nils-herrmann/clean_scirepeval huggingface dataset:
Pharmacokinetics and antiviral activity of PHX1766, a novel HCV protease inhibitor, using an accelerated Phase I study design.

PHX1766 is a novel HCV NS3/4 protease inhibitor with robust potency and high selectivity in replicon studies (50% maximal effective concentration 8 nM). Two clinical trials investigated the safety, tolerability, pharmacokinetics and antiviral activity of PHX1766 in healthy volunteers (HV) and chronic hepatitis C patients, by use of a dose-adaptive overlapping clinical trial design.



Two randomized, double-blind, placebo-controlled clinical trials were conducted. Single doses of PHX1766 or placebo were administered to 25 HV and six HCV genotype 1-infected patients (50 mg once daily -1,000 mg once daily, 250 mg twice daily and 100 mg of a new formulation of PHX1766 once daily). Multiple doses of PHX1766 or placebo were administered to 32 HV and seven HCV genotype 1-infected patients (50 mg once daily -800 mg twice daily).



Oral administration of PHX1766 was safe and well tolerated at all dose levels with rapid absorption (time at which concentration maximum is reached of 1-4 h) and with mean terminal half-lives of 4-23 h. Multiple doses of PHX1766 800 mg twice daily in HCV patients produced an area under the plasma concentration-time curve from time of drug administration to the last time point with a measurable concentration after dosing accumulation ratio of 2.3. The mean maximal observed HCV RNA decline was 0.6 log(10) IU/ml in the first 24 h in the single-dose protocol and 1.5 log(10) IU/ml after 6 days of PHX1766 dosing.



An overlapping, dose-adaptive single-dose and multiple-dose escalating design in HV and HCV-infected patients proved to be highly efficient in identifying a therapeutic dose. Although in vitro replicon studies indicated a robust HCV RNA viral decline of PHX1766, the study in HCV patients demonstrated only modest viral load reduction.
Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is clinically used to treat neutropenia. G-CSF also has non-hematopoietic functions and could potentially be used to treat neuronal injury. To confirm the safety and feasibility of G-CSF administration for acute spinal cord injury (SCI), we have initiated a phase I/IIa clinical trial of neuroprotective therapy using G-CSF. The trial included a total of 16 SCI patients within 48 h of onset. In the first step, G-CSF (5 μg/kg/day) was intravenously administered for 5 consecutive days to 5 patients. In the second step, G-CSF (10 μg/kg/day) was similarly administered to 11 patients. We evaluated motor and sensory functions of patients using the American Spinal Cord Injury Association (ASIA) score and ASIA impairment scale (AIS) grade. In all 16 patients, neurological improvement was obtained after G-CSF administration. AIS grade increased by one step in 9 of 16 patients. A significant increase in ASIA motor scores was detected 1 day after injection (P < 0.01), and both light touch and pin prick scores improved 2 days after injection (P < 0.05) in the 10 μg group. No severe adverse effects were observed after G-CSF injection. These results indicate that intravenous administration of G-CSF (10 μg/kg/day) for 5 days is essentially safe, and suggest that some neurological recovery may occur in most patients. We suggest that G-CSF administration could be therapeutic for patients with acute SCI.
Conventional pulmonary vein isolation compared with the “box isolation” method: a randomized clinical trial

Esophageal injury is a potential complication with radiofrequency ablation in the posterior wall of the left atrium (LA). The “box isolation” method isolates the posterior LA wall including the pulmonary veins without ablation on the posterior LA wall. This study compares the acute and long-term efficacy of the box isolation method with conventional circumferential pulmonary vein isolation (PVI) for catheter ablation of AF. Twenty-nine patients (age 60±9 years, 62% male, 79% paroxysmal) with drug refractory AF underwent catheter ablation. Sixteen of the 29 patients (55%) underwent box isolation. Recurrence of AF was detected by checking the daily recorded rhythm strip on a portable home ECG monitor, irrespective of the symptoms. Mean follow-up duration was 10±2 months. Complete isolation of the posterior LA using box isolation lesions was achieved in three of 16 (19%) patients. The other 13 patients underwent creation of additional lesions until all PVs were isolated. Of the 16 patients who underwent box isolation, four patients (25%) had complete success, six patients (38%) had improvement, and the remaining six patients (37%) had failure. Of the 13 patients who underwent the standard PV isolation, two patients (15%) had complete success, eight patients (62%) had improvement, and the remaining three patients (23%) had failure (p=0.44). In this pilot study, the efficacy of box isolation is similar to the circumferential PVI for catheter ablation of AF. Few patients achieved PVI with box method alone. Based on these results, we do not recommend the box isolation strategy.
In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques: initial results of the SPECTACL study.

To determine whether catheter-based near-infrared spectroscopy (NIRS) signals obtained with a novel catheter-based system from coronaries of patients are similar to those from autopsy specimens and to assess initial safety of NIRS device.



An intravascular NIRS system for detection of lipid core-containing plaques (LCP) has been validated in human coronary autopsy specimens. The SPECTACL (SPECTroscopic Assessment of Coronary Lipid) trial was a parallel first-in-human multicenter study designed to demonstrate the applicability of the LCP detection algorithm in living patients.



Intracoronary NIRS was performed in patients undergoing percutaneous coronary intervention. Acquired spectra were blindly compared with autopsy NIRS signals with multivariate statistics. To meet the end point of spectral similarity, at least two-thirds of the scans were required to have >80% of spectra similar to the autopsy spectra.



A total of 106 patients were enrolled; there were no serious adverse events attributed to NIRS. Spectroscopic data could not be obtained in 17 (16%) patients due to technical limitations, leaving 89 patients for analysis.  Of the remaining 59 blinded cases, after excluding 11 due to inadequate data, spectral similarity was demonstrated in 40 of 48 spectrally adequate scans (83% success rate, 95% confidence interval: 70% to 93%, median spectral similarity/pullback: 96%, interquartile range 10%). The LCP was detected in 58% of 60 spectrally similar scans from both cohorts.



This intravascular NIRS system safely obtained spectral data in patients that were similar to those from autopsy specimens. These results demonstrate the feasibility of invasive detection of coronary LCP with this novel system.
Narrative exposure therapy for PTSD increases top-down processing of aversive stimuli - evidence from a randomized controlled treatment trial

Little is known about the neurobiological foundations of psychotherapy for Posttraumatic Stress Disorder (PTSD). Prior studies have shown that PTSD is associated with altered processing of threatening and aversive stimuli. It remains unclear whether this functional abnormality can be changed by psychotherapy. This is the first randomized controlled treatment trial that examines whether narrative exposure therapy (NET) causes changes in affective stimulus processing in patients with chronic PTSD. 34 refugees with PTSD were randomly assigned to a NET group or to a waitlist control (WLC) group. At pre-test and at four-months follow-up, the diagnostics included the assessment of clinical variables and measurements of neuromagnetic oscillatory brain activity (steady-state visual evoked fields, ssVEF) resulting from exposure to aversive pictures compared to neutral pictures. PTSD as well as depressive symptom severity scores declined in the NET group, whereas symptoms persisted in the WLC group. Only in the NET group, parietal and occipital activity towards threatening pictures increased significantly after therapy. Our results indicate that NET causes an increase of activity associated with cortical top-down regulation of attention towards aversive pictures. The increase of attention allocation to potential threat cues might allow treated patients to re-appraise the actual danger of the current situation and, thereby, reducing PTSD symptoms.  "Change of Neural Network Indicators Through Narrative Treatment of PTSD in Torture Victims" ULR: http://www.clinicaltrials.gov/ct2/show/NCT00563888
Sotalol versus Class I and II antiarrhythmic agents

In two separate, double-blind, multicenter antiarrhythmic studies, sotalol was compared with propranolol or quinidine using placebo for baseline and/or washout periods. The comparison with quinidine was a crossover study. To be enrolled in these studies, patients were required to have a premature ventricular contraction (PVC) rate of at least 30/hr on a baseline 24-hour ambulatory ECG. At doses calculated to produce equivalent degrees of beta blockade, sotalol was more effective than propranolol in reducing the frequency of PVCs, and the two drugs produced similar reductions in ventricular tachycardia (VT) events. The side effects for sotalol and propranolol were mainly due to beta blockade, and the incidence of side effects with the two drugs was similar. Sotalol was comparable with quinidine in reducing PVCs and VT events. The side effects on sotalol were primarily related to beta-adrenergic blockade, while those on quinidine were predominantly gastrointestinal or neurologic in nature.
Comparison of mental health between individuals with spinal cord injury and able-bodied controls in Neiva, Colombia.

Although research has investigated the mental health of individuals with spinal cord injury (SCI), an overwhelming majority of this research has been conducted in the United States, Western Europe, and other developed countries. The purpose of this study was to compare the mental health of individuals with SCI with able-bodied controls in Neiva, Colombia, South America. Subjects included 40 Colombians with SCI and 42 age- and sex-matched controls (N = 82). The groups did not differ based on age, sex, years of education, or socioeconomic status. However, controls were twice as likely to be married. Four measures assessed mental health, including satisfaction with life (Satisfaction with Life Scale), depressive symptoms (Patient Health Questionnaire-9), self-esteem (Rosenberg Self-Esteem Scale), and anxiety (State-Trait Anxiety Inventory). In comparison with able-bodied controls, individuals with SCI reported significantly lower mental health on both depressive symptoms and satisfaction with life. These effect sizes were medium and large, respectively. The groups did not differ significantly on measures of self-esteem or anxiety. Mental health of individuals with SCI should be considered a central part of SCI rehabilitation interventions, particularly in Latin America.
Psychometric properties of the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia

The Scale to Assess Unawareness in Mental Disorder (SUMD) is widely used in clinical trials and epidemiological studies but more rarely in clinical practice because of its length (74 items). In clinical practice, it is necessary to provide shorter instruments. The aim of this study was to investigate the validity and reliability of the abbreviated version of the SUMD.



We used data from four cross-sectional studies conducted in several psychiatric hospitals in France.



a diagnosis of schizophrenia based on DSM-IV criteria.



socio-demographic and clinical data (including duration of illness, Positive and Negative Syndrome Scale, and the Calgary Depression Scale); quality of life; SUMD.



confirmatory factor analyses, item-dimension correlations, Cronbach's alpha coefficients, Rasch statistics, relationships between the SUMD and other parameters. We tested two different scoring models and considered the response 'not applicable' as '0' or as missing data.



Five hundred and thirty-one patients participated in this study. The 3-factor structure of the SUMD (awareness of the disease, consequences and need for treatment; awareness of positive symptoms; and awareness of negative symptoms) was confirmed using LISREL confirmatory factor analysis for the two models. Internal item consistency and reliability were satisfactory for all dimensions. External validity testing revealed that dimension scores correlated significantly with all PANSS scores, especially with the G12 item (lack of judgement and awareness). Significant associations with age, disease duration, education level, and living arrangements showed good discriminant validity.



The abbreviated version of the SUMD appears to be a valid and reliable instrument for measuring insight in patients with schizophrenia and may be used by clinicians to accurately assess insight in clinical settings.
Long-term results of dose density therapy in patients with aggressive lymphoma

To evaluate the long-term outcome of dose density chemotherapy in the treatment of aggressive lymphoma, we analyzed 142 patients with untreated aggressive lymphoma. Chemotherapy was an eight-drug regimen given in weekly intervals in two prospective trials. The median observation period was 8 years; the longest follow-up was 13 years. Overall survival at 8 years was 0.583. The 8-year survival of patients ≤60 years was significantly better than that of older patients, namely 0.713 vs 0.304 (p=0.000000697). This excellent survival of patients aged ≤60 years was identical for high-risk and high-intermediate-risk patients compared with low-risk and low-intermediate-risk patients in the age-adjusted international prognostic index (IPI). The excellent long-term results of the CEOP/IMVP-Dexa regimen (cyclophosphamide, epirubicin, vincristine, and prednisone/ifosfamide with systemic mesna, methotrexate, etoposide, and dexamethasone) for patients aged ≤60 years suggest that this regimen might be superior to the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and needs to be tested in comparison to high-dose regimens and novel approaches including antibody treatment.
Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study.

GAUGUIN evaluated the safety and efficacy of obinutuzumab (GA101) monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). In phase 1 (dose escalation), 13 patients received obinutuzumab 400 to 1200 mg (days 1 and 8 of cycle 1; day 1 of cycles 2-8). In phase 2, 20 patients received a fixed dose of 1000 mg (days 1, 8, and 15 of cycle 1; day 1 of cycles 2-8). Infusion-related reactions occurred in nearly all patients, but few were grade 3/4. Grade 3/4 neutropenia occurred in 7 patients in phase 1 (but was not dose-related) and in 4 patients in phase 2. Overall end-of-treatment response (all partial responses) was 62% (phase 1) and 15% (phase 2); best overall response was 62% and 30%, respectively. Phase 2 median progression-free survival was 10.7 months and median duration of response was 8.9 months. In summary, obinutuzumab monotherapy is active in patients with heavily pretreated relapsed/refractory CLL.
High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance.

Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 +/- 2 microM) levels. Thirty-two diabetic subjects with low plasma vitamin C (<40 microM) were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C (800 mg/day for 4 wk). Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to ACh, sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 wk of treatment. In the placebo group (n = 17 subjects), plasma vitamin C (22 +/- 3 microM), fasting glucose (159 +/- 12 mg/dl), insulin (19 +/- 7 microU/ml), and SI(Clamp) [2.06 +/- 0.29 x 10(-4) dl x kg(-1) x min(-1)/(microU/ml)] did not change significantly after placebo treatment. In the vitamin C group (n = 15 subjects), basal plasma vitamin C (23 +/- 2 microM) increased to 48 +/- 6 microM (P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (>80 microM). No significant changes in fasting glucose (156 +/- 11 mg/dl), insulin (14 +/- 2 microU/ml), SI(Clamp) [2.71 +/- 0.46 x 10(-4) dl x kg(-1) x min(-1)/(microU/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes.
Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer.

To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer.



Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living.



The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01).



A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.
Personality and medication non-adherence among older adults enrolled in a six-year trial.

Personality factors parsimoniously capture the variation in dispositional characteristics that affect behaviours, but their value in predicting medication non-adherence is unclear. We investigated the relationship between five-factor model personality factors (Conscientiousness, Neuroticism, Agreeableness, Extraversion, and Openness) and medication non-adherence among older participants during a six-year randomized placebo-controlled trial (RCT).



Observational cohort data from 771 subjects aged ≥ 72 years enrolled in the Ginkgo Evaluation of Memory study, a RCT of Ginkgo biloba for prevention of dementia.



Random effects logistic regression analyses examined effects of NEO Five-Factor Inventory scores on medication non-adherence, determined via pill counts every 6 months (median follow-up 6.1 years) and defined as taking <80% of prescribed pills. Analyses adjusted for covariates linked with non-adherence in prior studies.



Each 5 year increment in participant age was associated with a 6.7% greater probability of non-adherence (95% confidence interval, CI [2.4, 11.0]). Neuroticism was the only personality factor associated with non-adherence: a 1 SD increase was associated with a 3.8% increase in the probability of non-adherence (95% CI [0.4, 7.2]). Lower cognitive function was also associated with non-adherence: a 1 SD decrease in mental status exam score was associated with a 3.0% increase in the probability of non-adherence (95% CI [0.2, 5.9]).



Neuroticism was associated with medication non-adherence over 6 years of follow-up in a large sample of older RCT participants. Personality measurement in clinical and research settings might help to identify and guide interventions for older adults at risk for medication non-adherence.
Vascular responses at proximal and distal edges of paclitaxel-eluting stents: serial intravascular ultrasound analysis from the TAXUS II trial.

On the basis of brachytherapy experience, edge stenosis has been raised as a potential limitation for drug-eluting stents. We used serial intravascular ultrasound (IVUS) to prospectively analyze vessel responses in adjacent reference segments after implantation of polymer-controlled paclitaxel-eluting stents.



TAXUS II was a randomized, double-blind trial with 2 consecutive patient cohorts that compared slow-release (SR) and moderate-release (MR) paclitaxel-eluting stents with control bare metal stents (BMS). By protocol, all patients had postprocedure and 6-month follow-up IVUS. Quantitative IVUS analysis was performed by an independent core laboratory, blinded to treatment allocation, in 5-mm vessel segments immediately proximal and distal to the stent. Serial IVUS was available for 106 SR, 107 MR, and 214 BMS patients. For all 3 groups, a significant decrease in proximal-edge lumen area was observed at 6 months. The decrease was comparable (by ANOVA, P=0.194) for patients in the SR (-0.54+/-2.1 mm2) and MR (-0.88+/-1.9 mm2) groups compared with the BMS (-1.02+/-1.9 mm2) group. For the distal edge, a significant decrease in lumen area was only observed with BMS (-0.91+/-2.0 mm2, P<0.0001); this decrease was significantly attenuated with SR (0.08+/-2.0 mm2) and MR (-0.19+/-1.7 mm2) stents (P<0.0001 by ANOVA). Negative vessel remodeling was observed at the proximal (-0.48+/-2.2 mm2, P=0.011) but not the distal edges of BMS and at neither edge of SR or MR stents.



The marked reduction in in-stent restenosis with SR or MR stents is not associated with increased edge stenosis at 6-month follow-up IVUS. In fact, compared with BMS, there is instead a significant reduction in late lumen loss at the distal edge with TAXUS stents.