nils-herrmann/clean_scirepeval huggingface dataset:
Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study

To compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer.



The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor-positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring.



In total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed.



There are several limitations of this OS analysis, including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed, and that not all patients participated in additional OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast Cancer) trial (ClinicalTrials.gov identifier: NCT01602380).
Influence of anticancer therapy on oxidation phenotype and acetylation phenotype in patients with acute myeloblastic leukemia.

The aim of this study was to determine whether antineoplastic cytostatic therapy induces changes in the oxidation or acetylation phenotypes in patients with acute myeloblastic leukemia (AML). The investigations involved 22 patients with AML undergoing chemotherapy with daunorubicin, cytosine arabinoside, etoposide and mitoxantrone. The oxidation phenotype prior to therapy and after termination of induction was examined in all 22 patients and was examined in 10 patients after termination of the first consolidation cycle. The acetylation phenotype was examined prior to therapy and after termination of induction in 21 patients and after termination of the first remission consolidation cycle in 9 patients. The oxidation phenotype was determined by means of the method by Eichelbaum and Gross. The acetylation phenotype was determined using Varley's modification of the Bratton-Marshall method. Anticancer therapy affected the oxidation phenotype, causing decreased activity of the cytochrome P450 isoenzyme CYP2D6. This decrease suggests that daunorubicin, cytosine arabinoside, etoposide and mitoxantrone may impair the metabolism of other active substances metabolized by this isoenzyme, which should be taken into consideration in planning the dosage scheme in individual patients and considering interactions between drugs. Evaluation of the effect of administered cytostatic drugs on acetylation phenotype revealed no statistically significant decrease in the rate of sulfadimidine acetylation.
Piloting and validation of a novel self-administered online cognitive screening tool in normal older persons: the Cognitive Function Test.

Subtle cognitive changes have been described that may predate the onset of clinically recognizable Alzheimer's disease (AD) and may reflect pathological changes in the brain that are detectable up to 10 years before the onset of AD. Early screening for cognitive status can have benefits in terms of early management and prevention strategies for cognitive decline.



A novel computerized cognitive screening tool, the Cognitive Function Test (CFT), was compared with established paper tests of episodic memory, executive function and processing speed, domains previously shown to be predictive of AD, with 50 normal participants, Mini Mental State Examination ≥24, mean age 58.1, SD 5.6 years (range 50-65). 
Significant correlations (r = 0.75, p < 0.0001) were found between the CFT and paper tests in a pilot study, showing concurrent validity. The pilot computerized tests were compared with the online version, and no differences were found in mean scores on the total test and domain-specific scores using an algorithm derived from the pilot CFT scores, thus showing internal consistency and reliability of the online format. Norms and 1.5 SD cut-offs for the CFT are presented.



The online CFT was shown to be suitable for self-administration in online format (with a mouse response mode) for this midlife age group. Individuals may wish to monitor their cognitive performance before memory concerns are sufficient to warrant visiting a GP or memory clinic.
Random number generation on parallel processors

Recent development of high speed supercomputers has enabled us to perform large scale Monte Carlo simulations which need a tremendous amount of random numbers. There are two types of supercomputers, i.e. pipeline type and processor array type, and we will confine ourselves in this paper to the random number generation on a computer of the latter type. It is desired that not only a sequence of random numbers generated on each processor is of good quality but also sequences generated on different processors are uncorrelated. If we use a linear congruential method on a 32-bit supercomputer, the whole period may be consumed in several seconds to several minutes. Random numbers with a much longer period can be generated by a GFSR algorithm. Using this algorithm, we will propose a method to generate uncorrelated series of random numbers on parallel processors.
Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment.

To assess the efficacy and safety of glucagon-like peptide-1 (GLP-1) on the plasma glucose level when given as a continuous infusion for either 16 or 24 h per day to type 2 diabetic patients who were poorly controlled on sulfonylurea treatment.



This single-center, randomized, parallel, double-blind, placebo-controlled trial was conducted in 40 hospitalized patients who were randomized to receive infusions of either placebo or GLP-1 4 or 8 ng. kg(-1). min(-1) for either 16 or 24 h per day for 7 days. At predetermined intervals, 24-h profiles of glucose, glucagon, and insulin were measured. Adverse events and clinical chemistry and hematology were recorded.



For all active treatment groups, the change in average glucose (area under the curve [AUC] for day 7 minus AUC for day 0 divided by 24 h) was statistically significantly different from placebo (P < or = 0.001). The GLP-1 8 ng. kg(-1). min(-1) dose given for 24 h was more efficacious than any of the other doses (P < or = 0.05). Nocturnal and fasting plasma glucose levels at day 7 were greater in the 16-h groups compared with the 24-h groups (P < or = 0.05). Insulin AUC did not show any treatment effect for any of the treatment groups when change was assessed from day 0 to day 7. However, for the 16-h groups, the pattern of the insulin profiles changed; the insulin profiles were considerably higher during the initial 3-4 h after restart of the GLP-1 infusion on day 7, although there was a tendency for insulin levels to decrease during the afternoon and evening. Glucagon AUC decreased significantly for all active treatment groups compared with placebo. GLP-1 was generally well tolerated.



This study demonstrated that GLP-1 should be given continuously to obtain the most optimal glycemic control. Because of the short plasma half-life of native GLP-1, long-acting derivatives should be developed to make GLP-1 treatment clinically relevant.
A longitudinal twin study on Tojikomori and depressive symptoms in Japanese elderly.

Genetic factors associated with Tojikomori (being housebound without any limitations in physical functioning or mental problems) are unclear. We performed a twin study to help clarify the causes of Tojikomori and investigate the association between Tojikomori and depressive symptoms.



Participants were members of the Osaka University Aged Twin Registry. A total of 157 twin pairs (314 individuals) who provided data in 2008 and 2012 were included. Depressive symptoms were measured by the Geriatric Depression Scale short version (GDS). Social Activities Scores (SAS) were measured with questions assessing the frequency of going out and contact with others. Activities of daily living were assessed with the Barthel index. Structural equation modelling analysis was used to evaluate the relative importance of genes and environments for the phenotypes measured.



In the first analysis, for SAS (2012), 25% of the variance was explained by additive genetic effects, and 75% was explained by unique environmental (including error) effects. For the GDS (2012), 28% of the variance was explained by additive genetic effects, and 72% was explained by unique environmental (including error) effects. In the second analysis, 25% of the total variance in SAS (2012) was explained by additive genetic factors, which influenced GDS scores (2008 and 2012). However, only 10% of the total variance in GDS scores (2012) was explained by additive genetic factors that influenced SAS (2008 and 2012).



Tojikomori was influenced by genetic factors in the elderly Japanese subjects. The association between Tojikomori and depressive symptoms was explained by genetic and environmental factors that are common to both phenotypes. Depressive symptoms were a cause of future Tojikomori and were affected by additive genetic factors. Genetic factors of Tojikomori were not a major cause of future depressive symptoms.
Outcomes and costs associated with hospitalist comanagement of medically complex children undergoing spinal fusion surgery.

The goal of this study was to assess outcomes and costs associated with hospitalist comanagement of medically complex children undergoing spinal fusion surgery for neuromuscular scoliosis.



A hospitalist comanagement program was implemented at a children's hospital. We conducted a retrospective case series study of patients during 2003-2008 to compare clinical and cost outcomes for 87 preimplementation patients, 40 patients during a partially implemented program, and 80 patients during a fully implemented program.



When compared with preimplementation patients, full implementation program patients did not demonstrate a statistically significant difference in median length of stay on the medical/surgical unit after transfer from the PICU (median: 6 vs 8 days; P = .07). Patients in the full implementation group received fewer days of parenteral nutrition (median: 0 vs 6 days; P = .0006) and had fewer planned and unplanned laboratory studies on the inpatient unit. There was no statistically significant change in returns to the operating room (P = .08 between preimplementation and full implementation), other complications, or 30-day readmissions. Median hospital costs increased from preimplementation ($59372) to partial implementation ($89302) and remained elevated during full implementation ($81 651) compared with preimplementation (P = .004). Mean physician costs followed a similar trajectory from preimplementation ($18425) to partial implementation ($24101) to full implementation ($22578; P = .0006 [versus preimplementation]).



A hospitalist comanagement program can significantly affect the care of medically complex children undergoing spinal fusion surgery. Initial program costs may increase.
[Child battering and adult psychopathology: an empiric study].

Childhood trauma and battering have been associated with adult psychopathology.



To explore the relationship between childhood trauma, somatization, post traumatic stress disorder (PTSD), affective disorder and borderline personality disorder in hospitalized patients of four Chilean hospitals.



Five hundred five patients were screened by a short seven item trauma recollection scale (70 from San Bernardo Hospital, 193 from Salvador Hospital, 97 from El Trabajador Hospital and 147 from Curico Hospital). A random sample of 85 cases was studied in depth using the CIDI 2.1, depression, PTSD and somatization scales, Inventory of Personality Organization (IPO) and the OQ 45.2 scale.



Forty five percent of patients did not report traumatic experiences, 38.4% recalled one or two events and 16.3% three or more traumatic experiences. The most remembered event was physical punishment (28.7%), followed by traumatic separation from parents (27.1%), alcohol and drug use by an adult at home (22%) and presence of family violence (22%). Thirty two percent of the 85 selected cases met CIDI criteria for affective disorder, 20% for post traumatic stress disorder and 11.8% for somatization disorder. There were statistically significant correlations between the frequence of trauma and post traumatic stress disorder (p <0.001), as well as somatization and depressive disorder (p <0.007 and 0.008).



This study supports the concept that traumatic psychosocial environments during childhood are a risk factor for diverse psychiatric syndromes during adulthood.
Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine.

A novel nanomedicine, CYT-6091, constructed by simultaneously binding recombinant human tumor necrosis factor alpha (rhTNF) and thiolyated polyethylene glycol to the surface of 27-nm colloidal gold particles, was tested in a phase I dose escalation clinical trial in advanced stage cancer patients.



CYT-6091, whose dosing was based on the amount of rhTNF in the nanomedicine, was injected intravenously, and 1 cycle of treatment consisted of 2 treatments administered 14 days apart.



Doses from 50 μg/m(2) to 600 μg/m(2) were well tolerated, and no maximum tolerated dose (MTD) was reached, as the highest dose exceeded the target dosage of 1-mg rhTNF per treatment, exceeding the previous MTD for native rhTNF by 3-fold. The first 2 patients on the study, each receiving 50 μg/m(2), did not receive any prophylactic antipyretics or H2 blockade. A predicted, yet controllable fever occurred in these patients, so all subsequently treated patients received prophylactic antipyretics and H2 blockers. However, even at the highest dose rhTNF's dose-limiting toxic effect of hypotension was not seen. Using electron microscopy to visualize nanoparticles of gold in patient biopsies of tumor and healthy tissue showed that patient biopsies taken 24 hours after treatment had nanoparticles of gold in tumor tissue.



These data indicate that rhTNF formulated as CYT-6091 may be administered systemically at doses of rhTNF that were previously shown to be toxic and that CYT-6091 may target to tumors. Future clinical studies will focus on combining CYT-6091 with approved chemotherapies for the systemic treatment of nonresectable cancers.
Does the Finger-to-Nose Test measure upper limb coordination in chronic stroke?

We aimed to kinematically validate that the time to perform the Finger-to-Nose Test (FNT) assesses coordination by determining its construct, convergent and discriminant validity. Experimental, criterion standard study. Both clinical and experimental evaluations were done at a research facility in a rehabilitation hospital. Forty individuals (20 individuals with chronic stroke and 20 healthy, age- and gender-matched individuals) participated.. Both groups performed two blocks of 10 to-and-fro pointing movements (non-dominant/affected arm) between a sagittal target and the nose (ReachIn, ) at a self-paced speed. Time to perform the test was the main outcome. Kinematics (Optotrak, 100Hz) and clinical impairment/activity levels were evaluated. Spatiotemporal coordination was assessed with slope (IJC) and cross-correlation (LAG) between elbow and shoulder movements. Compared to controls, individuals with stroke (Fugl-Meyer Assessment, FMA-UE: 51.9 ± 13.2; Box & Blocks, BBT: 72.1 ± 26.9%) made more curved endpoint trajectories using less shoulder horizontal-abduction. For construct validity, shoulder range (β = 0.127), LAG (β = 0.855) and IJC (β = −0.191) explained 82% of FNT-time variance for ReachIn and LAG (β = 0.971) explained 94% for ReachOut in patients with stroke. In contrast, only LAG explained 62% (β = 0.790) and 79% (β = 0.889) of variance for ReachIn and ReachOut respectively in controls. For convergent validity, FNT-time correlated with FMA-UE (r = −0.67, p < 0.01), FMA-Arm (r = −0.60, p = 0.005), biceps spasticity (r = 0.39, p < 0.05) and BBT (r = −0.56, p < 0.01). A cut-off time of 10.6 s discriminated between mild and moderate-to-severe impairment (discriminant validity). Each additional second represented 42% odds increase of greater impairment. For this version of the FNT, the time to perform the test showed construct, convergent and discriminant validity to measure UL coordination in stroke.
Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinson’s disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in “off” UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a “lesion-like” effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.
Adefovir dipivoxil is effective for the treatment of cirrhotic patients with lamivudine failure.

Data on the efficacy of adefovir dipivoxil (ADV) in elderly and cirrhotic patients with lamivudine-resistant (LAM-R) chronic hepatitis B are scarce. This retrospective cohort study evaluated the safety and efficacy of ADV in this specific patient population.



Sixty-eight cirrhotic LAM-R patients, of whom 19 (27.9%) were elderly (>or=65 years of age) and nine had severe disease (two post-orthotopic liver transplantation, four pre-orthotopic liver transplantation and three decompensated), with hepatitis B virus (HBV) infection received ADV. Virological and biochemical responses to the addition of ADV were analysed.



At inclusion, all patients were receiving LAM; ADV was added. 75.4% of patients received a combination of LAM and ADV throughout this study for a median treatment duration of 12.6 months; the remainder received ADV with an overlap with LAM treatment for a median duration of 7.9 months. At the end of follow-up, 41.2% of patients had undetectable HBV DNA (<or=2000 copies/ml) with a median reduction of 3.4 log(10) copies/ml. Time to reach undetectable HBV DNA was dependent on baseline alanine aminotransferase (ALT) levels and HBeAg status. Normalization of serum ALT levels was observed in 55.2% (32/58) of patients. In patients who were HBeAg positive at baseline, HBeAg loss and seroconversion occurred in 23% (9/39) and 10% (4/39) respectively. No resistance mutations and no significant side effects were observed during the study period.



Adefovir dipivoxil provides effective and safe treatment in cirrhotic and elderly patients who failed LAM therapy.
Potential mechanism of acute stent thrombosis with bivalirudin following percutaneous coronary intervention in acute coronary syndromes.

Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromes patients (ACS) undergoing percutaneous coronary intervention (PCI) with bivalirudin compared to heparin. We aimed to investigate the potential mechanisms responsible for thrombus formation under bivalirudin.



We compared heparin and bivalirudin during PCI for ACS in a prospective monocentre randomized study. Twenty patients were included after coronary angiography and received a loading dose (LD) of 180mg of ticagrelor at the time of PCI. They were randomly assigned to heparin (70UI/kg) intra-venous (IV) bolus or bivalirudin IV bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg/h until the end of the PCI. The VASP index and thrombin generation test were used to assess the course of platelet reactivity (PR) and thrombin generation.



Thrombin generation and PR were identical in both groups at baseline. There was no difference in the course of PR following the LD over time. An optimal PR inhibition was reached 4h after the LD of ticagrelor. Heparin and bivalirudin infusion effectively inhibited thrombin generation during PCI. However, 4h after the end of bivalirudin infusion, thrombin generation had returned to its baseline value whereas in the heparin group it remained significantly inhibited compared to baseline and to the bivalirudin group 4h after the end of the infusion (p<0.01 and p<0.02 respectively).



The present study suggests that the short half-life of bivalirudin and the quick restoration of thrombin activity at a time when optimal PR is not reached may be responsible for acute stent thrombosis.
Fatigue in HIV-Infected People: A Three-Year Observational Study.

HIV-related fatigue remains the most frequent complaint of seropositive patients.



To describe the natural course of fatigue in HIV infection, in a sample (n=128) followed for a three-year period.



A longitudinal prospective design was used to determine what factors influenced changes in fatigue intensity and fatigue-related impairment of functioning in a community-dwelling sample of HIV-infected individuals. Participants were followed every six months for a three-year period. At each study visit, we collected data on a large number of physiological and psychosocial markers that have been shown to be related to fatigue in HIV-infected people. At three month intervals between study visits, we collected data on fatigue via mailed questionnaires.



Fatigue in HIV infection is largely a result of stressful life events, and is closely tied to the anxiety and depression that accompany such events. Fatigue did not remit spontaneously over the course of the study, indicating the need for interventions to ameliorate this debilitating symptom.



Intervening to help people who are suffering from HIV-related fatigue to deal with stressful life events may help to ameliorate this debilitating symptom.