled, parallel study design, we examined the effects of DHA supplementation (3 grams/day, 90 days) in the absence of EPA on glucocentric and lipocentric markers of IR in hypertriglyceridemic men (n=14-17/group).



DHA supplementation increased fasting plasma glucose concentration by 4.7% (P<0.05), but did not alter other indices of IR based on fasting (insulin and homeostasis model assessment of insulin resistance [HOMA-IR]) or postprandial insulin and glucose concentrations (areas under curves for insulin and glucose, Matsuda index). Glucose increased by 2.7% in the placebo group and was not significant; increases in glucose in the two groups did not differ from each other. DHA decreased circulating concentrations of several lipocentric markers of IR, including plasma concentrations of nonesterified fatty acids (13.0%), small, dense low-density lipoprotein (LDL) particles (21.7%), and ratio of tryglycerides to high-density lipoprotein cholesterol (TG/HDL-C) (34.0%) (P<0.05). None of the variables changed in the placebo group.



Our results suggest that lipocentric markers of IR are more responsive to DHA supplementation than the glucocentric markers. Future studies with DHA in prediabetic subjects and direct measures of insulin sensitivity are needed.
Effect of low- and intermediate-purity clotting factor therapy on progression of human immunodeficiency virus infection in congenital clotting disorders. Transfusion Safety Study Group.

Low- and intermediate-purity clotting-factor therapies are believed to accelerate human immunodeficiency virus (HIV) progression in hemophiliacs through adverse immune effects of the other plasma proteins in the preparations. To investigate this postulate, we evaluated data from six clinical centers that observed persons with congenital factor deficiencies at 6-month intervals. The present analysis is based on HIV-infected subjects who received intermediate purity factor VIII or factor IX concentrates, or cryoprecipitate. For long-term outcome, we classified 374 subjects by the type and amount of treatment during our first year of observation, and determined the subsequent rate of progression to a CD4 count less than 200 cells/microL. A second analysis of this group used a repeated-measures, random-effect model that allowed for individual differences in CD4 decline. Finally, we compared short-term rates of change in CD4 count in each treatment interval of 525 subjects with the type and amount of factor therapy received in the same interval. There was no overall or dose-related deleterious effect of any form of treatment on CD4 trend. The CD4 decrease was less when cryoprecipitate was administered alone or combined with concentrate, but not significantly so. Our results counter the assertion that low- and intermediate-purity products accelerate the rate of CD4 decrease in HIV-1-infected hemophiliacs.
Can diabetes management be safely transferred to practice nurses in a primary care setting? A randomised controlled trial.

To determine whether the management of type 2 diabetes mellitus in a primary care setting can be safely transferred to practice nurses.



Because of the increasing prevalence of type 2 diabetes mellitus and the burden of caring for individual patients, the demand type 2 diabetes mellitus patients place on primary health care resources has become overwhelming.



Randomised controlled trial.



The patients in the intervention group were cared for by practice nurses who treated glucose levels, blood pressure and lipid profile according to a specified protocol. The control group received conventional care from a general practitioner. The primary outcome measure was the mean decrease seen in glycated haemoglobin (HbA1c) levels at the end of the follow-up period (14 months).



A total of 230 patients was randomised with 206 completing the study. The between-group differences with respect to reduction in HbA1c, blood pressure and lipid profile were not significant. Blood pressure decreased significantly in both groups; 7.4/3.2 mm Hg in the intervention group and 5.6/1.0 mm Hg in the control group. In both groups, more patients met the target values goals for lipid profile compared to baseline. In the intervention group, there was some deterioration in the health-related quality of life and an increase in diabetes-related symptoms. Patients being treated by a practice nurse were more satisfied with their treatment than those being treated by a general practitioner.



Practice nurses achieved results, which were comparable to those achieved by a general practitioner with respect to clinical parameters with better patient satisfaction.


 TO CLINICAL PRACTICE
This study shows that diabetes management in primary care can be safely transferred to practice nurses.